Keratitis-ichthyosis-deafness syndrome: Phenotypic heterogeneity and treatment perspective of patients with p.Asp50Asn GJB2 mutation.

Keratitis-ichthyosis-deafness (KID) syndrome is caused by mutations in the GJB2 gene encoding connexin 26, a component of transmembrane hemichannels which form gap junction channels, critical for cell-cell communication. Here, we report two patients from two distinct families with KID syndrome with the same GJB2 mutation (p.Asp50Asn); in both cases the mutation was de novo, as the parents depicted the wild-type allele only. The patients' cutaneous manifestations were strikingly different illustrating the wide spectrum of phenotype of these patients, even with the same GJB2 mutation. One of the patients was treated with acitretin with dramatic improvement in his skin findings, illustrating the role of oral acitretin in treatment of patients with KID syndrome. Collectively, these patients attest to the phenotypic spectrum of KID syndrome, with therapeutic perspective.

Serum and tissue angiotensin-converting enzyme in patients with alopecia areata.

BACKGROUND: Alopecia areata is an immune-dependent disorder characterized by the interaction of T-lymphocytes with follicular antigens. Recent studies have shown the existence of a local renin-angiotensin system in the skin, where angiotensin-converting enzyme (ACE) plays a role in autoimmunity and inflammation. AIM: The objective of this study was to evaluate serum and tissue ACE activity in patients with alopecia areata. METHODS: This case-control study was conducted on patients with alopecia areata and healthy controls. Serum and tissue ACE activity were assessed and compared between the two groups. RESULTS: Twenty-five alopecia areata patients (60% male, mean age 32.1 ± 9.9 years) and 24 controls (50% male, mean age 37.4 ± 8.8 years) were included. Mean serum ACE activity was 52.1 ± 9 U/L in cases and 55.3 ± 14.7 U/L in controls (P = 0.37). Tissue ACE activity was significantly lower in cases in all parts of the skin i.e. epidermis (P = 0.016), follicular epithelium (P = 0.004), and endothelium (P = 0.037). Among cases, serum ACE activity was significantly higher in patients with more severe disease (P = 0.030), nonpatchy alopecia areata (alopecia universalis; ophiasis, patchy and ophiasis, diffuse) (P = 0.029), and with nail involvement (P = 0.027). LIMITATIONS: The sample size was too small to draw definite conclusions. Further, most of the patients had only mild or moderate alopecia areata. CONCLUSION: Unlike in some other inflammatory diseases, the tissue level of ACE seems to be significantly lower in alopecia areata compared to normal controls. Serum ACE was significantly higher in patients with more severe disease.

G-CSF loaded nanofiber/nanoparticle composite coated with collagen promotes wound healing in vivo.

Sustained release of functional growth factors can be considered as a beneficial methodology for wound healing. In this study, recombinant human granulocyte colony-stimulating factor (G-CSF)-loaded chitosan nanoparticles were incorporated in Poly(ε-caprolactone) (PCL) nanofibers, followed by surface coating with collagen type I. Physical and mechanical properties of the PCL nanofibers containing G-CSF loaded chitosan nanoparticles PCL/NP(G-CSF) and in vivo performance for wound healing were investigated. G-CSF structural stability was evaluated through SDS_PAGE, reversed phase (RP) HPLC and size-exclusion chromatography, as well as circular dichroism. Nanofiber/nanoparticle composite scaffold was demonstrated to have appropriate mechanical properties as a wound dresser and a sustained release of functional G-CSF. The PCL/NP(G-CSF) scaffold showed a suitable proliferation and well-adherent morphology of stem cells. In vivo study and histopathological evaluation outcome revealed that skin regeneration was dramatically accelerated under PCL/NP(G-CSF) as compared with control groups. Superior fibroblast maturation, enhanced collagen deposition and minimum inflammatory cells were also the beneficial properties of PCL/NP(G-CSF) over the commercial dressing. The synergistic effect of extracellular matrix-mimicking nanofibrous membrane and G-CSF could develop a suitable supportive substrate in order to extensive utilization for the healing of skin wounds. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2830-2842, 2017.

Tumor-Infiltrating CD8+ Lymphocytes Effect on Clinical Outcome of Muco-Cutaneous Melanoma.

BACKGROUND: Recent data have changed our views of prognostic factors in cutaneous melanoma, while some newer methods have yielded better prognostic information. Tumor-infiltrating lymphocytes are believed to represent the immune reaction/response to melanoma cells which is often found in melanocytic cancer. AIM AND OBJECTIVE: We carried out an analysis, aiming to establish pooled estimates for clinical outcomes based on the presence of CD8+ T cell in melanocytic cancer. MATERIALS AND METHODS: We have included 42 patients with primary cutaneous melanocytic cancer without preoperative treatments in our study. We next analyzed the proliferative activity of CD8+ T cells that infiltrated in tumor cell nests. The intratumoral and adjacent to invasive margin of tumor CD+ T-cell infiltration were analyzed which could also reflect antitumor immunity. RESULTS: The total number of CD8+ cells especially adjacent to invasive margin of tumor was positively correlated with anatomical tumor thickness (P < .001) and not correlated with patient's age and sex. The stage of tumor which is related to vascular-neural invasion, regional lymph nodes involvement and tumor thickness shows positive correlation with CD8+ infiltration in tumor (P < .004, P < .005, P < .001), respectively. Acral melanoma shows more CD8 lymphocytes infiltration and also recurrence rate of tumor (P < .005). CONCLUSION: We believe that CD8+ T-cell infiltration in primary cutaneous melanocytic cancer represents the immune reaction/response to melanoma which could be an important new therapy for melanoma although more research is needed on this treatment modality.

Accelerated epidermal regeneration and improved dermal reconstruction achieved by polyethersulfone nanofibers.

INTRODUCTION: In this study, thick polyethersulfone (PES) nanofibrous scaffolds were prepared by fine tuning of electrospinning parameters and was evaluated for wound dressing applications. MATERIALS AND METHODS: Scanning electron microscopy and Brunauer-Emmett-Teller methods were used for PES nanofibers characterization. The interaction between fibroblasts and nanofibers was studied in vitro. Further, a mouse model was used to evaluate the effectiveness of the PES scaffold in wound healing. Vaseline gauze dressing and a conventional gas permeable bandage were used as a control. The wound repair process was evaluated by histological examination and immunohistochemistry staining using antibodies to cytokeratin 10 (CK10), proliferating cell nuclear antigen (PCNA), and alpha-smooth muscle actin (alpha-SMA). RESULTS AND CONCLUSION: The characterization of nanofibers showed that the PES membrane has nanoscale, porous, high surface area structure. These properties conferred higher exudate absorption capacity for the PES scaffold which is essential for effective wound healing. In vitro results indicated that the PES scaffold can support fibroblast proliferation similar to that with tissue culture polystyrene. Epithelial regeneration was expeditiously accelerated under PES as compared with Vaseline gauze. Greater fibroblast maturation, improved collagen deposition and faster edema resolution were the superior properties of PES over the commercial dressing. Based on these results we conclude that the biocompatible PES nanofibers can effectively be used as a dressing to accelerate wound healing.