The isolation and identification of dermatologically active constituents of coal tar

The production and uses of coal tar are reviewed as are the uses of steroids and cytotoxic agents in the treatment of psoriasis with a review of the condition also. An attempt was made to improve the efficaciousness and cosmetic acceptability of a low temperature tar, by screening fractions of this tar, derived from a variety of separation procedures. The most efficacious fraction was the highest boiling acid fraction, which is believed to consist mainly of mono- and di-hydric phenols. A time and concentration study showed that the optimum regime was the application of a 10% concentration in 5% wool fat in soft, yellow paraffin daily for 21 days. The mouse tail skin was selected as an experimental model, to ascertain the efficaciousness of fractions, because of the similarities between this skin and the psoriatic lesion. The activity of a fraction was monitored by the inducement of a granular layer in the mouse tail epidermis. Because coal tar is not an easy medium to work with, and the active fractions showed no increase in cosmetic acceptability over the parent coal tar, likely coal tar constituents were selected for screening on the basis of phenolic character, and the molecular weight range elucidated by mass spectroscopy. 32 potential anti-psoriatic agents were screened on mouse tail. Two catechols, 3,5-di-t-butyl and 4-t-butyl catechols were active. Other structures showed little or no activity. 24 catechols were screened and two extremely active catechols were discovered, 3-methyl-5-t-octyl and 5-methyl-3-t-octyl catechols. The screening of catechol-rich coal tar fractions and a coal tar fraction which had had the catechols removed by oxidation, showed that some anti-psoriatic activity was contained in the catechol fraction of coal tar. Attempts to elucidate the mode of action of these two compounds met with little success, but two modes of action are suggested

The influence of emotional reaction on help seeking by victims of school bullying

Research has started to focus on how victims of school bullying cope, but there is still very little understanding if why pupils cope in one way and not another. This paper aimed to examine the effects of gender, school-stage, frequency of victimization and different emotions (anger, vengeance, self-pity, indifference, and helplessness) upon the choice of social support that children report using. Questionnaires were completed by 6282 Maltese schoolchildren aged between 9 and 14 years old. Analyses revealed that specific patterns of emotion and victimization predict whether pupils report using certain sources of social support. Results are discussed in relation to their relevance for possible intervention, future research needs and implications for the theoretical framework used

Structure-activity relationships of the Human Immunodeficiency Virus type 1 maturation inhibitor PF-46396

This work was funded by the University of St Andrews and Society for Applied Microbiology New Lecturer Research Grant awarded to CSA, Wellcome Trust grant (093228) awarded to TKS.HIV-1 maturation inhibitors are a novel class of antiretroviral compounds, which consist of two structurally distinct chemical classes; betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by a similar mode of action to generate aberrant non-infectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study we utilized a series of novel analogues, with decreasing similarity to PF-46396, to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into WT immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) the tert-butyl group is essential for antiviral activity, but not an absolute requirement for Gag binding, (ii) the trifluromethyl group is optimal but not essential for antiviral activity and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but not essential as its replacement is tolerated.Publisher PDFPeer reviewe

The lymphocyte secretome from young adults enhances skeletal muscle proliferation and migration, but effects are attenuated in the secretome of older adults.

Older people experience skeletal muscle wasting, in part due to impaired proliferative capacity of quiescent skeletal muscle satellite cells which can be reversed by exposure to young blood. To investigate the role of immune cells in muscle regeneration, we isolated lymphocytes from whole blood of young and older healthy volunteers and cultured them with, or without, anti-CD3/CD28 activators to induce release of cytokines, interleukins, and growth factors into the media. The secreted proteins were collected to prepare a conditioned media, which was subsequently used to culture C2C12 myoblasts. The conditioned media from the activated young lymphocytes increased the rate of proliferation of myoblasts by around threefold (P < 0.005) and caused an approximate fourfold (P < 0.005) increase in migration compared with nonactivated lymphocyte control media. These responses were characterized by minimal myotube formation (2%), low fusion index (5%), low myosin heavy chain content, and substantial migration. In contrast, myoblasts treated with conditioned media from activated old lymphocytes exhibited a high degree of differentiation, and multi-nucleated myotube formation that was comparable to control conditions, thus showing no effect on proliferation or migration of myoblasts. These results indicate that secreted proteins from lymphocytes of young people enhance the muscle cell proliferation and migration, whereas secreted proteins from lymphocytes of older people may contribute to the attenuated skeletal muscle satellite cell proliferation and migration

Mild cold effects on hunger, food intake, satiety and skin temperature in humans.

BACKGROUND: Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake. OBJECTIVE: To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography. METHODS: We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18°C (mild cold) or 24°C (thermoneutrality) for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure. RESULTS: We could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure. CONCLUSIONS: It is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure.The study was funded by NIHR, BRC Seed Fund, individual grants: ML and MS: Marie Curie Fellowship, CYT: Welcome Trust Fellowship, SV: MRC, BHF and BBSRC, AVP: BBSRC.This is the final version of the article. It first appeared from Bioscientifica via https://doi.org/ 10.1530/EC-16-000

Does bariatric surgery prior to total hip or knee arthroplasty reduce post-operative complications and improve clinical outcomes for obese patients? Systematic review and meta-analysis.

