Evaluation of vitamin D receptor gene polymorphisms (ApaI and TaqI) as risk factors of vitiligo and predictors of response to narrowband UVB phototherapy.

Vitiligo is acquired depigmentation due to multiple factors. Vitamin D in skin, through its receptors (VDR), regulates cell growth, differentiation, immune response and exerts both stimulatory and protective effects on melanocytes. The gene sequence encoding VDR has polymorphic forms such as ApaI and TaqI that may affect vitamin D actions. Narrowband ultraviolet B (NB-UVB) phototherapy became the mainstay of vitiligo treatment because of its efficacy and little side effects. The current work aimed at evaluating the possible association between VDR gene polymorphisms (TaqI and ApaI) and susceptibility of vitiligo and if they could be predictors of response to NB-UVB phototherapy in Egyptian vitiligo patients. 100 vitiligo patients indicated for NB-UVB phototherapy and 100 healthy age and sex matched controls were included. All participants were subjected to history taking, general and dermatological examinations, and VDR ApaI and TaqI gene polymorphisms analysis by PCR-RFLP. The patients received NB-UVB 3times per week for 6 months then revaluated. There was significant increase in Aa genotype of ApaI polymorphism in patients associated with significant increase in vitiligo activity. 66% of patient showed variable degrees of response to NB-UVB. The responders significantly had AA genotype of ApaI polymorphism. TaqI polymorphism showed nonsignificant effects on vitiligo susceptibility and response to NB-UVB. A allele of ApaI was significant independent predictor of NB-UVB phototherapy responders. VDR gene polymorphism (ApaI) may share in vitiligo pathogenesis and response to NB-UVB. Knowing the genetic background of the patient helps individualization of treatment to get better results.

Bilateral Anterior Displaced Sigmoid Sinus in Cochlear Implantation: A Proposed Solution.

To assess the safety, time consumption and presumed postoperative complications of posterior repositioning in cases with bilateral anterior displaced sigmoid sinus (ADSS) having cochlear implant surgery. Cases with bilateral ADSS were included. A cortical bone chip was harvested. Sinus plate was drilled thin and removed, ADSS was repositioned posteriorly and secured by the bone chips. The procedure was completed using the standard posterior tympanotomy (PT) technique. Follow up was done both clinically and by computed tomography (CT). Out of 632 cases operated upon in more than 7 years, only 7 cases had Bilateral ADSS (1.1%) of which 5 were females (71.45%). The average age was 8.2 ± 12 (6 children and an adult). No intraoperative bleeding was encountered in any of the 7 cases. The average operative time was 103.6 ± 9.7 min. No minor nor major complications were detected in all 7 cases. To keep the advantages of PT, repositioning of ADSS in bilateral cases can be done safely with a reasonable increase in the average operative time.

MTHFR C677T Polymorphism and Serum Homocysteine Level as Risk Factors of Coronary Heart Disease in Patients with Androgenetic Alopecia: A Case Control Study.

BACKGROUND: Androgenetic alopecia (AGA) is associated with a risk of coronary heart disease (CHD), although the causes underlying this association are not clear. Serum homocysteine (SH) is a known risk factor for CHD, and methylene tetrahydrofolate reductase enzyme (MTHFR) plays a crucial role in the remethylation of homocysteine to methionine. The polymorphism C677T that affects the catalytic domain of the MTHFR protein leads to a high levels of SH. Our hypothesis was that this polymorphism and SH level are risk factors for CHD in patients with AGA. MATERIALS AND METHODS: A total of 106 patients with AGA and 100 well-matched healthy controls were enrolled in the study. SH levels were estimated. DNA was extracted and polymerase chain reaction amplification, followed by restriction enzyme digestion for MTHFR (C677T) gene, was conducted. RESULTS: SH levels were significantly higher in the patient group and highest in those with the TT genotype. The mutant T allele was associated with hyperhomocysteinemia and an increased risk of CHD in patients with AGA. CONCLUSIONS: AGA is associated with a higher risk of developing CHD due to the associated higher level of SH that, in turn, depends on and is correlated with mutant MTHFR genotypes. Cardiac evaluation and follow-up of patients with AGA is recommended for early detection and treatment of CHD to avoid an overall detrimental course.

Oral dapoxetine versus topical lidocaine as on-demand treatment for lifelong premature ejaculation: A randomised controlled trial.

