Dopamine as a potential diagnostic biomarker in women's sexual dysfunction.

Dopamine and prolactin are the key mediators involved in sexual function in both males and females, but the role of dopamine in female sexual dysfunction (FSD) is still unclear. The aim was to investigate the possible role of dopamine and their relationship with sex steroid hormones (estrogen, progesterone and dehydroepiandrosterone; DHEA) and prolactin levels in Egyptian women suffering from sexual dysfunction. This study included 84 women having sexual dysfunction (FSD group) and 84 normal sexual function (control group). All women were subjected to the questionnaire to assess their demographic and gynecological data as well as female sexual function index (FSFI). Blood samples were collected from all women for measuring serum estradiol, progesterone, DHEA, prolactin and dopamine levels. FSD patients had significantly higher serum progesterone and DHEA and prolactin levels; while significantly lower dopamine and estradiol levels versus controls (p < 0.001). In all women, dopamine level appeared as a predictor of FSD at cut-off point ≤8.8 ng/mL with sensitivity (75%), specificity (92%) and accuracy (83%) (p < 0.001). The low levels of dopamine were associated with significantly higher prevalence in patients with low estradiol (p < 0.001) and high progesterone (p < 0.001), DHEA (p < 0.001) and prolactin (p = 0.004). Also, dopamine was significantly positive correlation with arousal score (r = 0.16, p = 0.04), and negative correlation with age (r = -0.31, p < 0.001), pain score (r = -0.19, p = 0.01), DHEA (r = -0.45, p < 0.001) and prolactin (r = -0.28, p < 0.001). Low serum dopamine level is a potential diagnostic biomarker in women's sexual dysfunction and their association with high prolactin and sex steroid hormones dysfunction.

Human beta-defensin 1 circulating level and gene polymorphism in non-segmental vitiligo Egyptian patients

Abstract Background: Vitiligo is an acquired depigmented skin disorder. It has a genetic and autoimmune background. Human beta defensin-1(HBD-1) plus its gene polymorphism were linked to some autoimmune disorders. Objectives: To elucidate the possible role of HBD-1 in the pathogenesis of non-segmental vitiligo (NSV) through evaluation of HBD-1 serum levels and its single nucleotide polymorphism (SNP) in patients having NSV, in addition, to correlating the results with the extent of vitiligo in those patients. Methods: A current case-control study included 50 patients having NSV and 50 controls. The authors used Vitiligo Area Scoring Index (VASI) score to assess vitiligo severity and laboratory investigations to assess serum HBD-1 level using ELISA and defensin-beta1 (DEFB1) SNP using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There were significantly lower HBD-1 serum levels in NSV cases than in controls (p < 0.001). There was a significant predominance of GG DEFB1 genotype and G allele in NSV patients in comparison to controls (p < 0.001). The levels of serum HBD-1 and DEFB1 genotypes were not associated or correlated significantly with any of the personal and clinical parameters of vitiligo patients. Study limitations: The small sample size. Conclusions: DEFB1 gene polymorphism (GG genotype and G allele) may modulate vitiligo risk and contribute to vitiligo development in Egyptian populations. Decreased circulating HBD-1 levels might have an active role in vitiligo etiopathogenesis that could be mediated through its possible anti-inflammatory effects.

Human beta-defensin 1 circulating level and gene polymorphism in non-segmental vitiligo Egyptian patients.

BACKGROUND: Vitiligo is an acquired depigmented skin disorder. It has a genetic and autoimmune background. Human beta defensin-1(HBD-1) plus its gene polymorphism were linked to some autoimmune disorders. OBJECTIVE: To elucidate the possible role of HBD-1 in the pathogenesis of non-segmental vitiligo (NSV) through evaluation of HBD-1 serum levels and its single nucleotide polymorphism (SNP) in patients having NSV, in addition, to correlating the results with the extent of vitiligo in those patients. METHODS: A current case-control study included 50 patients having NSV and 50 controls. The authors used Vitiligo Area Scoring Index (VASI) score to assess vitiligo severity and laboratory investigations to assess serum HBD-1 level using ELISA and defensin-beta1 (DEFB1) SNP using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: There were significantly lower HBD-1 serum levels in NSV cases than in controls (p < 0.001). There was a significant predominance of GG DEFB1 genotype and G allele in NSV patients in comparison to controls (p < 0.001). The levels of serum HBD-1 and DEFB1 genotypes were not associated or correlated significantly with any of the personal and clinical parameters of vitiligo patients. STUDY LIMITATION: The small sample size. CONCLUSIONS: DEFB1 gene polymorphism (GG genotype and G allele) may modulate vitiligo risk and contribute to vitiligo development in Egyptian populations. Decreased circulating HBD-1 levels might have an active role in vitiligo etiopathogenesis that could be mediated through its possible anti-inflammatory effects.

