Search Results (709)

Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating factor (PAF) pathway, a key mediator of inflammation. This study aimed to evaluate the effects of several commonly used cardiovascular and anti-inflammatory drug classes—including clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor blockers (ARBs), β-blockers, and analgesics—on platelet function via both the ADP and PAF pathways. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet aggregation in response to these two agonists in the absence and presence of graded concentrations of each of these drugs or of their usually prescribed combinations. The study identified differential drug effects on platelet aggregation, with some agents showing pathway-specific activity. Clopidogrel and NSAIDs demonstrated expected antiplatelet effects, while some (not all) antihypertensives exhibited additional anti-inflammatory potential. These findings highlight the relevance of evaluating pharmacological activity beyond traditional targets, particularly in relation to PAF-mediated inflammation and thrombosis. This dual-pathway analysis may contribute to a broader understanding of drug mechanisms and inform the development of more comprehensive therapeutic strategies for the prevention and treatment of cardiovascular, hypertension, and inflammation-driven diseases. Full article

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article

Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as neurogenic HO (NHO). This review outlines the cellular and molecular mechanisms driving HO, focusing on the inflammatory response, progenitor cell reprogramming, and current treatment strategies. HO is primarily fuelled by a prolonged and dysregulated inflammatory response, characterized by sustained expression of osteoinductive cytokines secreted by M1 macrophages. These cytokines promote the aberrant differentiation of fibro-adipogenic progenitor cells (FAPs) into osteoblasts, leading to ectopic mineralization. Additional factors such as hypoxia, BMP signalling, and mechanotransduction pathways further contribute to extracellular matrix (ECM) remodelling and osteogenic reprogramming of FAPs. In the context of NHO, neuroendocrine mediators enhance ectopic bone formation by influencing both local inflammation and progenitor cell fate decisions. Current treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, and surgical excision offer limited efficacy and are associated with significant risks. Novel therapeutic strategies targeting inflammation, neuropeptide signalling, and calcium metabolism may offer more effective approaches to preventing or mitigating HO progression. Full article

Background: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or inflammatory conditions. However, both drug classes pose risks of adverse effects, and their interaction may lead to clinically significant drug–drug interactions. Objectives: This study analyzed FDA Adverse Event Reporting System (FAERS) data (2004–2024) to assess gastrointestinal bleeding, thrombocytopenia, and acute kidney injury (AKI) potential risks linked to SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) and NSAIDs (propionic/acetic/enolic acid derivatives, COX-2 inhibitors) in depression patients, alone and combined. Methods: Disproportionality analysis (crude reporting odds ratios, cROR) identified possible associations; drug interactions were evaluated using Ω shrinkage, additive, multiplicative, and combination risk ratio (CRR) models. Results: Gastrointestinal bleeding risk was potentially elevated with citalopram (cROR = 2.81), escitalopram (2.27), paroxetine (2.17), fluvoxamine (3.58), sertraline (1.69), and propionic acid NSAIDs (3.17). Thrombocytopenia showed a potential correlation with fluoxetine (2.11) and paroxetine (2.68). AKI risk may be increased with citalopram (1.39), escitalopram (1.36), fluvoxamine (3.24), and COX-2 inhibitors (2.24). DDI signal analysis suggested that citalopram in combination with propionic acid derivatives (additive model = 0.01, multiplicative model = 1.14, and CRR = 3.13) might increase the risk of bleeding. Paroxetine combined with NSAIDs (additive model = 0.014, multiplicative model = 2.65, and CRR = 2.99) could potentially increase the risk of thrombocytopenia. Sertraline combined with NSAIDs (Ω₀₂₅ = 0.94, multiplicative model = 2.14) might be associated with an increasing risk of AKI. Citalopram combined with propionic acid derivatives (Ω₀₂₅ = 1.08, multiplicative model = 2.17, and CRR = 2.42) could be associated with an increased risk of acute kidney injury. Conclusions: Certain combinations of SSRIs and NSAIDs might further elevate these risks of gastrointestinal bleeding, thrombocytopenia, and acute kidney injury in patients with depression. Given the potential drug–drug interactions, heightened clinical vigilance is advised when prescribing SSRIs and NSAIDs in combination to patients with depression. Full article