This trial aimed to assess the efficacy of on-demand oral dapoxetine versus topical lidocaine treatments for lifelong PE. Cases with lifelong PE were randomised to start treatment by oral dapoxetine 60 mg or topical lidocaine 10% spray. The intravaginal ejaculatory latency time (ILET), validated Arabic Index for PE (AIPE), Sexual Health Inventory for Men (SHIM) and frequency of intercourse/week were recorded at the baseline and after 12 weeks treatment period of the first medication before two weeks washout period and then crossing over to the other one for another 12 weeks. Results showed that both medications significantly increased both IELT and AIPE scores compared with the baseline being significantly better with topical lidocaine (63.44 s, 179.4 s versus 21.87 s, p < .05). Significant decrease of SHIM score was recorded with lidocaine but not with dapoxetine. Global Efficacy Question for the patient's assessment of the effectiveness of drugs showed that lidocaine was described as being effective by 43 cases and ineffective by 12 cases, oral dapoxetine was described as being effective by 16 cases and ineffective by 39 cases. From these accumulated data, it is concluded that topical lidocaine is more effective on-demand therapy for lifelong PE compared with oral dapoxetine.

Antimelanocyte Antibodies: A Possible Role in Patients with Vitiligo.

BACKGROUND: Vitiligo is an acquired depigmenting skin disorder with multifactorial pathogenesis including genetic, autoimmune, and neuronal factors. Both humoral- and cell-mediated immunities are supposed to have a role in the pathogenesis of vitiligo. Patients with vitiligo have an increased concentration of circulating autoantibodies that are specific to melanocyte cytoplasm and surface antigens that related to the extent of the disease. AIMS AND OBJECTIVES: The aim of the present study was to evaluate the role of antimelanocyte antibodies (AMAs), complement 3 and 4 (C3 and C4), and antinuclear antibodies (ANAs) in the pathogenesis of vitiligo. MATERIALS AND METHODS: This study included 49 patients with nonsegmental vitiligo and 36 healthy individuals as a control group. All participants were subjected to detailed history, general examination, and detailed dermatological examination of the skin, hair, nails, and oral mucosa. The severity of vitiligo was assessed according to the Vitiligo Area Scoring Index (VASI). AMA, C3 and C4, and ANA serum levels were measured for patients and controls. RESULTS: ANA, AMA, and C4 levels were significantly higher in the sera of patients than in controls. ANA, AMA, and C4 serum levels showed significant positive correlations with VASI score. CONCLUSION: Our results support the role of AMA in the pathogenesis of nonsegmental vitiligo, correlating with the disease extent and severity. However, a longitudinal study in a large cohort of patients to evaluate the clinical and predictive value of AMA is warranted.

Assessment of the Possible Role of FOXP3 Gene (rs3761548) Polymorphism in Psoriasis Vulgaris Susceptibility and Pathogenesis: Egyptian Study.

BACKGROUND: Psoriasis is an autoimmune-related chronic inflammatory skin disorder. Psoriasis vulgaris (PV) is the most common form of psoriasis. T regulatory cells (Tregs) are typically considered inhibitors of autoimmune responses. FOXP3 is a master control transcription factor for development and function of Tregs. FOXP3 gene polymorphism changes FOXP3 protein function and quantity leading to Tregs dysfunction that subsequently may be related to PV pathogenesis. OBJECTIVE: The objective of the present study was to evaluate the possible role of FOXP3 gene (rs3761548) polymorphism in PV pathogenesis. MATERIALS AND METHODS: One hundred sixty subjects were included in the present study (80 PV patients and 80 well-matched healthy controls). All participants were evaluated by detailed history, general examination, dermatological examination, and psoriasis area and severity index (PASI) score. The detection of FOXP3 gene (rs3761548) polymorphism in patients and controls by PCR-restriction fragment length polymorphism technique was done. RESULTS: There was statistically significant increase in CC genotype and C allele in patients compared to controls, whereas there were non-significant differences in AA and AC genotypes. However, there were non-significant associations between genotype distribution and each of age, sex, family history, PASI score, hair affection, nail affection, hypertension, diabetes mellitus, and body mass index. CONCLUSION: FOXP3 gene (rs3761548) polymorphism may increase susceptibility of PV and share in its pathogenesis as it leads to changes in FOXP3 protein function and quantity that subsequently affect T-regs functions. Further investigations for the role of other FOXP3 genes polymorphisms in psoriasis pathogenesis and their effects on the treatment response in psoriasis patients are strongly recommended.

Genome-wide association study of psoriasis in an Egyptian population.