Interleukin-17A in Egyptian leprosy patients: a clinical, genetic, and biochemical study

Abstract Background: Leprosy represents a long-term communicable disease resulting from Mycobacterium leprae infection. IL-17A is one of the pro-inflammatory cytokines that protects humans against many fungal and bacterial pathogens. Objective: To investigate IL-17A (rs2275913) gene polymorphism and its circulating level in leprosy patients, and to correlate the detected results with different clinical aspects of leprosy in the investigated patients. Methods: 60 patients with leprosy, and 29 age and sex-matched volunteers were investigated for IL-17A serum level and IL-17A single nucleotide polymorphism (SNP) by ELISA and RFLP-PCR respectively. Results: IL-17A serum level was significantly higher in leprosy patients than in controls (p = 0.034), and in TL than LL (p = 0.017). IL-17A (rs2275913 A/G) G allele and GG genotype were associated significantly with LL (p = 0.005and 0.001 respectively). IL-17A (rs2275913 A/G) AG genotype carriers demonstrated the highest IL-17A serum levels; however, its lowest levels were found in IL-17A (rs2275913 A/G) AA genotype carriers (p = 0.005). Grade 2 disability (p = 0.030) and positive slit skin smear (SSS) (p = 0.005) were significantly associated with IL-17A (rs2275913 A/G) GG genotype. Study limitations: The small number of studied subjects. Conclusions: IL -17A may have a pivotal role in leprosy pathogenesis. IL-17A (rs2275913) GG genotype plus G allele might be related to the development of LL in the Egyptian population.

Interleukin-17A in Egyptian leprosy patients: a clinical, genetic, and biochemical study.

BACKGROUND: Leprosy represents a long-term communicable disease resulting from Mycobacterium leprae infection. IL-17A is one of the pro-inflammatory cytokines that protects humans against many fungal and bacterial pathogens. OBJECTIVE: To investigate IL-17A (rs2275913) gene polymorphism and its circulating level in leprosy patients, and to correlate the detected results with different clinical aspects of leprosy in the investigated patients. METHODS: 60 patients with leprosy, and 29 age and sex-matched volunteers were investigated for IL-17A serum level and IL-17A single nucleotide polymorphism (SNP) by ELISA and RFLP-PCR respectively. RESULTS: IL-17A serum level was significantly higher in leprosy patients than in controls (p=0.034), and in TL than LL (p=0.017). IL-17A (rs2275913 A/G) G allele and GG genotype were associated significantly with LL (p=0.005and 0.001 respectively). IL-17A (rs2275913 A/G) AG genotype carriers demonstrated the highest IL-17A serum levels; however, its lowest levels were found in IL-17A (rs2275913 A/G) AA genotype carriers (p=0.005). Grade 2 disability (p=0.030) and positive slit skin smear (SSS) (p=0.005) were significantly associated with IL-17A (rs2275913 A/G) GG genotype. STUDY LIMITATIONS: The small number of studied subjects. CONCLUSIONS: IL -17A may have a pivotal role in leprosy pathogenesis. IL-17A (rs2275913) GG genotype plus G allele might be related to the development of LL in the Egyptian population.

S100A8 (rs3806232) gene polymorphism and S100A8 serum level in psoriasis vulgaris patients: A preliminary study.

BACKGROUND: S100A8 single nucleotide polymorphism (SNP) and S100A8 blood level are related to many inflammatory disorders with no available conclusion in psoriasis. AIM: The aim of this study was to evaluate the possible role of S100A8 in psoriasis pathogenesis through analyzing its S100A8 (rs3806232) gene polymorphism and S100A8 serum level in psoriasis vulgaris patients, in addition to correlate the detected results with severity psoriasis in those patients. METHODS: This case-control study was conducted on 50 patients having psoriasis vulgaris, and 26 controls. Severity of psoriasis was evaluated using psoriasis area and severity index (PASI) score. S100A8 serum level and S100A8 (rs3806232) SNP were evaluated by ELISA and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. RESULTS: Serum S100A8 level was significantly higher in psoriatic patients than controls and was positively correlated with PASI score (r = 0.826, p < 0.001). S100A8 (rs3806232) AA genotype and A allele were significantly increased among psoriasis patients than controls (p < 0.001) increasing risk of psoriasis development by about 5, 12, and 6 times than AG, GG, and G alleles. AA genotype was significantly associated with psoriasis severity (p = 0.005) and high S100A8 serum levels (p = 0.018). CONCLUSIONS: Circulating S100A8 could associated with disease severity and have an active role in psoriasis pathogenesis. S100A8 (rs3806232) SNP (AA genotype and A allele) might contribute to development and severity of psoriasis in the Egyptian population.

