Search Results (179)

In ruminants, the survival and development of the conceptus are heavily dependent on the composition of the uterine lumen fluid (ULF), which is influenced by prostaglandins (PGs). However, the variations in underlying PG-mediated ULF remain unclear. Herein, cycling heifers received an intrauterine infusion of vehicle as a control (CON) or meloxicam (MEL) on days 12–14 of the estrous cycle. Then, the ULF was collected on day 15 and alternations in its protein and lipid levels were analyzed. The suppression of prostaglandins induced by meloxicam resulted in 1343 differentially abundant proteins (DAPs) and 59 differentially altered lipids. These DAPs were primarily associated with vesicle-mediated transport, immune response, and actin filament organization, and were mainly concentrated on the ribosome, complement and coagulation cascades, cholesterol metabolism, chemokine signal pathway, regulation of actin cytoskeleton and starch and sucrose metabolism. These differential lipids reflected a physiological metabolic shift as the abundance of cell membrane-related lipids was modulated, including an accumulation of triacylglycerols and reductions in lysophosphatidylcholines, hexosyl ceramides, ceramides, and sphingomyelins species. Integration analysis of the DAPs and differentially altered lipid metabolites revealed that glycerophospholipid metabolism and choline metabolism were the core pathways. These findings highlight the potential roles of prostaglandins in ULF, providing new insights into the contributions of prostaglandins in the development of the conceptus. Full article

The self-administration of meloxicam via medicated feed is a novel concept that could enable non-invasive, pre-emptive and long-term analgesia. Forty Bos taurus male calves were randomly allocated to four treatment groups: no castration (PC), surgical castration (NC), surgical castration with subcutaneous meloxicam (M), and surgical castration with medicated lick blocks (ML). Data collection occurred at various timepoints over 13 days following treatment. Plasma concentration of meloxicam was greater in ML compared to M calves at all timepoints except day 1 (p < 0.001); however, variation between ML individuals was high (standard deviation = 1.68). There was no effect of treatment on scrotal diameter or scrotal temperature. Wound morphology scores were improved in ML compared to NC calves. Eating observations were greater in ML calves immediately post-castration, followed by M calves at 3 h post-castration (p < 0.001). ML calves were observed locomoting more (p = 0.0032) and lying less (p < 0.001) than PC calves. These findings indicate that meloxicam-medicated lick blocks may provide a practical option for a longer duration of pain mitigation for surgically castrated calves. Conclusions are limited by the complexities of assessing pain in cattle, and further research into the toxicity effects of continued administration of meloxicam is recommended. Full article

Pain management requires the identification of certain indicators to recognize pain. Various tools have been suggested to achieve an objective evaluation, including infrared thermography (IRT). The objective of this study was to assess the facial thermal nociceptive response produced by the use of cannabidiol (CBD) alone and in combination with meloxicam in female dogs undergoing elective ovariohysterectomy anesthetized with isoflurane. Sixty-four female dogs of different breeds were randomly distributed into four study groups according to the treatment received. G1: Placebo group (n = 16); G2: Group receiving intravenous meloxicam as premedication (0.2 mg Kg⁻¹) and every 24 h postoperatively 0.1 mg Kg⁻¹ (n = 16); G3: Group treated with CBD (n = 16) at a dose of 2 mg kg⁻¹ orally every 12 h; and G4: Group medicated with the combination of both treatments (n = 16). All treatments were administered for 48 h postoperatively. After the anesthetic surgical procedure, radiometric images were captured using IRT and physiological parameters during the events E_Basal, E_30min, E_1h, E_2h, E_3h, E_4h, E_8h, E_12h, E_24h and E_48h. Overall, it was found that the high, medium and low temperatures of the thermal windows of the eye, upper eyelid and lower eyelid, as well as the average temperature of the lacrimal gland in G1 between events, were significantly lower at E_30min, E_1h and E_2h compared to E_Basal (p = 0.01). Among treatments, a significantly higher temperature was observed in groups G2, G3 and G4 compared to G1 (p = 0.001) in the thermal windows of the upper eyelid, lower eyelid, lacrimal gland and ocular areas. Regarding physiological parameters, heart rate (HR) was higher in G1 compared to the animals in G2, G3 and G4 (p = 0.03). The respiratory rate (RR) was significantly lower in all four study groups during the postoperative events compared to their respective E_Basal (p < 0.05), while among treatments, G2, G3 and G4 had a lower RR compared to G1 (p = 0.03). Mild hypothermia was observed in all study groups at E_30min and E_1h compared to E_Basal (p = 0.001). No significant correlation was found between the temperatures of the assessed thermal regions and the physiological traits. In conclusion, CBD, whether administered alone or in combination with meloxicam, demonstrated comparable analgesic efficacy, which could control nociceptive cardiorespiratory and hemodynamic autonomic responses, as there were no significant changes in the facial thermal response between treatments G2, G3 and G4. Full article

