scholarly journals Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model

2021 ◽  
Vol 22 (22) ◽  
pp. 12600
Author(s):  
Mako Naniwa ◽  
Chihiro Nakatomi ◽  
Suzuro Hitomi ◽  
Kazunari Matsuda ◽  
Takuya Tabuchi ◽  
...  

Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca2+ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca2+ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL® are needed to sufficiently induce the therapeutic effects.

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Qu ◽  
Yuefei Li ◽  
Qi Dong ◽  
Shupeng Li ◽  
Hongliang Du ◽  
...  

Forsythiae Fructus (FF), the dry fruit of Forsythia suspensa (Thunb.) Vahl, has a long history of use in traditional Chinese Medicine for its heat-clearing and detoxifying properties. It possesses clinical therapeutic effects and biological functions showing efficacy in handling different diseases. To investigate the FF differences in Henan, Shanxi, and Shaanxi in August and October, the surface morphology, mid-infrared and near-infrared spectrums, and HPLC were analyzed. Concurrently, the anti-inflammatory and antioxidant effects on LPS-induced J774A.1 cells were evaluated by western blot and RT-qPCR. The results showed that FF from different Harvest Seasons and Regions are provided with different microstructures and mid-infrared and near-infrared spectrums, and the levels of forsythiaside A and phillyrin of FF from Shanxi in August and phillygenin of FF from Shaanxi in August were the highest. Meanwhile, FF from Shanxi and Shaanxi in August markedly reduced the levels of inflammatory cytokines and mediators (TNF-α, IL-1β, NF-κB, and iNOS) and the protein expression levels of phosphorylated total IKKα/β and nuclear NF-κB. In August, SXFF and SAXFF also promoted the mRNA expression levels of HO-1 and NQO1 and the protein expression levels of HO-1 and nuclear Nrf2 and suppressed the protein expression levels of KEAP1. Spearman correlation analysis showed that phillygenin had a strong correlation with the protein expression on LPS-induced J774A.1 cells. In summary, our results showed that FF from harvest seasons and regions contributed to the distinct differences in microstructure, the mid-infrared and near-infrared spectrums, and compound content. More importantly, FF from Shanxi and Shaanxi in August showed marked anti-inflammatory and antioxidant activities, but with some differences, which may be because of different contents of phillygenin and phillyrin of lignans in FF.


2020 ◽  
Vol 21 (22) ◽  
pp. 8870 ◽  
Author(s):  
Jakub Mlost ◽  
Marta Bryk ◽  
Katarzyna Starowicz

Cannabis has a long history of medical use. Although there are many cannabinoids present in cannabis, Δ9tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the two components found in the highest concentrations. CBD itself does not produce typical behavioral cannabimimetic effects and was thought not to be responsible for psychotropic effects of cannabis. Numerous anecdotal findings testify to the therapeutic effects of CBD, which in some cases were further supported by research findings. However, data regarding CBD’s mechanism of action and therapeutic potential are abundant and omnifarious. Therefore, we review the basic research regarding molecular mechanism of CBD’s action with particular focus on its analgesic potential. Moreover, this article describes the detailed analgesic and anti-inflammatory effects of CBD in various models, including neuropathic pain, inflammatory pain, osteoarthritis and others. The dose and route of the administration-dependent effect of CBD, on the reduction in pain, hyperalgesia or allodynia, as well as the production of pro and anti-inflammatory cytokines, were described depending on the disease model. The clinical applications of CBD-containing drugs are also mentioned. The data presented herein unravel what is known about CBD’s pharmacodynamics and analgesic effects to provide the reader with current state-of-art knowledge regarding CBD’s action and future perspectives for research.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Mradu Gupta ◽  
Saumyakanti Sasmal ◽  
Arup Mukherjee

Saraca asoca has been traditionally used in Indian system for treatment of uterine, genital, and other reproductive disorders in women, fever, pain, and inflammation. The hypothesis of this study is that acetone extract of Saraca asoca seeds is an effective anti-inflammatory treatment for arthritis in animal experiments. The antiarthritic effect of its oral administration on Freund’s adjuvant-induced arthritis has been studied in Wistar albino rats after acute and subacute toxicities. Phytochemical analysis revealed presence of high concentrations of phenolic compounds such as flavonoids and tannins, while no mortality or morbidity was observed up to 1000 mg/kg dose during acute and subacute toxicity assessments. Regular treatment up to 21 days of adjuvant-induced arthritic rats with Saraca asoca acetone extract (at 300 and 500 mg/kg doses) increases RBC and Hb, decreases WBC, ESR, and prostaglandin levels in blood, and restores body weight when compared with control (normal saline) and standard (Indomethacin) groups. Significant (P<0.05) inhibitory effect was observed especially at higher dose on paw edema, ankle joint inflammation, and hydroxyproline and glucosamine concentrations in urine. Normal radiological images of joint and histopathological analysis of joint, liver, stomach, and kidney also confirmed its significant nontoxic, antiarthritic, and anti-inflammatory effect.


