Nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, are widely used for the management of inflammatory pain in human and veterinary medicine, although their clinical utility is limited by dose-dependent adverse effects. Strategies aimed at reducing NSAID dosage while preserving analgesic efficacy are therefore warranted. We investigated whether ultramicronized palmitoylethanolamide (PEAum), an endogenous prohomeostatic lipid amide with improved bioavailability, could enhance the antinociceptive effects of meloxicam in preclinical models of acute and chronic inflammatory pain. Acute pain was induced by intraplantar lipopolysaccharide (LPS) injection, while chronic pain was induced by intra-articular injection of Complete Freund's Adjuvant (CFA). Mechanical hyperalgesia and allodynia were measured by the Paw pressure and von Frey tests, respectively. In the LPS model, PEAum confirmed its superior anti-hyperalgesic profile compared with micronized and native PEA. PEAum (10 mg/kg) markedly enhanced the analgesic activity of low-dose meloxicam (3 mg/kg), with the combination fully reversing inflammatory hypersensitivity and outperforming high-dose meloxicam (30 mg/kg). In the CFA model, the same association completely counteracted mechanical hyperalgesia, reproducing the antalgic effect of high-dose meloxicam. A pharmacodynamic study demonstrated that pharmacological blockade of PPAR-α with the selective receptor antagonist GW6471 (2 mg/kg) significantly reduced, but did not abolish, the analgesic effect of the combination, suggesting both PPAR-α-dependent and independent mechanisms. Overall, the combined treatment produced a greater-than-additive antinociceptive effect, demonstrating a synergistic interaction between PEAum and meloxicam in both acute and chronic inflammatory pain. This synergy enables substantial meloxicam dose-reduction while maintaining full analgesic activity, supporting a promising dose-sparing strategy for inflammatory pain management.

This case demonstrates the successful application of a cruciate suture pattern using silk suture for umbilical hernia repair in a ram. A one-year-old local breed ram was presented to the Professor Feseha Gebreab Memorial Veterinary Teaching Hospital, Addis Ababa University, Ethiopia, with a progressively enlarging umbilical swelling. Clinical examination revealed a non-painful, large umbilical hernia, for which the ram was admitted for surgical repair. Herniorrhaphy was conducted after circular infiltration of 2% lidocaine. The hernial sac was opened through a longitudinal incision cranial to the prepuce, and the herniated omentum and intestine were reduced. The hernial ring was closed using a cruciate suture pattern with size 2 silk. Postoperatively, Penicillin-streptomycin and meloxicam were administered for three consecutive days. Recovery was uneventful, with complete healing. The outcome suggests this technique is a viable and effective suture pattern for hernias of similar size, in addition to timely diagnosis, accurate surgical execution, and diligent postoperative care.

Inflammatory pain severely impacts patient well-being. Current treatments focus heavily on resolving inflammation yet often fail to offer rapid pain relief, leading to poor clinical compliance. To bridge this gap, we designed self-assembled nanoparticles that pair instant pain relief with long-term control of inflammation. The core consists of co-assembled lidocaine (LDC), capsaicin (CAP), and meloxicam (MLX) covered by a protective polyethylene glycol (PEG) shell. Upon reaching the weakly acidic inflammatory microenvironment, intermolecular interactions weaken, causing the drug to release rapidly. While local tissue acidity normally protonates LDC and blocks it from crossing nerve cell membranes, the co-released CAP specifically opens transient receptor potential vanilloid 1 (TRPV1) channels. This allows the protonated LDC to flow directly into neurons, securing rapid pain relief. Concurrently, MLX provides sustained anti-inflammatory action by blocking cyclooxygenase-2 (COX-2) and reducing prostaglandin E2 (PGE2) levels, along with other pro-inflammatory mediators. By syncing rapid nerve blockade with continuous anti-inflammatory action, this self-assembled nanosystem overcomes the pharmacokinetic mismatch in drug mixtures, offering a practical and highly effective strategy for inflammatory pain management.

Background: Vaterite calcium carbonate (CaCO3) particles are promising pH-sensitive carriers for oral drug delivery, but the influence of drug hydrophilicity on loading and release is still not well defined. In this study, we evaluate the encapsulation and release profiles of six specific formulations utilizing metformin and meloxicam across distinct CaCO3 carrier variants and loading methodologies. Methods: We prepared vaterite CaCO3 particles as native (and PVP-stabilized) carriers and utilized co-precipitation, post-loading (adsorption), and sonication-assisted loading techniques. We subsequently evaluated carrier morphology, phase stability, encapsulation efficiency, surface adsorption capacity, and in vitro drug release in simulated gastric (pH 1.2) and intestinal (pH 6.8) media. Results: Quantitative image analysis confirmed that porous vaterite particles formed primarily in the micron range, with PVP stabilization significantly reducing the mean particle diameter compared to native carriers (0.966 µm versus 1.189 µm). Furthermore, extended exposure to aqueous media induced partial transformation to calcite. The highest encapsulation efficiency for metformin (93.0 ± 1.5%) was achieved using co-precipitation, whereas for meloxicam (79.6 ± 1.9%), it was optimized through sonication-assisted adsorption on the PVP-modified carriers. In vitro release showed a clear pH-dependent behavior; the fast dissolution of the vaterite through gastric pH was associated with the fast release of metformin, especially in the calcite-containing formulation that produced the greatest release (98.0 ± 3.3%) in 15 min. At intestinal pH, metformin and meloxicam exhibited sustained release as in the Korsmeyer-Peppas model. Conclusions: The evaluated carrier compositions and loading methodologies distinctly influenced the encapsulation and release profiles of the six prepared formulations. These specific formulation comparisons highlight practical considerations for utilizing vaterite carriers for varied release targets.

