Analysis of phases 1 and 2 metabolism enzymes in human skin suggests important role of phase 2 enzymes in the detoxification

2008 ◽  
Vol 180 ◽  
pp. S121 ◽  
Author(s):  
Van Luu-The ◽  
Daniel Duché ◽  
Corinne Ferraris ◽  
Jacques Leclaire ◽  
Fernand Labrie
Keyword(s):  
Human Skin ◽  
Phase 2 ◽  
Metabolism Enzymes ◽  
Phase 2 Enzymes

Therapeutic potential of dietary phase 2 enzyme inducers in ameliorating diseases that have an underlying inflammatory component

2001 ◽  
Vol 79 (3) ◽  
pp. 266-282 ◽  
Author(s):  
Bernhard HJ Juurlink
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Effects ◽  
Phase 2 ◽  
Phase 2 Enzymes ◽  
Anti Oxidant ◽  
Inflammatory Component ◽  
Enzyme Inducers

Many diseases associated with ageing have an underlying oxidative stress and accompanying inflammatory component, for example, Alzheimer's disease or atherosclerosis. Reviewed in this manuscript are: the role of oxidative stress in activating the transcription factor nuclear factor kappa B (NFκB), the role of NFκB in activating pro-inflammatory gene transcription, strong oxidants produced by cells, anti-oxidant defense systems, the central role of phase 2 enzymes in the anti-oxidant defense, dietary phase 2 enzyme inducers and evidence that dietary phase 2 enzymes decrease oxidative stress. It is likely that a diet containing phase 2 enzyme inducers may ameliorate or even prevent diseases that have a prominent inflammatory component to them. Research should be directed into the potential therapeutic effects of dietary phase 2 enzyme inducers in ameliorating diseases with an underlying oxidative stress and inflammatory component to them.Key words: Alzheimer's disease, atherosclerosis, diet, glutathione, inflammation, stroke.

scholarly journals Phase-2 reentry in cardiac tissue: Role of the slow calcium pulse

2010 ◽  
Vol 82 (1) ◽  
Author(s):  
Inma R. Cantalapiedra ◽  
Angelina Peñaranda ◽  
Blas Echebarria ◽  
Jean Bragard
Keyword(s):  
Cardiac Tissue ◽  
Phase 2

Bruton's tyrosine kinase inhibition in the treatment of preclinical models and multiple sclerosis

2021 ◽  
Vol 27 ◽  
Author(s):  
Anja Steinmaurer ◽  
Isabella Wimmer ◽  
Thomas Berger ◽  
Paulus Stefan Rommer ◽  
Johann Sellner
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Bruton’S Tyrosine Kinase ◽  
Cumulative Number ◽  
Phase 2 ◽  
Bruton's Tyrosine Kinase ◽  
Relapsing Remitting

: Significant progress has been made in understanding the immunopathogenesis of multiple sclerosis (MS) over recent years. Successful clinical trials with CD20-depleting monoclonal antibodies have corroborated the fundamental role of B cells in the pathogenesis of MS and reinforced the notion that cells of the B cell lineage are an attractive treatment target. Therapeutic inhibition of Bruton's tyrosine kinase (BTK), an enzyme involved in B cell and myeloid cell activation and function, is regarded as a next-generation approach that aims to attenuate both errant innate and adaptive immune functions. Moreover, brain-penetrant BTK inhibitors may impact compartmentalized inflammation and neurodegeneration within the central nervous system by targeting brain-resident B cells and microglia, respectively. Preclinical studies in animal models of MS corroborated an impact of BTK inhibition on meningeal inflammation and cortical demyelination. Notably, BTK inhibition attenuated the antigen-presenting capacity of B cells and the generation of encephalitogenic T cells. Evobrutinib, a selective oral BTK inhibitor, has been tested recently in a phase 2 study of patients with relapsing-remitting MS. The study met the primary endpoint of a significantly reduced cumulative number of Gadolinium-enhancing lesions under treatment with evobrutinib compared to placebo treatment. Thus, the results of ongoing phase 2 and 3 studies with evobrutinib, fenobrutinib, and tolebrutinib in relapsing-remitting and progressive MS are eagerly awaited. This review article introduces the physiological role of BTK, summarizes the pre-clinical and trial evidence, and addresses the potential beneficial effects of BTK inhibition in MS.

