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Journal of Animal Science Mar 2022Hot-iron branding uses thermal injury to permanently identify cattle causing painful tissue damage. The primary objective was to examine the physiological and behavioral...
Hot-iron branding uses thermal injury to permanently identify cattle causing painful tissue damage. The primary objective was to examine the physiological and behavioral effects of oral meloxicam (MEL), compared to a control, administered at the time of hot-iron branding in Angus and Hereford steers and heifers. The secondary objectives were to investigate breed and sex effects on pain biomarkers. A total of 70 yearlings, consisting of 35 heifers and 35 steers (Angus, Hereford, or Angus × Hereford), were enrolled in the study. Animals were blocked by sex, randomized across weight, and assigned to receive MEL (1 mg/kg) or a placebo (CON). Biomarkers were assessed for 48 h after branding and included infrared thermography (IRT), mechanical nociceptive threshold (MNT), accelerometry and a visual analog scale (VAS), and serum cortisol and prostaglandin E2 metabolites (PGEM). Wound healing was assessed for 12 wk. Hair samples to quantify cortisol levels were taken prior to and 30 d post-branding. Responses were analyzed using repeated measures with calf nested in treatment as a random effect, and treatment, time, treatment by time interaction, breed, and sex as fixed effects. There was a treatment by time interaction for PGEM (P < 0.01) with MEL having lower values than CON at 6, 24, and 48 h (MEL: 18.34 ± 3.52, 19.61 ± 3.48, and 22.24 ± 3.48 pg/mL, respectively; CON: 32.57 ± 3.58, 37.00 ± 3.52, and 33.07 ± 3.48 pg/mL; P < 0.01). MEL showed less of a difference in maximum IRT values between the branded (2.27 ± 0.29 °C) and control site (3.15 ± 0.29 °C; P < 0.01). MEL took fewer lying bouts at 0-12 h (4.91 bouts ± 0.56) compared with CON (6.87 bouts ± 0.55; P < 0.01). Compared with Hereford calves, Angus calves exhibited greater serum but lower hair cortisol, greater PGEM, more lying bouts, and less healed wound scores at 3, 4, and 5 wk. Compared with heifers, steers exhibited lower PGEM, lower branding site and ocular IRT, higher MNT, and lower plasma meloxicam levels. Steers spent more time lying, took more lying bouts and had greater VAS pain, and more healed wound scores at 5 wk than heifers. Meloxicam administration at branding reduced branding and control site temperature differences and reduced lying bouts for the first 12 h. Breed and sex effects were observed across many biomarkers. Changes from baseline values for IRT, MNT, lying time, step count, VAS pain, and wound scoring all support that branding cattle is painful.
Topics: Animals; Biomarkers; Cattle; Female; Iron; Meloxicam; Pain; Pain Measurement
PubMed: 35137141
DOI: 10.1093/jas/skac038 -
Oxidative Medicine and Cellular... 2020Hepatocellular carcinoma (HCC) is regarded as a leading cause of cancer-related deaths, and its progression is associated with hypoxia and the induction of...
Hepatocellular carcinoma (HCC) is regarded as a leading cause of cancer-related deaths, and its progression is associated with hypoxia and the induction of hypoxia-inducible factor (HIF). Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, induces cell death in various malignancies. However, the underlying mechanism remains to be elucidated in HCC, especially under hypoxic conditions. The alteration of COX-2 and HIF-1 oncogenicity was evaluated in HCC specimens by tissue microarray. Cell viability, angiogenesis assays, and xenografted nude mice were used to evaluate the effects of meloxicam, along with flow cytometry to detect the cell cycle, apoptosis, and mitochondrial membrane potential () of HCC. qRT-PCR, Western blotting, immunofluorescence, immunohistochemistry, luciferase assay, and RNAi were carried out to determine the HIF-1 signaling affected by meloxicam. In this study, we showed that meloxicam exerts antiproliferative and antiangiogenesis efficacy and and causes disruption of mitochondrial membrane potential (), thus leading to caspase-dependent apoptosis under hypoxic environments. Exposure to meloxicam significantly reduced HIF-1 transcriptional activation and expression through sequestering it in the cytoplasm and accelerating degradation via increasing the von Hippel-Lindau tumor suppressor protein (pVHL) in HCC. These data demonstrated that inhibition of HIF-1 by meloxicam could suppress angiogenesis and enhance apoptosis of HCC cells. This discovery highlights that COX-2 specific inhibitors may be a promising therapy in the treatment of HCC.
