Morphometric and ultrastructural analysis of tramadol effects on epididymis: an experimental study.

The effect of tramadol addiction on epididymal structure was not investigated before. Therefore, this experimental study was carried out to investigate the effect of chronic tramadol use on the epididymal structure using light and electron microscopies. Thirty adult Wister Albino male rats were divided into two groups: control group (five rats) and tramadol-treated group (25 rats), which was further subdivided into five subgroups that received tramadol orally at 4.5, 9, 45, 90, and 135 mg/kg/day, respectively, for 18 weeks. Epididymal tissues were dissected and processed for histopathological examination. Morphometric analysis showed significantly reduced mean values of epididymal ducts' diameters and epithelial height in the tramadol-treated group compared with the control group. Light microscopic examination revealed degeneration and necrosis of epididymal cells in the tramadol-treated group. Electron microscopic (EM) examination showed ultrastructure alterations in a dose-dependent manner. In conclusion, tramadol can adversely affect all epididymal cells, which subsequently deteriorate epididymal function and may affect sperm maturation, leading to subfertility.

Intrinsic versus Extrinsic Aging: A Histopathological, Morphometric and Immunohistochemical Study of Estrogen Receptor ß and Androgen Receptor.

Skin is a target organ of sex steroids which play important roles in skin health and disease. The aim of this study is to investigate the expression of estrogen receptor ß (ERß) and androgen receptor (AR) in human skin from different age groups for a better understanding of the hormonal regulation of skin aging. Using standard immunohistochemical techniques, biopsies of sun-unprotected and sun-protected skin were taken from 60 normal subjects. Sun-protected skin showed significantly higher immunoreactivity for ERß and AR compared to sun-unprotected skin of all age groups. Significantly higher ERß H score and percent of expression were associated with the 20-35 years age group compared to the groups that were 35-50 years and >50 years old (p < 0.02, p = 0.03, respectively) in sun-unprotected and sun-protected skin (p < 0.001, p = 0.01, respectively). AR H score showed a negative correlation with age (p = 0.04) with no significant difference in immunoreactivity in different age groups, either in sun-unprotected or sun-protected skin. There was also a significant correlation between ERß H score and epidermal thickness in sun-unprotected (p = 0.04) and sun-protected skin (p = 0.04) in studied subjects regardless of age. The same relationships did not reach significance with AR expression. However, a significant positive correlation was detected between H scores and percent of expression of ERß and AR in sun-unprotected (p = 0.01, p = 0.02, respectively) and sun-protected skin (p = 0.005, p = 0.02, respectively) regardless of age. In conclusion, both ERß and AR decline gradually with intrinsic and extrinsic aging. This decline is more obvious with extrinsic aging. Further large-scaled studies are recommended to expand, validate and translate current findings to clinically significant, diagnostic and therapeutic applications. Molecular studies to investigate the probable ligand-independent action of both receptors are warranted. In addition, their gene expression patterns and associated signaling and metabolic pathways can also be tackled to provide a basis for further interventions in pathological processes that involve their dysregulation.

Immunohistochemical expression of sperm-associated antigen 9 in nonmelanoma skin cancer.

Sperm-associated antigen 9 (SPAG9) is a scaffold protein for c-Jun-NH2-kinases, which play an important role in cell survival, proliferation, apoptosis, and tumor development. SPAG9 was claimed to be involved in the pathogenesis of carcinoma in different organs. The aim of this work was to investigate its role in the pathogenesis of nonmelanoma skin cancer (NMSC) through its immunohistochemical (IHC) localization in skin biopsies of these tumors. This retrospective and prospective study included 67 cutaneous specimens; 42 of NMSC [20 cases with basal cell carcinoma (BCC) and 22 cases with squamous cell carcinoma (SCC)] and 25 normal sun-exposed skin biopsies from age and gender-matched healthy subjects as a control group. SPAG9 expression was evaluated using standard IHC techniques. SPAG9 was expressed in 90% of BCC cases and in 81.8% of SCC cases. Positive expression in inflammatory cells was detected in 100% and 63.6% of BCC and SCC cases, respectively. Positive stromal expression was detected in 20% of BCC cases and was absent in all SCC cases. A significant negative correlation (r = -0.55, P = 0.008) was noted between SPAG9 H score and SCC histological grade and a significant association between SPAG9 H score and tumor grade was also detected where higher values were present in grade I tumors (P = 0.001). SPAG9 was upregulated in NMSC when compared with normal skin. In conclusion, SPAG9 is expressed in NMSC cases. It should be evaluated in large-scale studies to determine if it plays an active pathogenic role or its expression is an epiphenomenon not related to NMSC pathogenesis. Large-scale studies are warranted to determine its potential utility in guiding treatment decisions and following disease progression in theses cases. Its expression in normal skin needs further investigation.

