The global burden of diabetic wounds Schreml, S.; Berneburg, M.
British journal of dermatology (1951),
April 2017, 2017-04-00, 20170401, Letnik:
176, Številka:
4
Journal Article
Background
Polymorphous light eruption (PLE) is a common, immunologically mediated, photosensitive skin disease. After ultraviolet‐B (UV‐B) irradiation, patients with PLE show reduced Langerhans cell ...(LC) depletion in the epidermis, which results in a non‐suppressive microenvironment in the skin. Interestingly, severe acute graft‐versus‐host disease (aGvHD) occurred in stem cell transplanted patients that showed no or incomplete depletion of LCs after UVB irradiation. Genetic variation in nucleotide‐binding oligomerization domain 2 (NOD‐2) and toll‐like receptor 5 (TLR‐5) genes also confers susceptibility to aGvHD.
Objectives
We hypothesized that PLE is associated with genetic variation in the NOD‐2 and TLR‐5 genes.
Methods
We investigated single‐nucleotid polymorphisms (SNPs) of NOD‐2 (R702W, G908R, 3020Cins) and TLR‐5 (A592S, P616L, N392STOP) in skin biopsies of patients with PLE (n = 143) and in healthy controls (n = 104) using restriction fragment length polymorphism analysis.
Results
The frequency of NOD‐2 alleles with the SNP R702W was significantly higher in PLE than in controls (31.8% vs. 6.3%; P < 0.0001), and homozygous carriers of this mutation were more common in PLE (27.9% vs. 0%; P < 0.0001). For SNP 3020Cins, the allele frequency (7.3% vs. 0.7%; P = 0.0025) and the number of heterozygotes (14.7% vs. 1.3%; P = 0.0019) were higher in PLE. The frequency of alleles with the N392STOP SNP of the TLR5 gene, which is associated with a truncated, non‐functional receptor, was significantly higher in PLE (21% vs. 5%; 7% vs. 1% homozygotes, 28% vs. 8% heterozygotes; P < 0.0001). The other SNPs did not differ significantly.
Conclusions
This study yielded a high frequency of functional SNPs in the NOD‐2 and TLR‐5 genes in PLE. The same SNPs are associated with aGvHD and there are similarities in the reaction of LCs after UVB irradiation between aGvHD and PLE. This leads to the hypothesis that patients with PLE may be more susceptible to developing GvHD after stem cell transplantation, an assumption that needs to be investigated further.
The exposure to UVA (320–400 nm) irradiation is a major threat to human skin concerning photoaging and carcinogenesis. It has been shown that UVA irradiation can induce reactive oxygen species (ROS) ...and DNA mutations, such as 8-hydroxydeoxyguanosine. Furthermore, UVA induces the expression of photoaging-associated matrix metalloproteases (MMPs), especially of matrix metalloprotease 1 (MMP 1) and matrix metalloprotease 3 (MMP 3). In addition to this, it was recently shown that UVA-induced ROS also increase glucose metabolism of melanoma cells, however, the influence of UVA on the glucose metabolism of non-malignant cells of the human skin has, so far, not been investigated in detail. Here, we investigated the UVA-induced changes in glucose metabolism and the functional relevance of these changes in primary fibroblasts—normal non-malignant cells of the skin. These cells showed an UVA-induced enhanced glucose consumption and lactate production and changes in pyruvate production. As it has been proposed that pyruvate could have antioxidant properties we tested the functional relevance of pyruvate as protective agent against UVA-induced ROS. Our initial experiments support earlier publications, demonstrating that pyruvate treated with H
2
O
2
is non-enzymatically transformed to acetate. Furthermore, we show that this decarboxylation of pyruvate to acetate also occurs upon UVA irradiation. In addition to this, we could show that in fibroblasts pyruvate has antioxidant properties as enhanced levels of pyruvate protect cells from UVA-induced ROS and partially from a DNA mutation by the modified base 8-hydroxydeoxyguanosine. Furthermore, we describe for the first time, that the interaction of UVA with pyruvate is relevant for the regulation of photoaging-associated MMP 1 and MMP 3 expression.
