mobic and Body-Weight

The pro-inflammatory cyclooxygenase (COX)-derived prostaglandins and the anti-inflammatory cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of renal injury. The current study examined whether COX inhibition augments the reno-protective effects of increased EETs levels via inhibiting EETs degradation by soluble epoxide hydrolase (sEH) in diabetic rats. Streptozotocin (50mg/kg, i.v) was used to induce diabetes in male Sprague Dawley rats. Rats were then divided into 5 groups (n=6-8); control non diabetic, diabetic, diabetic treated with the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), diabetic treated with the COX inhibitor meloxicam and diabetic treated with meloxicam plus t-AUCB for 2 months. Glomerular albumin permeability and urinary albumin and nephrin excretion levels were significantly elevated in diabetic rats together with decreased glomerular α3 integrin and nephrin expression levels. Inhibition of sEH reduced glomerular albumin permeability, albumin and nephrin excretion levels and restored the decrease in glomerular α3 integrin and nephrin expression in diabetic rats. Meloxicam failed to reduce renal injury or even to synergize the reno-protective effects of sEH inhibition in diabetic rats. Furthermore, inhibition of sEH reduced the elevation in renal collagen deposition and urinary MCP-1 excretion levels together with a reduction in the number of renal TUNEL positive cells in diabetic vs. control rats (P<0.05). Meloxicam did not reduce renal inflammation or apoptosis in diabetic rats or even exacerbate the anti-inflammatory and anti-apoptotic effects of sEH inhibition. Renal 20-hydroxyeicosatetranoic acid (20-HETE) levels were elevated in diabetic rats and meloxicam further exacerbated this elevation. In conclusion, our study suggests that inhibition of COX failed to provide renal protection or to augment the reno-protective effects of sEH inhibition in diabetic rats, at least in part, via increased inflammatory 20-HETE levels.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Cytochrome P-450 Enzyme System; Cytoprotection; Diabetes Mellitus, Experimental; Drug Synergism; Enzyme Inhibitors; Epoxide Hydrolases; Gene Expression Regulation, Enzymologic; Hydroxyeicosatetraenoic Acids; Kidney; Male; Meloxicam; Rats; Rats, Sprague-Dawley; Solubility; Thiazines; Thiazoles

Objectives of this study were to determine effects of meloxicam administered in 2 forms on IgG uptake, growth, and health of preweaned calves. Sixteen Holstein bulls and 14 heifers with a body weight (BW) of 44.3 ± 5.24 kg were blocked by birth date in a randomized complete block design. Calves were removed from the dam before suckling, weighed, and randomly assigned to 1 of 3 treatments: (1) colostrum replacer (CR) at 0 h with no meloxicam (control; CON), (2) 1 mg/kg of BW of meloxicam in pill form before CR (PL), or (3) 1 mg/kg of BW of meloxicam mixed in solution with CR (SL). Calves were fed 675 g of dry matter of CR, providing a volume of 3 L and 180 g of IgG. Blood samples were collected at 0 h to analyze initial IgG and ketone concentrations, and at 6, 12, 18, and 24 h to analyze IgG uptake. At 24 h, calves were fed 432 g of dry matter of 24% crude protein milk replacer (MR) split in 2 feedings, and free choice starter and water until 42 d. Weekly blood samples were analyzed for glucose, plasma urea nitrogen, and ketone concentrations. Time of consumption of MR, BW, length, hip and withers height, and heart girth were recorded weekly. All calves achieved adequate transfer of immunity. Meloxicam did not affect apparent efficiency of absorption, serum total protein, or IgG uptake at 6, 18, and 24 h; however, meloxicam-treated calves had lesser IgG concentrations at 12 h (24.40 and 22.59 g/L for PL and SL, respectively) compared with CON (28.47 g/L). Meloxicam treatment did not affect BW. Calves that received PL tended to gain length at a faster rate (0.24 cm/d) than those that received SL (0.19 cm/d). Meloxicam treatment did not affect MR intake, time of consumption of MR, total dry matter intake, or feed efficiency. Meloxicam-treated calves tended to consume more starter (560.4 and 515.4 g/d for PL and SL, respectively) than those that received CON (452.6 g/d). Ketone levels tended to be greater in meloxicam-treated calves (0.15 and 0.17 mmol/L for PL and SL, respectively), suggesting improved rumen development compared with those that received CON (0.12 mmol/L). Meloxicam treatment did not affect plasma urea nitrogen . Glucose concentrations of calves that received PL (73.2 mg/dL) were less than those that received SL (83.3 mg/dL). Results of this study suggest that meloxicam given at 0 h offers positive effects on starter intake, and possibly rumen development, of preweaned dairy calves. Treatment PL, as compared with SL, offered positive results