Immunohistochemical Evaluation of Leptin Role in Skin Tags.

Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of loose fibrous tissue. However, their exact etiology is not fully understood. Leptin is a major player in the biology and pathology of the skin and its appendages. It is linked to cell differentiation, proliferation, migration, and survival with pronounced effects on angiogenesis, blood flow, and tissue perfusion. This study aimed at investigating the possible role of leptin in STs pathogenesis and correlating its expression with different clinical and histopathological parameters. Using immunohistochemical techniques, we examined 90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and Body Mass Index-matched normal subjects as a control group. Leptin was overexpressed in STs compared with normal skin (p < .001). Nuclear and nucleocytoplasmic patterns were significantly associated with cases both in epidermis (p < .04) and dermis (p < .001). Higher epidermal leptin H score was significantly associated with female gender (p = .004) and haphazard collagen arrangement (p < .03). Higher dermal leptin H score was significantly associated with smooth skin tags (p = .01), dilated blood vessels (p = .04), presence of mast cells (MCs) (p = .002), presence of inflammatory cells (p = .004), and haphazard collagen arrangement (p < .001). In conclusion, leptin may play a role in STs pathogenesis through its effects on keratinocytes, fibroblasts and vascular endothelium. Further studies are recommended to clarify the molecular interplay between leptin and MCs in ST pathogenesis. Further studies are also needed to determine the significance of its nuclear expression.

Evaluation of Aquaporin-3 Role in Nonmelanoma Skin Cancer: An Immunohistochemical Study.

Aquaporin-3 (AQP3), is an aquaglyceroporin, that plays a role in cell proliferation, tumorigenesis, and cell migration. This study aimed at evaluating the possible role of AQP3 in nonmelanoma skin cancer (NMSC) pathogenesis through its immunohistochemical expression in skin biopsies of these diseases. One-hundred and thirty cutaneous specimens were studied. These included 60 cases of NMSC and 40 normal skin and 30 psoriasis samples, from age- and gender-matched subjects, as a control group. AQP3 was expressed in 66.7% of basal cell carcinoma (BCC) cases and in 93.3% of squamous cell carcinoma (SCC) cases. Higher AQP3 expression (p = .01), expression percentage (p = .01), and H score (p = .04) were significantly associated with SCC compared to BCC. Normal skin and psoriasis showed significantly higher AQP3 expression (p = .001, p < .001, respectively), expression percentage (p < .001 for both), and H score values (p < .001, p = .001, respectively) compared to NMSC. Higher H score values in BCC were significantly associated with female gender (p = .02) and with nodular lesions (p > .001). Higher H score values in SCC were significantly associated with grade III tumors (p = .04) and AQP3 percentage of expression was significantly correlated with grade III tumors (r = .48, p = .009). In conclusion, AQP3 may play a role in NMSC pathogenesis. This probably occurs through aquaporin-mediated glycerol transport and ATP generation. Its downregulation, observed in the current work, is mostly a result of excessive proliferation. Further studies are needed to investigate the therapeutic effect of its inhibition in NMSC treatment.

Immunolocalization of glioma-associated oncogene homolog 1 in non melanoma skin cancer.