Background: Ibuprofen is one of the most accessible non-steroidal anti-inflammatory drugs (NSADs), exhibiting non-selective reversible inhibition on COX-1 and COX-2. A series of common adverse reactions have been mentioned through the years: gastrointestinal (gastritis, ulceration, hemorrhage, or perforation), renal, hematologic, and cardiovascular. Objective: The aim of this study was to assess the real-world impact of ibuprofen regarding cardiovascular safety, utilizing an established pharmacovigilance database. Methods: Descriptive and disproportionality-based methods were used. Forty specific descriptors of cardiovascular effects were selected. Eight other NSADs and the combination of ibuprofen and pseudoephedrine were used as comparators. Results: A total of 58,760 cases were identified as being associated with ibuprofen in EudraVigilance. Stroke was reported for ibuprofen with a lower probability compared with etoricoxib (ROR: 0.34; 95% CI: 0.21–0.55), celecoxib (ROR: 0.07; 95% CI: 0.06–0.10), meloxicam (ROR: 0.25; 95% CI: 0.14–0.43), acetylsalicylic acid (ROR: 0.07; 95% CI: 0.05–0.09), and ibuprofen/pseudoephedrine (ROR: 0.11; 95% CI: 0.05–0.25). Thrombosis was reported for ibuprofen with a higher probability only relative to ketoprofen (ROR: 2.95; 95% CI: 1.71–5.09). Hypertension was reported for ibuprofen as being more probable than for acetylsalicylic acid (ROR: 1.58; 95% CI: 1.43–1.76). Myocardial infarction was reported as being more probable for ibuprofen than ketoprofen (ROR: 2.31; 95% CI: 1.57–3.40) or nimesulide (ROR: 2.43; 95% CI: 1.25–4.73). Conclusions: Overall, according to our study, the probability of reported cardiovascular adverse reactions is lower than those determined for the rest of the NSAIDs; however, taking into consideration the inherent limitations of the study, further clinical investigations would contribute to a better understanding of the cardiovascular safety of ibuprofen. Full article

Objective: Lower third impacted molar extraction, despite being a routinary procedure for oral and maxillo-facial surgeons, may often result in a significantly negative impact in patient’s post-operatory quality of life. Among others, treatments based on oxygen-enriched oils have been shown to provide valuable therapeutic benefits in promoting wound healing, and therefore improving the immediate post-operatory symptomatology. The aim of this triple-blinded randomized controlled study is to supplement the existing evidence in the scientific literature by assessing the effectiveness of NovoX^®-Drop (Moss S.p.A., Lesa, Novara), a specific type of oxygen enriched oil-based device in reducing pain and inflammatory stimulus of post-surgical wounds following the extraction of lower third impacted molars. Materials and methods: Seventy-one patients undergoing surgical extraction of a single lower third impacted molar were randomly assigned to receive either NovoX^®-Drop (Group A) or a glycerin-based gel (Group B). Additionally, both patient groups followed the same standard therapy with amoxicillin-clavulanic acid and ibuprofen. Data were collected preoperative (T0) and after three (T3) and seven (T7) days postoperative in order to assess the following outcomes: mean visual analogue scale (VAS) score during the seven days protocol treatment, total duration of nonsteroidal anti-inflammatory drug (NSAID) usage, trismus (maximum mouth opening) and facial oedema. Results: Group A (treatment group) reported significatively lower pain levels at T7 compared to group B (average VAS value during the week: Group A: 3.57 ± 0.39 cm; Group B: 4.47 ± 0.40 cm; p-value = 0.0014) despite a significatively shorter period of NSAID usage (average NSAID usage duration: Group A: 2.43 ± 0.38 days; Group B: 3.38 ± 0.44 days; p-value = 0.00001). Therefore, trismus seems to be better controlled in group A, although the difference between the groups did not reach the threshold for statistical significance. Conclusions: The results of this study suggest that application of NovoX^®-Drop is capable of significantly reducing the post-operatory pain as well as NSAID usage, representing a promising and effective option for third impacted molar extraction surgery management. Full article