Relationship of steroid sex hormones with female sexual dysfunction in female patients having urinary incontinence.

To investigate serum estradiol, progesterone and dehydroepiandrosterone levels on FSD in females having urinary incontinence (UI), we studied 150 females [100 having UI (50 with FSD and 50 without FSD) and 50 controls]. There were significant lower estradiol and progesterone and higher DHEA serum levels in patients than controls (P = 0.001for all). In UI patients, females having sexual disruption had significantly low levels of estradiol (p = 0.001). Low estradiol serum level represented an isolated predictive factor for sexual dysfunction in incontinent female patients (p = 0.001). A low estradiol serum level might be a possible risk factor for FSD in women having UI.

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo

Abstract Background: Vitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world's population and is linked to inflammatory skin diseases including vitiligo. Fatty AcidBinding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS. Objectives: To evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases. Methods: This case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured. Results: There were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001). Study limitations: The small number of studied subjects. Conclusions: FABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.

Fatty acid-binding protein 4 circulating levels in non-segmental vitiligo.

BACKGROUND: Vitiligo is an acquired and progressive mucocutaneous disease resulting from the loss of active epidermal melanocytes. Metabolic syndrome (MetS) affects about 25% of the world's population and is linked to inflammatory skin diseases including vitiligo. Fatty Acid-Binding Protein 4 (FABP4) is an intracellular lipid chaperone. FABP4 is closely associated with MetS. OBJECTIVES: To evaluate the serum level of FABP4 in vitiligo patients and its relation to MetS in the investigated cases. METHODS: This case control study was conducted on 45 patients having non segmental vitiligo and 45 matched controls. Their lipid profile, blood glucose and serum FABP4 levels were measured. RESULTS: There were significant elevations in FABP4 (p < 0.001), cholesterol (p < 0.001), triglycerides (p = 0.005), and glucose (fasting [p = 0.001] and 2 hours post prandial [p < 0.001]) levels in patients in comparison with controls. MetS was significantly more prevalent among vitiligo patients (p < 0.001) and associated with high FABP4 serum levels (p = 0.037). In vitiligo patients, there were significant positive correlations between FABP4 serum levels and triglycerides (p = 0.047), cholesterol (p = 0.001) and LDL (p = 0.001) levels and negative correlation regarding HDL level (p = 0.009). FABP4 level was a significantly good diagnostic test for early detection of vitiligo (p < 0.001). STUDY LIMITATIONS: The small number of studied subjects. CONCLUSIONS: FABP4 may play an active role in the disease process of vitiligo that could be mediated through associated dyslipidemia and hyperglycemia. FABP4 may be a marker of vitiligo helping in its early diagnosis, but it does not appear to be useful for determining vitiligo severity, activity or associated MetS.

Methimazole in the Treatment of Melasma: A Clinical and Dermascopic Study.

BACKGROUND: Melasma is a chronic hypermelanotic disorder that is challenging to treat; no single effective therapeutic agent for it has been discovered. Methimazole, an oral antithyroid drug, has a skin depigmenting effect when used topically. OBJECTIVE: We sought to evaluate the efficacy and safety of methimazole, applied during microneedling sessions and additional topical use in between sessions, for the treatment of melasma. METHODS: This split-face study included 30 Egyptian patients with melasma, each of whom received 12 microneedling sessions once per week for 12 weeks followed by topical methimazole on the right side of face and placebo on the left side. In between the sessions, topical methimazole 5% cream was applied twice per day on the right side and placebo on the left side. Assessments were performed using the Hemi-melasma Area and Severity Index (hemi-MASI) percentage of improvement, patient satisfaction, dermoscopy, and thyroid-stimulating hormone (TSH) serum levels. RESULTS: There were significant clinical and dermoscopic improvements; hemi-MASI scores on the methimazole-treated right sides were decreased (p<0.001). The percent of hemi-MASI score improvement was significantly associated with the malar pattern (p=0.031) and epidermal type (p=0.04) of melasma. About 70 percent of our studied patients reported being satisfied with their treatment response (7% excellent, 33% good, 30% fair). No significant local or systemic side effects were observed. Pre- and posttreatment serum TSH levels were within the normal range in all treated cases. CONCLUSIONS: Methimazole has the potential to be a safe and promising therapeutic agent for the treatment of melasma via dermapen-delivered microneedling sessions with topical use in between sessions.

The Role of TROP2 in BCC and Cutaneous SCC: A Clinical and Immunohistochemical Study.

