Topical Anti-inflammatory Agents Research Articles

Use of topical anti-inflammatory and antineoplastic agents in the treatment of young-aged actinic cheilitis: A systematic review.

Several treatments have been used to reduce inflammation and to reverse epithelial alterations in actinic cheilitis (AC). A systematic review was conducted to analyze the potential of topical treatments for remission and clinical improvement of AC as well as patient acceptability. A systematic review of clinical trials was conducted following the PICO strategy to answer the following question: Are topical anti-inflammatory and antineoplastic agents effective in the treatment of actinic cheilitis? The quality of the studies was assessed by ROB-2, and the certainty of evidence was rated by GRADE guidelines. Eight clinical trials were selected, including four that investigated the use of anti-inflammatory drugs and four use of antineoplastic agents. The use of 3% diclofenac sodium was associated with partial remission of AC, while 5% imiquimod and ingenol mebutate promoted complete remission. Furthermore, 5% fluorouracil was the drug most associated with complications during treatment. Diclofenac sodium (3%) and fludroxycortide showed the best acceptance by the patients, especially in terms of symptom relief and comfort provided. The anti-inflammatory and antineoplastic agents analyzed largely provided good clinical outcomes, with evidence of remission of AC lesions, development of few local adverse reactions during treatment, and good patient adherence.

Effect of an anti-inflammatory pomegranate otic treatment on the clinical evolution and microbiota profile of dogs with otitis externa.

Canine otitis externa (OE) is a common disease characterised by inflammation of the epithelial tissue of the external ear canal. Secondary infections are frequent, and Malassezia pachydermatis and Staphylococcus pseudintermedius are routinely isolated and treated with antifungal and antibiotic compounds. To analyse the otitis ear microbiome before and after a treatment with prednisolone plus pomegranate or antimicrobial drugs ANIMALS: 15 dogs with nonpurulent OE. A 30 day, double-blinded, multicentre, randomized and controlled parallel-group (1:1) trial was conducted in 15 dogs with nonpurulent OE, following two different topical treatments (prednisolone plus pomegranate versus prednisolone plus antibiotic and antifungal drugs). On days (D)0, D15 and D30, serum and skin otic samples were collected, and clinical examination and microbiome analysis (bacteria and fungi) were performed. Results were compared with validated otitis clinical scores to assess the effectiveness of both treatments. Nine bacterial and four fungal families were detected during the three time-points tested. An increase in fungal diversity (Shannon index) and composition was the most significant change observed after both treatments. At treatment D15 and D30, the reduction in clinical signs was statistically significant in both treatment groups (P≤0.05). Prednisolone plus pomegranate cleanser treatment was able to control the clinical signs of otitis as well as the bacterial and fungal overgrowth. Mild otitis cases associated with microbial overgrowth may be managed with topical antiseptic and anti-inflammatory agents without the need for antibiotic and/or antifungal compounds.

Возможности применения бромфенака в офтальмологической практике

Non-steroidal anti-inflammatory drugs (NSAIDs) are essential for the treatment of ocular disorders. While corticosteroids are the gold standard for inflammatory ocular diseases, comparative studies on the efficacy of NSAIDs and corticosteroids have demonstrated no significant differences in outcomes. Given the chemical structure of NSAIDs, it should be noted that salicylates, phenamates, and pyrazoline derivatives are either toxic or unstable. Solubilizers and preservatives also account for toxicity. Bromfenac-based medications are characterized by high safety and contain minimum benzalkonium chloride. This paper reviews advantages of a modern topical NSAID, bromfenac, for ocular use. This medication is more effective than diclofenac (by 3.7 times), amfenac (by 6.5 times), and ketorolac (by 18 times) in terms of inhibiting COG-2. Furthermore, the regimen of use (twice daily), no discomfort, and excellent safety profile with minimal adverse effects improve treatment adherence. In addition, Bromfenac, a topical antiinflammatory agent, improves patients’ satisfaction with surgical outcomes since patients achieve maximum possible visual acuity as early as possible. Keywords: non-steroidal anti-inflammatory drugs, NSAIDs, bromfenac, arachidonic acid, inflammation, corticosteroids, eye surgery, cataract, cystoid macular edema. For citation: Maksimov M.L., Zvegintseva A.A., Kanner I.D., Lapkin N.M. Bromfenac in ophthalmic practice. Russian Journal of Clinical Ophthalmology. 2021;21(4):241–248 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-241-248.

