Serum and Tissue Lipocalin-2 Expression in Chronic Kidney Disease Pruritic Patients.

BACKGROUND: Uremic pruritus is an irritating symptom for patients with end-stage kidney disease. Lipocalin-2 (LCN2) has relevant importance in several biological cellular processes and immunity. It is also a major player in the progression of many disorders, such as renal injury. AIM: To evaluate LCN2 expression in chronic kidney disease (CKD) pruritic patients in serum together with immunohistochemical expression in skin samples and further correlation of their results with the studied clinicopathologic parameters. MATERIALS AND METHODS: Serum level of LCN2 (assessed by enzyme-linked immunosorbent assay) and skin immunohistochemical expression were investigated in 25 CKD patients and 25 healthy controls. Ten patients were subjected to narrowband ultraviolet B phototherapy for 12 weeks then re-evaluated for serum and tissue LCN2 after therapy. RESULTS: LCN2 expression was increased significantly in both the epidermis and dermal adnexa in CKD patients over controls. Also, serum LCN2 level was higher in patients than in healthy subjects and was significantly associated with itching severity, grades of CKD, urea, and creatinine serum level. Tissue and serum levels of LCN2 were significantly diminished in CKD patients following narrowband therapy along with improvement of the severity of pruritus. CONCLUSIONS: The increased serum and tissue LCN2 expression in CKD pruritic patients and its pronounced decrease, in addition to the improvement of pruritus after treatment, suggest a major pathogenic role of LCN2 in uremic pruritus.

Assessment of cytochrome P450 1A1 gene polymorphism and vitamin A serum level in psoriasis vulgaris.

Psoriasis is characterized by cutaneous hyperproliferation, secondary to immune system dysregulation. Vitamin A regulates the immune response and sustains epithelial tissue hemostasis. The CYP1A1 gene, has many biological actions, including vitamin A metabolism. To evaluate CYP1A1 gene polymorphism and serum vitamin A level in patients with psoriasis vulgaris, a case-control study involving two groups was conducted: group 1 (45 patients with psoriasis vulgaris) served as the cased group and group 2 (45 healthy participants who were sex and age matched) acted as the control group. CYP1A1 (rs1048943) gene polymorphism and vitamin A serum level were assessed by TaqMan allelic discrimination (PCR) and ELISA, respectively. AG genotype was present only in cases (22.2%), while AA genotype was present in all controls (P=.001). Vitamin A levels were lower in cases than in controls (32.0 ± 7.41 vs. 46.2 ± 15.7 µg/ml, respectively) (P<.001). AG genotype was associated with a lower vitamin A level (P=.001). The detected genotype difference between psoriasis patients and controls, which was associated with a lower serum vitamin A level and was also lower in more severe cases, suggests a role of the CYP1A1 gene and vitamin A in disease pathogenesis and prognosis.

Study of purine derivatives and their relation to renal disorders in patients with psoriasis.

BACKGROUND: Psoriasis (Pso) is a chronic proliferative skin condition associated with hyperuricemia that may impair renal function. OBJECTIVES: The current study investigates the correlation between purine derivatives (PDs) and renal function in patients with Pso. PATIENTS/METHODS: This case-control study comprises 30 psoriatic patients and 30 age- and sex-matched healthy controls. The enzyme-linked immunosorbent assay (ELISA) was used to assess serum xanthine oxidase (XO) and urine albumin levels. Serum uric acid (SUA) and urinary creatinine were measured using the colorimetric method. RESULTS: There was a rise in the related PDs levels in patients with Pso compared to controls, as evidenced by the enhanced SUA levels (p < 0.001) and XO levels (p < 0.001). The presence of the related PDs in the serum was linked to the severity of Pso, and there was also a connection between the related PDs levels in the blood and indicators of renal dysfunction. Moreover, SUA and urinary albumin creatinine ratio (UACR) were found to be significantly correlated (r = 0.371 and p = 0.044), as were XO and UACR (r = 0.422 and p = 0.020). In psoriatic patients with itching and palmoplantar affection, mean SUA levels were considerably more significant than those in other instances (p = 0.005 and p = 0.018, respectively). CONCLUSION: Pso, being a hyperproliferative disease, is associated with hyperuricemia, which has a harmful effect on kidney function. The related PDs may be unique serological biomarkers for patients with Pso who are at high risk of developing renal abnormalities, especially with higher severity scores.

