633 Comparison of soluble proteins from skin sections of acne and TCA induced postinflammatory hyperpigmentation and erythema

Postinflammatory hyperpigmentation (PIH) is an acquired hypermelanosis occurring after cutaneous inflammation or injury that can arise in all skin types, but more frequently affects skin-of-color. The differences in the ethology of PIH and Postinflammatory erythema (PIE) in skin of color were evaluated from soluble protein extracts collected from skin section samples, using Somascan protein kit1.3 k (n=5). The skin samples were collected from selected gluteal TCA-induced lesions and truncal acne pustules, of either PIH or PIE, at day 28 post initial evaluation. Differences between proteins (FDR\u3c0.05) from PIH and PIE were analyzed with STRING version 11.5 and analysis points toward involvement of JAK/STAT signaling pathway and enhanced IL17 signaling in PIH compared to PIE lesions (OSM, CSF3, IL10RA, IL12RB2, IL10RB, IL3, CSF2, IL17D, IL17F, IFNA2, IFNA10, CRLF2, IL5RA, TYK2, IL12RB1, PRLR, GHR). The involvement of JAK/STAT signaling pathway has been described for some chronic cutaneous inflammatory conditions and acne. A higher occurrence of dermal remodeling proteases and inhibitors were found in PIE (MMP1, MMP2, MMP7, TIMP2) indicating a dermal remodeling phase at the time of excision. Concurrently, elevated levels of IL-1β, and TGF-β (critical for triggering and continuing differentiation programs of naïve CD4+ T cells to IL-17 secreting Th17 cells) in PIH samples suggests continuing promotion of macrophage infiltration and sustained inflammation. In addition to MMP13 and MMP16, the protein Keap1 was found to be increased in the PIH samples. Keap1, a repressor of master cellular defense against oxidative and electrophilic stresses, has been reported to be involved in the imbalance of proteolysis that can lead towards premature aging and in a senescent phenotype of endothelial cells. The sustained inflammation with excess of Keap1 protein might contribute to an altered proteostasis and ethology of PIH

Factors affecting continuation of clean intermittent catheterisation in people with multiple sclerosis: results of the COSMOS mixed-methods study

Background:  Clean intermittent catheterisation (CIC) is often recommended for people with multiple sclerosis (MS).  Objective:  To determine the variables that affect continuation or discontinuation of the use of CIC.  Methods:  A three-part mixed-method study (prospective longitudinal cohort (n = 56), longitudinal qualitative interviews (n = 20) and retrospective survey (n = 456)) was undertaken, which identified the variables that influenced CIC continuation/discontinuation. The potential explanatory variables investigated in each study were the individual’s age, gender, social circumstances, number of urinary tract infections, bladder symptoms, presence of co-morbidity, stage of multiple sclerosis and years since diagnosis, as well as CIC teaching method and intensity.  Results:  For some people with MS the prospect of undertaking CIC is difficult and may take a period of time to accept before beginning the process of using CIC. Ongoing support from clinicians, support at home and a perceived improvement in symptoms such as nocturia were positive predictors of continuation. In many cases, the development of a urinary tract infection during the early stages of CIC use had a significant detrimental impact on continuation.  Conclusion:  Procedures for reducing the incidence of urinary tract infection during the learning period (i.e. when being taught and becoming competent) should be considered, as well as the development of a tool to aid identification of a person’s readiness to try CIC

Effect of Surface Roughness on the Squeeze Film Characteristics of Circular Plates in the Presence of Conducting Couplestress Fluid and Transverse Magnetic Field

The combined effect of surface roughness and magnetic field on the performance characteristic of the circular plates lubricated with conducting couplestress fluid (CCSF) has been studied. On the basis of the Christensen Stochastic model, the generalized stochastic Reynold’s equation is derived. Modified equations for the nondimensional pressure, load load-carrying capacity, and squeeze film time are derived. The results are presented both numerically and graphically and compared with conducting smooth surface case. It is observed that the surface roughness effects are more pronounced for couplestresses as compared to nonconducting Newtonian fluid (NCNF) in the presence of magnetic field

The functions of the A1A2A3 domains in von Willebrand factor include multimerin 1 binding.