Glioma-associated oncogene homolog (GLI)1 is involved in controlling cell proliferation and angiogenesis. The aim of this work was to explore its possible role in non-melanoma skin cancer pathogenesis through its immunohistochemical (IHC) expression in skin biopsies of these diseases and correlating this expression with the clinico-pathological parameters of the studied cases. Seventy-six cutaneous specimens were studied; 30 cases with basal cell carcinoma (BCC), 30 cases with squamous cell carcinoma (SCC) and 16 normal skin samples, from age- and gender-matched subjects, as a control group. GLI1 was expressed in all BCC cases and in 60% of SCC cases. All SCC cases showed cytoplasmic, while 70% of BCC cases showed nucleocytoplasmic immunoreactivity. It was over expressed in BCC and SCC compared to normal skin (p = 0.01 and 0.0006, respectively). Higher Histo (H) score in BCC cases was significantly associated with female gender (p = 0.04), multiple lesions, desmoplastic stromal reaction and stromal angiogenesis (p < 0.001 for all). Higher H score in SCC cases was significantly associated with scalp location, nodular type, recurrent lesions, high tumor grade, lymphovascular invasion (p = 0.004 for all), inflammatory stromal reaction (p = 0.01), lymph node involvement and absence of calcification (p = 0.001 for both). In conclusion, GLI1 may play a role in BCC pathogenesis through its role in cell proliferation, migration, and angiogenesis. Its upregulation and cytoplasmic localization in SCC may suggest that its role in tumor pathogenesis is through mechanisms other than Hedgehog pathway activation. Further studies are needed to clarify the exact molecular basis of its oncogenic action.

Nuclear factor kappa B and cyclo-oxygenase-2: two concordant players in psoriasis pathogenesis.

Nuclear factor kappa B (NFκB) is a key regulatory element in a variety of immune and inflammatory pathways, cellular proliferation, differentiation and apoptosis. Cyclo-oxygenase 2 (COX2) is one of the downstream targets of NFκB. The current work aimed to explore the possible role of NFκB and COX2 in psoriasis pathogenesis through their immunohistochemical (IHC) expression in skin biopsies of this disease and correlating this expression with clinico-pathological parameters of studied cases. 103 subjects were studied; including 58 cases with psoriasis vulgaris (lesional and perilesional skin) and 45 normal, age- and gender-matched subjects, as a control group. NFκB and COX2 expressions were evaluated using standard IHC techniques. NFκB and COX2 were upregulated in psoriasis lesional skin compared to perilesional (p < 0.001 for both) and control skin (p < 0.001 for both). Higher NFκB and COX2 H scores were significantly associated with absent granular cell layer (p = 0.02 for both), severe degree of perivascular inflammatory infiltrate (p = 0.03 and 0.002, respectively) and thin suprapapillary epidermis (p = 0.003 and 0.006, respectively). Significant positive correlation was noted between NFκB and COX2 H scores in epidermis (r = 0.41, p = 0.02) and dermis (r = 0.6, p = 0.04) of lesional skin. Significant positive correlation between NFκB H score and PASI score (r = 0.38, p = 0.04) and between COX2 H score and PASI score (r = 0.52, p < 0.001) were detected in lesional epidermis. In conclusion, both NFκB and COX2 play a role in the pathogenesis of chronic plaque psoriasis. This may open an avenue for research for new therapeutic modalities based on their inhibition.

Idiopathic acquired true leukonychia totalis.

Idiopathic acquired true leukonychia totalis is a rare nail disorder not associated with other abnormalities. We present a case in a 12-year-old Egyptian boy.

Immunolocalization of androgen receptor and estrogen receptors in skin tags.