Topics: Animals; Animals, Newborn; Body Weight; Cattle; Colostrum; Diet; Eating; Female; Immunoglobulin G; Intestine, Small; Ketones; Male; Meloxicam; Milk Substitutes; Pregnancy; Rumen; Weaning

Most dairy cows experience a transient decrease in feed intake in the 1 to 2 wk before calving, which has been associated with systemic inflammation (SI), indicated by increased blood haptoglobin (Hp) concentration. We aimed to characterize the association between prepartum decrease in feed intake and the onset of SI and, if present, the ability of meloxicam (MEL), a non-steroidal anti-inflammatory drug, to mitigate SI. Holstein cows (n = 45) were assigned to control (n = 13), feed restriction (FR) untreated (FR-U; n = 15), and FR treated with MEL (FR-T; n = 17) groups. Daily feed intake was measured from -22 d from expected parturition until 35 d postpartum. Control cows were fed ad libitum, whereas FR-U and FR-T cows were reduced to 60% of their average intake for 4 consecutive days (-15 to -12 d from expected calving). The FR-T cows received MEL (0.5 mg/kg of body weight) once daily for 4 consecutive days (-13 to -10 d from expected calving). Blood samples were collected -22, -15, -14, -13, -12, -10, -7, -5, -3, 0, 1, 3, 5, 7, 15, 22, and 35 d relative to calving to measure serum concentrations of total calcium, total protein, albumin, globulin, cholesterol, urea, glucose, gamma-glutamyl transferase, aspartate aminotransferase, glutamate dehydrogenase, β-hydroxybutyrate, nonesterified fatty acids, Hp, and insulin-like growth factor-1. Serum concentrations of lipopolysaccharide-binding protein were measured -22, -15, -14, -13, -12, and -10 d from expected calving. Simplified glucose tolerance tests were performed on -15, -12, -5, 1, and 5 d relative to calving. Mixed linear regression models were used to assess the effects of FR and MEL on each metabolite. The interaction between treatment group and blood sampling day was forced into each model. All models accounted for body condition score, parity, and the cow as a random effect. Nonesterified fatty acids concentrations in both the FR-U and FR-T groups significantly increased from the second until the last day of FR. Feed restriction increased urea concentrations compared with the control group on -14 d but decreased urea concentrations on -10 d from expected calving. Control cows had greater β-hydroxybutyrate concentrations compared with FR cows on 15, 21, and 35 d postpartum. For all other metabolites, no differences were found. This model of FR produced substantial fat mobilization but based on serum Hp and lipopolysaccharide-binding protein concentrations did not generate measurable SI; therefore,

Topics: 3-Hydroxybutyric Acid; Animal Feed; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cattle; Cattle Diseases; Diet; Fatty Acids, Nonesterified; Female; Inflammation; Insulin; Lactation; Meloxicam; Milk; Parity; Parturition; Postpartum Period; Pregnancy; Pregnancy Complications

Managing postoperative pain in rodents is an important part of any animal care and use program, and identifying an optimal analgesic plan for a surgical procedure is critical to providing for animal welfare. Opioids and NSAID are commonly used in rodents, but few studies have evaluated their efficacy in surgical models. The current study aimed to evaluate the therapeutic efficacy of clinically relevant doses of buprenorphine (2 formulations) or meloxicam used in combination with ketamine and xylazine anesthesia in a Sprague-Dawley rat ovariohysterectomy surgical model. Rats received either subcutaneous saline once daily for 3 d, low-dose (0.05 mg/kg SC) or high-dose (0.1 mg/kg SC) buprenorphine twice daily for 3 d, a single injection of sustained-release buprenorphine (1.2 mg/kg SC), or low-dose (1 mg/kg SC) or high-dose (2 mg/kg SC) meloxicam once daily for 3 d. Clinical analgesic efficacy was assessed over 8 d according to cageside observation scoring, body weight, and behavioral testing. Ovariohysterectomy was associated with 2 d of postoperative pain, and all 3 buprenorphine dosing strategies and both doses of meloxicam demonstrated varying amounts of analgesia. Given the results of the current study, we recommend 0.05 mg/kg SC buprenorphine at least twice daily or a single dose of 1.2 mg/kg SC of sustained-release buprenorphine for rats undergoing midline laparotomy with ovariohysterectomy. Alternatively, meloxicam at 1 to 2 mg/kg SC once daily could be used for this indication.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Female; Laboratory Animal Science; Laparotomy; Meloxicam; Pain Measurement; Pain, Postoperative; Rats; Rats, Sprague-Dawley

Parturition is often a stressful period, when the incidence of disease is high after calving, which has been associated with an uncontrolled inflammatory response. Therefore, the objective of this study was to test the effect of the administration of a nonsteroidal anti-inflammatory drug (meloxicam) on the behavior, health, and production of peripartum cows. Meloxicam was dosed at 1 mg/kg of body weight, and an empty gel capsule served as a placebo. Both were administered orally with a balling gun. Dairy cows and heifers were randomly assigned to 1 of 3 treatment groups: (1) meloxicam administration before calving, with a placebo administered after calving (MEL-PRE, n = 60), (2) placebo administered before calving, and meloxicam administered after calving (MEL-POST, n = 69), and (3) a placebo administered before calving and after calving (CTL, n = 65). To identify imminent calving events, a vaginal thermometer was inserted approximately 2 wk before the expected calving date and a drop in temperature was used to identify cows close to calving. Calving events were monitored via video cameras, and the amount of time that elapsed between the appearance of the amniotic sac at the vulva until delivery of the calf was used to determine calving difficulty score. Eutocic calving events were defined as cows that calved in ≤70 min, and dystocia was defined as cows that took longer than 70 min to calve. Milk yield and components were measured for the first 15 wk of lactation and accelerometers were used to record activity and lying behaviors. The effects of treatment, breed, parity, calving difficulty, and, when applicable, a repeated measure, along with interaction terms, were analyzed in mixed models. Regardless of the time of administration, dystocic cattle that received meloxicam were less active than dystocic CTL. Dystocic animals displayed more lying bouts on the day of calving and then displayed fewer lying bouts and were less active during the days following calving. No effect of treatment was noted on any health outcomes. Eutocic MEL-PRE animals produced 6.8 kg/d more milk than eutocic CTL. Regardless of calving difficulty, MEL-PRE animals produced more milk fat, protein, and lactose (kg/d) than CTL. In conclusion, meloxicam administration before calving appears promising in increasing milk yield in eutocic cows.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Temperature; Body Weight; Cattle; Dystocia; Female; Health Status; Lactation; Meloxicam; Milk; Parity; Parturition; Peripartum Period; Pregnancy; Random Allocation; Reproduction; Vagina

Beef bull calves (n = 62) were assigned randomly, within sire breed, to 1 of 4 treatments at birth. Treatments were 1) surgical castration near birth, 2) surgical castration near birth with oral administration of meloxicam (1 mg/kg BW), 3) surgical castration at weaning (WNG), or 4) surgical castration at weaning with oral administration of meloxicam (1 mg/kg BW; WMX). A subset of calves (n = 7/treatment group) were selected randomly near birth for blood collection, behavioral analyses, and rectal temperature (RT) records for a 7-d postcastration period on d 0 (birth), 1, 3, and 7, and on d 214 (weaning), 214 + 6 h, 215, 217, 221, and 228. Calf standing and lying activity were monitored from the same subsets by recording x- and y-axis positions of an accelerometer attached to the right metatarsus for 7 d postcastration. Calf BW was recorded throughout the entire production cycle, and carcass data were collected at slaughter. For statistical analyses, bulls left intact at birth were considered a positive control (BUL) for observations that occurred before their treatment application at weaning; likewise, bulls castrated at birth were considered a negative control (STR) during postweaning observations. No difference (P > 0.88) occurred in ADG between treatments throughout the preweaning period (d 0 to 214); however, 56-d postweaning ADG was greatest ( P= 0.02) in STR, intermediate in WMX, and least in WNG. At weaning, haptoglobin (Hp) was greater (P ≤ 0.005) for WNG and WMX compared to STR on d 214+6 h, 215, and 217, and Hp was greater (P = 0.05) in WNG compared to WMX on d 217. Neutrophils increased (P < 0.001) and red blood cells decreased (P ≤ 0.03) for WNG and WMX on d 214+6 h and 217, respectively. Postweaning behavior observations indicated that STR calves spent the least proportion of time standing (P = 0.002) when compared to WNG and WMX. Furthermore, WMX calves exhibited a greater proportion of time spent standing (P = 0.03) compared to WNG. Grazing and finishing phase ADG and carcass measurements did not differ (P ≥ 0.24) across treatments. In this study, surgical castration at weaning, but not near birth, altered the acute phase response, behavior, and growth performance. Oral meloxicam reduced serum Hp and improved ADG briefly when administered to calves castrated at weaning. Oral administration of meloxicam may be efficacious for mitigating some of the stress and inflammation associated with castration of weaning-age bull calves.

