Post-surgical photobiomodulation therapy improves outcomes following elective gastropexy in dogs.

PURPOSE: To evaluate the effect of post-surgical photobiomodulation therapy in dogs. METHODS: Twenty dogs were selected for elective gastropexy and randomly divided into a control (CG, n = 10) and a PBMT group (PBMTG, n = 10). Pre­medication consisted of medetomidine and butorphanol. Meloxicam was administered before the procedure. Induction was performed with propofol and maintained with sevoflurane. Local blocks with lidocaine were used. Incisional gastropexy was performed in all animals. PBMTG received PBMT immediately after surgery. The need for postoperative rescue analgesia, if the animal had eaten by the evaluation momen, and pain scores were collected using the Glasgow Composite Measure Pain Scale - Short Form (CMPS­SF) at 1, 2, 4, 6, 8, 12, 16, 20, and 24 h post­endotracheal extubation. CMPS­SF scores were compared with the Mann-Whitney Test and proportions of animals that required rescue analgesia and had eaten with a χ2 test. P was set at < 0.05. RESULTS: No rescue analgesia was needed for any animal. Still, significant differences were observed in CMPS-SF scores between CG and PBMTG between 1 and 4 h post-extubation. PBMTG had a significantly higher proportion of animals eating up to the 8 h post-extubation evaluation moment. CONCLUSION: Adding post-surgical photobiomodulation to a standard anesthesia and analgesia protocol reduced CMPS-SF scores and increased the proportion of animals that resumed eating compared to the standard protocol alone.

Oxidative stress in relation to serotonin under general anaesthesia in dogs undergoing ovariectomy.

Abdominal surgery such as ovariectomy is a traumatic event that can cause oxidative stress. The aim of the present study was to evaluate the concentration of serotonin in relation to ovariectomy-induced oxidative stress in dogs undergoing general anesthesia. Thirty-two female dogs, under general anesthesia, received meloxicam before surgery (0.2 mgkg-1 SC) and after surgery (0.1 mgkg-1 OS every 24 h). The physiological, hematological, and biochemical parameters: glycemia, aspartate transaminase (AST), alanine aminotransferase (ALT), total protein, albumin and BUN were evaluated. Oxidative stress was determined by malondialdehyde (MDA) assay, catalase (CAT), superoxide dismutase (SOD), myeloperoxidase (MPO) and butyrylcholinesterase (BuChe) at baseline, 36 and 48 h after the last administration of meloxicam. Serotonin (5-HT) concentration was also evaluated at baseline, 36 and 48 h after the last administration of meloxicam. Responses to surgical stimulus were evaluated. Physiological and hematological parameters they fell within the normal ranges for anesthetized dogs. Glycemia increased, albumin levels decreased after surgery. No rescue analgesia was required. MDA and 5-HT concentrations significantly increased from the baseline at 36 and 48 h after surgery (p < .001). 5-HT levels could be used as an indicator for oxidative stress induced by surgery and it might be employed for objectively quantifying the well-being of the surgical patient.

Comparison of grapiprant and meloxicam for management of postoperative joint pain in dogs: A randomized, double-blinded, prospective clinical trial.

BACKGROUND: Grapiprant is a novel anti-inflammatory drug approved for the treatment of pain associated with osteoarthritis in dogs. OBJECTIVE: Compare the efficacy of grapiprant vs meloxicam for the management of postoperative joint pain in dogs. ANIMALS: Forty-eight dogs presented with cranial cruciate ligament disease and treated by tibial plateau leveling osteotomy (TPLO) between May 2020 and May 2022. METHODS: In this randomized, double blinded, prospective clinical trial, client-owned dogs with naturally occurring unilateral cruciate ligament rupture were enrolled on the day of surgery. The day after surgery, all animals received a subcutaneous injection of 0.2 mg/kg of meloxicam and were randomly assigned to receive either oral grapiprant (2 mg/kg) or meloxicam (0.1 mg/kg), once a day for 14 days, in a blinded manner. The primary endpoint of the study was the pain severity (PSS) and interference (PIS) scores, assessed by the Canine Brief Pain Inventory (CBPI) at day 3, 7, 10 and 15 after the surgery. RESULTS: Three days after surgery, grapiprant treated dogs had lower PSS compared to meloxicam treated dogs with a mean ± SD of 2.76 ± 0.18 vs 3.25 ± 0.23, respectively (difference of -0.49 [95% CI -0.94 to -0.04], P = .032). Pain Interference Score was also lower in grapiprant group at day 3 (4.11 ± 0.18 vs 4.69 ± 0.16 in meloxicam group [difference of -0.58 {95% CI -1.03 to -0.13}, P = .013]) and at day 10 (2.23 ± 0.13 vs 2.72 ± 0.28 [difference of -0.49 {95% CI -0.92 to -0.01}, P = .049]). CONCLUSIONS AND CLINICAL IMPORTANCE: Our study supports the use of grapiprant as an alternative analgesic to meloxicam for management of postoperative joint pain in dogs.