Topics: Animals; Carcinoma, Hepatocellular; Cyclooxygenase 2 Inhibitors; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Liver Neoplasms; Meloxicam; Mice; Mice, Nude; Middle Aged; Signal Transduction; Transfection
PubMed: 32273947
DOI: 10.1155/2020/7079308 -
Frontiers in Veterinary Science 2020Postpartum dysgalactia syndrome (PPDS) is a major economic problem in modern sow farms. General treatment of PPDS consists of the use of oxytocin to promote milk...
Postpartum dysgalactia syndrome (PPDS) is a major economic problem in modern sow farms. General treatment of PPDS consists of the use of oxytocin to promote milk ejection and non-steroidal anti-inflammatory drugs (NSAIDs) to alleviate inflammatory processes. So far, studies investigated the use of a single administration of NSAIDs after parturition in healthy and non-healthy sows. The current study investigated whether administration of meloxicam or paracetamol in sows prior to parturition improves sow and piglet health as well as performance in a farm with PPDS problems in sows. Sixty sows and 978 piglets from a Belgian farrow-to-finish farm were enrolled. Sows were randomly divided into three groups: a non-treated control group, a meloxicam-treated group and a paracetamol-treated group. Treatment was administered orally for 7 days from gestation day 113 onwards. Performance and health parameters investigated in sows were gestation length, farrowing duration, litter characteristics, colostrum yield and quality (Immunoglobulin G), litter weight gain, weaning-to-estrus interval, pregnancy rate, rectal temperature, acute phase proteins and inflammatory markers serum amyloid A, haptoglobin, interferon γ, interleukin 1β and 6 backfat, constipation and feed refusal. Performance and health parameters in piglets were birthweight, average daily weight gain, colostrum intake and mortality. Paracetamol-treated sows showed a significantly ( = 0.04) lower rectal temperature (mean ± SD: 38.09 ± 0.18°C) than the meloxicam-treated sows (38.24 ± 0.18°C), but not than the control group (38.22 ± 0.18°C). Sows of the paracetamol-treated group had a significantly ( = 0.001) longer gestation length (116.3 ± 0.9 days) than sows of the control group (115.3 ± 0.6 days), but not than meloxicam-treated sows (115.9 ± 0.9 days). No significant differences between the three groups were found for all the other parameters. In conclusion, the prophylactic oral administration of either meloxicam or paracetamol for 7 days starting 2 days prior to farrowing did not show beneficial effects on both health and performance parameters of sows and piglets.
PubMed: 33426024
DOI: 10.3389/fvets.2020.603719 -
Animals : An Open Access Journal From... Sep 2022Field evidence indicates that livestock producers are motivated by access to products that readily deliver pain management during husbandry interventions and, more... (Review)
Review
Field evidence indicates that livestock producers are motivated by access to products that readily deliver pain management during husbandry interventions and, more recently, viral epidermal infectious diseases, including FMD. There has been impressive adoption in Australia of a farmer-applied spray-on topical anaesthetic wound formulation (TAF; Tri-Solfen, Medical Ethics, Australia), initially for managing pain of the breech modification 'mulesing' procedure that reduces susceptibility of sheep to flystrike. Over 120 million lambs have now received pain relief and cattle producers have commenced using the TAF for a range of husbandry procedures. This product has demonstrated efficacy for surgical castration and tail docking of lambs, surgical castration and dehorning of calves, surgical castration of piglets, debridement of lesions of the hoof for lame cattle and, importantly, treatment of clinical FMD lesions, including decubitus ulcerations occurring from prolonged recumbency. Multimodal use of an NSAID for improved pain management is advocated, particularly meloxicam, available by prescription from veterinarians for injection and as an oral formulation (Ilium Buccalgesic, Troy Laboratories, Australia), with current work assessing the potential for prolonged delivery in molasses blocks. Increased use of TAF with NSAIDs significantly reduces pain and suffering in livestock, with enhanced healing of FMD lesions, reduced viral loads from Orf infections in lambs and diminished necessity of 'antibiotic cover', assisting antimicrobial-resistance (AMR) stewardship.
PubMed: 36139319
DOI: 10.3390/ani12182459 -
Pharmaceutics Feb 2024The study focuses on the synthesis and characterization of Meloxicam-halloysite nanotube (HNT) composites as a viable approach to enhance the solubility and dissolution...
