Philosophical Reflections on Experimenting with Human Subjects

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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Intradermal challenge with interleukin-8 causes tissue oedema and neutrophil accumulation in atopic and non-atopic human subjects

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.1996.d01-291.x ◽

1996 ◽

Vol 26 (12) ◽

pp. 1371-1379 ◽

Cited By ~ 1

Author(s):

J. Douglass ◽

D. Dhami ◽

M. Bulpitt ◽

I. J. Lindley ◽

J. Shute ◽

...

Keyword(s):

Human Subjects ◽

Interleukin 8 ◽

Neutrophil Accumulation ◽

Tissue Oedema

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Research Recommendations for Applying Vitamin A-Labelled Isotope Dilution Techniques to Improve Human Vitamin A Nutrition

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000185 ◽

2014 ◽

Vol 84 (Supplement 1) ◽

pp. 52-59 ◽

Cited By ~ 5

Author(s):

Sherry A. Tanumihardjo ◽

Anura V. Kurpad ◽

Janet R. Hunt

Keyword(s):

Public Health ◽

Vitamin A ◽

Vitamin A Deficiency ◽

Human Subjects ◽

The Body ◽

Pool Size ◽

Serum Retinol ◽

Vitamin A Status ◽

Status Assessment ◽

Total Body

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.

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Delay Discounting in Impulsive Behavior

European Psychologist ◽

10.1027/1016-9040/a000360 ◽

2019 ◽

Vol 24 (4) ◽

pp. 312-321 ◽

Cited By ~ 4

Author(s):

Diana Moreira ◽

Fernando Barbosa

Keyword(s):

Delay Discounting ◽

Human Subjects ◽

Empirical Studies ◽

Cochrane Collaboration ◽

Initial Assessment ◽

Impulsive Behavior ◽

Manual Search ◽

Study Results ◽

Depth Analysis ◽

The Future

Abstract. Delay discounting (DD) is the process of devaluing results that happen in the future. With this review, we intend to identify specificities in the processes of DD in impulsive behavior. Studies were retrieved from multiple literature databases, through rigorous criteria (we included systematic reviews and empirical studies with adult human subjects), following the procedures of the Cochrane Collaboration initiative. Of the 174 documents obtained, 19 were considered eligible for inclusion and were retained for in-depth analysis. In addition, 13 studies from the manual search were included. Thus, a total of 32 studies were selected for review. The objectives/hypotheses, results, and the main conclusion(s) were extracted from each study. Results show that people with pronounced traits of impulsivity discount rewards more markedly, that is, they prefer immediate rewards, though of less value, or postponed losses, even though they worsen in the future. Taken together, the existing data suggest the importance of inserting DD as a tool for initial assessment in conjunction with measures of addiction and stress level, as well as the consideration of new therapies.

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Minimizing Carry-Over Effects After Treatment Failure and Maximizing Therapeutic Outcome

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000180 ◽

2014 ◽

Vol 222 (3) ◽

pp. 171-178 ◽

Cited By ~ 3

Author(s):

Mareile Hofmann ◽

Nathalie Wrobel ◽

Simon Kessner ◽

Ulrike Bingel

Keyword(s):

Treatment Failure ◽

Human Subjects ◽

Subsequent Treatment ◽

Clinical Samples ◽

Administration Route ◽

Healthy Human ◽

Negative Experiences ◽

Analgesic Treatment ◽

Balanced Design ◽

Carry Over

According to experimental and clinical evidence, the experiences of previous treatments are carried over to different therapeutic approaches and impair the outcome of subsequent treatments. In this behavioral pilot study we used a change in administration route to investigate whether the effect of prior treatment experience on a subsequent treatment depends on the similarity of both treatments. We experimentally induced positive or negative experiences with a topical analgesic treatment in two groups of healthy human subjects. Subsequently, we compared responses to a second, unrelated and systemic analgesic treatment between both the positive and negative group. We found that there was no difference in the analgesic response to the second treatment between the two groups. Our data indicate that a change in administration route might reduce the influence of treatment history and therefore be a way to reduce negative carry-over effects after treatment failure. Future studies will have to validate these findings in a fully balanced design including larger, clinical samples.

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