Injectable polyamide-amine dendrimer-crosslinked meloxicam-containing poly-γ-glutamic acid hydrogel for prevention of postoperative tissue adhesion through inhibiting inflammatory responses and balancing the fibrinolytic system.

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.

Evaluation of Efficacy of 2 Extended-release Bupivacaine Products in a Porcine Model of Incisional Pain.

Extended-release (ER) local anesthetics are often incorporated in multi-modal analgesia or as an alternative when the effect of systemic analgesics may confound research. In this study, we compared the analgesic efficacy of 2 ER bupivacaine anesthetics with different ER mechanisms, a slow-release bupivacaine-meloxicam polymer (BMP) and a sucrose acetate isobutyrate bupivacaine (SABER-B) system. We used a full-thickness unilateral skin incision porcine model to evaluate the efficacy of these 2 ER bupivacaine analgesics. Eighteen male swine were randomized into 3 groups: control (saline; n = 6), bupivacaine:meloxicam (10 mg/kg, 0.3 mg/kg; n = 6), and SABER-B (10 mg/kg; n = 6). After surgery, pigs were assessed for changes in body weight, salivary cortisol level, and response to von Frey testing at 1, 3, 6, 24, 48, 72, 96, 120, and 168 h. Body weight and salivary cortisol levels were not significantly different between groups. Based on the von Frey testing, the pigs that received analgesics showed a significantly higher withdrawal threshold of nociceptive stimulus than those that received saline at 1, 3, 6, and 24 h after the surgery. At 48 h after surgery, the SABER-B group had a significantly higher withdrawal threshold than the saline group. The withdrawal threshold was not significantly different from the baseline measurement on intact skin at 3 and 6 h after surgery in the BMP group or 1 and 3 h for the SABERB group. The analgesic effects of BMP were greatest at 3 and 6 h after surgery and that of SABER-B as 1 and 3 h SABER-B provided an earlier onset of analgesia and longer analgesia duration than did BMP. This study demonstrates that ER bupivacaine can provide pigs with 24 to 48 h of analgesia for incisional pain.

Effects of meloxicam on the welfare of Holstein calves from 6 weeks to 6 months old undergoing amputation dehorning.

Amputation dehorning (AD) is a common practice performed on calves, causing harmful effects such as pain, distress, anxiety, and fear. These effects extend to behavioral, physiological, and hematological responses, prompting serious ethical concerns regarding animal welfare, even when performed with local anesthesia. Meloxicam, a nonsteroidal anti-inflammatory drug, has been widely used to mitigate the side effects of dehorning and disbudding in calves. However, there is a notable gap in research regarding the effects of meloxicam on calves aged 6 wk to 6 mo undergoing AD procedures. This study was designed to assess the effectiveness of co-administering meloxicam with lidocaine, a cornual nerve anesthetic, in alleviating the adverse effects caused by the AD procedure in calves within this age range, compared with the use of lidocaine alone. Thirty Holstein calves were enrolled and randomly divided into 2 groups. The first group received a subcutaneous injection of 5 mL of lidocaine in the horn area and a subcutaneous injection of 0.9% saline at a dose of 0.025 mL/kg in the neck, administered 10 min before the AD procedure. The second group received a combination of lidocaine and meloxicam: a subcutaneous injection of 5 mL of lidocaine in the horn area and a subcutaneous injection of 20 mg/mL meloxicam at a dose of 0.025 mL/kg in the neck, also administered 10 min before the AD procedure. To avoid subjective bias, the researchers were blinded to the treatment groups. Pain-related behaviors, including tail flicking, head shaking, ear flicking, head rubbing, head crossing bar, and kicking, were observed, and physiological parameters, including heart rate, rectal temperature, respiration rate, mechanical nociceptive threshold (MNT), daily active steps, and food intake were monitored. Hematological conditions were determined using enzyme-linked immunosorbent assays and routine blood tests. The data were processed using a generalized linear mixed model. The outcomes demonstrated that the AD procedure increased the frequencies of ear flicking and resulted in rises in the respiration rate, heart rate, rectal temperature, and daily active steps. It also led to decreases in total food intake, forage intake, hay intake, MNT, and increased concentrations of prostaglandin E2 (PgE2), IL-1ß, tumor necrosis factor-α (TNF-α), nitric oxide (NO), and malondialdehyde, as well as glutathione peroxidase activity. However, calves that received meloxicam treatment showed significant improvements in response to the AD procedure, including lower respiration rates, heart rates, and rectal temperatures; higher MNT; and lower intermediate cell ratio. They also had higher red blood counts, hemoglobin levels, hematocrit values; larger mean platelet volumes; and lower concentrations of PgE2, IL-1ß, TNF-α, and NO. These results suggest that co-administration of lidocaine and meloxicam may aid in mitigating the adverse effects induced by the AD procedure on these calves, thereby supporting the use of meloxicam in conjunction with a local anesthetic in AD procedures for calves aged 6 wk to 6 mo.

Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated Cyclooxygenase-2.

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

Effect of meloxicam or robenacoxib administration timing on renal function and postoperative analgesia in cats undergoing ovariohysterectomy: A randomized, blinded, controlled clinical trial.

We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo-oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB2) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post-surgery in admission groups compared to induction groups (p = .01). Serum TxB2 was lower with meloxicam than robenacoxib (p = .001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p = .033). In conclusion, the renin-angiotensin system was activated during anaesthesia despite cyclo-oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury.

Avaliação clínica e laboratorial de cão com osteoartrose tratado com formulação de meloxicam em spray oral. Relato de caso / Clinical and laboratory evaluation of a dog with osteoarthritis treated with oral spray meloxicam formulation. Case report / Avaliación clínica y de laboratorio de un perro con osteoartrosis tratado con formulación de meloxicam en spray oral. Reporte de caso

O presente relato de caso avaliou o meloxicam solução oral spray com o sistema de absorção transmucosa no tratamento de um cão tripedal acometido por osteoartrose em joelho e coluna. Além da avaliação ortopédica, foram realizados questionários de avaliação de dor, baropodometria, termografia e monitoramento de atividade.

The present case report evaluated the meloxicam oral solution spray with the transmucosal absorption system in the treatment of a three-legged dog affected by osteoarthritis in the knee and spine. In addition to the orthopedic evaluation, assessments of pain, baropodometry, thermography, and activity monitoring were carried out.

El presente informe de caso evaluó el spray de solución oral de meloxicam con el sistema de absorción transmucosa en el tratamiento de un perro de tres patas afectado por osteoartritis en la rodilla y columna. Además de la evaluación ortopédica, se realizaron cuestionarios de evaluación del dolor, baropodometría, termografía y monitoreo de la actividad.

Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis.

Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone Metridium senile is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain. We used a model of monosodium iodoacetate (MIA)-induced osteoarthritis to evaluate the anti-inflammatory properties of Ms 9a-1 in comparison with APHC3 (a polypeptide modulator of TRPV1 channel) and non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ibuprofen. Administration of Ms 9a-1 (0.1 mg/kg, subcutaneously) significantly reversed joint swelling, disability, thermal and mechanical hypersensitivity, and grip strength impairment. The effect of Ms 9a-1 was equal to or better than that of reference drugs. Post-treatment histological analysis revealed that long-term administration of Ms9a-1 could reduce inflammatory changes in joints and prevent the progression of cartilage and bone destruction at the same level as meloxicam. Peptide Ms 9a-1 showed significant analgesic and anti-inflammatory effects in the model of MIA-induced OA, and therefore positive allosteric modulators could be considered for the alleviation of OA symptoms.