Skin tags (STs) are benign connective tissue tumors of the dermis. Several clinical observations suggested the involvement of sex steroids in their development. This study aimed at investigating the possible role of androgen receptor (AR) and estrogen receptors (ERs) in STs pathogenesis through their immunohistochemical (IHC) localization in skin biopsies of this disease and to correlate their expression with different clinical and histopathological parameters. Using IHC techniques, we examined 62 cases with STs and 30 gender- and age-matched, healthy subjects, representing the control group. ERα, ERß, and AR were upregulated in STs compared to normal skin in epidermis and dermis (p < .001 for all). Higher AR H score was significantly associated with axillary STs (p = .02), skin colored tags (p = .03), acanthosis, and papillomatosis (p = .04 for both). Higher ERα H score was significantly associated with hyperpigmented tags (p < .001) and positive family history (p = .003). Higher ERß H score was significantly associated with female gender and obesity (p = .004 for both). Higher ERα and AR H scores were significantly associated with loose collagen arrangement (p = .02, p = .004, respectively). Higher AR, ERα, and ERß H scores were significantly associated with the presence of mast cells (p = .01, p = .04, p = .002, respectively) and dilated blood vessels (p = .006, p = .04, p = .04, respectively). In conclusion, AR and ERs may share in STs pathogenesis through their effect on keratinocytes, fibroblasts, and mast cells.

Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo; a clue to interfollicular melanocyte stem cell reservoir.

There has been a long lasting controversy over whether melanocytes (MCs) in vitiligo are actually lost or still present but functionally inactive. We aimed to evaluate the MC cell lineage in follicular and interfollicular vitiliginous epidermis through immunohistochemical localization of Human Melanoma Black-45 (HMB-45) and Tyrosinase Related Protein 2 (TRP2) and to correlate it with clinicopathologic parameters. Using immunohistochemical techniques, skin biopsies from 50 vitiligo patients and 20 age- and gender-matched healthy subjects were examined. Differentiated active MCs were detected in 44% of interfollicular epidermis (IFE) and 46.7% of follicular epidermis (FE) in lesional skin. Melanocyte precursors/stem cells were detected in 54% of IFE and 63.3% of FE in lesional skin. Melanocyte precursors/stem cells of IFE were significantly associated with residual melanin pigment (p = 0.007) and with absence of angiogenesis (p = 0.05). HMB-45 percentage of expression in IFE was positively correlated with MC precursors/stem cells percentage in FE (r = +0.65, p < 0.001) and IFE (r = +0.33, p = 0.01). Melanocyte precursors/stem cells positivity (p < 0.001) was progressively decreasing with advanced histopathologic grading. There was no significant association between interfollicular or follicular expression of HMB-45, TRP2 or MC precursors/stem cells and the clinical type of vitiligo or its duration. In conclusion, functioning MCs may exist in vitiligo. The presence of MC precursors/stem cells in IFE may provide an additional reservoir needed for repigmentation.

Hematopoietic stem cells: do they have a role in keloid pathogenesis?

Keloids are slow growing neoplasms characterized by benign proliferation of fibroblasts that is due, at least in part, to altered cytokine profiles. Stem cells were claimed to play a role in skin tumor development. However, their role in keloid formation is unclear. The current study investigated the immunoreactivity of CD34 and c-KIT antibodies in 30 cases with keloid lesions together with normal skin biopsies of 30, sex and age-matched subjects representing the control group. Examined keloid sections showed positive dermal stromal immunoreactivity for CD34 in 76.7% of cases. CD34 expression intensity and H score were upregulated in keloid tissue relative to normal skin (p < 0.0001, p = 0.0002, respectively) and in perilesional relative to lesional tissue (p = 0.03, p < 0.001, respectively). c-KIT showed positive dermal stromal expression in all cases. Dermal c-KIT expression intensity and H score were upregulated in keloid tissue relative to normal skin (p < 0.008, p < 0.001, respectively) and in perilesional relative to lesional tissue (p < 0.0001, p < 0.001, respectively). Lesional skin showed more staining of basal keratinocytes when compared to perilesional tissue (p < 0.0001). Hematopoietic stem cells may share in keloid pathogenesis. Further studies are warranted to gain firmer conclusion about the exact role played by these cells and the significance of their perilesional accumulation. The future therapy of keloid scars may have to target this stem cell population in order to deprive these tumors of their regenerative cell pools.

Immunohistochemical expression of aberrant Notch-1 signaling in vitiligo: an implication for pathogenesis.