Clinical approach to skin eruptions induced by anti-TNF agents among patients with inflammatory bowel diseases: insights from a multidisciplinary IBD-DERMA clinic.

Background and Aims:Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic.Methods:This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel.Results:Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age – 35.2 ± 13.5 years, disease duration – 7.1 (interquartile range: 3.7–13.9) years; Crohn’s disease – 94/118 (79.6%). Skin eruption induced by an anti–tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) – 31/46 (67.4%) and inflammatory alopecia (IA) – 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P = .09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P = NS).Conclusion:Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab.

Anti-oxidant and Anti-inflammatory Effects of the Fermented Rhododendron weyrichii Flower Extracts in Shindari, a Traditional Jeju Fermented Drink

The aim of this study was to investigate the anti-oxidant and anti-inflammatory activities of the Rhododendron weyrichii flower extract fermented using Shindari, a traditional Jeju barley Nuruk-based fermentation. In this study, we examined the antioxidant potential of R. weyrichii flower extracts (RF) and R. weyrichii flower extracts fermented with Nuruk or Shindari (RFFN or RFFS, respectively) using various in vitro antioxidant assays including DPPH and ABTS radical scavenging assays, total phenol content and FRAP assays. We also evaluated the anti-inflammatory activity of the RF and RFFS on murine RAW 264.7 cells. The anti-inflammatory activity was evaluated by treating the RAW 264.7 cells with various concentrations (6.25, 12.5, 25, and 50 μg/ml) of RF or RFFS. As a result, we observed that the ABTS radical scavenging activity and total phenol content of RFFS was higher than that of RF and RFFN. Additionally, lipopolysaccharide- induced nitric oxide (NO) production was significantly lower in RFFS-treated cells when compared to the LPS-treated control. In addition, RFFS-treated cells exhibited decreased expression of inducible NO synthase (iNOS) proteins and high-performance liquid chromatography (HPLC) fingerprinting showed that both the quercetin and quercetin glucoside (quercitrin and isoquercitrin) levels were affected by the fermentation process. In conclusion, our data suggests that traditional fermentation could be an important strategy in improving the biological properties of raw materials including their antioxidant and antiinflammatory activities. Finally, RFFS may be a candidate for developing topical antioxidant and antiinflammatory agents.

Aspirin’s Protective Effects Highlight the Role of Inflammation in UV-Induced Skin Damage and Carcinogenesis

Aspirin’s Protective Effects Highlight the Role of Inflammation in UV-Induced Skin Damage and Carcinogenesis

Childhood rosacea and related disorders.

Rosacea is a chronic inflammatory condition that affects the skin and the eyes. The pathogenesis of rosacea is complex and includes the interaction between genetic and environmental factors, dysregulation of the innate immune system, neurovascular modifications and the interaction with skin commensals. Clinical manifestations in children include the telangiectatic form, papulopustular rosacea, ocular rosacea, periorificial dermatitis, granulomatous rosacea and idiopathic facial aseptic granuloma. Management is aimed at identifying and avoiding triggers. Topical therapy is used for mild cases with topical antibiotics and anti-inflammatory agents. Oral agents are indicated, in combination with topical therapy, for moderate to severe cases. Prolonged therapy may be required.

ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Magnetic resonance and mass spectrometric characterization and conformational analysis of α,α-bis(4-fluorophenyl)-β-methyl-1H-imidazole-1-ethanol

A complete multinuclear magnetic resonance characterization of α,α-bis(4-fluorophenyl)-β-methyl-1H-imidazole-1-ethanol (a representative carbinoloimidazole topical anti-inflammatory agent) is presented, the first such assignment of a compound with diastereotopic fluorophenyl rings. The relative orientation of the 4-fluorophenyl rings was probed experimentally by 1H nuclear Overhauser effect spectroscopy experiments; these confirm the results of a density functional theory based optimization of the structure, in which the phenyl rings are oriented to avoid coplanarity. High resolution time-of-flight mass spectrometry confirmed the structure of the molecule.

Seborrheic dermatitis and its relationship with Malassezia spp

Seborrheic dermatitis (SD) is a chronic inflammatory disease that that is difficult to manage and with a high impact on the individual’s quality of life. Besides, it is a multifactorial entity that typically occurs as an inflammatory response to Malassezia species, along with specific triggers that contribute to its pathophysiology. Since the primary underlying pathogenic mechanisms include Malassezia proliferation and skin inflammation, the most common treatment includes topical antifungal keratolytics and anti-inflammatory agents. However, the consequences of eliminating the yeast population from the skin, the resistance profiles of Malassezia spp. and the effectivity among different groups of medications are unknown. Thus, in this review, we summarize the current knowledge on the disease´s pathophysiology and the role of Malassezia sp. on it, as well as, the different antifungal treatment alternatives, including topical and oral treatment in the management of SD.

Potential development of turmeric extract nanoparticles as a topical anti-inflammatory agent

Turmeric is the most commonly studied herbal ingredient because it has antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Considering that most inflammatory skin diseases are localized, it is considered that the topical application of turmeric extract can be beneficial because it has a local effect on the skin. The topical application of turmeric extract has limitations because the active ingredient content of curcumin (CUR) has poor solubility in water, low absorption, and rapid elimination of metabolites, which results in low bioavailability of the drug. Recent studies have focused more on nanoparticle formulations that can improve the stability and bioavailability of CUR.

Impact of sun exposure on adult patients affected by atopic dermatitis.

Atopic dermatitis management is challenging and usually requires intermittent or continuous, long-term treatment with topical and/or systemic anti-inflammatory agents and appropriate skin care. Most patients affected by atopic dermatitis improve during sun exposure. It has been reported that the change from a subartic/temperate to a subtropical climate for 4 weeks improved significantly skin symptoms and quality of life in children, even for 3 months after return. However, until now the effect of sun exposure on adult patients with atopic dermatitis has never been investigated. We conducted a retrospective study to assess the short-term effect of sun exposure during summer holidays on skin symptoms of adults affected by AD. One hundred and fourteen patients were enrolled in the study (62 males; aged 18-72 years, mean age 35.3±12.6). Seventy-three out of 114 patients (64%) spent their holidays at the seaside, and 41/114 (36%) in the mountains; 38/41 (92.7%) subjects from the latter group reported that during their holidays they frequented outdoor swimming pools or solariums almost every day of their vacation. The sunlight effect was considered beneficial by 68/114 (59.6%) of patients. In particular, 38/114 patients (33.3%%) reported the improvement of AD and 30/114 (26.3%) the complete resolution of the disease during summer holiday. Our data seem to suggest that sun exposure is beneficial in most patients, but not in all patients. In fact, sun exposure does not appear to improve skin symptoms or even aggravate them in about 4 out of 10 patients. This could be particularly important also considering ongoing climate changes that may affect the clinical history of several skin diseases, among which AD.

Solidagenone from Solidago chilensis Meyen inhibits skin inflammation in experimental models

Solidagenone (SOL) is a labdane-type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti-inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil-, arachidonic acid (AA)- and phenol-induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glucocorticoid receptor, estradiol-17-β-dehydrogenase and prostaglandin-E(2)-9-reductase were established using molecular docking. SOL significantly inhibited croton oil-, AA- and phenol-induced ear oedema (P<.001) at doses of 0.1, 0.5 and 1.0mg/ear. The MPO and NAG activities and TNF-α, IL-6 and NO levels were decreased (P<.001). The histopathological data revealed that inflammatory parameters (oedema thickness, leucocyte infiltration and vasodilatation) were reduced by treatment with SOL at doses of 0.1, 0.5 and 1.0mg/ear. The docking study showed that SOL interacts with COX-1 and prostaglandin-E(2)-9-reductase through hydrogen bonding, inhibiting these enzymes. These results indicate that SOL may be a promising compound for the treatment of cutaneous inflammatory disorders and has potential as a topical anti-inflammatory agent.

Preclinical studies indicate that INFLATIV, an herbal medicine cream containing Pereskia aculeata, presents potential to be marketed as a topical anti-inflammatory agent and as adjuvant in psoriasis therapy

A previous study reported that the hexane fraction (HF) obtained from Pereskia aculeata leaves showed promising topical anti-inflammatory activity. Intending its future use in clinical practice, a herbal medicine cream named INFLATIV was developed. Its anti-inflammatory and antipsoriatic potential were investigated. INFLATIV was subjected to preliminary accelerated stability tests and to a degradation profile assessment. INFLATIV was prepared at 6% and 12%. The anti-inflammatory activity was assessed by croton oil single and multiple application challenge in mice. Mouse tail test was used for antipsoriatic potential investigation. Cutaneous atrophy test was performed. Preliminary accelerated stability tests were performed together with a degradation profile by GC-MS analysis. The anti-inflammatory activity shown by INFLATIV was comparable to dexamethasone. However, the skin atrophy caused by that drug was not observed. INFLATIV modified skin parakeratotic differentiation into orthokeratosis, which revealed its antipsoriatic potential. The ingredients used were suitable to carry the bioactives as they were well permeated by the skin. The preliminary accelerated stability tests indicated that INFLATIV 6% is more stable than 12%. The results demonstrated the relevant therapeutic and marketing potentials of INFLATIV, which is likely to be further evaluated in clinical trials for drug registration process with regulatory agencies.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020. Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries. Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The 207 eligible studies included 32959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence). Only English-language studies were included. The number of head-to-head comparisons was limited. Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms. National Safety Council. (PROSPERO: CRD42018094412).

Results of Histidine (His) Supplementation in a Case of Severe Nummular Eczema (NE)

Abstract Objectives NE (coin-shaped, severely pruritic skin lesions) is an idiopathic, histologically indistinguishable form of atopic dermatitis (AD). NE is chronic, relapsing and debilitating. Treatment is limited to skin moisturizers and anti-inflammatory agents. Recurrence is common. Recent studies suggest that lack of the protein, filaggrin (FLG) and its derivative natural moisturizing factors (NMFs) play a role. Because FLG is a His-rich compound, l-His supplementation (LHS) may provide a nutritional NE option. In this report, we present a patient with severe, resistant NE who responded to LHS. Methods The patient is a 57 yo female with NE, unresponsive to topical emollients, topical and oral steroids, oral antihistamines, phototherapy, topical calcineurin inhibitors and immune modulating agents. She attempted nutritional options by eliminating food allergens (dairy, nuts, wheat, eggs) and followed an anti-inflammatory diet. Because these had only modest effects, a trial of oral LHS (8 gm/d) was begun. After 4 months on therapy NE improved significantly. Lesions diminished in size and number. The pruritus was nearly eliminated. Liver and kidney function remained normal. Results NE is a debilitating form of AD. Current therapy is essentially palliative, relying on the use of topical emollients and anti-inflammatory agents. Phototherapy and even systemic immune modulation provide only partial results. Standard nutritional approaches are generally of little value. In this case, LHS was attempted after all other options failed. LHS had a dramatic effect on the patient's NE, markedly reducing the pruritus and visibly improving the rash. The NE lesions became smaller and less numerous. LHS was well tolerated without notable adverse effects. His is an essential amino acid whose deficiency results in negative nitrogen balance, anemia and decreased histamine and carnosine production. His is a major component of FLG (∼10%). FLG degrades into NMFs which contribute to skin hydration and stratum corneum acidity. LHS is believed to increase FLG and NMF production. Conclusions LHS produced symptomatic improvement in a case of severe, treatment-resistant NE. We believe this effect was the result of increased FLG production due to LHS, with subsequent improvements in NMFs and skin hydration. LHS may be a therapeutic option for selected cases of resistant NE. Funding Sources None.

Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis: Systematic Literature Review and Network Meta-Analysis.

IntroductionThere is a need to compare efficacy and safety profiles of crisaborole ointment, 2%, versus other topical treatments across randomized clinical trials (RCTs). We performed this review/network meta-analysis to evaluate the comparative efficacy and safety of crisaborole versus other topical pharmacologic therapies for mild-to-moderate atopic dermatitis (AD) among patients aged ≥ 2 years.MethodsSearches were conducted in MEDLINE, Embase, the Cochrane Collection Central Register of Clinical Trials, and the Database of s of Reviews of Effects using Ovid to identify English language articles reporting RCTs of topical anti-inflammatory agents in patients aged ≥ 2 years with mild-to-moderate AD published between inception and 10 March 2020. This review used a prespecified protocol with eligibility criteria for population, interventions, comparisons, outcomes, and study design. Efficacy was evaluated using the Investigator’s Static Global Assessment (ISGA) of clear (0) or almost clear (1) and expressed by hazard ratios (HR) with 95% credible intervals.ResultsPatients treated with crisaborole or tacrolimus ointment, 0.1% or 0.03%, versus vehicle alone were significantly more likely to achieve ISGA 0/1 at 28–42 days, with the greatest point estimate observed for the crisaborole comparison (hazard ratio: 2.07; 95% credible interval 1.76 to − 2.36; probability HR above 1 [p better]: 100.0%). Patients were also more likely to achieve ISGA 0/1 with crisaborole than with pimecrolimus cream, 1% (HR: 1.62; 95% credible interval 1.04–2.48; p better: 98.3%). While network meta-analysis for safety was not feasible because of data limitations, crisaborole pivotal studies (AD-301/AD-302) showed crisaborole was well tolerated.ConclusionsCrisaborole was shown to be superior to vehicle and pimecrolimus and comparable to tacrolimus, 0.1% or 0.03%, with respect to ISGA 0/1 at 28–42 days in patients aged ≥ 2 years with mild-to-moderate AD. This evaluation of comparative efficacy of crisaborole further supports use of crisaborole as an effective therapeutic option in this population.Electronic supplementary materialThe online version of this article (10.1007/s13555-020-00389-5) contains supplementary material, which is available to authorized users.

Glutaryl Melatonin Niosome Gel for Topical Oral Mucositis: Anti- Inflammatory and Anticandidiasis.

Glutaryl melatonin, which is synthesized from melatonin and is a pineal glandderived neurohormone with anti-inflammatory and anti-oxidant properties, was comparatively investigated for its potential use as a topical anti-inflammatory agent. Glutaryl melatonin, synthesized and screened for in vitro anti-candidiasis and in vitro and in vivo anti-inflammatory activities, was formulated as a niosome gel for topical oral evaluation in 5- fluorouracil-induced oral mucositis in mice. In vitro anti-fungal activity in Candida albicans, in vitro anti-inflammatory activity in Escherichia coli liposaccharide-induced RAW cells and in vivo anti-inflammatory activity using a croton oilinduced ear edema model in ICR mice were investigated. Mucositis in mice (n= 6/group, 10-week-old mice) was induced by intraperitoneal injections of 5-fluorouracil, and the mice were subjected to a topical oral application of niosome gel containing melatonin (2% w/w) or glutaryl melatonin (2% w/w) and were compared with mice subjected to blank, fluocinolone acetonide (0.5% w/w) and control conditions. Glutaryl melatonin, at a 14.2 mM concentration, showed the highest fungicidal effect on C. albicans using the broth dilution method, indicating a nonsignificant difference from 1 μM of nystatin (p = 0.05). Nitric oxide, interleukin-6 and tumor necrosis factors were analyzed by ELISA. Liposaccharide-induced RAW cells were significantly reduced by glutaryl melatonin (p < 0.01). Ear edema inhibition of glutaryl melatonin was significant 1 h after application compared with that of melatonin (p = 0.03). Food consumption and body weight of the 5-fluorouracil-treated mice were significantly lower than those of the normal mice before all treatments (p < 0.05). Differences in the amount of licking behavior, which were observed in the control group for 5 min, were noticeable in the 5- fluorouracil-treated mice but not in the mice treated with the glutaryl melatonin niosome gel. Glutaryl melatonin exhibited mild anti-candidiasis and anti-inflammatory properties. The incorporation of glutaryl melatonin in a niosome gel formulation, demonstrated the potential for topical oral applications to reduce oral discomfort caused by 5-fluorouracil treatment in mice.

Efficiency of topical and systemic flurbiprofen on pain and edema after impacted third molar surgery and comparison of gastrointestinal adverse effects

Purpose: The aim of this study was to evaluate the effects of systemic and topical nonsteroidal anti-inflammatory agents on postoperative pain and edema and also gastrointestinal side effects after impacted third molar surgery.Materials and Methods: In this clinical study, 100 healthy patients with mandibular impacted third molar teeth in a similar position were included. After the operation, patients were divided into two groups, one group received Flurbiprofen tablets and the other group received Flurbiprofen 0.25% Oral spray. The pain was assessed postoperatively by Visual Analog Scale (VAS). The edema evaluation was measured on preoperative and postoperative 2nd and 7th days. Gastrointestinal adverse effects related to the use of nonsteroidal anti-inflammatory drug such as nausea, heartburn, dyspepsia, vomiting, and diarrhea were recorded according to information received from patients.Results: There was a statistically significant difference between the groups with regard to Visual Analog Scale levels at 6th, 8th, 12th, 24th, and 48th hours. 2nd-day edema measurements of the systemic nonsteroidal anti-inflammatory drug group were found to be statistically lower than the local-topical nonsteroidal anti-inflammatory drug group.Conclusion: Although the efficacy of topical nonsteroidal anti-inflammatory drugs on pain and edema is lower than systemic nonsteroidal anti-inflammatory drugs, it may be preferred because it has less gastrointestinal side effects.

Expanding the anti-inflammatory potential of Moringa oleifera: topical effect of seed oil on skin inflammation and hyperproliferation

Ethnopharmacological relevancePopularly used in India and sub-Hymalaian region, Moringa oleifera (Moringaceae) is associated with healing properties demonstrated in its use as treatment of acute and chronic skin diseases. Our study aimed at investigating the effects of M. oleifera seed oil (MOSO) in animal models for inflammatory and hyperproliferative skin conditions. Materials and methodsMOSO was analyzed using gas chromatography/mass spectrometry. The anti-inflammatory and anti-hyperproliferative effects of treatment with either MOSO or oleic acid (OA), its main constituent, was evaluated. Acute and chronic inflammation was induced by applying 12-O-Tetradecanoylphorbol-13-acetate (TPA) and acute inflammation with either Arachidonic Acid (AA) or Phenol onto the ear of Swiss mice. Systemic activity and the influence of glucocorticoid receptors (GC) was also evaluated. ResultsTopical application of MOSO and OA inhibited ear edema caused by TPA, and Phenol. Only MOSO inhibited ear edema induced by AA. Neutrophil migration was also inhibited by treatment with MOSO. Topical application of MOSO, but not OA, significantly reduced chronic skin inflammation and epidermal hypertrophy induced by multiple TPA applications. Pre-treatment with GC antagonist mifepristone reversed the anti-inflammatory effect of MOSO and OA on the TPA model. Repeated administration of MOSO show a similar effect to dexamethasone on thymus weight, though MOSO did not present any influence on skin thickness, as well as in the weight of the spleen, adrenal gland and lymph node. ConclusionThe results suggest that MOSO is effective as a treatment for skin diseases that rely on keratinocyte hyperproliferation. OA is also effective in acute inflammation. Both MOSO and OA depend on GC activation for anti-inflammatory effect but do not exhibit the same adverse effects seen in topical treatment with dexamethasone. We hereby evidence the use of MOSO as a topical anti-inflammatory agent in inflammatory skin diseases, thus, expanding its therapeutic potential.