Seasonal distribution of repeat breeder cows and evaluation of modified protocols for post AI treatment during summer.

An important problem of dairy industry worldwide is repeat breeder cows (RB). In this study, one farm in Northern Greece was chosen on the basis of subfertility. First, the available reproductive data of the previous year were evaluated; then, the farmer was advised to use the most common treatments for RB [GnRH with the third artificial insemination (AI+GnRH) or ovsynch in cows found empty after the second AI], and their efficacy was monitored throughout the year. Cows (n = 147) 2.5 to 4.5 years old were included. During the next year, post AI treatments (meta-ovsynch and meta-AI) were used during summer; GnRH (100 µg of gonadorelin) alone or in combination with meloxicam (0.5 mg/kg BW) was used during summer. Meta-ovsynch protocols were administered to 29 cows detected as non-pregnant after 3 AIs; cows were divided randomly into 3 meta-ovsynch (OS) groups: group OS (controls, n = 10), standard ovsynch protocol; group OS+GnRH (n = 10), OS plus GnRH 10 days after AI; and group OS+GnRH+NSAID (n = 9), OS plus GnRH 10 days after AI plus meloxicam 15 days after AI. Meta-AI protocols were tested in 27 RB cows; cows were divided randomly into 3 AI groups: GnRH (n = 9), 1 dose of GnRH with AI; GnRH-GnRH (n = 9), two doses of GnRH, one with AI and another 10 days later; and GnRH-GnRH-NSAID (n = 9), two doses of GnRH as in GnRH-GnRH group and one dose of meloxicam 15 days after AI. Pregnancy diagnosis was performed by ultrasound 38 days after AI. During the 1st year of evaluation, 53.79% of cows had received ≥ 3 AIs; the highest percentage (38.48%) of RB cows was recorded during autumn. After treatment for RB, the lowest (P < 0.05) pregnancy rate (PR) was recorded in August (18.18%) compared to January (75.0%), May (53.33%), and December (50.0%, P < 0.1). The efficacy of ovsynch during winter was significantly higher compared to all the other seasons. The percentage of cows with increased estrous cycle duration (24-37 days) after RB treatment and AI was the highest (P < 0.05) in spring and summer after AI+GnRH and the lowest (P < 0.05) during winter after ovsynch. Concerning the post AI treatments during summer, significantly higher pregnancy rate was recorded in the OS+GnRH+NSAID group (55.55%) compared to OS+GnRH (10%) and OS (10%) groups. Pregnancy rates did not differ among AI groups. It seems that OS+GnRH+NSAID is a promising protocol for RB cows during summer although further research is needed to support the present results.

Comparison of Systemic Extended-release Buprenorphine and Local Extended-release Bupivacaine-Meloxicam as Analgesics for Laparotomy in Mice.

Extended-release (ER) local anesthetics can be used in multi-modal analgesia or in situations in which systemic analgesics may alter animal physiology and thus introduce interpretational confounds. In this study, we compared the analgesic efficacy of an ER buprenorphine formulation with that of a synergistic combination of ER bupivacaine and meloxicam. Female and male CD1 mice were randomly assigned to receive subcutaneous buprenorphine (3.25mg/kg) preemptively, subcutaneous infiltration of bupivacaine???meloxicam (0.03mL at incision closure (bupivacaine, 35mg/kg; meloxicam, 1mg/kg), or saline (10mL/kg SC) after induction of anesthesia. After laparotomy, mice were assessed for changes in daily body weight, rearing frequency, nest consolidation scores, time-to-integrate-nest test (TINT), and response to von Frey testing at 4, 8, 24, 48, and 72h after surgery. Daily weight, nest consolidation scores and rearing frequency were not significantly different among the 3 groups. TINT had fallen significantly response at 24 and 48h after injection in the ER buprenorphine group as compared with the saline and ER bupivacaine-meloxicam groups. Nociceptive thresholds, as assessed with von Frey testing, differed between saline controls and both analgesic groups at 4, 8, 24, 48, and 72 h after surgery. None of the mice in the bupivacaine???meloxicam group developed signs of neurotoxicity, a potential side effect of high-dose local anesthetics. This study demonstrates that local ER bupivacaine???meloxicam may be a useful alternative to systemic, ER buprenorphine for the relief of pain after laparotomy in mice.