Topics: Acute-Phase Reaction; Administration, Oral; Age Factors; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Composition; Body Weight; Cattle; Haptoglobins; Inflammation; Male; Meloxicam; Orchiectomy; Thiazines; Thiazoles; Time Factors

This experiment evaluated the effects of meloxicam administration on physiological and performance responses of transported cattle during feedlot receiving. Eighty-four Angus × Hereford steers were ranked by BW on d -10 and assigned to 21 dry lot pens. From d -10 to 0, pens were fed alfalfa-grass hay ad libitum and 2.4 kg/steer daily (DM basis) of a corn-based concentrate. On d 0, pens were randomly assigned to 1) transport for 1,440 km in a livestock trailer and oral administration of meloxicam (1 mg/kg of BW) at loading (d 0), unloading (d 1), and daily from d 2 to 7 of feedlot receiving (MEL; n = 7); 2) the same transportation and treatment schedule of MEL but oral administration of lactose monohydrate (1 mg/kg of BW) instead of meloxicam (TRANS; n = 7); or 3) no transport and oral administration of lactose monohydrate (1 mg/kg of BW) concurrently with treatment administration to MEL and TRANS (CON; n = 7). Upon arrival (d 1), MEL and TRANS steers returned to their pens for a 21-d feedlot receiving with the same diet offered from d -10 to 0. Treatments were administered to steers via oral drench on d 0 and 1 or mixed daily with the concentrate from d 2 to 7. Full BW was recorded before (d -2, -1, and 0) treatment application and at the end of experiment (d 20, 21, and 22) for ADG calculation. Daily DMI was recorded from d 1 to 21. Blood samples were collected on d 0, 1, 3, 5, 7, 10, 14, and 21. During the initial 7 d of feedlot receiving, hay and total DMI were reduced (P ≤ 0.03) in TRANS vs. CON and MEL and similar between CON and MEL (P ≥ 0.26), whereas concentrate DMI did not differ (P = 0.16) among treatments. Mean ADG was reduced (P ≤ 0.03) in TRANS vs. MEL and CON but similar (P = 0.82) between MEL and CON. Moreover, TRANS had reduced G:F vs. CON (P = 0.01) and MEL (P = 0.05), whereas G:F was similar (P = 0.39) between CON and MEL. Serum NEFA concentrations were greater (P < 0.01) for TRANS and MEL vs. CON on d 1. Plasma haptoglobin concentrations were greater (P ≤ 0.03) for TRANS vs. CON and MEL on d 5 and greater (P ≤ 0.03) for CON vs. TRANS on d 10. Plasma ceruloplasmin concentrations were greater (P ≤ 0.04) for TRANS vs. CON on d 3, 5, 7, 10, and 14, greater (P ≤ 0.03) for TRANS vs. MEL on d 5 and 7, and also greater (P = 0.05) for MEL vs. CON on d 3. In conclusion, meloxicam administration to feeder steers modulated the haptoglobin and ceruloplasmin responses and prevented the performance losses caused by long-distance transportation.

Topics: Administration, Oral; Animals; Body Weight; Cattle; Ceruloplasmin; Diet; Haptoglobins; Meloxicam; Thiazines; Thiazoles; Transportation

To assess the efficacy of oral transmucosal meloxicam for pain relief in lambs at marking.. A blinded, placebo-controlled, randomised, block design field study of 60 Merino lambs aged 7-10 weeks allocated to placebo and meloxicam treatments and studied in two cohorts of 30. Placebo-treated lambs received 1 mL/10 kg of drug vehicle and meloxicam-treated lambs received 1 mg/kg meloxicam at 10 mg/mL. Treatments were administered into the buccal cavity immediately before knife castration and hot-iron tail docking. Lambs were then released into a grassed paddock (0.34 ha). Time to mother-up was recorded and behaviours were observed every 15 min for 8 h and again for 45 min at 24 h. The sequence in which lambs exited the paddock with their mothers was then recorded. Weight change and wound scores were recorded 4 and 7 days after marking.. Meloxicam did not affect mothering-up. In the 8 h following marking, meloxicam led to a 7-fold reduction (P < 0.001) in combined abnormal behaviours (hunched standing, standing with a stretched posture, walking stiffly). The meloxicam group spent significantly less time in standing postures and tended to spend more time grazing, suckling and in normal lying postures. At 24 h, the meloxicam group spent more time lying and less time standing. There was no effect of treatments on the sequence in which lambs moved into a fresh paddock or on weight change.. The buccal meloxicam formulation provided substantial analgesia to lambs on the day of marking. Slight benefits were evident the following morning.