Endometriosis is a chronic inflammatory disease characterized by the presence of ectopic endometrial tissue, mainly in the pelvic cavity. It primarily affects women of reproductive age and is associated with significant morbidity, particularly chronic pelvic pain and infertility. Despite its high prevalence, diagnosis is often delayed, contributing to prolonged suffering and increased healthcare burden. This review examines the management of endometriosis in Primary Care, focusing on clinical presentation, risk factors, diagnostic approaches, and therapeutic options. A comprehensive bibliographic search was conducted using PubMed, Scopus, and Uptodate, including evidence-based clinical guidelines and literature up to January 2025. Women diagnosed with endometriosis in Primary Care are typically of reproductive age, with symptoms including dysmenorrhea, dyspareunia, and abnormal uterine bleeding. Risk factors include early menarche, low birth weight, short menstrual cycles, and family history. Transvaginal ultrasound is the recommended first-line imaging tool. Treatment includes analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and hormonal therapies such as combined oral contraceptives or progestins. Non-pharmacological interventions, including dietary modifications and psychological support, are also relevant. Early identification in Primary Care is key to improving out-comes. Enhancing awareness among healthcare providers and promoting multidisciplinary management are essential to optimize care and reduce diagnostic delays. Full article

Background: Caesarean section is considered one of the surgeries with the highest prevalence of postoperative pain, yet this is often underestimated and undertreated. This study was aimed at evaluating the prevalence and severity of postoperative pain, assessing which analgesic strategy is the most effective and identifying those risk factors associated with poorer analgesic results. Methods: A multi-centre observational study was conducted on 514 women undergoing elective caesarean section. The primary endpoints included postoperative pain severity at rest and with movement at 6 and 24 h. Results: The combination of intrathecal morphine and fentanyl with acetaminophen and Non Steroid Anti-inflammatory Drugs (NSAIDs) was associated with better pain control than any of the following treatments: intrathecal fentanyl with systemic acetaminophen and NSAIDs (2.49 ± 2.04 vs. 3.91 ± 2.75, ES = −0.610, p = 0.01), elastomeric pump at 6 h at rest (2.49 ± 2.04 vs. 4.10 ± 2.86, ES −0.733, p = 0.04) and with movement (4.44 ± 2.41 vs. 6.14 ± 3.08, ES −0.671, p = 0.01) or epidural analgesia (4.44 ± 2.41 vs. 5.65 ± 2.57, ES −0.496, p = 0.02). No risk factors predicting poorer postoperative analgesia were found. Conclusions: The prevalence of postoperative pain control after elective caesarean section is high. The best analgesic postoperative regimen includes intrathecal morphine together with fentanyl and systemic analgesics. No risk factors associated with poorer outcomes were found. Full article

Meloxicam is a promising non-steroidal anti-inflammatory drug (NSAID) for acute and chronic pain prevention and treatment. Due to its poor water solubility, the clinical use of meloxicam is limited. In addition, for transdermal applications, the impermeability of the skin makes it difficult to conceive an appropriate NSAID-based delivery system that can penetrate through the skin barrier. Hydrophilic/hydrophobic gels, designed as transdermal drug delivery systems, can considerably improve other drug administration types (such as oral or intravenous), avoiding or limiting the side effects. The main purpose of this paper is to present some physicochemical and pharmaceutical considerations about meloxicam and to review the most important research concerning the gels used for the transdermal delivery of meloxicam. Thus, smart polymeric networks, semi-solid systems (lipogels, emulgels), β-cyclodextrin-based gels, liposomes (ethosomes, niosomes, flexosomes, transferosomes, menthosomes, invasomes), and nanostructured lipid carriers, with analgesic and anti-inflammatory activity, are discussed. The key objective of this study was to highlight various gel formulations with enhanced properties, which could be used in a minimally invasive manner for the sustained administration of meloxicam. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause hypersensitivity reactions and lead to anaphylactic shock. These drugs also act as cofactors in allergic reactions. Lipid transfer proteins (LTPs), found in plants, represent a unique group of allergens in which cofactors play a crucial role. This case report describes a 26-year-old female who developed anaphylactic symptoms after ingesting grapes and taking ketoprofen. The patient experienced swelling of the lips, tongue, and throat, as well as shortness of breath, dizziness, and loss of consciousness, after consuming grapes and taking ketoprofen. She had previously used ketoprofen and acetylsalicylic acid without issues but had developed urticaria on several occasions after consuming multi-ingredient dishes. Skin prick tests showed positive results for peanut and orange allergens. Further testing using the ALEX multiparametric test detected antibodies to several LTP allergens. Intradermal tests with ketoprofen yielded a positive result, although irritant reactions could not be ruled out. A provocation test with acetylsalicylic acid (ASA) showed no adverse reactions. Skin tests with ibuprofen were negative, and provocation tests confirmed its tolerance. A diagnosis of LTP allergy and selective ketoprofen allergy was made, with the recommendation to avoid ketoprofen and follow a diet excluding foods from the LTP group. Full article