Multimerin 1 (MMRN1) is a massive, homopolymeric protein that is stored in platelets and endothelial cells for activation-induced release. In vitro, MMRN1 binds to the outer surfaces of activated platelets and endothelial cells, the extracellular matrix (including collagen) and von Willebrand factor (VWF) to support platelet adhesive functions. VWF associates with MMRN1 at high shear, not static conditions, suggesting that shear exposes cryptic sites within VWF that support MMRN1 binding. Modified ELISA and surface plasmon resonance were used to study the structural features of VWF that support MMRN1 binding, and determine the affinities for VWF-MMRN1 binding. High shear microfluidic platelet adhesion assays determined the functional consequences for VWF-MMRN1 binding. VWF binding to MMRN1 was enhanced by shear exposure and ristocetin, and required VWF A1A2A3 region, specifically the A1 and A3 domains. VWF A1A2A3 bound to MMRN1 with a physiologically relevant binding affinity (KD: 2.0 ± 0.4 nM), whereas the individual VWF A1 (KD: 39.3 ± 7.7 nM) and A3 domains (KD: 229 ± 114 nM) bound to MMRN1 with lower affinities. VWF A1A2A3 was also sufficient to support the adhesion of resting platelets to MMRN1 at high shear, by a mechanism dependent on VWF-GPIbα binding. Our study provides new information on the molecular basis of MMRN1 binding to VWF, and its role in supporting platelet adhesion at high shear. We propose that at sites of vessel injury, MMRN1 that is released following activation of platelets and endothelial cells, binds to VWF A1A2A3 region to support platelet adhesion at arterial shear rates.This study was supported by the Heart and Stroke Foundation (CPMH), the Canadian Institutes of Health Research (CPMH), the British Heart Foundation (RWF), The Wellcome Trust (RWF), and the National Institutes of Health (JES).This is the author accepted manuscript. The final version is available from Schattauer Publishers via http://dx.doi.org/10.1160/TH15-09-070

Effects of green tea and chamomile tea on plaque pH, salivary pH, Streptococcus mutans count

Aim: Green tea is healthy beverage and is a part of our day to day life. Similarly, chamomile tea is known for its aspirin like properties. Beneficial effects of these tea includes protection against dental caries, periodontal disease and tooth loss and found that can a decrease in streptococcus mutans count as well as increase in pH. Hence the present study was to compare the pH of saliva and plaque, before and after the intake of green tea and to evaluate the role of green tea and chamomile tea on growth of s.mutans in culture using saliva. Material and Methods: Salivary samples were collected from 30 healthy individuals aged 20-30 years with certain criteria. The pH of saliva was determined by collecting samples before, immediately after and 15 min, 30 min after drinking tea using pH meter. Similarly the microbial colonies were also counted. The Data obtained were analyzed using Wilcoxon’s, Friedman's and Mann Whitney test. Results: There was statistically no significant difference between salivary streptococcus mutans count before and after (p 0.001) intake of green tea and chamomile tea. Conclusion: The result of the present study has proved that consumption of green tea and chamomile tea inhibit salivary Streptococcus mutans count and cause reduction of pH in saliva. So, it is advisable to encourage the regular consumption of this widely available, tasty and inexpensive beverage as an interesting alternative to other drinks

Evaluation of Essential and Toxic Elements in Blood Samples of Male Smokers Having Different Types of Cancers with Reference to Healthy Male Smokers

Immense epidemiologic studies have been reported about the role of essential trace and toxic elements as risk factors for incidence of different type of cancers in population of developed and developing countries. In present work the levels of carcinogenic, Arsenic, Cadmium, and Nickel (As, Cd and Ni) and anti-carcinogenic, Zinc and Selenium (Zn and Se) elements were measured in blood of male cancer patients (urinary bladder, lung, mouth and esophageal) and healthy referents. The all patients and referents were smoker. The blood samples were analysed with atomic absorption spectrometry after microwave assisted acid digestion. The resulted data indicated that the levels of toxic elements As, Ni and Cd were considerably elevated whereas essential elements, Zn and Se were lower in blood samples of all cancer cases as compared to those values found in noncancerous subjects. As the levels of essential trace elements were low in blood samples of male cancerous patients but difference was highly significant in lung and mouth cancer subjects (p<0.001), whereas sequence of decreasing order was not uniform. The levels of Zn in blood samples of different cancerous patients were found in decreasing order as: esophagus< mouth< urinary bladder<lung, whereas in case of Se as mouth<lung<urinary bladder<esophagus.The study revealed that the carcinogenic processes are significantly affecting the essential and toxic elements levels in biological samples of cancerous patients as related to those obtained for controls/referents

A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.Comment: Accepted by Physical Biology; includes a supplement and a supplementary mpeg movie can be found at http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp