Topical nonsteroidal anti-inflammatory drugs for macular edema.
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ABSTRACT:
SUBMITTER: Russo A
PROVIDER: S-EPMC3818914 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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Topical nonsteroidal anti-inflammatory drugs for macular edema.
Russo Andrea A Costagliola Ciro C Delcassi Luisa L Parmeggiani Francesco F Romano Mario R MR Dell'Omo Roberto R Semeraro Francesco F
Mediators of inflammation 20131021
Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the ...[more]
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Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in ophthalmology for pain and photophobia after photorefractive surgery and to reduce miosis, inflammation, and cystoid macular edema following cataract surgery. In recent years, the US Food and Drug Administration has approved new topical NSAIDs and previously approved NSAIDs have been reformulated. These changes may allow for greater drug penetration into the retina and thereby offer additional therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on the scientific rationale and clinical use of NSAIDs for retinal disease.
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Project description:PurposeStimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial cells promotes angiogenesis and vascular permeability in animal models. The safety and bioactivity of topical mecamylamine, an antagonist of nACh receptors, was tested in patients with diabetic macular edema.DesignA multicenter phase I/II clinical trial.MethodsTwenty-three patients with chronic diabetic macular edema received 1% mecamylamine topically twice daily for 12 weeks, the primary end point. Patients underwent safety assessments, measurement of best-corrected visual acuity (BCVA), and measurement of foveal thickness using optical coherence tomography at baseline, 1, 4, 8, 12, and 16 weeks.ResultsMecamylamine drops were well tolerated and there were no drug-related safety problems. Mean improvement in BCVA at 1, 4, 8, 12, and 16 weeks was 2.8, 1.9, 2.4, 0.8, and 3.1 letters, respectively. There was little change in mean excess foveal thickness. There was substantial heterogeneity in response, because 8 patients showed convincing improvement in BCVA, foveal thickness, or both, 9 patients showed equivocal or no substantial changes, and 4 patients showed worsening. Five patients showed a substantial improvement in BCVA, foveal thickness, or both between their last visit while receiving mecamylamine and 1 month after stopping mecamylamine.ConclusionsThis study suggested that administration of topical mecamylamine, a nonspecific nACh receptor blocker, may have heterogeneous effects in patients with diabetic macular edema. Variable expression of nACh receptor subtypes on endothelial cells that have different effects on permeability would provide an explanation for these results and should be investigated, because more specific nACh receptor blockers may dissociate antipermeability and propermeability effects.
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Project description:Nonsteroidal anti-inflammatory drugs are considered as potential therapeutic agents against Alzheimer's disease. Using replica exchange molecular dynamics and atomistic implicit solvent model, we studied the mechanisms of binding of naproxen and ibuprofen to the Abeta fibril derived from solid-state NMR measurements. The binding temperature of naproxen is found to be almost 40 K higher than of ibuprofen implicating higher binding affinity of naproxen. The key factor, which enhances naproxen binding, is strong interactions between ligands bound to the surface of the fibril. The naphthalene ring in naproxen appears to provide a dominant contribution to ligand-ligand interactions. In contrast, ligand-fibril interactions cannot explain differences in the binding affinities of naproxen and ibuprofen. The concave fibril edge with the groove is identified as the primary binding location for both ligands. We show that confinement of the ligands to the groove facilitates ligand-ligand interactions that lowers the energy of the ligands bound to the concave edge compared with those bound to the convex edge. Our simulations appear to provide microscopic rationale for the differing binding affinities of naproxen and ibuprofen observed experimentally.
| S-EPMC3058518 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies.
| S-EPMC8280659 | biostudies-literature
Project description:Oxicams are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) structurally related to the enolic acid class of 4-hydroxy-1,2-benzothiazine carboxamides. They are used clinically to treat both acute and chronic inflammation by inhibiting the activity of the two cyclooxygenase (COX) isoforms, COX-1 and COX-2. Oxicams are structurally distinct from all other NSAIDs, exhibiting a novel binding pose in the COX active site. The 4-hydroxyl group on the thiazine ring partners with Ser-530 via hydrogen bonding while two coordinated water molecules mediate a polar interaction between the oxicam and COX. The rotation of Leu-531 in the complex opens a new pocket, which is not used for binding other NSAIDs to the enzyme. This structure provides the basis for understanding documented structure-activity relationships within the oxicam class. In addition, from the oxicam template, a series of potent microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors represents a new direction for drug development. Here, we review the major route of oxicam synthesis and structure-activity for COX inhibition, as well as recent advances in oxicam-mediated mPGES-1 inhibition.