5-MOP Induced Protection Against Epidermal DNA Damage by Ultraviolet Radiation in Human Skin: The Role of the Skin Type

1991 ◽  
pp. 201-209
Author(s):  
Antony R. Young ◽  
Christopher S. Potten ◽  
Caroline A. Chadwick ◽  
Gillian M. Murphy ◽  
A. Jeffrey Cohen
Keyword(s):  
Dna Damage ◽  
Ultraviolet Radiation ◽  
Human Skin ◽  
Skin Type

scholarly journals The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Victor Blokhin ◽  
Maria Shupik ◽  
Ulyana Gutner ◽  
Ekaterina Pavlova ◽  
Albert T. Lebedev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sphingolipid Metabolism ◽  
Nigrostriatal System ◽  
Dopaminergic Cell ◽  
Metabolism Enzymes ◽  
Clinical Stages ◽  
Sphingosine 1 Phosphate

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

scholarly journals Evaluating the specialist palliative care clinical nurse specialist role in an acute hospital setting: a mixed methods sequential explanatory study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Michael Connolly ◽  
Mary Ryder ◽  
Kate Frazer ◽  
Eileen Furlong ◽  
Teresa Plazo Escribano ◽  
...  
Keyword(s):  
Palliative Care ◽  
Phase 1 ◽  
Hospital Setting ◽  
Acute Hospital ◽  
Nurse Specialist ◽  
Phase 2 ◽  
Specialist Palliative Care ◽  
Clinical Nurse ◽  
Acute Hospital Setting

Abstract Background Special palliative care is provided in a range of settings including a patient’s home (their primary place of dwelling), a hospice in-patient unit, or an acute hospital. The aim of the study was to evaluate the role of the specialist in palliative care clinical nurse specialist (SPC CNS) role in an acute hospital setting. Methods This study was conducted using a mixed methods sequential explanatory approach in two phases; phase 1 involved completion of a study questionnaire (n = 121) and phase 2 involved part-taking in a focus group (n = 6) or individual interview (n = 4). Results Phase 1 results indicated that respondents held positive attitudes towards the Specialist Palliative Care Clinical Nurses Specialist (SPC CNS) in relation to clinical care, education and patient advocacy. Phase 2 qualitative findings identified the importance of the role in terms of symptom management, education and support. Conclusions This study provides an evaluation of a SPC CNS role since it was established in an acute hospital setting. The evidence indicates that there is a varied understanding of the role of the SPC CNS. The role was seen as an important one particularly in terms of referrals to and support provided by the SPC CNS, as well as recognition of the importance of the role is providing ongoing education to staff.

scholarly journals Expression of drug transporters in the human skin: comparison in different species and models and its implication for drug development

ADMET & DMPK ◽  
2017 ◽  
Vol 5 (2) ◽  
pp. 75 ◽  
Author(s):  
Hanan Osman-Ponchet ◽  
Alexandre Gaborit ◽  
Jean-Michel Linget ◽  
Claire E. Wilson
Keyword(s):  
Human Skin ◽  
Drug Absorption ◽  
Transdermal Delivery ◽  
Drug Transporters ◽  
Drug Distribution ◽  
Skin Surface ◽  
Pharmacological Intervention ◽  
Novel Targets

<p class="ADMETabstracttext">It is clear that many drug transporters (both ABCs and SLCs) are present in the human skin. Different in vitro skin models can be used to investigate the role of drug transporters in the skin despite quantitative differences in expression profile across species. P-gp was shown to have an important influence on transdermal drug absorption in the skin and to function in “absorptive” transport, carrying substrate drugs from the skin surface to the dermis. This observation might be used to modulate drug distribution inside the skin. If drugs can be retained in the epidermis compartment by inhibition of the transporters, such property of the drug would be beneficial for treatment of dermatological diseases. Therefore, it might be feasible to control transdermal delivery of drugs to specific locations in the skin, by modulating the function of the transporters in the skin. We are at the dawn of an exciting period where drug transporters might be novel targets for improvement of drug delivery to the skin and for pharmacological intervention.</p>

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