The etiopathogenetic mechanisms leading to pigment loss in vitiligo are not fully understood. Notch signaling is required for development and maintenance of melanocyte lineage and acts as a key component among keratinocyte-melanocyte interactions. The current study aimed to investigate the possible role of Notch signaling and its effect on the whole melanocyte lineage in vitiligo and correlating it with the different clinicopathologic parameters. Using immunohistochemical technique, Notch-1 expression was evaluated in 50 lesional and 20 perilesional biopsies of patients with vitiligo in comparison with 20 normal skin biopsies as a control group. Lesional biopsies were stained with human melanoma black-45 and tyrosinase-related protein-2 to demonstrate the melanocyte lineage. Membranous and/or nuclear expression of Notch-1 was in favor of control and perilesional skin, whereas cytoplasmic expression appeared only in vitiliginous lesions (P < .05). Membranous and/or nuclear expression of Notch-1 was significantly associated with epidermal human melanoma black-45 positivity (P = .01) and percentage of expression in both epidermis (P = .02) and hair follicles (P = .03) of lesional skin. Cytoplasmic pattern of Notch-1 expression in epidermis was significantly found in lesions with white hair (P = .04) and in cases with marked keratinocyte vacuolization (P = .03). Segmental and acrofacial vitiligo were associated with mild to moderate Notch-1 intensity, whereas generalized vitiligo was associated with strong intensity of expression (P = .02). In conclusion, Notch-1 signaling is inactivated in vitiligo with consequent loss of epidermal and/or follicular active melanocytes. Aberrant Notch signaling in vitiliginous white hair and acral and segmental vitiligo may be the cause of their treatment resistance.

Immunohistochemical expression of granzyme B and perforin in discoid lupus erythematosus.

Discoid lupus erythematosus (DLE) is a chronic photosensitive dermatosis characterized by scarring and atrophy. Granzyme B is a serine protease found in the cytoplasmic granules of cytotoxic lymphocytes and natural killer cells. Perforin permits delivery of the cytotoxic granzymes A and B into target cells to induce apoptosis and cause target cell death. The current study investigated the expression of granzyme B and perforin in 25 cases of DLE and in 10 cases of normal skin by immunohistochemistry and correlated their expression with the clinicopathological features in the studied DLE group. Both granzyme B and perforin were expressed in DLE with absent expression in normal skin. They were parallelly expressed in DLE where granzyme B was associated with features of chronicity such as old age (p = 0.05) and long duration of the disease (p = 0.05). Perforin expression in DLE was associated with male gender (p = 0.04) and outdoor workers (p = 0.04). Finally, expression of both granzyme B and perforin in dermal lymphocytic inflammatory infiltrate in DLE may indicate the cytotoxicity of the infiltrate. The parallel expression of both molecules may refer to the cooperative relationship between them to enhance cytotoxicity. Higher expression of granzyme B than perforin may indicate the presence of other pathways for granzyme B release independent from perforin.

Vitamin D Receptor Gene Polymorphisms Taq-1 and Cdx-1 in Female Pattern Hair Loss.

BACKGROUND: Female pattern hair loss (FPHL) is an important cause of hair loss in adult women and has a major impact on patient's quality of life. It evolves from the progressive miniaturization of follicles that leads to a subsequent decrease of hair density, leading to non-scarring diffuse alopecia, with characteristic clinical, dermoscopic, and histological patterns. Vitamin D receptor (VDR) is expressed in follicular keratinocytes and dermal papilla cells and is shown to have important role in hair growth and regulation of hair cycle. VDR polymorphism was not extensively investigated in hair disorders including FPHL. AIM: To investigate the association between VDR gene polymorphism (Cdx-1 and Taq-1) and FPHL to explore if these polymorphisms affect the disease occurrence or influence its clinical presentation. METHODS: A case-control study was conducted on 30 female patients with FPHL and 30 age-matched female healthy subjects, as a control group. Degree of hair loss was assessed by Ludwig grading. VDR gene polymorphisms, Taq-1 and Cdx-1 were investigated by real time polymerase chain reaction. RESULTS: CC genotype, TC genotype, and T allele of Taq-1 were more prevalent in FPHL patients than in control group. They increased disease risk by 12.6, 2.1, and 2.9 folds, respectively. AA genotype, GA genotype, and G allele of Cdx-1 were significantly more prevalent among FPHL patients than in control group. They increased disease risk by 7.5, 5.2, and 5.5 folds, respectively. CONCLUSION: Taq-1 and Cdx-1 can be considered as risk factors for FPHL. They may play role in disease persistence rather than disease initiation. This association may be explained by failure of new anagen growth and decreased proliferation of hair follicle stem cells. Further studies are recommended to confirm current findings.