Toxicological effects of meloxicam on physiological and antioxidant status of common carp (Cyprinus carpio).

BACKGROUND: Fish in aquatic environments are end consumers of the food chain and are widely used for the evolution effects of environmental pollution and their interactions in aquatic ecosystem. OBJECTIVE: In the present study, common carp (Cyprinus carpio) fingerlings were selected to assess the potential risk and aquatic toxicity of meloxicam as a non-steroidal anti-inflammatory and a commonly used pharmaceutical drug. METHODS: In order to evaluate meloxicam toxicological effect on haematological, antioxidant status, enzymological and histological parameters, based on its LC50 24 h acute toxicity (10.05 mg L-1 ), fish fingerlings were exposed to four doses of meloxicam including; 0 (control), 0.1 (low), 1 (medium) and 2 mg L-1 (high) under static bioassay method for 28 days. RESULTS: The results showed that sublethal doses of meloxicam significantly decreased alanine aminotransferase, alkaline phosphatase, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels in comparison with the control group after 28 days (p < 0.05). However, red blood cell, haematocrit, haemoglobin and malondialdehyde values in fish exposed to meloxicam significantly increased alongside its concentration (p < 0.05) more than the control group after 28 days. SOD, CAT and GPX mRNA expression levels in gill, liver, kidney and brain organ of fish under meloxicam treatment were significantly down-regulated compared to the control group (p < 0.05). Histopathological assessment showed the increased vacuolation in hepatocytes in liver of fish exposure to medium and high doses of meloxicam. CONCLUSION: In conclusion, meloxicam induces oxidative stress in common carp which results a disruption of physiological and health status of this species based on our current findings.

A Clinical Trial on the Welfare Effects of Administering Meloxicam to 10 to 21 Day Dairy Calves Following Caustic Paste Disbudding.

Caustic paste disbudding (CPD) is widely utilized for calves, which has been known to result in adverse effects on the calves and ethical concerns related to animal welfare, despite the use of local anesthetics. The administration of meloxicam has been demonstrated to provide benefits in alleviating pain and inflammation in juvenile calves under 9 d old and subjected to CPD. Nonetheless, there is a scarcity of literature documenting the beneficial impact of meloxicam in alleviating pain in calves aged over 9 d that have undergone CPD. Therefore, the objective of this clinical trial was to evaluate the efficacy of administering meloxicam and lidocaine for cornual nerve block together in mitigating the deleterious effects of CPD, as opposed to using lidocaine alone in calves older than 9 d. Thirty Holstein calves, aged between 10 and 21 d, were enrolled and randomly assigned to 1 of 2 treatments: lidocaine alone (Placebo), lidocaine and normal saline treatment before CPD, and lidocaine plus meloxicam, lidocaine and 0.5 mg/kg of meloxicam treatment prior to CPD. The researchers were blind to the treatment of calves to control the subjective error. The occurrences of actions associated with pain, which included head shaking, head rubbing, ear flicking, tail flicking, kicking, and head passing through the fence, were recorded. Physiological performance, including the respiration rate, heart rate, rectal temperature, mechanical nociceptive threshold (MNT), food intake, and daily activity level, was monitored. Hematological conditions were ascertained through the use of routine blood tests and enzyme-linked immunosorbent assay. The generalized linear mixed model was employed to analyze the data. The research findings revealed that applying the CPD procedure significantly elevated the frequencies of tail flicking, head shaking, and kicking, resulted in increases in respiratory rate, heart rate, daily active steps, and food intake and a decrease in MNT, and led to alterations in hematological markers, including platelet counts, mean platelet volume, prostaglandin E2, constitutive nitric oxide synthase, and hydroxyl radical. Considerable benefits, such as lower heart rates, higher food intake, and MNTs, as well as lower levels of white blood cell counts, lymphocyte counts, hemoglobin, mean platelet volume, prostaglandin E2, tumor necrosis factor-α, constitutive nitric oxide synthase, malondialdehyde, and hydroxyl radical, were observed in the calves that received meloxicam treatment in response to CPD. The findings of the study indicate that the co-administration of lidocaine and meloxicam provides obvious benefits in mitigating pain, inflammation, and oxidative stress in calves aged over 9 d and undergoing CPD. This endorses the use of meloxicam during the disbudding and dehorning procedures of calves.