BACKGROUND: Nonmelanoma skin cancer (NMSC) mainly includes basal (BCC) and squamous (SCC) cell carcinoma. Trophoblast cell-surface antigen2 (TROP2), a cell-signal transduction, is one of the tumor-related calcium signal transducer gene family. TROP2 was highly expressed in many cancers, however, its role in BCC and SCC has not yet been studied. OBJECTIVE: To investigate TROP2 immunohistochemical expression in BCC and SCC (lesional and peri-lesional) skin compared to controls and correlates its expression with the clinicopathologic parameters of the studied cases. METHODS: This case-control study included 17 BCC and 15 SCC patients as well as 12 age and sex matched controls. History and clinical examination were completed. Histological examination of skin biopsies was done together with TROP2 immune-staining. RESULTS: In the studied BCC and SCC cases, there was a significant stepwise up-regulation of TROP2 H score from control to peri-lesional, ended by lesional epidermis in one hand (p=0.003 for BCC and p<0.001 for SCC) and tumor island in another hand (p=0.001 for BCC and p=0.003 for SCC). TROP2 expression in both BCC and SCC tumor tissues was not affected by any of the studied clinicopathological parameters of the investigated cases. CONCLUSION: TROP2 could have an important role in BCC and SCC pathogenesis. TROP2 targeting may have appraising effect in clinical application in BCC and SCC management.

Tissue expression of IL-17A and FOXP3 in acne vulgaris patients.

BACKGROUND/OBJECTIVES: CD4+  T helper (Th) cells through its pro-inflammatory cell type, interleukin-17 (IL-17)-generating cells and its anti-inflammatory category forkhead box P3-positive (FOXP3+ ) regulatory T (Treg) cells, play a vital role in the immune balance in inflammatory disorders. Therefore, assessment of both IL-17 and FOXP3 in acne vulgaris (AV), a chronic inflammatory disease of the pilosebaceous unit, could be of value in understanding AV pathogenesis. This study aimed to investigate the immunohistochemical expression of IL-17A and FOXP3 in acne vulgaris lesions versus normal skin. METHODS: Forty-five AV patients and 25 controls were included in this case-control study. Biopsies from participants were analyzed for IL-17A and FOXP3 immunohistochemical profiles using IL-17A and FOXP3 polyclonal antibodies. RESULTS: Compared to controls, AV patients exhibited a significant increase of IL-17A percent of expression in epidermis (P ≤ .001), in lymphocytes in papillary dermis (P ≤ .001), and in perifollicular lymphocytic inflammatory infiltrate in AV lesions. Also, there was a significant elevation in FOXP3 percent of expression in epidermis (P = .049) and in lymphocytes in papillary dermis (P ≤ .027) in acne patients than control. A significant positive correlation between IL-17A expression in papillary lymphocytes and in epidermal keratinocyte was observed (r = .537, P = .001). In acne vulgaris patients, the associations between IL-17A and FOXP3 expressions could not reach level of significance. CONCLUSIONS: There was an up-regulation of IL-17A and FOXP3 in acne vulgaris development, but with independent roles. Moreover, targeting of IL-17A and FOXP3 may open the door for development of new therapeutic agents in acne vulgaris treatment.

Neuronal Precursor Cell Expressed Developmentally Down Regulated 4 (NEDD4) Gene Polymorphism Contributes to Keloid Development in Egyptian Population.

BACKGROUND: Keloids represent chronic fibroproliferative skin disorders in which there is deposition of extracellular components, especially type 1 collagen, fibronectin and elastin, in excessive amounts. NEDD4 is associated with fibrosis found in abnormal wound healing through increased fibroblast proliferation and regulation of type 1 collagen expression. The exact etiology of keloid formation is undefined, but the role of genetic factors was demonstrated. OBJECTIVE: To investigate the polymorphism of the NEDD4 gene rs8032158 in a sample of Egyptian patients who have keloids. METHODS: The current case-control study was conducted in 160 unrelated subjects; 100 keloid patients and 60 ages and sex coincided with apparently healthy controls. All subjects underwent a complete history, and weight and length were measured to calculate body mass index (BMI). The Vancouver Scar Scale (VSS) was used to assess keloid severity. An analysis of the polymorphism of the NEDD4 gene rs8032158 T/C was performed using taqman allelic discrimination (real-time PCR). RESULTS: The rs8032158 CC genotype was observed significantly in keloid patients and increased the risk of keloid development by approximately 2 times (p = 0.003, OR = 1.80). The C allele significantly increased the risk of keloid development by approximately 2 times (P = 0.002, OR = 2.08). The carriers of the CC genotype were significantly associated with severe keloid form and with the highest VSS values. CONCLUSION: The polymorphism of the NEDD4 gene rs8032158 could participate in the formation of keloids in the Egyptian population. The NEDD4 rs8032158 CC genotype may have a role in keloid severity.