Sulfated polysaccharides from red seaweeds are emerging as versatile bioactive macromolecules. Here, we report that funoran-type galactans from Gelidiopsis variabilis (GV) function as immunometabolic reprogrammers, orchestrating inflammation resolution through targeted remodeling of amino acid and fatty acid metabolism in macrophages, potentially via receptor-mediated pathways. Cold and hot water extraction yielded structurally distinct fractions (360-3006 kDa) characterized by NMR as sulfated galactans with κ-carrageenan motifs and variable sulfation (6.6-21.5%). In RAW264.7 macrophages, fractions GV-1A and GV-2A induced an anti-inflammatory metabolic state characterized by arginine accumulation (from 4.61% to 7.06% of the total amino acid pool), reduced ornithine levels, and complete the elimination of pro-inflammatory myristate (14:0), while upregulating phagocytosis (149% of control). In a carrageenan-induced paw edema model, GV-1A and GV-2A dose-dependently upregulated pro-resolution markers (IL-10, IL-4, TGF-β1, Arg1, HO-1), outperforming the standard drug meloxicam. While the in vitro arginine accumulation suggests functional arginase inhibition, the in vivo Arg1 upregulation reflects a transcriptional response in a complex tissue environment. We propose that these findings collectively support a 'resolution-phase metabolic phenotype', a working model whereby GV polysaccharides reprogram macrophage metabolism toward inflammation resolution through context-dependent mechanisms. These findings establish G. variabilis polysaccharides as metabolically active immunomodulators that promote inflammation resolution, with the potential for applications in inflammatory diseases and as a pharmaceutical platform for drug development.

The emergence of antimicrobial resistance (AMR) due to biofilm-forming S. aureus is a worldwide issue associated with a variety of persistent infections, including mastitis. This study investigated the prevalence and molecular characterization of biofilm-forming S. aureus, risk factors associated with subclinical mastitis (SCM), and simulation-based computational modeling for biofilm-associated protein. Moreover, repurposing of non-steroidal anti-inflammatory drugs as adjunct therapies against biofilm-forming S. aureus was investigated in combination with antibiotics. Overall, 384 camel milk samples were collected and subjected to the California mastitis test (CMT), and 51.30% SCM prevalence was found in sampled animals. Among these, 59.39% of SCM-positive milk isolates were positive for S. aureus, while the prevalence of staphylococcal biofilm-positive isolates by Congo red agar (CRA) and tube method was 41.88% and 31.6%, respectively. Further, on genotypic investigation, 47.86% and 31.62% of isolates were found to have icaA and icaD genes, respectively. After this, biofilm-forming isolates were subjected to phylogenetic assessment, and results exhibited strong sequence identity of local icaA and icaD isolates with neighbouring countries. Moreover, phylogenetic analysis was further validated with simulation-based computational modeling by using different tools, and results depicted a close evolutionary relationship and predominant structural integrity of the icaA protein. Drug susceptibility profiling of biofilm-positive isolates showed high resistance against amoxicillin, trimethoprim+sulphamethoxazole, and cefixime. Furthermore, In-Vitro combination therapy trials showed synergistic effect of amoxicillin and trimethoprim+sulphamethoxazole with flunixin meglumine and cefixime with meloxicam. This study will provide baseline data on biofilm-forming S. aureus persistence in the camel population, along with devising an effective therapy against biofilm-forming S. aureus infections.

Meloxicam (MLX) and tenoxicam (TNX) remain analytically important across pharmaceutical, biological, veterinary, and environmental applications, yet their reliable determination is strongly influenced by matrix complexity and drug-specific physicochemical behavior. This review moves beyond conventional method-centered summaries by critically comparing MLX and TNX across matrices and linking their physicochemical, pharmacokinetic, metabolic, and stability characteristics to analytical performance. Sample-preparation strategies, chromatographic and mass-spectrometric platforms, spectroscopic techniques, and electrochemical methods are evaluated for selectivity, sensitivity, matrix tolerance, robustness, sustainability, and practical applicability. Particular emphasis is placed on unresolved limitations in parent drug-metabolite-degradation product discrimination, matrix-effect control, method transferability, and harmonized validation. Importantly, the review integrates emerging chemometric optimization, artificial intelligence, machine learning, automated workflows, and Green and White Analytical Chemistry as converging directions for next-generation analysis. Future progress should shift from isolated improvements in detection sensitivity toward matrix-adaptive, digitally assisted, sustainability-aware analytical systems that integrate automated sample preparation, intelligent data interpretation, robust validation, and lifecycle-based performance assessment. This integrated perspective identifies priorities for transforming the determination of MLX and TNX from fragmented, matrix-specific methodologies into more transferable, intelligent, and sustainable analytical frameworks.