2016 ◽  
Vol 11 (11) ◽  
pp. 1934578X1601101 ◽  
Author(s):  
María Inés Isla ◽  
María Alejandra Moreno ◽  
Gabriela Nuño ◽  
Fabiola Rodriguez ◽  
Antonella Carabajal ◽  
...  

Zuccagnia punctata Cav. (Fabaceae, Caesalpiniaceae) is a plant with a long history of use in Argentine traditional medicines; it belongs to a monotypic genus, and is an endemic species of Argentina. This review provides a comprehensive overview of the traditional uses, phytochemistry, pharmacological activity and toxicology of Z. punctata. A wide range of traditional uses are cited in the literature such as antibacterial, antifungal, anti-inflammatory, and antitumor, among others. Pharmacological studies to date have demonstrated significant activities that support the traditional uses of this plant. No human clinical trials had been completed up to the time of this review and no toxic effect had been detected in animals. Compounds from different chemical groups have been isolated such as phenolic compounds and essential oils. Plant extracts and phytochemicals isolated exhibit a broad range of activities, anti-inflammatory, antibacterial, antifungal, antigenotoxic, antioxidant, antiulcer, and nematicidal. The main bioactive phytochemicals in the aerial parts (leaf, stem and flower) were identified as 2′, 4′-dihydroxy-3′-methoxychalcone and 2′, 4′-dihydroxychalcone and were proposed as chemical markers. Consequently, standardized dry extracts of aerial parts of Z. puntacta could be used in herbal medicinal products. Also, they could be included in phytotherapeutic preparations such as capsules, creams, and gels, and for microencapsulation.


2021 ◽  
Vol 21 (2) ◽  
pp. 1008-1017
Author(s):  
Shaobo Qiu ◽  
Jingjing Gao ◽  
Jinkai Liu ◽  
Chen Wang ◽  
Aijun Li ◽  
...  

Spontaneous basilar artery occlusive disease is a disease characterized by thickening of the intima of the bilateral internal carotid artery and the anterior and middle cerebral arteries, gradually narrowing the arterial diameter, and compensatory dilatation of the perforating artery at the base of the brain. Aspirin (acetylsalicylic acid), as a classic non-steroidal anti-inflammatory drug, has been proven to have antiplatelet, anti-inflammatory, and immune-regulating effects. But how to achieve long-term sustained release of aspirin and achieve anti-platelet aggregation remains to be studied. This study intends to build a microsphere sustained-release system to achieve long-term stable and slow release of aspirin drug, thereby achieving a more ideal anti-platelet aggregation effect. The therapeutic effects of three groups of nanoparticle sustained-release drug regimens on platelet aggregation were compared. The results showed that the platelet inhibition rate and NIHSS scores before treatment were compared between the three groups; compared with the other groups, the PLGA group had higher AA and ADP pathway-induced platelet inhibition rates after treatment and lower plasma Lp-PLA2 and NIHSS scores. This shows that aspirin nanoparticle slow-release drugs can effectively increase platelet inhibition rate and improve the antiplatelet ability of patients with spontaneous basilar artery occlusive disease, which is beneficial to promoting prognosis recovery.


2017 ◽  
Vol 83 (22) ◽  
Author(s):  
Daniel C. Schlatter ◽  
Chuntao Yin ◽  
Scot Hulbert ◽  
Ian Burke ◽  
Timothy Paulitz

ABSTRACT Glyphosate is the most widely used herbicide worldwide and a critical tool for weed control in no-till cropping systems. However, there are concerns about the nontarget impacts of long-term glyphosate use on soil microbial communities. We investigated the impacts of repeated glyphosate treatments on bacterial communities in the soil and rhizosphere of wheat in soils with and without long-term history of glyphosate use. We cycled wheat in the greenhouse using soils from 4 paired fields under no-till (20+-year history of glyphosate) or no history of use. At each cycle, we terminated plants with glyphosate (2× the field rate) or by removing the crowns, and soil and rhizosphere bacterial communities were characterized. Location, cropping history, year, and proximity to the roots had much stronger effects on bacterial communities than did glyphosate, which only explained 2 to 5% of the variation. Less than 1% of all taxa were impacted by glyphosate, more in soils with a long history of use, and more increased than decreased in relative abundance. Glyphosate had minimal impacts on soil and rhizosphere bacteria of wheat, although dying roots after glyphosate application may provide a “greenbridge” favoring some copiotrophic taxa. IMPORTANCE Glyphosate (Roundup) is the most widely used herbicide in the world and the foundation of Roundup Ready soybeans, corn, and the no-till cropping system. However, there have been recent concerns about nontarget impacts of glyphosate on soil microbes. Using next-generation sequencing methods and glyphosate treatments of wheat plants, we described the bacterial communities in the soil and rhizosphere of wheat grown in Pacific Northwest soils across multiple years, different locations, and soils with different histories of glyphosate use. The effects of glyphosate were subtle and much less than those of drivers such as location and cropping systems. Only a small percentage of the bacterial groups were influenced by glyphosate, and most of those were stimulated, probably because of the dying roots. This study provides important information for the future of this important tool for no-till systems and the environmental benefits of reducing soil erosion and fossil fuel inputs.