The study focuses on the synthesis and characterization of Meloxicam-halloysite nanotube (HNT) composites as a viable approach to enhance the solubility and dissolution rate of meloxicam, a poorly water-soluble drug (BCS class II). Meloxicam is loaded on commercial and modified halloysite (acidic and alkaline etching, or APTES and chitosan functionalization) via a solution method. Several techniques (XRPD, FT-IR, C solid-state NMR, SEM, EDS, TEM, DSC, TGA) are applied to characterize both HNTs and meloxicam-HNT systems. In all the investigated drug-clay hybrids, a high meloxicam loading of about 40 wt% is detected. The halloysite modification processes and the drug loading do not alter the structure and morphology of both meloxicam and halloysite nanotubes, which are in intimate contact in the composites. Weak drug-clay and drug-functionalizing agent interactions occur, involving the meloxicam amidic functional group. All the meloxicam-halloysite composites exhibit enhanced dissolution rates, as compared to meloxicam. The meloxicam-halloysite composite, functionalized with chitosan, showed the best performance both in water and in buffer at pH 7.5. The drug is completely released in 4-5 h in water and in less than 1 h in phosphate buffer. Notably, an equilibrium solubility of 13.7 ± 4.2 mg/L in distilled water at 21 °C is detected, and wettability dramatically increases, compared to the raw meloxicam. These promising results can be explained by the chitosan grafting on the outer surface of halloysite nanotubes, which provides increased specific surface area (100 m/g) disposable for drug adsorption/desorption.
PubMed: 38543233
DOI: 10.3390/pharmaceutics16030338 -
Translational Animal Science Apr 2021The purpose of this study was to investigate the effects of perioperative administration of oral meloxicam prior to and following the application of caustic paste to...
The purpose of this study was to investigate the effects of perioperative administration of oral meloxicam prior to and following the application of caustic paste to disbud neonatal dairy calves. Sixty-one 3-4-d-old Holstein heifer calves were randomly assigned to one of four treatment groups of 15-16 calves. The treatment groups were: 1) M1, caustic paste disbudding and oral meloxicam (45 mg) with a placebo 24 h later; 2) M2, treatment M1 followed by a second 45-mg dose of meloxicam 24 h later instead of placebo; 3) CONTROL, treatment M1 with placebo in place of meloxicam; and 4) SHAM, sham disbudding with placebo in place of meloxicam. Infrared thermography was used to quantify eye and horn bud temperatures. Pressure algometry was used to measure Mechanical nociceptive threshold (MNT) surrounding the horn bud. Average daily gain and body weight (BW) were obtained by weighing each animal throughout the study and calculating the changes over time. Plasma was collected and analyzed for cortisol and substance P concentrations. Substance P and cortisol decreased in all animals over time, regardless of treatment. Mean plasma substance P concentration across all time points was greater ( < 0.05) in the SHAM group than M1 or M2 but not different ( > 0.05) than the CONTROL group. The MNT and ocular temperatures decreased over time across all treatments ( < 0.05). Mean BW increased over time across all treatments ( < 0.05). A significant interaction ( < 0.05) between treatment and sampling time was observed at 12 h following treatment application for both mean horn bud temperature and the ratio between horn bud and ocular temperature. Overall, the results of this study suggest that meloxicam administration at a dose of 45 mg per animal may have limited influence as the primary modulator of pain and inflammatory response in calves that have been disbudded with caustic paste at 3 d of age.
PubMed: 34151196
DOI: 10.1093/tas/txz151 -
Molecules (Basel, Switzerland) Dec 2021The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the...
The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes , , , and as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and and downregulated . They inhibited and and their effect on and depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only and were not upregulated in tumors, nor was in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, and were upregulated, while , and were downregulated in tumors. Tumor and increased along with advancing T and and along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating and interfering with NF-κB signaling.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Caco-2 Cells; Chemokines; Colorectal Neoplasms; Female; HCT116 Cells; Humans; Macrophages; Male; Meloxicam; Piroxicam
PubMed: 34885960
DOI: 10.3390/molecules26237375 -
Nanomaterials (Basel, Switzerland) Mar 2023This study was aimed at the investigation of the supramolecular systems based on cationic surfactants bearing cyclic head groups (imidazolium and pyrrolidinium) and...