Psoriasis is a chronic inflammatory disorder of the skin, with genetic factors reportedly involved in the disease pathogenesis. Numerous studies reported psoriasis candidate genes. However, these tend to involve mostly in the European and Asian populations. Here, we report the first genome-wide association study (GWAS) in an Egyptian population, identifying susceptibility variants for psoriasis using a two-stage case-control design. In the first discovery stage, we carried out a genome-wide association analysis using the Infinium® Global Screening Array-24 v1.0, on 253 cases and 449 control samples of Egyptian descent. In the second replication stage, 26 single-nucleotide polymorphisms (SNPs) were selected for replication in additional 321 cases and 253 controls. In concordance with the findings from previous studies on other populations, we found a genome-wide significant association between the MHC locus and the disease at rs12199223 (Pcomb  = 6.57 × 10-18 ) and rs1265181 (Pcomb  = 1.03 × 10-10 ). Additionally, we identified a novel significant association with the disease at locus, 4q32.1 (rs12650590, Pcomb  = 4.49 × 10-08 ) in the vicinity of gene GUCY1A3, and multiple suggestive associations, for example rs10832027 (Pcomb  = 7.28 × 10-06 ) and rs3770019 (Pcomb  = 1.02 × 10-05 ). This proposes the existence of important interethnic genetic differences in psoriasis susceptibility. Further studies are necessary to elucidate the downstream pathways of the new candidate loci.

Spermatozoal Fractalkine Signaling Pathway Is Upregulated in Subclinical Varicocele Patients with Normal Seminogram and Low-Level Leucospermia.

BACKGROUND: Fractalkine is produced in seminal plasma in small amounts and correlates with sperm motility. PURPOSE: To investigate the possible effect of low-level leucospermia on spermatozoa oxidative stress and sDNA fragmentation in patients with subclinical varicocele and apparently normal seminogram, and also to study the role of spermatozoal fractalkine and its receptor (CX3CR1) gene expression as a marker of spermatozoa inflammatory response. METHODS: This study included 80 patients with subclinical varicocele (45 fertile and 35 infertile) and 45 age-matched fertile volunteers. In semen samples, fractalkine and CX3CR1 gene expression were investigated by qRT-PCR. Moreover, seminal plasma malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. RESULTS: There are significant decrease in semen quality and significant increase in seminal leucocytes count in subclinical varicocele. Our results show a significant increase in MDA and TAC levels, DNA fragmentation, and expression levels of fractalkine and its receptor (CX3CR1) in subclinical varicocele groups. CONCLUSION: Subclinical varicocele induces seminal and spermatozoal subclinical inflammatory response in the form of low-level leucospermia and increased mRNA expression of the fractalkine signaling pathway, leading to increased spermatozoal ROS production, oxidative stress, and DNA fragmentation. These could cooperate in the pathogenesis of delayed fertility in males with subclinical varicocele.

Spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentation in infertile men with metabolic syndrome and normal seminogram.

BACKGROUND: This is the first study to investigate spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentations in the spermatozoa of men diagnosed with metabolic syndrome (MS) who have normal seminograms with unexplained infertility, and to correlate these parameters with seminal glucose concentration. METHODS: This study included 120 participants: 75 male subjects with MS (38 fertile and 37 infertile), and a control group of 45 fertile males without MS. HOMA-IR, semen analysis, and biochemical measurement of seminal plasma insulin and glucose levels were carried out. Spermatozoal insulin gene and CIDEA gene expressions were performed by the RT-PCR method. The percentage of spermatozoal DNA fragmentation was also estimated. RESULTS: The spermatozoal insulin and CIDEA gene expression, as well as the DNA fragmentation, were significantly higher in the infertile MS group than in the fertile MS group, and significantly higher in both the MS groups than in the control group. Seminal glucose concentration showed significant positive correlations with seminal insulin level, spermatozoa insulin, CIDEA gene expression, and DNA fragmentation. Moreover, there was a positive correlation between spermatozoa CIDEA gene expression and DNA fragmentation. CONCLUSIONS: It can be concluded that MS may affect male fertility at the molecular level, through its possible inducing effect of spermatozoa CIDEA and insulin gene expression, DNA fragmentation, and increased seminal glucose.

Possible Relationship between Chronic Telogen Effluvium and Changes in Lead, Cadmium, Zinc, and Iron Total Blood Levels in Females: A Case-Control Study.

