Vitamin D has well documented effects on calcium homeostasis and bone metabolism but recent studies suggest a much broader role for this secosteroid in human health. Key components of the vitamin D system, notably the vitamin D receptor (VDR) and the vitamin D activating enzyme (1α-hydroxylase), are present in a wide array of tissues, notably macrophages, dendritic cells and T lymphocytes (T cells) from the immune system. Thus, serum 25-hydroxyvitamin D (25D) can be converted to hormonal 1,25-dihydroxyvitamin D (1,25D) within immune cells, and then interact with VDR and promote transcriptional and epigenomic responses in the same or neighbouring cells. These intracrine and paracrine effects of 1,25D have been shown to drive antibacterial or antiviral innate responses, as well as attenuating inflammatory T cell adaptive immunity. Beyond these mechanistic observations, association studies have reported correlation between low serum 25D levels and the risk and severity of human immune disorders including autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis. The proposed explanation for this is that decreased availability of 25D compromises immune cell synthesis of 1,25D leading to impaired innate immunity and over-exuberant inflammatory adaptive immunity. The aim of the current review is to explore the mechanistic basis for immunomodulatory effects of 25D and 1,25D in greater detail with specific emphasis on how vitamin D-deficiency (low serum levels of 25D) may lead to dysregulation of macrophage, dendritic cell and T cell function, and increase risk of inflammatory autoimmune disease.
Objective: Despite treatment advances over the past 30 years, the societal impact of hard-to-heal wounds is increasingly burdensome. An unresolved issue is wound pain, which can make many treatments, such as compression in venous leg ulcers, intolerable. The aim of this review is to present the evidence and stimulate thinking on the use of electrical stimulation devices as a treatment technology with the potential to reduce pain, improve adherence and thus hard-to-heal wound outcomes. Method: A literature search was conducted for clinical studies up to August 2020 reporting the effects of electrical stimulation devices on wound pain. Devices evoking neuromuscular contraction or direct spinal cord stimulation were excluded. Results: A total of seven publications (three non-comparative and four randomised trials) were identified with four studies reporting a rapid (within 14 days) reduction in hard-to-heal wound pain. Electrical stimulation is more widely known for accelerated healing and is one of the most evidence-based technologies in wound management, supported by numerous in vitro molecular studies, five meta-analyses, six systematic reviews and 30 randomised controlled trials (RCTs). Despite this wealth of supportive evidence, electrical stimulation has not yet been adopted into everyday practice. Some features of electrical stimulation devices may have hampered adoption in the past. Conclusion: As new, pocket-sized, portable devices allowing convenient patient treatment and better patient adherence become more widely available and studied in larger RCTs, the evidence to date suggests that electrical stimulation should be considered part of the treatment options to address the challenges of managing and treating painful hard-to-heal wounds.
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