Immunohistochemical expression of Axin-2, as an implication of the role of stem cell in scar pathogenesis and prognosis.

BACKGROUND: Wound healing is a multi-phased process. A disruption in these phases could result in a persistent wound or an atypical scar. Wounding activates wingless proteins (Wnt) signaling, which aids in the healing process. Axis inhibition protein-2 regulates a variety of cellular activities through the Wnt and other pathways. AIM: To assess the role of Axin-2 in patients with abnormal scars, using immunohistochemical study. METHODS: This case-control study enrolled a total of 60 participants: 30 patients with abnormal scars (12 hypertrophic scars, 13 atrophic scars, and 5 keloid scars) and 30 age, sex, and site matched, apparently healthy controls. For immunohistochemistry examination of Axin-2 expression, skin samples were obtained from (i) lesional and (ii) perilesional skin of patients with aberrant scars, as well as (iii) normal control's skin. RESULTS: Epidermal Axin-2 expression positivity, cellular topography, intensity, and H score showed significant differences between the groups (p < 0.05). In the dermis (fibroblast/myofibroblast), there were significant differences in Axin-2 expression positivity, location, intensity, and H score (p < 0.001 for all). The epidermal Axin-2 H score and the Manchester scale had a significant positive correlation (r = 0.832, p = 0.001). The epidermal Axin-2 H score and age (r = -0.576, p = 0.001), and the Stony Brook scale (r = -0.419, p = 0.021), had significant negative correlations. CONCLUSION: Axin-2 overexpression might be accused in pathogenesis of abnormal scar and clinical worse scar outcome. In order to deprive scars of their regenerative cell pools, future scar therapies may target Axin-2 as a stem cell marker.

Study of calprotectin gene polymorphism and serum level in acne vulgaris patients.

BACKGROUND: Acne vulgaris (AV) is an inflammatory skin disease of the pilosebaceous unit. S100A8 and S100A9 (the light subunits of calprotectin) gene polymorphisms have been known to be associated with inflammatory disorder. Until now, no study investigated calprotectin gene polymorphism in acne patients. OBJECTIVE: This study was designed to investigate calprotectin serum levels and gene polymorphism (rs3806232) in acne vulgaris patients and to correlate them with different clinical aspects of them. METHODS: This case-control study included 50 patients having variable degrees of acne vulgaris (AV) severity, in addition to a control group of 26 age- and gender-matched seemingly healthy volunteers. RESULTS: Acne vulgaris patients had considerably greater (P < 0.001) mean serum calprotectin levels than the control group (3.86 ± 2.58 pg/ml vs. 0.29 ± 0.14). AA genotype of calprotectin S100 A8 (rs3806232) was significantly predominant over AG or GG genotypes in patients compared to the controls, and the A allele was significantly (P < 0.001) predominant in patients (80%), while A and G alleles were equally distributed in controls; also, there was a significantly higher serum calprotectin level in calprotectin AA genotype than in AG or GG (P < 0.001) in acne vulgaris patients. CONCLUSION: The serum levels of calprotectin were considerably greater in AV patients than in controls. AA genotype and A allele of the S100 A8 gene were significantly higher in patients, which was associated with significantly higher calprotectin serum levels. Thus, calprotectin, both gene and serum level, might participate in disease pathogenesis, which needs further studies.

Light chain 3 immunoexpression in psoriasis.

Autophagy dysregulation is involved in many diseases. The implication of autophagy in psoriasis pathogenesis is still uncertain. To investigate the role of Light Chain 3 (LC3), a good marker for autophagy, in psoriatic skin based on immunohistochemical study and correlate its expression - for the first time to the best of our knowledge - to clinicopathological data Prospective case-control study was conducted on 60 subjects (30 control, 30 psoriasis patients). Skin biopsies from control, lesional, and perilesional skin were processed for routine histopathological examination and LC3 immunoreaction assessment. There was a significant upregulation of the epidermal and dermal LC3 immunoreaction in the lesional skin compared with the control and perilesional skin specimens (P < .001). A significant positive correlation between the epidermal and dermal LC3 H scores in the lesional and perilesional skin was recorded. There was a non-significant relationship between the H score in the lesional skin and disease severity. LC3 could be considered in psoriasis pathogenesis; however, LC3 was not related to the severity of the disease. The findings might offer a novel target therapy for psoriasis patients.