Topics: Administration, Buccal; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Weight; Cohort Studies; Female; Male; Meloxicam; Orchiectomy; Pain; Sheep; Single-Blind Method; Statistics, Nonparametric; Thiazines; Thiazoles; Wound Healing

Parturition is a necessary event for production in dairy cattle, and assistance at calving is common. There is limited use of nonsteroidal antiinflammatory drugs for the alleviation of calving pain and a paucity of research on the effects of these drugs on postpartum health and performance. This randomized triple blind clinical trial involved Holstein cows (n=42) and heifers (n=61) that experienced an assisted parturition. These animals received either 1 injection of meloxicam (0.5mg/kg of body weight) or placebo subcutaneously 24h following calving. Outcome measures included dry matter intake (DMI) and milk production for the first 14d in milk, blood metabolites sampled over 12d, health events for the first 60d in milk, as well as lying and feeding behavior 24h following injection. Continuous data were analyzed using multivariable regression models. Binary outcomes were analyzed using a mixed logistic model with cow modeled using a random intercept. This study failed to show any significant effects of treatment on DMI, milk production, blood metabolites, or health events. A possible explanation for the lack of treatment differences could be that the meloxicam was administered too late after calving. Meloxicam increased feeding time as well as bunk visit frequency in the 24h following injection. Regardless of treatment, animals that had retained fetal membranes produced less milk and had higher serum haptoglobin concentrations. Future research is warranted to examine the effects of antiinflammatory drugs administered closer to the time of calving on health and production.

Topics: 3-Hydroxybutyric Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Weight; Cattle; Cattle Diseases; Dystocia; Eating; Fatty Acids, Nonesterified; Feeding Behavior; Female; Lactation; Meloxicam; Milk; Pain; Parturition; Placebos; Pregnancy; Thiazines; Thiazoles

The aim of this study was to examine the efficacy of meloxicam (MEL) as supportive therapy for calves with neonatal calf diarrhea complex. For this double-blind controlled trial, 62 Holstein male calves were purchased at birth and transported to a research facility. At the naturally occurring onset of diarrhea, defined as the first occurrence of a fecal score greater than 2 on a 4-point scale, calves were enrolled in the study. Each calf with diarrhea was randomly assigned to receive a single subcutaneous injection of MEL at a rate of 0.5 mg/kg of BW or an equal volume of placebo (PLA) solution. Milk, starter ration, and water intakes were determined daily for each calf from arrival until 56 d of age. The calves were weighed on arrival and each week thereafter. Time to weaning and weaning weight were recorded for each calf. Crude associations between treatment and each outcome variable were examined using t-tests and Pearson chi-squared tests. Subsequently, multivariable regression models were constructed to examine the impact of MEL therapy on meaningful outcome variables. The primary experimental unit in all analyses was the individual calf. In total, 56 calves presented with clinical signs of diarrhea and were enrolled in the study. Two PLA-treated calves died after being enrolled in the study, and there was no calf mortality among the MEL-treated calves. For calves that developed diarrhea after 10 d of age, MEL-treated calves were more likely to consume their entire daily milk allowance (P < 0.05) as compared with PLA-treated calves. Meloxicam-treated calves began consuming starter ration earlier (P < 0.01) and at a greater rate (P < 0.001), and consumed more water (P < 0.001) compared with PLA-treated animals. Over the study period, calves treated with MEL gained BW at a faster rate (P < 0.01) than calves treated with PLA. There was no difference in weaning weight (P > 0.05), but MEL-treated calves tended to wean earlier (P = 0.11) than PLA-treated calves. These results demonstrate that calves receiving a single injection of MEL at the onset of diarrhea had improved appetite and performance compared with PLA-treated calves. Thus, MEL is an effective supportive therapy for neonatal calf diarrhea complex.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cattle; Cattle Diseases; Diarrhea; Double-Blind Method; Eating; Male; Meloxicam; Regression Analysis; Thiazines; Thiazoles

