UCHL1/PGP 9.5 Dynamic in neuro-immune-cutaneous milieu : focusing on axonal nerve terminals and epidermal keratinocytes in psoriatic itch

Psoriasis is an immunogenetic skin disease manifesting as plaque lesions on the skin. Patients with psoriasis frequently suffer from itch, an unpleasant sensation causing a desire to scratch. Psoriatic itch is mainly transmitted by unmyelinated C-fibers; however, the exact molecular mechanism of psoriatic itch is still unexplained. Protein gene product 9.5 (PGP 9.5) is a panneurological marker commonly used for analysis of peripheral peptidergic and nonpeptidergic nerves and identification of cutaneous neuro-immune-endocrine cells. However, some studies suggested that nonneuronal cells, like keratinocytes, may also express PGP 9.5. This phenomenon might be linked with impaired axonal transport, keratinocyte injury, or dysfunctions of neuro-immune-cutaneous connections. The aim of this study was to analyze the expression of PGP 9.5 in psoriatic skin. We observed significantly altered density of PGP 9.5-positive axonal nerve terminals in pruritic lesional (p=0.04) and nonlesional psoriatic skin (p>0.001) compared with controls. In contrast, no significant differences were observed between psoriatic skin without itch and controls. Furthermore, PGP 9.5 expression by suprabasal keratinocytes (SBKs) was significantly increased in itchy skin lesions (p=0.007) compared to skin without itch, and a positive correlation was observed between PGP 9.5 expression and itch intensity (r=0.64; p=0.02). Our findings indicate changes in peripheral innervations and psoriatic keratinocytes, which may influence neuro-immune-cutaneous homeostasis and modulate itch transmission

Surface Properties of Graffiti Coatings on Sensitive Surfaces Concerning Their Removal with Formulations Based on the Amino-Acid-Type Surfactants

Water-in-oil (w/o) nanoemulsions stabilized with amino acid surfactants (AAS) are one example of nanotechnology detergents of the “brush on, wipe off”-type for removing graffiti coatings from different sensitive surfaces. The high-pressure homogenization (HPH) process was used to obtain the nanostructured fluids (NSFs), including the non-toxic and eco-friendly components such as AAS, esterified vegetable oils, and ethyl lactate. The most effective NSF detergent was determined by response surface methodology (RSM) optimization. Afterwards, several surface properties, i.e., topography, wettability, surface free energy, and the work of water adhesion to surfaces before and after their coverage with the black graffiti paint, as well as after the removal of the paint layers by the eco-remover, were determined. It was found that the removal of graffiti with the use of the NSF detergent is more dependent on the energetic properties and microporous structure of the paint coatings than on the properties of the substrates on which the layers were deposited. The use of NSFs and knowledge of the surface properties could enable the development of versatile detergents that would remove unwanted contamination from various surfaces easily and in a controlled way

Polymorphism in intron 23 of the endothelial nitric oxide synthase gene (NOS3) is not associated with hypertension.

Nitric oxide (NO) is synthesised in the vascular endothelium by nitric oxide synthase (NOS3) and is an important factor in the regulation of blood pressure. Impaired synthesis of NO due to mutations in the NOS3 gene is associated with hypertension. To date several allelic variants of the NOS3 gene have been identified and their possible linkage with hypertension investigated. We studied the distribution of genotypes and frequency of alleles of the G11T polymorphism in intron 23 of the NOS3 gene in patients with hypertension and in a control group of healthy individuals. The polymorphism was determined by PCR-RFLP analysis. The distribution of genotypes in the patients with hypertension and in the healthy individuals did not differ significantly from the values predicted from Hardy-Weinberg equilibrium for the general population. No major differences in the distribution of the G11T polymorphism in the patients and healthy individuals were found (P > 0.05)

Correction: Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage.

[This corrects the article DOI: 10.1371/journal.pone.0156171.]

Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage

<div><p>Background</p><p>Toll-like receptor (TLR) signalling begins early in subarachnoid haemorrhage (SAH), and plays a key role in inflammation following cerebral aneurysm rupture. Available studies suggest significance of endogenous first-line blockers of a TLR pathway—soluble TLR2 and 4.</p><p>Methods</p><p>Eighteen patients with SAH and acute hydrocephalus underwent endovascular coiling and ventriculostomy; sTLR2 and 4 levels were assayed in cerebrospinal fluid (CSF) collected on post-SAH days 0–3, 5, and 10–12. Release kinetics were defined. CSF levels of sTLR2 and 4 were compared with a control group and correlated with the clinical status on admission, the findings on imaging, the degree of systemic inflammation and the outcome following treatment.</p><p>Results</p><p>None of study group showed detectable levels of sTLR2 and 4 on post-SAH day 0–3. 13 patients showed increased levels in subsequent samples. In five SAH patients sTLR2 and 4 levels remained undetectable; no distinctive features of this group were found. On post-SAH day 5 the strongest correlation was found between sTLR2 level and haemoglobin level on admission (cc = -0.498, P = 0.037). On post-SAH day 10–12 the strongest correlation was revealed between sTLR2 and treatment outcome (cc = -0.501, P = 0.076). Remaining correlations with treatment outcome, status at admission, imaging findings and inflammatory markers on post-SAH day 5 and 10–12 were negligible or low (-0.5 ≤ cc ≤ 0.5).</p><p>Conclusions</p><p>In the majority of cases, rupture of a cerebral aneurysm leads to delayed release of soluble TLR forms into CSF. sTLR2 and 4 seem to have minor role in human post-SAH inflammation due to delayed release kinetics and low levels of these protein.</p></div

Study group patients’ characteristic.

<p>Study group patients’ characteristic.</p

Increase of Soluble RAGE in Cerebrospinal Fluid following Subarachnoid Haemorrhage

Receptors for advanced glycation end-products (RAGE) mediate the inflammatory reaction that follows aneurysmal subarachnoid haemorrhage. Soluble RAGE (sRAGE) may function as a decoy receptor. The significance of this endogenous anti-inflammatory mechanism in subarachnoid haemorrhage (SAH) remains unknown. The present study aims to analyse sRAGE levels in the cerebrospinal fluid (CSF) of SAH patients. sRAGE levels were assayed by ELISA kit in 47 CSF samples collected on post-SAH days 0–3, 5–7, and 10–14 from 27 SAH patients with acute hydrocephalus. CSF levels of sRAGE were compared with a control group and correlated with other monitored parameters. In the control group, the CSF contained only a trace amount of sRAGE. By contrast, the CSF of 20 SAH patients collected on post-SAH days 0–3 was found to contain statistically significant higher levels of sRAGE (mean concentration 3.91 pg/mL, p<0.001). The most pronounced difference in CSF sRAGE levels between good and poor outcome patients was found on days 0–3 post-SAH but did not reach the significance threshold (p=0.234). CSF sRAGE levels did not change significantly during hospitalisation (p=0.868) and correlated poorly with treatment outcome, systemic inflammatory markers, and other monitored parameters. Our study revealed an early and constant increase of sRAGE level in the CSF of SAH patients