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Conclusion
Published in Jay A. Goldstein, Chronic Fatigue Syndromes, 2020
Augmenting the synthesis and release of CRH in CFS would make sense, but appears difficult to accomplish. Fenfluramine, reported to be an effective secretagogue in other situations, 23 is ineffective, as is DDAVP. 24 An agent worth trying would be a thymic peptide such as thymopentin or alpha-1 thymosin which appears to increase CRH secretion, 25 or perhaps only ACTH, by a direct mechanism. Protein kinase C stimulates CRH production, and CFS/FM lymphocytes are deficient in this kinase where stimulated with IL-2. Low doses of phorbol esters may be of benefit, although high doses may be harmful. Research on the neuroendocrine thymus gives conflicting results. One study finds CRH in rat thymus, 26 while another reports that intraventricular thymosin alpha-1 decreases ACTH and TSH but stimulates it when given at the pituitary leve1. 27
Biological Response Modifiers and Chemotherapeutic Agents that Alter Interleukin 2 Activities
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
William L. West, Allen R. Rhoads, Clement O. Akogyeram
A second class of BRMs is comprised of a number of structurally unrelated synthetic or natural compounds that appear to act as adjuvants: they enhance antitumor as well as other responses and modulate various components of the immune system. Synthetic levamisole has been used as an adjuvant to chemotherapy in cancer patients as well as in chronic infections, i.e., chronic polyarthritis and rheumatoid arthritis. Levamisole is an adjuvant with efficacy in the immunotherapy of melanoma and colon cancer (4). Ketoconazole is also of value in the immunosuppressed individual. Moreover, synthetic phorbol myristate acetate (PMA) and natural bryostatins (macrocyclic lactones isolated from BuQula neritina) are important in lymphocyte activation (5). Unlike tumor promoting phorbol esters, bryostatins are also antineoplastic. It is likely that among these agents are adjuvants that may increase efficacy and/or reduce toxicity of other therapeutic agents. Moreover, phorbol esters have the disadvantage of causing inhibition of effector cell cytotoxicity (6).
Activation of Human Inflammatory Cells
Published in William S. Lynn, Inflammatory Cells and Lung Disease, 2019
Phase II in leukocytes is activated primarily by the chemotactic peptide receptors whereas the phorbol receptor or detergents activate Phase III. Phase II ligands, such as F•met-leu-phe or ionophores can also lead to activation of Phase III, probably by releasing fatty acids, diacyl glycerides or lysolecithins internally. However, under conditions in which the ion pumps are uncoupled and the membrane potential is O, i.e., 0.14M KC1 and valinomycin, Phase II ligands do not activate Phase III. Phorbol esters, however, remain active. Thus, although changes in ion fluxes or membrane potential precede Phase III events, they are not required to activate Phase III.
Himalayan poisonous plants for traditional healings and protection from viral attack: a comprehensive review
Published in Toxin Reviews, 2022
Shriya Pathania, Diksha Pathania, Priyanka Chauhan, Mamta Sharma
These diterpenes are classified as phorbol esters and they stimulate protein kinase. In contact with skin, mucosal tissues or the eye they cause acute inflammation, with blister and ulcer formation. Furanocoumarins can penetrate the intercalate dermal cells and skin (Mutschler et al. 2008). When skin is supposed to expose daylight, the Furanocoumarins alkylate DNA, which kills the cells and incites necrosis and robust blister formation. Many species of the Ranunculaceae accumulate the glycoside ranunculin in the vacuole. It splits into the active protoanemonin, which can alkylate proteins and DNA, which causes skin and mucosal irritation, followed by severe inflammation. The proteases or other noxious proteins of plants further worsen the condition by their damaging activity.
Development of a nanotechnological hydrogel containing desonide nanocapsules in association with acai oil: design and in vivo evaluation
Published in Pharmaceutical Development and Technology, 2022
Priscila Rosa, Mariane Lago Friedrich, Juliana dos Santos, Natháli Schopf Pegoraro, Camila Camponogara, Sara Marchesan Oliveira, Cristiane de Bona da Silva, Andréa Inês Horn Adams
The antiedematogenic activity of the nanostructured hydrogels in an acute contact dermatitis model induced by croton oil was assessed. Croton oil contains 12-O-tetradecanoylphorbol-13-acetate (TPA) and other phorbol esters as main irritant agents (Saraiva et al. 2011). Its application triggers an inflammatory response characterized by edema, leading to increased vascular permeability, cell infiltration and proliferation, production of arachidonic acid metabolites, cytokines and other proinflammatory mediators (Patrick et al. 1987; Rao et al. 1993). A recognized immediate effect of TG includes vasoconstriction, which decreases the tissue edema, erythema and heat (Beltrani et al. 2005). Thus, our aim was to assess the antiedematogenic effect of the nanostructured hydrogels in a model of croton oil-induced skin inflammation, since it mimics several human skin diseases, such as psoriasis and atopic dermatitis (Sato et al. 2004; Pietrovski et al. 2011).
Fabrication and characterization of Agarwood extract-loaded nanocapsules and evaluation of their toxicity and anti-inflammatory activity on RAW 264.7 cells and in zebrafish embryos
Published in Drug Delivery, 2021
Manar A. Eissa, Yumi Z. H.-Y. Hashim, Mohd Hamzah Mohd Nasir, Yusilawati Ahmad Nor, Hamzah Mohd. Salleh, Muhammad Lokman Md. Isa, Saripah S. S. Abd-Azziz, Nor Malia Abd Warif, Eman Ramadan, Noha M. Badawi
The inflammatory mediator NO· reacts with oxygen to produce stable nitrate (NO3−) and nitrite (NO2·) that can be quantified using Griess reagent (Islam et al., 2016). As shown in Figure 8, LPS/IFNγ stimulation demonstrated significant increase (p < 0.05) in NO production (27.708 µM) compared to control group (15.649 µM). The extract at a concentration of 400 µg/ml showed an undesirable stimulating effect on NO production, while it showed significant reduction in NO production ranging from 58.124% to 13.090% at concentrations between 200–6.25 µg/ml compared to LPS/IFNγ-stimulated group (Figure 8). ALEX-M exhibited NO inhibitory activity with an EC50 value of 164.790 ± 6.318 µg/ml, compared to the standard Ibuprofen with an EC50 value of 30.91 ± 5.878 µg/ml. The finding signifies the anti-inflammatory activity of the extract, which can be attributed to the presence of phenolic compounds as recommended by previous studies (Mennen et al., 2004; Okoli and Akah, 2004). In a previous study, a number of phorbol esters isolated from A. malaccensis seeds obtained from Taiwan the demonstrated potent anti-inflammatory activity (Wagh et al., 2017). Similarly, sesquiterpenes derivatives isolated from agarwood chips of A. malaccensis tree obtained from an industrial plantation in Laos, showed ability to suppress inflammation (Thanh et al., 2021). The result of the present study is compatible with the anti-inflammatory activity of A. malaccensis leaf extract demonstrated through its ability to inhibit lipoxygenase enzyme (Eissa et al., 2020).