Systemic inflammatory response syndrome (SIRS) in donkeys is observed to be secondary to colic, diarrhea or pleuropneumonia, among other disorders. Horses with SIRS develop secondary disturbances such as hyperlipemia, laminitis, disseminated intravascular coagulopathy, and hemodynamic and cardiac derangements, which impair their prognosis and increase the mortality rate. In donkeys, no information is available on the effect of experimentally induced endotoxemia in the cardiovascular system. Acute experimental endotoxemia was induced by lipopolysaccharide (LPS) infusion in six healthy adult non-pregnant jennies. Physical signs, arterial (systolic, diastolic and mean) and central venous pressure were monitored during 360 min. Cardiac troponin I (cTnI) concentrations were measured in blood samples, and echocardiography was performed. LPS infusion caused an increase in cTnI, hypotension and diminution of central venous pressure, cardiac dysfunction, with a decrease in stroke volume (SV), cardiac output (CO) and cardiac index, and impairment of ultrasonographic ventricular function parameters. Intravenous meloxicam administration prevented the cTnI increase, hypotension, diminution of SV and CO, and changes in ultrasonographic parameters related to ventricular dysfunction. Thus, meloxicam could be proposed as an effective therapeutical option to control the hemodynamic and cardiac derangements observed in donkeys with SIRS. Full article

The administration of lidocaine as part of multimodal analgesia in dogs undergoing ovariohysterectomies demonstrates variable analgesic efficacy. The aim of this prospective, double–blinded clinical study was to evaluate the effectiveness of lidocaine 2% irrigation on the ovarian suspensory ligament, followed by localised massage, in achieving sufficient intraoperative analgesia. Thirty-eight female dogs were randomly divided to two groups and received either a splash block of 0.5 ml lidocaine 2% on each ovarian suspensory ligament (GL) or an equal volume of saline (GNS). All dogs were premedicated with dexmedetomidine (5 μg·kg⁻¹) and buprenorphine (20 μg·kg⁻¹) intramuscularly and meloxicam (0.2 mg·kg⁻¹) subcutaneously. Anaesthesia was induced with propofol and maintained with isoflurane. The surgical procedure was initiated after an adequate depth of anaesthesia was achieved. Heart rate (HR), respiratory rate (f_R) and mean arterial pressure (MAP) were continuously monitored. Fentanyl (2 μg·kg⁻¹) was administered as rescue analgesia in case of a 30% increase in HR, f_R, or MAP, compared to their values before manipulation of the ovaries. Data were analysed using a mixed model for repeated measures ANOVA and Pearson’s Chi-Square test. The need for rescue analgesia differed significantly between the two groups (p < 0.0005). In GNS, 89.47% (17/19) of the dogs required rescue analgesia, compared to 10.53% (2/19) of the dogs in GL. The relative risk of rescue for the GNS compared to the GL was approximately 8.5. In conclusion, intraoperative analgesia during ovariohysterectomies in dogs can be enhanced using a lidocaine 2% splash block combined with massage of the ovarian suspensory ligament. Full article