OBJECTIVES
This study was aimed at the investigation of the supramolecular systems based on cationic surfactants bearing cyclic head groups (imidazolium and pyrrolidinium) and polyanions (polyacrylic acid (PAA) and human serum albumin (HSA)), and factors governing their structural behavior to create functional nanosystems with controlled properties. Research hypothesis. Mixed PE-surfactant complexes based on oppositely charged species are characterized by multifactor behavior strongly affected by the nature of both components. It was expected that the transition from a single surfactant solution to an admixture with PE might provide synergetic effects on structural characteristics and functional activity. To test this assumption, the concentration thresholds of aggregation, dimensional and charge characteristics, and solubilization capacity of amphiphiles in the presence of PEs have been determined by tensiometry, fluorescence and UV-visible spectroscopy, and dynamic and electrophoretic light scattering.
RESULTS
The formation of mixed surfactant-PAA aggregates with a hydrodynamic diameter of 100-180 nm has been shown. Polyanion additives led to a decrease in the critical micelle concentration of surfactants by two orders of magnitude (from 1 mM to 0.01 mM). A gradual increase in the zeta potential of HAS-surfactant systems from negative to positive value indicates that the electrostatic mechanism contributes to the binding of components. Additionally, 3D and conventional fluorescence spectroscopy showed that imidazolium surfactant had little effect on HSA conformation, and component binding occurs due to hydrogen bonding and Van der Waals interactions through the tryptophan amino acid residue of the protein. Surfactant-polyanion nanostructures improve the solubility of lipophilic medicines such as Warfarin, Amphotericin B, and Meloxicam.
PERSPECTIVES
Surfactant-PE composition demonstrated beneficial solubilization activity and can be recommended for the construction of nanocontainers for hydrophobic drugs, with their efficacy tuned by the variation in surfactant head group and the nature of polyanions.
PubMed: 36985966
DOI: 10.3390/nano13061072 -
Frontiers in Neurology 2021Previous findings have indicated that pain relieving medications such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs) may be neuroprotective after...
Previous findings have indicated that pain relieving medications such as opioids and non-steroidal anti-inflammatory drugs (NSAIDs) may be neuroprotective after traumatic brain injury in rodents, but only limited studies have been performed in a blast-induced traumatic brain injury (bTBI) model. In addition, many pre-clinical TBI studies performed in rodents did not use analgesics due to the possibility of neuroprotection or other changes in cognitive, behavioral, and pathology outcomes. To examine this in a pre-clinical setting, we examined the neurobehavioral changes in rats given a single pre-blast dose of meloxicam, buprenorphine, or no pain relieving medication and exposed to tightly-coupled repeated blasts in an advanced blast simulator and evaluated neurobehavioral functions up to 28 days post-blast. A 16.7% mortality rate was recorded in the rats treated with buprenorphine, which might be attributed to the physiologically depressive side effects of buprenorphine in combination with isoflurane anesthesia and acute brain injury. Rats given buprenorphine, but not meloxicam, took more time to recover from the isoflurane anesthesia given just before blast. We found that treatment with meloxicam protected repeated blast-exposed rats from vestibulomotor dysfunctions up to day 14, but by day 28 the protective effects had receded. Both pain relieving medications seemed to promote short-term memory deficits in blast-exposed animals, whereas vehicle-treated blast-exposed animals showed only a non-significant trend toward worsening short-term memory by day 27. Open field exploratory behavior results showed that blast exposed rats treated with meloxicam engaged in significantly more locomotor activities and possibly a lesser degree of responses thought to reflect anxiety and depressive-like behaviors than any of the other groups. Rats treated with analgesics to alleviate possible pain from the blast ate more than their counterparts that were not treated with analgesics, which supports that both analgesics were effective in alleviating some of the discomfort that these rats potentially experienced post-blast injury. These results suggest that meloxicam and, to a lesser extent buprenorphine alter a variety of neurobehavioral functions in a rat bTBI model and, because of their impact on these neurobehavioral changes, may be less than ideal analgesic agents for pre-clinical studies evaluating these neurobehavioral responses after TBI.
PubMed: 34712199
DOI: 10.3389/fneur.2021.746370 -
Journal of the American Association For... May 2023Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for...
Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits ( = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E₂ (PGE₂ ) and thromboxane (TxB₂) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB₂ and PGE₂ plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE₂ concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.
Topics: Rabbits; Animals; Cats; Dogs; Meloxicam; Cyclooxygenase 2; Dinoprostone; Cat Diseases; Thiazines; Thiazoles; Dog Diseases; Anti-Inflammatory Agents, Non-Steroidal; Protein Isoforms; Pain; Administration, Oral
PubMed: 37045554
DOI: 10.30802/AALAS-JAALAS-22-000109