Caustic paste disbudding (CPD) is a widely used practice in the cattle industry, yet there is a shortage of literature on the effects of meloxicam on calves aged 10 to 21 d who have undergone this procedure. In this clinical trial, we conducted a comparative analysis of the pain-related behavioral, physiological, and hematological performance of calves that were administered with either lidocaine plus normal saline (n = 15) or lidocaine plus meloxicam (n = 15) before undergoing disbudding operations. The findings demonstrated that the CPD operation had a significant impact on the pain-related behavior, physiological functions, and serum anti-inflammatory and antioxidative markers of the calves. On the other hand, the administration of meloxicam had notable advantages for the calves by enhancing the physiological and hematological parameters.

Preemptive QP001, a fast-acting meloxicam formulation, provides analgesia and reduces opioid consumption following abdominal surgery: a randomized controlled trial.

BACKGROUND: QP001, a novel meloxicam formulation, has been developed to manage moderate to severe postoperative pain. This study aimed to evaluate the efficacy and safety of QP001 injections for moderate to severe pain following abdominal surgery. METHOD: This prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial enlisted patients experiencing moderate to severe pain following abdominal surgery. These patients were randomized to receive either QP001 injections (30 mg or 60 mg) or a placebo pre-surgery. The primary efficacy endpoint was the total morphine consumption within 24 h after the first administration. RESULTS: A total of 108 patients were enrolled, and 106 patients completed the study. The total morphine consumption in the QP001 30 mg group and 60 mg group, versus placebo group, were significantly lower over the following 24 h (5.11[5.46] vs 8.86[7.67], P = 0.011; 3.11[3.08] vs 8.86[7.67], P < 0.001), respectively. The total morphine consumption in the QP001 30 mg and 60 mg groups, versus placebo group, was also significantly decreased over the following 48 h, including the 24-48 h period (P ≤ 0.001). The QP001 30 mg and 60 mg groups, versus placebo, showed a significant decrease in the area under the curve for pain intensity-time as well as a significant decrease in the effective pressing times of the analgesic pump over the 24 h and 48 h periods (P < 0.05). The QP001 groups, versus placebo, show no significant different in Adverse Events or Adverse Drug Reactions (P > 0.05). CONCLUSION: Preoperative/preemptive QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain following abdominal surgery, while maintaining a favorable safety profile.

A comparative study of femtosecond pulsed laser ablation of meloxicam in distilled water and in air.

The increasing prevalence of water insoluble or poorly soluble drugs calls for the development of new formulation methods. Common approaches include the reduction of particle size and degree of crystallinity. Pulsed laser ablation is a clean technique for producing sub-micrometre sized drug particles and has the potential to induce amorphization. We studied the effect of femtosecond pulsed laser ablation (ELI ALPS THz pump laser system: λc = 781 nm, τ = 135 fs) on meloxicam in distilled water and in air. The ablated particles were characterized chemically, morphologically and in terms of crystallinity. We demonstrated that femtosecond laser ablation can induce partial amorphization of the particles in addition to a reduction in particle size. In the case of femtosecond pulsed laser ablation in air, the formation of pure meloxicam spheres showed that this technique can produce amorphous meloxicam without the use of excipients, which is a unique result. We also aimed to describe the ablation processes in both investigated media.

Randomised, prospective, blinded, clinical trial of opioid-free injectable anaesthesia with or without multimodal analgesia in kittens undergoing ovariohysterectomy.