Lung ultrasonography can facilitate bovine respiratory disease (BRD) detection and can potentially improve treatment outcomes. In this study, ninety-six veal calves were followed weekly with clinical and lung ultrasound examinations during the production cycle. Thirty-six calves had clinical signs and abnormal lung ultrasound scans (TRT, n = 36) and were promptly treated with florfenicol and meloxicam. Healthy veal calves without clinical signs and lung lesions were enrolled in the control group (CTR, n = 48), while 12 calves were excluded by the study. The clinical (Wisconsin and California scores), ultrasound and lung lesion scores, total lung consolidation area, treatment rates (success, relapse, mortality), average daily gain (ADG), carcass quality, and gross lesions of lungs at slaughterhouse were monitored. Results showed 91.7% of treatments were performed 3–28 days after arrival. Lung lesions occurred five days before the peak of clinical scores. Following treatment, lungs healed within 5 days with high treatment success rates (97.1% success rate in 45 days and 94.9% overall success rate without relapse). Finally, TRT had similar gross lung lesion prevalence, ADG, and carcass quality to CTR. These results suggest that early detection of BRD followed by a prompt treatment can lead to several key benefits for the health and the growth performances of veal calves. Full article

Klebsiella pneumoniae (K. pneumoniae) is a significant pathogen associated with clinical mastitis in cattle. Anti-inflammatory drugs are necessary to alleviate pain and inflammation during clinical mastitis. Among many drugs, meloxicam (MEL) has been widely used in clinical mastitis because of its excellent inhibitory effect on the cyclooxygenase-2 (COX-2) enzyme. However, the effectiveness of MEL on the inflammatory response and oxidative stress induced by K. pneumoniae are unclear. In the present study, primary BMECs were infected with K. pneumoniae in the presence or absence of plasma maintenance concentration of MEL (0.5 and 5 μM). Following 1 or 3 h of combined treatment with K. pneumoniae and MEL, BMECs were gathered to assess the related indicators. The results showed that MEL at plasma maintenance concentrations exerted no influence on the viability of uninfected BMECs and also had no impact on bacterial load in BMECs. At these concentrations, MEL was able to inhibit the mRNA expression of COX-2, Interleukin (IL)-1β, Tumor necrosis factor α (TNF-α), and IL-6 while simultaneously elevating the mRNA levels of IL-8 in K. pneumoniae-infected BMECs. MEL had clear effects on relieving oxidative stress by increasing the activity of superoxide dismutase (SOD) and catalase (CAT) and the level of total antioxidant capacity (T-AOC). The mechanisms by which MEL mitigated the inflammatory response and oxidative stress were partially attributed to inhibition of the nuclear transcription factor-kappa B (NF-κB) signaling pathway and improvement of the activation of the nuclear factor erythroid 2-related factors (Nrf2) signaling pathway. To conclude, the results manifested that MEL at plasma maintenance concentrations protected BMECs from inflammatory and oxidative damage induced by K. pneumoniae. Full article

Background/Objectives: This article reports on the scalability of a combined wet grinding technique applying planetary ball mill and ZrO₂ pearls as the grinding medium. After the determination of the parameters in a laboratory scale, the tenfold scale-up method was set. Meloxicam (MEL) was used as a nonsteroidal anti-inflammatory drug (NSAID) intended for per os delivery. During grinding, the PVA solution was used as a dispersion medium. Methods: The influence of the scaling-up on the particle size, morphology, crystallinity, and intra- and interparticulate phenomena has been studied. Formulation investigations of the milled suspensions were carried out. The dissolution test and the cytotoxicity analyses were accomplished. Results: Submicron MEL particle-containing samples were produced in both grinding scales. After the particle size determination was achieved from the suspensions, the wet milled, dried products were studied. The particle size of the dried products fell into the same range for both scales of milling (the maximum particle size was about 580 nm). There was no significant difference in drug crystallinity after the grindings; 70% of MEL remained crystalline in both cases. A remarkable interaction between the components did not develop as a result of milling. The polarity of the products increased, which resulted in a better dissolution, especially in the case of intestinal fluid (~100% in the first 5 min). The products were not found to be toxic. Conclusions: This research demonstrates that the scaling-up of combined wet grinding technique is feasible by adjusting the milling parameters and the adequate amount of excipient. Full article