Peroxisome Proliferator-Activated Receptor-γ Gene Polymorphism in Psoriasis and Its Relation to Obesity, Metabolic Syndrome, and Narrowband Ultraviolet B Response: A Case-Control Study in Egyptian Patients.

BACKGROUND: Psoriasis is a common dermatologic disease with multifactorial etiology in which genetic factors play a major role. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in keratinocytes and is known to affect cell maturation and differentiation in addition to its role in inflammation. AIM: To study the association between PPAR-γ gene polymorphism and psoriasis vulgaris in Egyptian patients to explore if this polymorphism influenced disease risk or clinical presentation. METHODS: Forty-five patients with psoriasis vulgaris and 45 age, sex and body mass index matched healthy volunteers who have no present, past or family history of psoriasis as a control group were enrolled. Selected cases included obese and nonobese participants. Detection of PPAR-γ gene polymorphism was done with restriction fragment length polymorphism polymerase chain reaction. Narrow-band ultraviolet B (NBUVB) was given for every case three times/week for 12 weeks. RESULTS: Homopolymorphism, heteropolymorphism, and Ala allele were significantly associated with cases (P = 0.01, P = 0.01, and P = 0.004, respectively) and increased risk of occurrence of psoriasis by 5.25, 3.65, and 3.37 folds, respectively. Heteropolymorphism was significantly associated with nonobese cases compared to obese ones (P = 0.01). Ala allele was significantly associated with obese cases (P = 0.001) and increased risk of occurrence of psoriasis in obese participants by 1.14 folds. Homopolymorphism, heteropolymorphism, and Ala allele were more prevalent among obese cases without metabolic syndrome (MS) than obese cases with MS but without statistical significance. Percentage of decrease of mean Psoriasis Area and Severity Index score before and after 3 months of treatment with NBUVB was higher in cases with heteropolymorphism with no significant difference between homo- and heteropolymorphism. CONCLUSION: PPAR-γ gene polymorphism is associated with and increased the risk of psoriasis and its associated obesity in Egyptian patients. It has no role in NBUVB response in those patients. Future large-scale studies on different populations are recommended.

Polymorphism of FAS and FAS Ligand Genes in Alopecia Areata: A Case-control Study in Egyptian Population.

BACKGROUND: Alopecia areata (AA) is a common dermatologic disease with suspected autoimmune etiology. Tumor necrosis factor superfamily member 6 or CD95 (FAS) and FAS ligand (FASL) are proapoptotic proteins. The relationship between apoptosis and autoimmunity is well recognized. Inflammatory T cells in AA are cytotoxic and possess FAS/FASL antigens. AIM: This study aims to investigate the association between FAS-670 A/G and FASL-124 A/G gene polymorphisms and AA to clarify if these polymorphisms influence disease occurrence or increase disease risk. MATERIALS AND METHODS: A case-control study was conducted on sixty patients with AA, and 40 age- and sex-matched healthy subjects, as a control group. Disease severity was assessed by severity of alopecia tool (SALT) Score. FAS 670A/G and FASL 124A/G gene polymorphisms were investigated by the restriction fragment length polymorphism polymerase chain reaction. RESULTS: For FAS gene, G/G genotype was significantly higher in cases than in control group with odds ratio 5.1. G allele was more prevalent among patient group with odds ratio 1.75. For FASL gene, A/G genotype was significantly higher in cases than in control group with odds ratio 4.53. G allele was more prevalent among patient group with odds ratio 1.88. GG genotype of FAS was significantly associated with longer disease duration (P =0.001), recurrent attacks (P =0.01), higher SALT score (P =0.009), alopecia universalis (P =0.002), and severe disease (P =0.006). CONCLUSION: FAS and FASL gene polymorphisms are associated with AA. Further large-scale studies on different ethnicities are required for more clarification of their role in disease development. Therapeutic modalities based on their inhibition could be promising in the treatment of a common disease like AA.