INTRODUCTION: Hair loss is a common and distressing problem that can affect both males and females of all ages. Chronic telogen effluvium (CTE) is idiopathic diffuse scalp hair shedding of at least 6 months duration. Hair loss can be one of the symptoms of metal toxicity. Lead (Pb) and cadmium (Cd) are highly toxic metals that can cause acute and chronic health problems in human. The aim of the present study is to determine if there is a relationship between these metals and CTE in women and if CTE is also associated with changes in zinc (Zn) or iron (Fe) blood levels. MATERIALS AND METHODS: Pb, Cd, Fe and Zn total blood levels were determined in 40 female patients fulfilling the criteria of CTH and compared with total blood levels of same elements in 30 well-matched healthy women. RESULTS: Quantitative analysis of total blood Fe, Zn, Pb and Cd revealed that there were no significant differences between patients and controls regarding Fe, Zn, and Pb. Yet, Cd level was significantly higher in patients than controls. In addition, Cd level showed significant positive correlation with the patient's body weight. CONCLUSION: Estimation of blood Pb and Cd levels can be important in cases of CTE as Cd toxicity can be the underlying hidden cause of such idiopathic condition.

Diagnostic value of CD10 and Bcl2 expression in distinguishing cutaneous basal cell carcinoma from squamous cell carcinoma and seborrheic keratosis.

The distinction between cutaneous basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and seborrheic keratosis (SK), which are common entities in clinical practice, can be difficult clinically and histologically. CD10 and Bcl2 antigens are important factors in tumor growth, survival and spread. The aim of the present study is to define the frequency of CD10 and Bcl2 expression in such cutaneous tumors and its relation to the clinicopathological characteristics as well as their possible diagnostic utility. CD10 and Bcl2 immunohistochemistry was performed on 30 BCC, 20 SCC and 15 SK. 93.3% of SK cases and 53.3% of BCC cases showed significant expression of CD10 in tumor cells when compared either with each other or with SCC cases (100% negative). Stromal CD10 expression was positive in 50% of BCC cases and 75% of SCC cases. Stromal CD10 expression was significantly higher in high risk BCC and BCC with infiltrating deep margins; furthermore, it showed a significant positive correlation with grade of SCC. A significant inverse correlation between CD10 expression in stromal and tumor cells of BCC was present. Bcl2 was significantly expressed in 93.3% of SK cases and 80% of BCC cases when compared with SCC cases (100% negative). It was found that for distinguishing BCC from SK, only CD10 expression in tumor cells provided a high diagnostic value with positive likelihood ratio (PLR) was 7.00. In addition, CD10 and Bcl2 expression in tumor cells could give convincing diagnostic value to distinguish SCC from SK (PLR=15.00 for each marker). Moreover, for differentiating BCC from SCC, only Bcl2 in the tumor cells could provide a high diagnostic value (PLR=5.5). In conclusion, CD10 and Bcl2 can help in differentiating cutaneous BCC from SK and SCC. The overexpression of CD10 in the stromal cells of SCC and some variants of BCC suggests the invasive properties of such tumors.

Possible effects of metallosis on spermatozoal apoptotic genes expression in individuals with intramedullary nailing prosthesis.

Seminal quality could be affected by metallosis caused by intramedullary nailing (IMN). Our objectives were to estimate metal ion levels in the seminal plasma of subjects with IMN, to determine their effects on semen parameters and on spermatozoal apoptotic gene expression, and to determine whether these expressed genes could be used as candidate biomarkers of seminal deterioration in individuals with IMN or not. Semen samples were collected from 60 subjects with IMN and 30 age-matched healthy controls. Seminal plasma contents of cobalt (Co), chromium (Cr), and molybdenum (Mo) were assayed. Spermatozoal Bcl-2 and Bax gene expressions were determined. Studied semen parameters were significantly lower in subjects with IMN for ≥5 years in relation to controls while the concentrations of Co, Cr, and Mo in the seminal plasma samples were significantly higher. There were significantly lower spermatozoal Bcl-2 expression, higher Bax expression, and lower Bcl-2/Bax ratio in subjects with IMN for ≥5 years than in controls. In subjects with IMN for ≥5 years, receiver operating characteristic (ROC) curve analysis of studied gene expressions and Bcl-2/Bax ratio were done showing priority of the ratio with 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value, and 93.8 % negative predictive value at cutoff values ≤0.777. Co, Cr, and Mo metals are found at high concentrations in the seminal plasma of individuals with IMN leading to increased spermatozoal apoptotic activity. Spermatozoal Bcl-2/Bax ratio could be used as a candidate biomarker of reproductive disorders in individuals with intramedullary nailing.