OBJECTIVES: This study compared an opioid-free injectable anaesthetic protocol with or without multimodal analgesia in kittens undergoing ovariohysterectomy. METHODS: In this prospective, randomised, blinded, clinical trial, 29 healthy kittens (mean ± SD weight 1.55 ± 0.46 kg; aged 10 weeks to 6 months) were included. Anaesthesia was performed with an intramuscular injection of ketamine (4 mg/kg), dexmedetomidine (40 µg/kg) and midazolam (0.25 mg/kg). In the multimodal group (MMG), cats (n = 14) received meloxicam (0.1 mg/kg SC) and intraperitoneal bupivacaine 0.25% (2 mg/kg), whereas the same volume of saline was administered in the control group (CG; n = 15). Atipamezole (0.4 mg/kg IM) was given 15 mins after ovariohysterectomy. Postoperative pain was assessed using the UNESP-Botucatu multidimensional feline pain assessment scale - short form. Rescue analgesia (buprenorphine 0.02 mg/kg IM in MMG/CG and meloxicam 0.1 mg/kg SC in CG) was administered if pain scores were ⩾4/12. Soft food intake (after 2 and 60 mins) was evaluated at specific time points postoperatively. Statistical analyses were performed with linear models and post-hoc pairwise comparison with Benjamini-Hochberg corrections (P <0.05). RESULTS: The prevalence of rescue analgesia was higher in the CG (n = 15/15) than the MMG (n = 1/14; P <0.001). Pain scores at 1 h, 2 h and 4 h postoperatively were higher in the CG (4.1 ± 2.8, 4.8 ± 3.0 and 5.3 ± 1.2, respectively) than in the MMG (1.6 ± 1.0, 1.1 ± 1.0 and 0.9 ± 0.8, respectively; P <0.001). Food intake (%) at 1 h postoperatively was higher in the MMG after 2 and 60 mins (10.4 ± 9 and 71.9 ± 29, respectively) than in the CG (1.4 ± 2 and 13.9 ± 7, respectively; P <0.001). CONCLUSIONS AND RELEVANCE: This opioid-free protocol using multimodal analgesia produced adequate postoperative pain relief, while almost eliminating the need for rescue analgesia in kittens undergoing ovariohysterectomy. Pain decreased food intake.

Manipulation and Processing of Spectral Signals for the Assay of the Newly Authorized Mixture of Bupivacaine/Meloxicam Using Fully Green Solvents and a Comparative Green Evaluation Supporting the Greenness and Sustainability of the Developed Smart Spectrophotometric Methods.

BACKGROUND: The bupivacaine (BVC)/meloxicam (MLX) combination is the first extended-release dual-acting local anesthetic (DALA) that provides 72 h of postoperative pain relief. It reduces opioid use after surgery and manages pain better than BVC alone over 72 h, and overcomes surgical site inflammation with a new synergistic mode of action that combines BVC with a low dosage of MLX. OBJECTIVE: In today's pharmaceutical research, we take great care to only use non-toxic solvents that pose no threat to either humans or the environment. This work determines BVC and MLX simultaneously, utilizing water and 0.1 M HCl in water as solvents. Moreover, the eco-friendliness of the specified solvents and the whole method development steps was evaluated based on how user-friendly they were using four standard methodologies. METHODS: The developed spectrophotometric methods depended on either zero-order, derivative, or ratio spectra that only required simple mathematical handling. The current techniques include dual wavelength (DW), Fourier self-deconvolution (FSD), first derivative (D1), ratio difference (RD), and first ratio derivative (DD1). RESULTS: Linearity was confirmed over a concentration range of 50-700 µg/mL for BVC and 1-10 µg/mL for MLX. For BVC and MLX, the LOQs were 26.85-41.33 µg/mL and 0.21-0.95 µg/mL, while the LODs were 8.86-13.64 µg/mL and 0.06-0.31 µg/mL, respectively. For the full validation of the proposed methods, ICH (international conference on harmonization) criteria were followed. CONCLUSION: Current methods have the advantage of sticking to the basis of zero-order, derivative, or ratio spectra and needing just the barest minimum of data processing: no complex software, lengthy stages, or transformations are needed. HIGHLIGHTS: No spectrophotometric methods have been published for the simultaneous analysis of BVC and MLX. As a result, the newly developed spectrophotometric approaches have great relevance and originality in the field of pharmaceutical analysis.