Osteoarthritis (OA) is a leading cause of disability worldwide, characterized by progressive cartilage degradation, chronic inflammation, and joint structural deterioration. Beyond its physical burden, OA significantly impacts psychological well-being and socioeconomic stability. Current pharmacological treatments, such as meloxicam (Mel), provide symptomatic relief but fail to comprehensively address the inflammatory mechanisms driving OA progression while also posing risks like liver toxicity. The study was designed to test whether exopolysaccharide (EPS) improves cartilage structural integrity in a ciprofloxacin (CIP)-induced OA-like experimental arthropathy, with inflammatory, oxidative, and signaling markers serving as supportive mechanistic outcomes. The EPS-producing Bacillus altitudinis strain BAE2023 was identified via 16S rRNA sequencing, with EPS composition confirmed through GC/MS and FTIR analyses. Forty male albino rats were divided into five groups: control, CIP-induced OA-like experimental arthropathy, and treatment groups receiving EPS, Mel, or their combination. Results demonstrated that combined EPS and Mel therapy significantly improved joint structural parameters, improved the measured redox profile by increasing SOD, GST, and GSH and by lowering MDA, a marker of lipid peroxidation, and suppressed key circulating inflammatory mediators. Gene expression analysis revealed that EPS successfully modulated the Nrf2/Ho-1 and Cox-2/Mmp1a signaling axes, highlighting its role in inflammation resolution and joint repair. Histopathological evaluation further confirmed cartilage regeneration and reduced hepatic toxicity. By effectively modulating inflammation and oxidative stress, EPS emerges as a promising therapeutic strategy for managing disability-related OA. This study underscores the potential of EPS in enhancing joint health, minimizing medication-induced toxicity, and improving overall quality of life for individuals suffering from OA. Integrating EPS into OA treatment paradigms may offer a more holistic, a chondroprotective and structure-preserving effect to disability management.

Thermosensitive polyurethane (PU) hydrogels were prepared and loaded with meloxicam (MX), a nonsteroidal anti-inflammatory drug (NSAID). The role of different excipients, i.e., eucalyptus essential oil as well as poly(vinylpyrrolidone), poly(ethylene glycol) and their mixture, was highlighted. The sol-gel transition induced by temperature increase was evidenced by rheological measurements in oscillatory shear conditions. The viscoelastic behavior was investigated at 37 °C in various shear conditions, evidencing the network strength and stability of formulations. The structural recovery was monitored after applying high strain values, and the self-healing ability was revealed. Depending on the excipient, the gel samples loaded with MX release between 60% and 90% of the active substance. It was shown that the Fickian and chain relaxation contributions compete during MX release from PU-based hydrogels. In vitro anti-inflammatory activity was evaluated and discussed.

Disbudding is a routine management practice on dairy farms, and cautery disbudding remains the most popular method in North America. Practitioners commonly employ 2 methods of cautery disbudding: retaining (BUD-IN) or removing (BUD-OUT) the cauterized horn bud. However, comparative evidence regarding healing and pain outcomes between these techniques is limited. The objective of this study was to compare pain sensitivity, wound characteristics, healing outcomes, and growth performance following cautery disbudding with BUD-IN or BUD-OUT in heifer dairy calves. We hypothesized that pain sensitivity and wound healing characteristics would differ between these 2 cautery disbudding methods. A total of 222 healthy female Holstein calves were enrolled at 16 d of age on a commercial dairy farm in New York and randomly assigned to BUD-IN (n = 111) or BUD-OUT (n = 111) treatment groups. All calves received meloxicam (1 mg/kg BW, orally) and a cornual nerve block with 5 mL of 2% lidocaine before disbudding. Wound diameter was the primary outcome variable. Other secondary outcome variables were mechanical nociceptive threshold (MNT), wound discharge, wound healing score, and calf health. All outcome variables were assessed weekly for 8 wk. Body weight was measured at disbudding (wk 0) and 8 wk after disbudding. The continuous outcomes MNT, wound diameter, and ADG were analyzed using generalized linear mixed models; the binary outcome (presence or absence of wound discharge) was analyzed using logistic regression; and time to complete healing was analyzed using Cox proportional hazards regression. Mechanical nociceptive threshold and wound diameter did not differ between groups. Wound discharge was observed during the initial 4 wk post-disbudding. Purulent wound discharge was more common in BUD-IN than BUD-OUT, with an odds ratio (95% CI) of purulent wound discharge in BUD-IN. Time to complete wound healing did not differ between treatments. Average daily gain was not different among groups. Under the conditions of this study, removal of the horn bud during cautery disbudding did not affect pain sensitivity, growth performance, or time to wound healing but was associated with reduced odds of early wound discharge. These findings suggest that both techniques produce comparable long-term outcomes when appropriate analgesia is provided, and the selection of technique may be guided by early wound management considerations.