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body’s inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby blocking the synthesis of prostaglandins (PGs), which play a role in inflammation, cancer, and various cardiovascular conditions. However, long-term COX inhibition and reduced PGs synthesis can result in serious side effects. Recent studies have increasingly shown that some selective COX-2 inhibitors and NSAIDs, such as Meloxicam, may exert effects beyond COX inhibition. This emerging understanding prompts a re-evaluation of the mechanisms by which NSAIDs operate, suggesting that their benefits in cancer and CVD treatment may not solely depend on COX targeting. In this review, we will explore the potential COX-independent mechanisms of Meloxicam and other NSAIDs in addressing oncology and cardiovascular health. Full article

Cyclooxygenase-2 (COX-2) is overexpressed in many human and animal cancers. Selective COX-2 inhibitors have shown antitumoral effects in tumors with a high expression of COX-2. This study evaluates (1) the expression of COX-2 in rabbit uterine adenocarcinomas, (2) the correlation between immunophenotypic expression and histopathological changes, and (3) the post-surgery response to therapy with COX-2 inhibitors. Forty rabbit uteri were divided into three groups: neoplastic, hyperplastic, and normal endometrium. A histological and immunohistochemical score was applied to investigate the tumor’s grade and the COX-2 expression. By histological evaluation, 30 cases of endometrial adenocarcinoma, 5 cases of endometrial hyperplasia and 5 normal endometria were found. Of the six cases of endometrial adenocarcinoma with follow-up available, four received a post-surgical treatment with meloxicam and two were treated by surgery alone. The survival time of the animals treated with meloxicam was longer than that observed in the untreated animals. A statistically significant difference in COX-2 IHS was observed between non-neoplastic endometrium and adenocarcinoma. The progressive increase in COX-2 expression from normal epithelium to carcinoma suggests that upregulation of COX-2 expression may play a role in tumor initiation and progression. Our findings suggest the possible use of COX-2 inhibitors in treating uterine adenocarcinoma in rabbits. Further study will be needed to confirm this hypothesis. Full article

Anthropogenic activities have negatively affected many birds, including owls. The Wildlife Hospital of Louisiana (WHL) has seen a 3.2-fold increase in barred owl (Strix varia) cases over the past eight years (2023, 134; 2015, 42). Because most of these animals present with traumatic injuries, analgesics should be considered in their treatment plan. To date, no study has measured the pharmacokinetics of an analgesic in barred owls. The goals of this study were to determine the harmonic means, times to maximum concentration, and elimination half-lives for single 1 mg/kg and 2 mg/kg intramuscular doses of meloxicam. Twelve barred owls (1 mg/kg, n = 6; 2 mg/kg, n = 6) admitted to the WHL and determined to be clinically normal based on examination and blood work were recruited for this study. Meloxicam was administered intramuscularly, and blood samples were collected intermittently over 12 h to measure plasma concentrations using high-performance liquid chromatography. Both doses had rapid elimination half-lives (1 mg/kg, 0.99 ± 0.1 h; 2 mg/kg, 1.07 ± 0.43 h) and were below the limits of quantification (0.1 µg/mL) by 6–12 h. Based on these results, 1 and 2 mg/kg doses of meloxicam were found to produce plasma concentrations below therapeutic concentrations for less than four hours, making current twice-daily recommended dosing intervals unlikely to provide desired analgesia. Full article

Meloxicam is a non-steroidal anti-inflammatory in the oxicam group. It has been extensively used in human and veterinary medicine for their anti-inflammatory, analgesic and antipyretic activities. Meloxicam has shown high therapeutic potential for disorders such as osteoarthritis, musculoskeletal disorder, acute respiratory infection, puerperal septicemia, mastitis and mastitis–metritis–agalactia syndrome. Although meloxicam pharmacokinetic has been described for numerous species, no paper summarizes the existing literature on this field. Thus, the aim of this review was to carry out a review of the literature on the pharmacokinetics of meloxicam in different animal species and gather the data in a single review article. A comprehensive review of the available literature in the PubMed, Web of Science and Scopus databases was performed. Meloxicam shows good bioavailability after oral and parenteral administration in most animal species (85–95%), with the lowest values in sheep after oral administration. It presents a rapid distribution with a small volume of distribution, which can be attributed to relatively high ionization state of meloxicam at physiological pH and its high plasma protein binding (close to 99%). It is extensively metabolized in the liver in several inactive polar metabolites, which are excreted, like unchanged meloxicam in urine and feces. Meloxicam also shows a long elimination half-life and low clearance. Full article