Re-appraisal of Keratinocytes' Role in Vitiligo Pathogenesis.

BACKGROUND: Vitiligo is a common pigmentary disorder. Studies on its pathogenesis extensively investigated melanocytes' abnormalities and few studies searched for keratinocytes' role in disease development. Liver X receptor-α (LXR-α) is a member of nuclear hormone receptors that acts as a transcription factor. Its target genes are the main regulators of melanocyte functions. AIM: The aim of this study is to investigate keratinocytes' role in vitiligo pathogenesis through immunohistochemical expression of LXR-α in lesional, perilesional, and distant nonlesional vitiligo skin. MATERIALS AND METHODS: This case-control study was carried out on 44 participants. These included 24 patients with vitiligo and 20 age- and sex-matched normal individuals as a control group. Biopsies, from cases, were taken from lesional, perilesional, and distant nonlesional areas. Evaluation was done using immunohistochemical technique. RESULTS: Keratinocyte LXR-α expression was upregulated in the lesional and perilesional skin (follicular and interfollicular epidermis) compared with control skin (P <0.001 for all). There was significant association between higher histoscore (H-score) in lesional epidermis (P <0.001) and in hair follicle (P =0.001) and the presence of angiogenesis. There was significant association between higher H-score in lesional epidermis and suprabasal vacuolization (P =0.02). No significant association was found between H-score or expression percentage and clinical data of selected cases. CONCLUSION: LXR-α upregulation is associated with keratinocyte damage in vitiligo lesional skin that leads to decreased keratinocyte-derived mediators and growth factors supporting the growth and/or melanization of surrounding melanocytes. Therefore, melanocyte function and survival are affected.

Identification of Genotypes and Allelic Frequencies of Vitamin D Receptor Gene Polymorphism (TaqI) in Egyptian Melasma Patients.

BACKGROUND: Melasma is a characteristic pattern of facial hyperpigmentation, occurring primarily on the forehead, cheeks, and chin, in a mask-like distribution. The pathogenesis of melasma is not fully understood. Vitamin D plays a role in skin pigmentation. It exerts its effect through vitamin D receptor (VDR), which is expressed in variable cells including normal melanocytes. AIM AND OBJECTIVE: The aim of the current work was to investigate if VDR gene polymorphism (TaqI) confers susceptibility to melasma in Egyptian patients. MATERIALS AND METHODS: A total of 45 female patients with melasma were recruited and 50 healthy subjects that were matched on age, sex, body mass index, and skin phototype, were included as a control group. TaqI polymorphism was investigated using restriction fragment length polymorphism polymerase chain reaction (RFLP PCR). RESULTS: Presence of (t) allele and (tt) genotype was significantly associated with melasma cases compared with control group (P < 0.001 for both). No significant association was found between (tt) genotype or (t) allele and clinical data of the studied cases. CONCLUSION: TaqI polymorphism is associated with melasma. Further, large-scale studies are recommended to underscore and validate the current findings. It is also necessary for future studies to extend the research to other populations and ethnicities. Investigating other VDR gene polymorphisms in melasma is also warranted. Since melasma is a multifactorial disease, gene-gene and gene-environment interactions should be considered in future genetic-epidemiologic researches to apply more comprehensive insight into the role of VDR gene in its pathogenesis.

Immunohistochemical Expression of Cyclo-oxygenase 2 and Liver X Receptor-α in Acne Vulgaris.