CD93 has a crucial role in pathogenesis of psoriasis.

BACKGROUND: Psoriasis is a chronic, immune-related disorder; inflammation, higher rate of epidermal proliferation, and angiogenesis are the main pathognomonic features. Cluster of differentiation 93 (CD93), an angiogenic element, plays a role in cell adhesion regulation and has a putative function in inflammation. OBJECTIVE: To assess CD93 immunohistochemical expression in psoriatic skin and the association of CD93 single nucleotide polymorphisms (SNPs) rs2749817 to disease pathogenesis and severity. METHODS: This case-control study was done on 50 patients with psoriasis vulgaris beside 50 age- and sex-matched healthy controls. Assessment of psoriasis severity was done by Psoriasis Area and Severity Index (PASI) score. 3 mm punch skin biopsies were taken from every participant, and hematoxylin and eosin staining and immunohistochemical staining for CD93 antibody were done. Assessment of CD93 rs2749817 gene polymorphism by the TaqMan allelic discrimination assay technique (real-time PCR) was done. RESULTS: Immunohistochemical expression of CD93 showed membrano-cytoplasmic localization in both endothelial and inflammatory cells of cases and controls with significant more positivity in dermal endothelial and inflammatory cells of cases than controls (p = 0.001 and 0.014 respectively). Strong intensity was present in 18 of cases endothelial cells and 24 inflammatory cells with absence in controls (p =  0.001 for both) with significantly higher H-score and higher percent of positive cells (p  =  0.001 for both). The TC genotype was lower in patients compared to control (p-value = 0.006) and CC genotype which was present only in cases (p-value = 0.021). CONCLUSION: Cluster of differentiation 93 has an essential role in psoriasis and an encouraging future therapy for psoriasis.

Evaluating the Serum and Seminal Plasma Levels of Zinc and Cadmium in Smokers and Their Relation to the Semen Parameters.

Cigarette smoking appears to have adverse effects of male reproductivity. The interplay between zinc and cadmium presumably plays a role in mediating toxic effects of smoking. This work was conducted to study serum and seminal plasma zinc and cadmium level in smokers compared to non-smokers. Seventy males were included: 35 smokers (group I) (smoking ˃20 cigarettes/day with mild smoking index <400) and 35 age-matched non-smokers (group II). Semen analysis was performed according to the WHO laboratory manual 2010. Atomic absorption spectrophotometer was used to detect zinc and cadmium amounts in both blood plasma and semen of any groups. Smoker group showed significantly lower sperm density, motility (P=0.001), and sperm viability (P=0.002) and higher abnormally formed sperms. Seminal zinc level was significantly lower in smokers (P=0.038).There was significant negative correlation between seminal zinc and smoking index and significant positive correlation between seminal zinc levels and sperm motility (P=0.008) and viability percentage (P=0.001). Seminal cadmium level was significantly higher in smoker (P=0.022). Significant positive correlation between seminal cadmium and both age and smoking index (P=0.003) and significant negative correlation between seminal cadmium and sperm density (P=0.005), motility (P=0.047), and viability (P=0.039). Seminal zinc level was negatively correlated to seminal cadmium level (P=0.020). Smoking has deleterious effects on semen quality hence fertility through several toxicants and chemicals. Reduced zinc levels and elevated cadmium levels were evident in smokers which have significant role in the adverse effects on the semen parameters.

Evaluation of serum and urinary orsomucoid protein A in psoriatic patients and their relation to severity of disease.