1994 ◽  
Vol 7 (4) ◽  
pp. 144-153
Author(s):  
Brian L. Erstad ◽  
Robert J. Lipsy

There are a substantial number of adverse reactions attributable to nonsteroidal anti-inflammatory drug (NSAID) therapy, particularly of the gastrointestinal (GI) tract. The stomach is most commonly affected, although injury may occur from esophagus to colon. The incidence of developing serious GI toxicity seems to be three times as great in users compared with nonusers of NSAIDs. Age greater than 60 years, history of GI problems, previous corticosteroid use, and recency of NSAID use seem to increase the risk of toxicity. Short-term studies have found differences in ulceration or bleeding caused by various NSAIDs. However, there are insufficient long-term clinical trials involving adequate numbers of patients to demonstrate substantial advantages for any particular NSAID based on its toxicity profile. Prostaglandin inhibition seems to be one mechanism responsible for the GI toxicity of NSAIDs, but it is probably not the only mechanism. When serious GI bleeding occurs, the NSAID use must be stopped, although omeprazole and misoprostol have been used successfully to treat gastroduodenal ulcerations in patients while continuing NSAID therapy. Misoprostol and possibly omeprazole have effectively prevented GI ulceration associated with NSAID therapy, but questions remain regarding patient selection, length of therapy, and their utility in preventing serious GI bleeding. At this time, routine prophylaxis for patients receiving long-term NSAID therapy cannot be recommended.


2018 ◽  
Vol 53 (3) ◽  
pp. 152-156
Author(s):  
Chelsey M. McPheeters ◽  
Jennifer A. Wiedmar ◽  
Christina M. Pinkston ◽  
Kyle A. Weant

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Ramchand ◽  
J Chahine ◽  
H Alnajjar ◽  
M Chetrit ◽  
P Cremer ◽  
...  

Abstract Background In recent years, there has been increasing recognition of a potentially-reversible, transient/ subacute form of constrictive pericarditis (CP). To date, studies have been small with lack of long-term longitudinal follow-up. Purpose We aimed to elucidate the causes and natural history of subacute CP. Methods Patients were included if (1) they had a diagnosis of CP, (2) had cardiac magnetic resonance (CMR) within 12 months of symptom onset with evidence of pericardial delayed enhancement/ inflammation (Figure) (3) received anti-inflammatory medications. Results A total of 78 individuals were included, comprising 61 men (78%) with a mean age of 59±14 years. Causes of subacute CP included idiopathic/ viral pericarditis (58%), post-pericardiotomy (29%), autoimmune (6%), radiation therapy (3%) and others (4%). After median follow-up of 4.4 years, 31 (40%) required pericardiectomy. There were no deaths. Patients who underwent pericardiectomy had longer duration of symptoms at presentation [6 (4–9) vs. 3 (2–5) months, P&lt;0.01], were more likely to be on diuretic therapy (87 vs. 45%, P&lt;0.001), had lower ultra-sensitive C-reactive protein [4.4 (2.6–13.1) vs. 11.95 (1.8–61.55) mg/dl, P&lt;0.001] and lower erythrocyte sedimentation rate [5 (2–10) vs. 25 (6–43 mm/hr), P=0.031] compared to those who were managed medically. There were no other significant differences in clinical characteristics or baseline anti-inflammatory therapy. The presence of elevated inflammatory markers (HR: 0.18; 95% CI: 0.06–0.58, P&lt;0.01) was an independent predictor of freedom from pericardiectomy after adjustment for relevant clinical and imaging parameters. Conclusions We present the original observations of the largest cohort of patients with transient CP to date and demonstrate that increased inflammatory markers were independently associated with long-term freedom from pericardiectomy. Our results suggest that a trial of anti-inflammatory therapy in the setting of elevated inflammatory markers may be appropriate prior to referral for surgery given the possible reversibility. Pericardial delayed enhancement Funding Acknowledgement Type of funding source: None


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