INTRODUCTION: Acne Vulgaris (AV) is a common inflammatory disease of pilosebaceous units. Liver X Receptor-α (LXR-α) is a ligand activated transcription factor. It controls transcription of genes involved in lipid and fatty acid synthesis. Cyclo-oxygenase 2 (COX2) is a rate limiting enzyme in prostaglandin synthesis. It plays important role in inflammation. AIM: To evaluate the immunohistochemical expression of LXR-α and COX2 in acne vulgaris skin biopsies to explore their possible pathogenic role in this disease. MATERIALS AND METHODS: Sixty five subjects were included (45 cases with AV and 20 age and gender-matched healthy controls). Skin biopsies were taken from lesional and perilesional skin of cases and from site-matched areas of control subjects. The evaluation of LXR-α and COX2 was done using immunohistochemical technique. Data were collected, tabulated and statistically analysed using a personal computer with "(SPSS) version 11" program. Chi-square test was used to study the association between qualitative variables. Mann-Whitney test was used for comparison between quantitative variables. Student's t-test was used for comparison between two groups having quantitative variables. Spearman's coefficient was used to study the correlation between two different variables. Differences were considered statistically significant with p<0.05. RESULTS: COX2 was upregulated in lesional skin compared with peilesional and control skin both in epidermis and pilosebaceous units (p<0.001 for all). Higher epidermal COX2% was significantly associated with papulopustular acne (p=0.009) and higher acne score (p=0.018). Higher pilosebaceous units COX2% was significantly associated with papulopustular acne (p=0.04). LXR-α was upregulated in lesional skin compared with peilesional and control skin both in epidermis and pilosebaceous units (p<0.001 for all). Higher LXR-α % in epidermis and pilosebaceous units was significantly associated with papulopustular acne (p=0.01 for both) and higher acne score (p=0.03 for both). Significant positive correlation was detected between COX2% and LXR-α % in epidermis (p=0.001, r=0.87) and pilosebaceous units (p=0.001, r=0.65). CONCLUSION: Both LXR-α and COX-2 play a role in the pathogenesis of acne vulgaris through their effects on cellular proliferation, inflammation and lipid synthesis. Research for new therapeutic modalities based on their inhibition is needed. More understanding of the interaction between LXR-α, COX2 and acne lesions may lead to effective interference, possibly directed toward specific cell types or steps within inflammatory pathways.

Evaluation of Hypoxia Inducible Factor-1α and Glucose Transporter-1 Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study.

INTRODUCTION: Hypoxia Inducible Factor-1 (HIF-1) is a mediator enabling cell adaptation to hypoxia. It plays its role mainly through transcription of many target genes including Glucose Transporter-1 (GLUT-1) gene. AIM: The present work aimed at evaluating the pattern and distribution of HIF-1α and GLUT-1 in each case and control. MATERIALS AND METHODS: A case-control and retrospective study was conducted on archival blocks diagnosed from pathology department as, Basal Cell Carcinoma (BCC, 20 cases), cutaneous Squamous Cell Carcinoma (SCC, 20 cases) and 20 normal site-matched skin biopsies from age and gender-matched healthy subjects as a control. Evaluation of both HIF-1α and GLUT1 expression using standard immunohistochemical techniques was performed on cut sections from selected paraffin embedded blocks. RESULTS: HIF-1α was expressed in 90%, 35% and 100% of normal skin, BCC and SCC tumour islands respectively. It was up regulated in both BCC and SCC compared with normal skin (p= 0.001, p<0.001 respectively). GLUT-1 was expressed in 100%, 70% and 100% of normal skin, BCC and SCC tumour islands respectively. It was down regulated in Non Melanoma Skin Cancer (NMSC) cases compared with normal skin (p=0.004). HIF-1α and GLUT-1 localization in tumour nests was central, peripheral or central and peripheral. Both HIF-1α and GLUT-1 showed variable expression in stroma, adnexa and inflammatory cells. No significant correlation was found between Histo (H) score or expression percentage values of HIF-1α and those of GLUT-1 in tumour islands or in overlying epidermis either in BCC or SCC. CONCLUSION: HIF-1α may have a role in NMSC pathogenesis through adaptation to hypoxia which results from excessive proliferation. GLUT-1 down regulation in NMSC may be explained by its consumption by proliferating tumour cells. The expression of HIF-1α and GLUT-1 in normal epidermis, stromal and adnexal structures needs further research.