BACKGROUND: Orsomucoid protein A (ORM) is a major acute-phase protein. Serum ORM (se-ORM) protein A elevates in infections, malignancies, and autoimmune diseases. Urinary ORM (u-ORM) protein A is more accurate and less invasive marker of inflammation. Elevated u-ORM was associated with pathomechanism factors related to psoriasis such as endothelial dysfunction; however, the clinical significance of it has not been explored yet. AIM: To evaluate se-ORM/u-ORM protein A and urinary orsomucoid protein A/urinary creatinine (u-ORM/u-CREAT) in patient with psoriasis and their relations to severity of the disease. METHODS: This case-control study was conducted at Dermatology and Andrology Department; 35 psoriasis patients and 35 age- and sex-matched healthy controls were included. They were subjected to history taking and general and dermatological examination. Psoriasis severity was assessed by Psoriasis Area and Severity Index (PASI) score. Measurement of se-ORM/u-ORM protein A using ELISA and u-ORM/u-CREAT using colorimetric method. RESULTS: Highly significant difference between psoriasis patients and controls regarding u-ORM protein A level (p value = 0.01). It was also higher in severe cases than moderate and mild ones and higher in moderate than mild cases (p value 0.001, 0.001, and 0.004, respectively). There were significantly higher u-ORM/u-CREAT (p Ë‚ 0.001) levels in psoriasis patients than in controls. Also, significantly higher U-ORM/u-CREAT levels were found in severe psoriasis cases than in mild and moderate cases (p = 0.003 and 0.006, respectively). While the se-ORM levels showed no significant differences between the studied groups. CONCLUSION: u-ORM/u-CREAT is a highly sensitive, easily available, and new inflammatory biomarker of psoriasis which correlates to the disease severity.

Serum lipocalin-2 levels are decreased in patients with leprosy.

Background Leprosy is an infectious disease caused by Mycobacterium leprae affecting the skin, peripheral nerves and mucosae. Lipocalin-2 is a key component of the immune system's antimicrobial defence - it prevents iron uptake by binding and sequestering iron-scavenging siderophores and thus inhibits bacterial growth. Aim We evaluated serum lipocalin-2 levels in leprosy patients and its relationship to the pathogenesis and prognosis of the disease. Materials and methods In this case-control study, serum lipocalin-2 levels were measured by ELISA in 20 patients with leprosy and 20 healthy controls. Results Serum levels of lipocalin-2 were significantly reduced (P < 0.001) in leprosy patients as compared to controls. The levels were significantly higher (P < 0.014) in patients with multibacillary leprosy than in those with paucibacillary leprosy. Although the levels of lipocalin-2 were higher in patients with multiple nerve involvement as compared to those with involvement of 1 or 2 nerves, the results were not statistically significant. Limitation of the study The small sample size and the lack of different ethnic groups in the study were the major limitations of this study. Conclusion The lower lipocalin-2 concentrations in leprosy patients point to the importance of the protective functions of lipocalin-2. The elevated levels of lipocalin-2 observed in leprosy patients with neural involvement may be related to the reported neurodegenerative role of lipocalin-2.

Measuring the serum level of retinol-binding protein can enhance the treatment of recalcitrant warts.

BACKGROUND: Warts are common benign (60%-65%) self-limited tumors of the epidermis caused by human papillomaviruses (HPVs). However, some warts fail to resolve despite of different treatments and become recalcitrant. Vitamin A has antiproliferative and antikeratinizing properties by which the disruption of HPV replication can be occurred. Concentrations of retinol-binding protein (RBP) and retinol in the circulation highly correlate with each others. AIM: To assess the serum level of RBP in patients with resistant warts to evaluate the possible role of retinol in the disease pathogenesis. PATIENTS: This case-control study included 30 patients with resistant cutaneous warts (defined as failure of cure after conventional treatment as 12 weeks of salicylic acid application, 4 or more cycles of cryotherapy or electrocautery and/or other physical treatment modalities) and 30 age- and sex-matched healthy controls. RBP level in the serum was measured by ELISA. RESULTS: There was a significant difference between cases and controls regarding the level of serum RBP (P = .001). However, serum RBP level did not differ significantly regarding sociodemographic or clinical data (P > .05 each). RBP is a good biomarker for significant early detection and discrimination between cases and controls (P = .001) at a cutoff point < 563.3 mg/l with sensitivity (93%) and specificity (80%). CONCLUSION: Low serum RBP level in our studied patients may suggest an important role of retinol in the resistant warts pathogenesis. Thus measuring serum RBP will help to identify patients who are going to have resistant warts in the future.