Graphical abstract
The damaging effects of solar ultraviolet (UV) radiation exposure to human skin are well known and can reach from accelerated skin aging (photoaging) to skin cancer. Much of the damaging effects of ...solar UVA (320–400 nm) radiation is associated with the induction of reactive oxygen species (ROS), which are capable to cause oxidative damage to DNA like the oxidized guanosine 8-hydroxy-2' -deoxyguanosine (8-OHdG). Therefore, new UV protective strategies, have to be tested for their efficiency to shield against UV induced damage. We investigated the protective effects of HelioVital sun protection filter foil against UVA1 irradiation in skin cells. It could be shown, that HelioVital sun protection filter foil has protective effects against UVA1 irradiation induced changes in matrix metalloproteinase (MMP) expression. Furthermore a UVA1-dependant regulation of MMP15 in human fibroblasts could be shown for the first time in this context. In addition, this study demonstrated the protective effect of the HelioVital filter film against UVA1-induced ROS production and DNA damage. These results could pave the way for clinical studies with HelioVital filter foil shielding against the damaging effects of phototherapy and other forms of irradiation therapy, thereby increasing the safety and treatment opportunities of these forms of therapy.
Graphical abstract
Summary
Primary immunodeficiencies (PIDs) are a heterogeneous group of rare diseases that result from defects in immune system development and/or function. The clinical manifestations of PIDs are ...highly variable, but most disorders involve at least an increased susceptibility to infection. Furthermore, cutaneous manifestations are very common in PIDs. As an easily accessible organ, the skin can be crucial for early diagnosis and treatment. This is relevant for preventing significant disease‐associated morbidity and mortality. We provide a table that enables the reader to find the possible diseases and corresponding gene defects based on the skin manifestations of the suspected PIDs. To our knowledge, this is the first review that allows the reader to find relevant PIDs and the respective gene defects through solitary or combined skin signs.
What's already known about this topic?
Primary immunodeficiencies (PIDs) comprise more than 300 distinct entities.
About half of these PIDs have skin signs.
What does this study add?
This review provides the reader with a framework on when and how to check for specific PIDs based on solitary or combined cutaneous signs.
Plain language summary available online
Background
Laser pulses with nanosecond duration (NSL) have been the golden standard to destroy the pigment particles in skin. It is still controversially discussed whether picosecond pulses (PSL) ...are superior for tattoo removal.
Objectives
To compare the efficacy and the adverse reactions of nanosecond and picosecond laser pulses in a comparative study.
Methods
The prospective study included 23 subjects with 30 black or coloured tattoos, which were split into two halves treated with either a new PSL (532, 1064 nm) or standard NSL (694 nm). The lasers were applied at regular time intervals of 4 weeks for up to eight treatments. Tattoo clearance (primary endpoint), pain and adverse reactions (secondary endpoints) were appraised by physicians, blinded observers, and by subjects. The extent and duration of adverse reactions were additionally assessed by using a questionnaire and photo‐documentation after each treatment session.
Results
The tattoo clearance appeared to be more effective for PSL compared to NSL but without statistical significance (P > 0.05). Pretreated tattoos responded better to laser treatments than previously untreated tattoos. Subjects felt significantly less pain with PSL than with NSL (P < 0.001). Transient adverse reactions were statistically less pronounced lasting shorter for PSL as for NSL, especially blistering, pruritus, and burning sensation. Hypopigmentation appeared after NSL treatments only, whereas hyperpigmentation was caused by both lasers. No scarring was detected with either laser.
Conclusions
Both laser systems enable acceptable clearance of most tattoos in the present study. PSL cause less collateral skin damage as compared to NSL.
原发性免疫缺陷的皮肤症状——如何找到要检查的基因 Ettinger, M.; Schreml, J.; Wirsching, K. ...
British journal of dermatology (1951),
February 2018, 20180201, Letnik:
178, Številka:
2
Journal Article
Summary
Primary immunodeficiencies are rare chronic disorders, in which parts of the immune system either lack or function improperly. Thus, the immune system is weakened, and patients are more ...susceptible to germs that can cause infections. Patients can have various symptoms, but all have repeated prolonged and/or serious infections, sometimes from uncommon germs. Half of the patients have symptoms on their skin, which can help a doctor to recognize the underlying immune disorder. Therefore, the authors of this study provide a table to make it easier for the physician to diagnose an immune disorder according to the skin signs once an immunodeficiency is suspected. They list typical skin manifestations and the according diseases and genes to check.
Linked Article: Ettinger et al. Br J Dermatol 2018; 178:335–349
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