AIMS: Our aim was to determine whether, based on the current literature, bariatric surgery prior to total hip (THA) or total knee arthroplasty (TKA) reduces the complication rates and improves the outcome following arthroplasty in obese patients. METHODS: A systematic literature search was undertaken of published and unpublished databases on the 5 November 2015. All papers reporting studies comparing obese patients who had undergone bariatric surgery prior to arthroplasty, or not, were included. Each study was assessed using the Downs and Black appraisal tool. A meta-analysis of risk ratios (RR) and 95% confidence intervals (CI) was performed to determine the incidence of complications including wound infection, deep vein thrombosis (DVT), pulmonary embolism (PE), revision surgery and mortality. RESULTS: From 156 potential studies, five were considered to be eligible for inclusion in the study. A total of 23 348 patients (657 who had undergone bariatric surgery, 22 691 who had not) were analysed. The evidence-base was moderate in quality. There was no statistically significant difference in outcomes such as superficial wound infection (relative risk (RR) 1.88; 95% confidence interval (CI) 0.95 to 0.37), deep wound infection (RR 1.04; 95% CI 0.65 to 1.66), DVT (RR 0.57; 95% CI 0.13 to 2.44), PE (RR 0.51; 95% CI 0.03 to 8.26), revision surgery (RR 1.24; 95% CI 0.75 to 2.05) or mortality (RR 1.25; 95% CI 0.16 to 9.89) between the two groups. CONCLUSION: For most peri-operative outcomes, bariatric surgery prior to THA or TKA does not significantly reduce the complication rates or improve the clinical outcome. This study questions the previous belief that bariatric surgery prior to arthroplasty may improve the clinical outcomes for patients who are obese or morbidly obese. This finding is based on moderate quality evidence. Cite this article: Bone Joint J 2016;98-B:1160-6

Ozone and Tracer Transport Variations in the Summer Northern Hemisphere Stratosphere

Constituent observations from the Upper Atmosphere Research Satellite (UARS) in combination with estimates of the residual circulation are used to examine the transport and chemical budgets of HF, CH4 and O3 in the summer Northern Hemisphere. Budget calculations of HF, CH4 and O3 show that the transport tendency due to the residual circulation increases in magnitude and is largely opposed by eddy motions through the summer months. Ozone budget analyses show that between 100 and 31 hPa, the magnitudes of the mean circulation and eddy transport terms increase through the summer months, producing tendencies that are factors of 2 to 3 times larger than the observed ozone change in the stratosphere. Chemical loss dominates the observed ozone decrease only at the highest latitudes, poleward of about 70°N. A comparison of observations from the Total Ozone Mapping Spectrometer with UARS-calculated total ozone suggests that poleward of 50°N, between 35% and 55% of the seasonal ozone decline during the summer occurs at altitudes below 100 hPa. The overall uncertainties, associated primarily with calculations of the residual circulation and eddy transport, are relatively large, and thus prevent accurate and useful constraints on the ozone chemical rate in the lower stratosphere

Rates of referable eye disease in the Scottish National Diabetic Retinopathy Screening Programme

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.Peer reviewedPublisher PD

Effects of exercise on adolescent and adult hypothalamic and hippocampal neuroinflammation.

Adolescence is a period of significant brain plasticity that can be affected by environmental factors, including the degree of physical activity. Here we hypothesized that adolescent rats would be more sensitive to the beneficial metabolic and anti-inflammatory effects of voluntary exercise than adult rats, whose more mature brains have less capacity for plasticity. We tested this by giving adolescent and adult Wistar rats four weeks' voluntary access to running wheels. At the end of this period we assessed metabolic effects, including weight and circulating leptin and ghrelin, as well as performance in a novel object recognition test of memory and central changes in neuronal proliferation, survival, synaptic density, and inflammatory markers in hippocampus. We found exercise reduced fat mass and circulating leptin levels in both adults and adolescents but suppressed total weight gain and lean mass in adults only. Exercise stimulated neuronal proliferation in the suprapyramidal blade of the dentate gyrus in both adults and adolescents without altering the number of mature neurons during this time frame. Exercise also increased dentate microglial numbers in adolescents alone and microglial numbers in this region were inversely correlated with performance in the novel object recognition test. Together these data suggest that adolescent hippocampal microglia are more sensitive to the effects of exercise than those of adults, but this leads to no apparent improvement in recognition memory. This article is protected by copyright. All rights reserved

Thermoregulatory, metabolic, and cardiovascular responses during 88 min of full-body ice immersion - A case study.

Exposure to extreme cold environments is potentially life-threatening. However, the world record holder of full-body ice immersion has repeatedly demonstrated an extraordinary tolerance to extreme cold. We aimed to explore thermoregulatory, metabolic, and cardiovascular responses during 88 min of full-body ice immersion. We continuously measured gastrointestinal temperature (Tgi ), skin temperature (Tskin), blood pressure, and heart rate (HR). Oxygen consumption (VO2 ) was measured at rest, and after 45 and 88 min of ice immersion, in order to calculate the metabolic heat production. Tskin dropped significantly (28-34°C to 4-15°C) and VO2 doubled (5.7-11.3 ml kg-1  min-1 ), whereas Tgi (37.6°C), HR (72 bpm), and mean arterial pressure (106 mmHg) remained stable during the first 30 min of cold exposure. During the remaining of the trial, Tskin and VO2 remained stable, while Tgi gradually declined to 37.0°C and HR and mean arterial blood pressure increased to maximum values of 101 bpm and 115 mmHg, respectively. Metabolic heat production in rest was 169 W and increased to 321 W and 314 W after 45 and 80 min of ice immersion. Eighty-eight minutes of full-body ice immersion resulted in minor changes of Tgi and cardiovascular responses, while Tskin and VO2 changed markedly. These findings may suggest that our participant can optimize his thermoregulatory, metabolic, and cardiovascular responses to challenge extreme cold exposure