Diabetics often face greater risk of cognitive impairment than nondiabetics. However, how to prevent this disease is still unconfirmed. In this study, we investigated the potential protection and mechanism of meloxicam on cognitive impairment in diabetic rats. The diabetic rat model was established with a high-fat diet and a small dose of streptozotocin (40 mg/kg). The changes of spatial learning and memory, histopathology, and the protein expressions of amyloid protein precursor (APP) and β-amyloid (Aβ) indicated that diabetic rats had neuronal injury and cognitive impairment. Tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C reactive protein (CRP) and prostaglandin E2 (PGE2) levels, and microglial cell number were significantly increased in the diabetic rat brain. Meanwhile, the protein expressions of APP, Aβ, cyclooxygenases2 (COX2), E-type prostanoid recptors 1 (EP1) and EP2, and the level of cyclic adenosine monophosphate (cAMP) were significantly increased, while the protein expressions of EP3 and phosphorylated protein kinase A (pPKA) were significantly decreased in the diabetic rat hippocampus and cortex. However, the EP4 protein expression had no significant changes. Meloxicam significantly improved neuronal injury and cognitive impairment, and significantly decreased inflammatory cytokines levels. Meloxicam also significantly decreased the protein expressions of APP, Aβ, COX2, EP1 and EP2, and the level of cAMP and significantly increased the EP3 and pPKA protein expressions in rat hippocampus and cortex. However, meloxicam did not significantly influence the levels of blood glucose, lipids, and insulin of rats. Our results suggest that meloxicam could significantly protect diabetic rats from cognitive impairment via a mechanism that may be associated with rebalancing the COX2-PGE2-EPs-cAMP/PKA pathway.

Topics: Animals; Blood Glucose; Body Weight; Cognitive Dysfunction; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclooxygenase 2; Immunohistochemistry; Inflammation; Insulin; Male; Maze Learning; Meloxicam; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin E, EP1 Subtype; Receptors, Prostaglandin E, EP2 Subtype; Signal Transduction

The aim of this study was to evaluate the effect of a single dose of subcutaneous (s.c.) meloxicam administered at the time of knife and band castration on inflammatory response and wound healing over 56-d post-castration. Seventy-two Angus crossbred calves (47.3 ± 6.70 kg of body weight [BW] and 7 to 8 d of age) were randomly assigned according to a 3 × 2 factorial design assessing castration method: sham (CT), band (BA), and knife (KN) castration, and pain mitigation: non-medicated (NM) and medicated calves (M) injected s.c. with meloxicam (0.5 mg/kg of BW). Calf BW, rectal temperature, swelling ("0": no swelling; "4": swelling needing intervention) and healing score ("1" to "5" with "5" being completely healed), scrotal circumference, and maximum scrotal temperature were measured on d -1, immediately before castration (d 0), and weekly thereafter over a 56-d period. Blood samples for haptoglobin (Hp), serum amyloid-A (SAA), and complete blood cell count were collected according to the same schedule. Hair samples were collected on d -1, 28, and 56 to determine cortisol concentrations. Standing and lying behaviors were measured using accelerometers that were placed on the calves on d -1 until d 35, and visual observations of behaviors related to pain were recorded once a week for 35 d. Knife-castrated calves achieved swelling scores of "3" and "2" between d 7 and 14, which was sooner (Z< 0.05) than in BA calves (from d 14 to 35). In addition, greater (P = 0.03) concentrations of SAA were observed in BA calves (76.9 ± 0.12 g/liter) compared with CT (57.6 ± 0.12 g/liter) and KN (51.6 ± 0.12 g/liter) from d 7 to 35. Healing scores of "2" and "4" tended to be achieved sooner (Z < 0.10) in KN calves than in BA calves, although healing scores of "3" tended to be achieved sooner (Z < 0.10) in BA calves than KN calves. No differences (P > 0.10) were observed among treatments for hair cortisol on d -1 and 28, but on d 56, hair cortisol concentrations in BA-NM calves were greater (P > 0.05) than for CT-NM, BA-M, KN-NM, and KN-M, and tended to be greater (P = 0.08) than for CT-M calves. Lying duration tended (P = 0.10) to be greater and suckling behavior tended (P = 0.08) to be lower in NM than M calves. A single s.c. injection of meloxicam did not reduce long-term inflammatory responses or improve wound healing; however, it may be useful in reducing pain and stress in band castrated calves as evidenced by reduced hair cortisol concentrations up to 56 d post-castra

Topics: Animals; Body Weight; Cattle; Hair; Haptoglobins; Hydrocortisone; Male; Meloxicam; Orchiectomy; Pain; Pain Measurement; Random Allocation; Wound Healing