Meloxicam (MLX), a member of the non-steroidal anti-inflammatory drugs (NSAIDs), is a preferential inhibitor of cyclooxygenase-2 (COX-2) responsible for the synthesis of pro-inflammatory prostaglandins. MLX, due to its inhibition of the COX-2 enzyme, which is overexpressed in many cancers, including melanoma, leading to rapid growth, angiogenesis, and metastasis, represents a potentially important compound with anticancer activity. This study aimed to investigate the potential anticancer activity of meloxicam against amelanotic C32 and melanotic COLO 829 melanoma cell lines. The objective was achieved by assessing cell metabolic activity using the WST-1 assay and analyzing mitochondrial potential, levels of reduced thiols, annexin, and caspases 3/7, 8, and 9 by imaging cytometry, as well as assessing reactive oxygen species (ROS) levels using the H₂DCFDA probe. The amelanotic melanoma C32 was more sensitive to MLX exposure, thus exhibiting antiproliferative effects, a disruption of redox homeostasis, a reduction in mitochondrial potential, and an induction of apoptosis. The results provide robust molecular evidence supporting the pharmacological effects of MLX, highlighting its potential as a valuable agent for in vivo melanoma treatment. Full article

Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations. Full article

Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease-Modifying Antirheumatic Drugs (DMARDs) for OA, current treatment strategies largely focus on symptom relief rather than disease modification. These symptomatic treatments often fail to account for the substantial inter-individual variability in drug response. Pharmacogenomics (PGx), the study of how genetic variation influences drug response, offers a promising approach to personalize OA therapy. This review explores the clinical and pharmacogenomic considerations of commonly used OA medications—acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol—focusing on gene–drug interactions that influence efficacy, safety, and metabolism. Evidence-based recommendations from the Clinical Pharmacogenetics Implementation Consortium guidelines are discussed, where applicable, to highlight actionable genetic variants in very important pharmacogenes such as CYP2D6, CYP2C9, and other important drug-metabolizing encoding genes such as CYP2E1 and UGT1A6. While PGx data are not currently embedded in OA clinical treatment guidelines, their integration into clinical practice may enhance therapeutic outcomes and minimize adverse drug events. This review underscores the potential of PGx as a clinical tool in OA pain management, paving the way toward truly personalized medicine. Full article

This study aims to demonstrate the feasibility of the use of chestnut waste as a green and circular material for developing iron-based photocatalysts for non-steroidal anti-inflammatory drug (NSAID) photodegradation. Four Fe-based catalysts and two pristine biochars were obtained upon a pyrolysis process at 500 and 700 °C and fully characterised. Due to the applied synthesis, iron is present in the form of isotropic grains of magnetite (Fe₃O₄), quite homogeneously dispersed onto the biochar. The textural properties of all the materials are mainly determined by the pyrolytic temperature, which results in macroporous materials at 500 °C and microporous ones at 700 °C. Fe-based catalysts were tested in Diclofenac (DFC) photodegradation. DFC removal was the result of both adsorption and photocatalytic reactions. Despite the good yield in DFC removal (80–100%), the formation of degradation by-products can partially invalidate the good effectiveness of this approach. However, the encouraging results of this study represent a step forward for the possible development of waste-derived biochar-based catalysts for in-field application. Full article

Disbudding is a husbandry practice that causes pain and discomfort to calves. As a prominent welfare concern, it is now standard practice for calves to be given analgesic treatment such as a nonsteroidal anti-inflammatory drug (NSAID) injection. Meloxicam is a commonly used NSAID as it provides pain relief for up to 44 h following disbudding. However, since symptoms can persist for up to two weeks, it was hypothesised that more prolonged analgesic treatment would promote better welfare outcomes than the conventional injection. This study tested a novel treatment whereby disbudded calves were fed grain-based pellets medicated with meloxicam over a 7-day period. Lower levels of horn site inflammation were observed for the pellet treatment across the 7-day feeding period in comparison to the conventional injection. The pellet treatment calves also exhibited less pain-specific and more positive social-specific behaviours during and beyond the feeding period. Together, these results suggest that lower levels of inflammation enacted by prolonged meloxicam administration have an active role in reducing pain and maintaining the affectivity of disbudded calves. With the goal of establishing sustained disbudding treatment as a new industry standard, future research will focus on larger-scale results reproducibility and maximising treatment practicality. Full article