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Project description:Background & aimsNonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested to protect against esophageal adenocarcinoma (EAC). This study examined the effect of NSAIDs on the risk of developing Barrett's esophagus (BE), the precursor lesion to EAC.MethodsWe conducted a case-control study among eligible patients scheduled for either elective esophagogastroduodenoscopy (EGD) or recruited from primary care clinics to undergo a study EGD. We compared 323 patients with BE (296 nondysplastic and 27 dysplastic) with 2 separate control groups: 1347 patients from the elective EGD group (endoscopy controls) and 502 patients from the primary care group (primary care controls) with no endoscopic or histopathologic BE. Use of aspirin products and 23 nonaspirin NSAIDs was ascertained from detailed, self-reported questionnaires. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models.ResultsThere were no significant differences in self-reported NSAID use between all BE cases and all controls (58.2% vs 54.6%; P = .33); this was seen for aspirin products (43.0% vs 37.4%; P = .08) and nonaspirin NSAIDs (7.7% vs 8.9%; P = .46). These findings persisted in the multivariable model for any NSAIDs (adjusted OR, 0.89; 95% CI, 0.75-1.28), aspirin (adjusted OR, 1.16; 95% CI, 0.90-1.51), and nonaspirin NSAIDs (adjusted OR, 0.88; 95% CI, 0.55-1.39). Use of a combination of aspirin and nonaspirin NSAIDs was reported in 7.4% of cases and 8.3% of controls, and a nonsignificant inverse association with BE was seen (adjusted OR, 0.70; 95% CI, 0.44-1.11). There was no significant association between BE and daily NSAID use (adjusted OR, 1.03; 95% CI, 0.78-1.37). Similar findings were observed for comparisons involving nondysplastic or dysplastic BE cases, and endoscopy or primary care control groups separately or combined.ConclusionsThe use of NSAIDs was not associated with a reduced risk of BE. It is likely that the protective mechanism of NSAIDs on EAC occurs subsequent to the development of BE.
| S-EPMC4214884 | biostudies-literature
Project description:ObjectivesObservational and experimental studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD); however, clinical trials and other observational studies, including the Adult Changes in Thought (ACT) study, show no protection or promotion of AD. The objective of this study is to determine the relationship between common dementia-associated pathologies and mid- to late-life NSAID exposure.MethodsWe examined the association of mid- to late-life NSAID use with neuropathologic findings on 257 autopsies from ACT, a population-based study of brain aging and incident dementia. Cumulative standard daily doses (SDD) of nonselective NSAIDs were determined from ≥10 years of computerized pharmacy dispensing data. Analyses were adjusted for selection bias to broaden generalizability of results to 3,026 eligible participants in the ACT cohort. Seven pathologic indices were evaluated: intermediate or frequent score for neuritic plaques, Braak stages V or VI for neurofibrillary tangles, >2 cerebral microinfarcts, the presence of any neocortical Lewy bodies, any macroscopic infarcts, any amyloid angiopathy, and moderate or severe atherosclerosis.ResultsOf the neuropathologic indices evaluated, only neuritic plaque score was significantly increased in participants with greater use of nonselective NSAIDs (p = 0.065), specifically in those with high levels of cumulative use: 1,000-2,000 SDD (adjusted relative risk [RR] 2.16, 95% confidence interval [CI] 1.02-4.25, compared to light/nonuse [<60 SDD]) and >2,000 SDD (adjusted RR 2.37, 95% CI 1.24-4.67).ConclusionsIncreased neuritic plaque accumulation may explain the association between heavy use of nonselective NSAIDs and increased risk of dementia among ACT participants.
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Project description:BackgroundRecent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients.MethodsStudy subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained from medical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology.ResultsFive hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR = 1.66, 95% CI = 1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR = 2.23, 95% CI = 1.19 to 4.18, two-sided P trend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors.ConclusionsIn this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.
| S-EPMC5161320 | biostudies-literature
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identify that the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent plant immune response. TNX treatment decreases NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. A cysteine labeling assay reveals that cysteine residues in NPR1 can be oxidized in vitro, leading to disulfide-bridged oligomerization of NPR1, but not in vivo regardless of SA or TNX treatment. Therefore, this study indicates that oxicam inhibits NPR1-mediated SA signaling without affecting the redox status of NPR1.
2021-11-09 | GSE154593 | GEO