Analgesic efficacy of an ultrasound-guided transversus abdominis plane block with bupivacaine in cats: a randomised, prospective, masked, placebo-controlled clinical trial.

OBJECTIVES: This randomised, prospective, masked clinical trial evaluated the postoperative analgesic efficacy of an ultrasound-guided transversus abdominis plane block (TAPB) with bupivacaine in cats undergoing ovariohysterectomy. METHODS: Thirty-two healthy adult female cats undergoing elective ovariohysterectomy were randomised to undergo TAPB with bupivacaine (treatment group [TG], n = 16) vs placebo (control group [CG], n = 16) in addition to preoperative analgesia with buprenorphine (0.02 mg/kg IM). All patients received a general anaesthetic and, before surgical incision, a bilateral two-point (subcostal and lateral-longitudinal) TAPB was performed using 1 ml/kg bupivacaine 0.25% (0.25 ml/kg/point) or saline. Each cat was assessed by a blinded investigator before premedication (0 h) and at 1, 2, 3, 4, 8, 10 and 24 h postoperatively using the UNESP-Botucatu Feline Pain Scale - short form. Buprenorphine (0.02 mg/kg IV) and meloxicam (0.2 mg/kg SC) were administered when pain scores were ⩾4/12. Ten hours postoperatively, meloxicam was administered to cats that did not receive rescue analgesia. Statistical analysis included Student's t-tests, Wilcoxon tests and χ2 tests, and a linear mixed model with Bonferroni corrections (P <0.05). RESULTS: Of the 32 cats enrolled, three in the CG were excluded from the analysis. The prevalence of rescue analgesia was significantly higher in the CG (n = 13/13) than in the TG (n = 3/16; P <0.001). Only one cat in the CG required rescue analgesia twice. Pain scores were significantly higher in the CG compared with the TG at 2, 4 and 8 h postoperatively. Mean ± SD pain scores were significantly higher in the CG, but not in the TG, at 2 (2.1 ± 1.9), 3 (1.9 ± 1.6), 4 (3.0 ± 1.4) and 8 h postoperatively (4.7 ± 0.6) than at 0 h (0.1 ± 0.3). CONCLUSIONS AND RELEVANCE: A bilateral ultrasound-guided two-point TAPB with bupivacaine in combination with systemic buprenorphine provided superior postoperative analgesia than buprenorphine alone in cats undergoing ovariohysterectomy.

Meloxicam inhibited oxidative stress and inflammatory response of LPS-stimulated bovine endometrial epithelial cells through Nrf2 and NF-κB pathways.

Meloxicam is a selective cyclooxygenase-2 inhibitor and has been widely used in combination with antibiotics to alleviate uterine inflammation and provide analgesia in postpartum cows. Studies have shown that meloxicam has antioxidant and anti-inflammatory effects. However, the link between meloxicam and uterine inflammation and oxidative stress in dairy cows has not been studied. The purpose of this study was to research the effects of meloxicam (0.5 or 5 µM) on oxidative stress and inflammatory response of primary bovine endometrial epithelial cells (BEEC) stimulated by Escherichia coli lipopolysaccharide (1 µg/mL LPS). As a result, LPS stimulated the production of oxidative stress markers and the expression of inflammatory factors, accompanied by a decrease in the activity and the gene transcription of antioxidant enzymes. Co-treatment of meloxicam and LPS reduced the content of oxidative stress markers and the mRNA levels of the pro-inflammatory genes, and improved antioxidant enzyme activities and the corresponding gene expression as compared with the cells treated with LPS alone. Meloxicam attenuated the inhibitory effect of the Nrf2 pathway and the phosphorylation levels of p65 and IκBα caused by LPS. In conclusion, meloxicam alone had no effect on BEEC, but prevented oxidative stress and inflammatory response in LPS-stimulated BEEC.