Pyrimidine derivatives exhibit a wide range of biological activities, including anti-inflammatory properties. The aim of this study was to investigate the effects of tested pyrimidine derivatives on the activity of cyclooxygenase isoenzymes (COX-1 and COX-2), antioxidant properties, and their ability to inhibit the growth of inflammatory cells. In vitro tests were conducted to assess the ability of pyrimidine derivatives L1–L4 to inhibit COX-1 and COX-2 activity using the TMPD oxidation assay (N,N,N′,N′-tetramethyl-p-phenylenediamine). The compounds’ ability to inhibit the growth of lipopolysaccharide (LPS)-stimulated THP-1 (human leukemia monocytic) monocyte cells and their impact on reactive oxygen species (ROS) levels in an inflammatory model were also evaluated. The binding properties of human serum albumin (HSA) were assessed using UV–Vis spectroscopy, circular dichroism (CD), and isothermal titration calorimetry (ITC). Among the tested pyrimidine derivatives, L1 and L2 showed high selectivity towards COX-2, outperforming piroxicam and achieving results comparable to meloxicam. In the sulforhodamine B (SRB) assay, L1 and L2 demonstrated dose-dependent inhibition of LPS-stimulated THP-1 cell growth. Additionally, ROS assays indicated that these compounds reduced free radical levels, confirming their antioxidant properties. Binding studies with albumin revealed that L1 and L2 formed stable complexes with HSA. These results suggest that these compounds could serve as a basis for further research into anti-inflammatory and anticancer drugs with reduced toxicity. Full article

In this study, an easy, efficient, economical, and eco-friendly green bio-synthesis method was utilized to synthesize silver nanoparticles (AgNPs) using the extracts of four plants: Ginkgo biloba, Cichorium Intybus, Adiantum Capillus-Veneris, and Rosmarinus Officinalis. The synthesis of AgNPs was confirmed by using a uv-vis spectrometer, which showed distinct surface plasmon resonance (SPR) bands. The surface of AgNPs was characterized using scanning electron microscopy and Fourier-transform infrared spectroscopy. The anti-inflammatory activity of Tenoxicam/Meloxicam-loaded AgNPs has been studied using the inhibition of albumin denaturation method. Tenoxicam-loaded AgNPs showed higher % Inhibition, but Meloxicam-loaded AgNPs showed lower % Inhibition. Furthermore, the AgNPs showed excellent antimicrobial activity on both Gram-negative and Gram-positive bacteria. Full article

The article aimed to formulate an MLX binary ethosome hydrogel for topical delivery to escalate MLX solubility, facilitate dermal permeation, avoid systemic adverse events, and compare the permeation flux and efficacy with the classical type. MLX ethosomes were prepared using the hot method according to the Box–Behnken experimental design. The formulation was implemented according to 16 design formulas with four center points. Independent variables were (soya lecithin, ethanol, and propylene glycol concentrations) and dependent variables (vesicle size, dispersity index, encapsulation efficiency, and zeta potential). The design suggested the optimized formula (MLX–Ethos–OF) with the highest desirability to perform the best responses formulated and validated. It demonstrates a 169 nm vesicle size, 0.2 dispersity index, 83.1 EE%, and −42.76 mV good zeta potential. MLX–Ethos–OF shows an amorphous form in PXRD and a high in vitro drug release of >90% over 7 h by diffusion and erosion mechanism. MLX–Ethos–OF hyaluronic acid hydrogel was fabricated and assessed. It shows an elegant physical appearance, shear thinning system rheological behavior, good spreadability, and skin-applicable pH value. The ex vivo permeation profile shows a flux rate of 70.45 μg/cm²/h over 12 h. The in vivo anti-inflammatory effect was 53.2% ± 1.3 over 5 h. compared with a 10.42 flux rate and 43% inflammatory inhibition of the classical ethosomal type. The conclusion is that binary ethosome is highly efficient for MLX local delivery rather than classical type. Full article