Meloxicam is an anti-inflammatory drug that has a potential protective effect in many common diseases. However, this molecule is quickly eliminated from the body due to it short half-life. One way to overcome this problem is to incorporate meloxicam into lipid-core nanocapsules which may increase it anti-inflammatory effects. In view of this, the objective of this work was to evaluate the potential toxicity and safety of these novel nanomaterials both in vitro and in vivo. Here, we evaluated the effects of uncoated meloxicam-loaded nanocapsules (M-NC), uncoated and not loaded with meloxicam or blank (B-NC), PEGylated meloxicam-loaded lipid-core nanocapsules (M-NCPEG), blank PEGylated lipid-core nanocapsules (B-NCPEG) and free meloxicam (M-F) in vitro through the analysis of cell viability, caspase activity assays and gene expression of perforin and granzyme B. Meanwhile, the in vivo safety was assessed using C57BL/6 mice that received nanocapsules for seven days. Thus, no change in cell viability was observed after treatments. Furthermore, M-NC, M-NCPEG and M-F groups reversed the damage caused by H

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Caspases; Cell Survival; Cells, Cultured; DNA Damage; Eating; Humans; Hydrogen Peroxide; Lymphocytes; Male; Meloxicam; Mice; Mice, Inbred C57BL; Nanocapsules; Organ Specificity; Polyethylene Glycols; Spleen; Toxicity Tests

Our objective was to investigate the effects of administering the nonsteroidal anti-inflammatory drug meloxicam (MEL) before transport on various indicators of protein metabolism and growth performance over the first 96 h after transport in Jersey calves. Calves (age ± SD; 2 ± 1 d) sourced from a commercial farm were randomly administered, at 1 mg/kg of body weight, either meloxicam (MEL; n = 11) or a whey protein placebo (CON; n = 10) orally before transport to a calf facility (669 km; 8.5-h road trip). Calves were weighed and rectal temperature was recorded before departure (0 h), on arrival (8.5 h), and 96 h after arrival. Blood was collected at the same time as calves were weighed, and samples were analyzed for total protein (0-h sample), cortisol (0- and 8.5-h samples), haptoglobin (0- and 96-h samples), and amino acids, 3-methylhistidine, and urea-N (96 h). Milk replacer (MR) intake was recorded on arrival and over the next 4 d. Serum total protein concentration did not differ for CON and MEL calves. Plasma cortisol concentration was similar across treatments at 0 h; however, it was lower for CON than for MEL calves at 8.5 h. Although serum haptoglobin concentration tended to be greater for CON than MEL calves 96 h after transport, 3-methylhistidine and plasma urea-N concentrations did not differ across treatments. Plasma Asp, Asn, Glu, Lys, Met, Ser, and Trp were greater and plasma Arg, Gly, Pro, and Thr concentrations tended to be greater at 96 h after arrival for MEL compared with CON calves. Intake of MR and average daily gain were higher in MEL than in CON calves. In summary, although it had no effect on 3-methylhistidine or urea-N concentrations, administration of MEL before transport tended to reduce haptoglobin concentration, altered the amino acid profile, and was beneficial in preventing a decrease in MR intake and average daily gain in Jersey calves.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cattle; Female; Haptoglobins; Hydrocortisone; Male; Meloxicam; Proteins; Random Allocation; Stress, Physiological; Transportation

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

Topics: Analgesics; Animals; Body Weight; Buprenorphine; Carbazoles; Delayed-Action Preparations; Male; Meloxicam; Pain, Postoperative; Random Allocation; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles

This study determined whether meloxicam in nanocapsules modifies stomach and liver damage caused by free meloxicam in mice. Male Swiss mice were treated with blank nanocapsules or meloxicam in nanocapsules or free meloxicam (10 mg/kg, intragastrically, daily for five days). On the seventh day, blood was collected to determine biochemical markers (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, total bilirubin, unconjugated bilirubin, albumin and alkaline phosphatase). Stomachs and livers were removed for histological analysis. There was no significant difference in the biochemical markers in the plasma of mice. Meloxicam in nanocapsules did not have an ulcerogenic potential in the stomach or cause lipid peroxidation in the stomach and liver. Free meloxicam increased the ulcerogenic potential in the stomach and lipid peroxidation in the stomach and liver. Meloxicam in nanocapsules caused less histological changes than free meloxicam. In conclusion, polymeric nanocapsules can represent a technological alternative to reduce the toxicity caused by meloxicam.

