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Sebastian A.,University of Manchester | Allan E.,The Christie NHS Foundation Trust | Allan D.,North Western Medical Physics | Allan D.,University of Manchester | And 2 more authors.
Journal of Dermatological Science | Year: 2011

Background: We recently reported use of photodynamic therapy (PDT) for treating keloid disease (KD). However, in view of high recurrence rates post any treatment modality, adjuvant therapies should be considered. Additionally, we previously demonstrated the effect of a novel electrical waveform, the degenerate wave (DW) on differential gene expression in keloid fibroblasts. Objective: In this study, we evaluated the in vitro cytotoxic effect of PDT at 5J/cm 2 and 10J/cm 2 of red light (633±3nm) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) with and without DW, on keloid fibroblasts compared to normal skin fibroblasts. Methods: The rate of intracellular photosensitizer (protoporphyrin IX, PPIX) generation and disintegration, reactive oxygen species (ROS) generation, LDH cytotoxicity, WST-1 cytoproliferation, apoptosis by Caspase-3 activation, mitochondrial membrane potential assessment by JC-1 aggregates, qRT-PCR, flow cytometry and In-Cell Western Blotting were performed. Results: PPIX accumulation and disintegration rate was higher in keloid than normal fibroblasts after incubation with MAL compared to ALA. Increased cytotoxicity and decreased cytoproliferation were observed for keloid fibroblasts after PDT. +. DW treatment compared to PDT alone. ROS generation, mitochondrial membrane depolarization, apoptosis (Caspase-3 activation) and collagens I and III gene down-regulation were higher in keloid compared to normal skin fibroblasts after MAL-PDT. +. DW treatment. An increase in the number of cells entering apoptosis and necrosis was observed after PDT. +. DW treatment by flow cytometry analysis. All positive findings were statistically significant (P<0.05). Conclusion: The cytotoxic effect of PDT on keloid fibroblasts can be enhanced significantly with addition of DW stimulation, indicating for the first time the utility of this potential combinational therapy. © 2011 Japanese Society for Investigative Dermatology. Source


Griffin M.,University of Manchester | Iqbal S.A.,University of Manchester | Sebastian A.,University of Manchester | Colthurst J.,Fenzian Ltd | Bayat A.,University of Manchester
PLoS ONE | Year: 2011

Non-unions pose complications in fracture management that can be treated using electrical stimulation (ES). Bone marrow mesenchymal stem cells (BMMSCs) are essential in fracture healing; however, the effect of different clinical ES waveforms on BMMSCs cellular activities remains unknown. We compared the effects of direct current (DC), capacitive coupling (CC), pulsed electromagnetic field (PEMF) and degenerate wave (DW) on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G 2/M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay. All above findings were shown to be statistically significant (p<0.05). We conclude that ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. Application of DW or CC to the fracture site may help in the recruitment of BMMSCs to the wound that may enhance rate of bone healing at the fracture site. © 2011 Griffin et al. Source


Sebastian A.,University of Manchester | Syed F.,University of Manchester | Perry D.,University of Manchester | Balamurugan V.,University of Manchester | And 3 more authors.
Wound Repair and Regeneration | Year: 2011

We previously demonstrated the beneficial effect of a novel electrical stimulation (ES) waveform, degenerate wave (DW) on skin fibroblasts, and now hypothesize that DW can enhance cutaneous wound healing in vivo. Therefore, a punch biopsy was taken from the upper arm of 20 volunteers on day 0 and repeated on day 14 (NSD14). A contralateral upper arm biopsy was taken on day 0 and treated with DW for 14 days prior to a repeat biopsy on day 14 (ESD14). A near-completed inflammatory stage of wound healing in ESD14, compared to NSD14 was demonstrated by up-regulation of interleukin-10 and vasoactive intestinal peptide using quantitative real time polymerase chain reaction and down-regulation of CD3 by immunohistochemistry (IHC) (p<0.05). In addition to up-regulation (p<0.05) of mRNA transcripts for re-epithelialization and angiogenesis, IHC showed significant overexpression (p<0.05) of CD31 (15.5%), vascular endothelial growth factor (66%), and Melan A (8.6 cells/0.95mm 2) in ESD14 compared to NSD14 (9.5%, 38% and 4.3 cells/0.95mm 2, respectively). Furthermore, granulation tissue formation (by hematoxylin and eosin staining), and myofibroblastic proliferation demonstrated by alpha-smooth muscle actin (62.7%) plus CD3+ T lymphocytes (8.1%) showed significant up-regulation (p<0.05) in NSD14. In the remodeling stage, mRNA transcripts for fibronectin, collagen IV (by IHC, 14.1%) and mature collagen synthesis (by Herovici staining, 71.44%) were significantly up-regulated (p<0.05) in ESD14. Apoptotic (TUNEL assay) and proliferative cells (Ki67) were significantly up-regulated (p<0.05) in NSD14 (5.34 and 11.9 cells/0.95mm 2) while the proliferation index of ESD14 was similar to normal skin. In summary, cutaneous wounds receiving DW electrical stimulation display accelerated healing seen by reduced inflammation, enhanced angiogenesis and advanced remodeling phase. © 2011 by the Wound Healing Society. Source


Sebastian A.,University of Manchester | Iqbal S.A.,University of Manchester | Colthurst J.,Fenzian Ltd | Volk S.W.,University of Pennsylvania | Bayat A.,University of Manchester
Journal of Investigative Dermatology | Year: 2015

Cutaneous wounds establish endogenous "wound current" upon injury until re-epithelialization is complete. Keratinocyte proliferation, regulated partly by p53, is required for epidermal closure. SIVA1 promotes human double minute 2 homolog (HDM2)-mediated p53 regulation. However, the role of SIVA1 in wound healing is obscure. Here, we report that electrical stimulation (ES) accelerates wound healing by upregulating SIVA1 and its subsequent ability to modulate p53 activities. Cultured donut-shaped human skin explants, subjected to ES, exhibited better epidermal stratification, increased proliferation, and upregulation of gene and protein expression of HDM2SIVA1, compared with non-ES-treated explants. ES significantly increased in vitro keratinocyte proliferation and phospho-p53-SIVA1 interaction; however, this showed stable expression of phospho-p53, which increased significantly in the absence of SIVA1. Here, HDM2 alone was unable to downregulate nuclear-accumulated phospho-p53, which was evident from decreased proliferation and increased sub-G 1 population seen by flow cytometry. Further examination of the epidermis of human cutaneous wounds showed higher p53-SIVA1 coexpression and proliferation 7 days after injury in ES-treated wounds compared with control wounds. In summary, ES-inducible SIVA1 modulates p53 activities in proliferating keratinocytes, and exogenous ES affects p53HDM2SIVA1 axis leading to increased proliferation during re-epithelialization. This highlights ES as a potential strategy for enhancing cutaneous repair. © The Society for Investigative Dermatology. Source


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FENZIAN Ltd and Eumedic Ltd | Date: 2006-01-31

Medical apparatus and equipment, namely, stimulators for nerves, skin and muscles; and electrically powered apparatus for the treatment of medical conditions and for fitness in general, namely, electronic stimulator apparatus for nerves, skin and muscles; specifically excluding intraocular lens implants and parts and fittings therefore. Education and training services, namely, conducting classes, seminars and workshops in the fields of healthcare and the provision of medical treatment and services. Providing healthcare and medical services and consultation related thereto; healthcare and medical services, namely, specialised treatment of medical conditions and medical diagnostic services; healthcare services provided at health centres and clinics; and massage.

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