Topics: Animals; Body Weight; Caproates; Dose-Response Relationship, Drug; Gastric Mucosa; Lactones; Lipid Peroxidation; Liver; Male; Meloxicam; Mice; Nanocapsules; Organ Size; Polysorbates; Stomach; Structure-Activity Relationship; Thiazines; Thiazoles

Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine-meloxicam (0.01 mg/kg-0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine-meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine-meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses.

Topics: Analgesia; Analgesics, Opioid; Anesthetics, Local; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Bupivacaine; Buprenorphine; Corticosterone; Drug Therapy, Combination; Feces; Glucocorticoids; Male; Meloxicam; Minimally Invasive Surgical Procedures; Pain, Postoperative; Rabbits; Thiazines; Thiazoles

The objective of present study was to investigate the protective effect of M-NC against aβ (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) aβ, (III) M-NC, (IV) M-F, (V) M-NC+aβ and (VI) M-F+aβ. Mice were pre-treated with M-NC (5mg/kg, by gavage), M-F (5mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, aβ peptide (3nmol) or filtered water were i.c.v. injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that aβ peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aβ peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aβ peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aβ peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by aβ peptide.

Topics: Amyloid beta-Peptides; Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Avoidance Learning; Behavior, Animal; Body Weight; Brain; Catalase; Disease Models, Animal; Exploratory Behavior; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Learning Disabilities; Male; Maze Learning; Meloxicam; Memory Disorders; Mice; Nanocapsules; Peptide Fragments; Superoxide Dismutase; Thiazines; Thiazoles; Time Factors

To compare the efficacy of cabergoline (Cb2) and meloxicam in curbing vascular endothelial growth factor (VEGF) expression and preventing ovarian hyperstimulation syndrome (OHSS).. Randomized controlled, animal study.. Academic facility.. We used a total of 50 immature Wistar female rats randomly to create an experimental OHSS model.. Ten rats each formed the control group and mild OHSS group. The remaining 30 were separated into three equal groups of severe OHSS. Mild and severe OHSS were induced through ovarian stimulation with gonadotropins. One group with severe OHSS was administered a low-dose 100 microg/kg Cb2 therapy; another group with severe OHSS received 600 microg/kg meloxicam. Body weight, vascular permeability (VP), VEGF expression, ovary weight, and diameter were then compared.. The efficacy of Cb2 and meloxicam for preventing OHSS.. Comparison of the severe OHSS groups with the controls and mild OHSS group revealed significant increases in VEGF expression, VP, ovary weight, and diameter. The increase in VEGF expression was demonstrated to be dependent on human chorionic gonadotropin doses. However, low-dose Cb2 and meloxicam therapies were shown to be ineffective in decreasing VEGF expression and VP, ovary weight, and ovary diameter in severe OHSS.. VEGF elevation played a critical part in OHSS pathogenesis, but the therapies administered failed to curb VEGF expression.

Topics: Analysis of Variance; Animals; Biopsy, Needle; Body Weight; Cabergoline; Chorionic Gonadotropin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Ergolines; Female; Immunohistochemistry; Injections, Intramuscular; Meloxicam; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy, Animal; Probability; Random Allocation; Rats; Rats, Wistar; Thiazines; Thiazoles; Vascular Endothelial Growth Factor A

Buprenorphine is administered to humans and animals for postoperative pain management, although its use is associated with complications. Alternative analgesics, including the nonsteroidal antiinflammatory meloxicam, are available, but information on their postoperative effects is limited. The objective of the present study was to compare buprenorphine (0.03 mg/kg SC twice daily for 3 d) with meloxicam (2 mg/kg SC initial dose followed by 1 mg/kg SC once daily for 2 d) by assessing parameters relating to postsurgical recovery in rats that underwent surgical implantation of radiotelemetric transducers. Rats treated after surgery with buprenorphine showed greater reductions in body weight, food consumption, locomotor activity, and nighttime heart rates than did meloxicam-treated rats. Buprenorphine and meloxicam treatments both had stimulatory effects on mean arterial pressure and daytime heart rate measurements, although effects on nighttime mean arterial pressure were greater in the buprenorphine-treated rats. In summary, the lesser physiologic changes associated with meloxicam, as compared with buprenorphine, suggest that meloxicam offers advantages for use as a postoperative analgesic after laparotomy and radiotelemetric transducer implantation in rats.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Buprenorphine; Feeding Behavior; Heart Rate; Male; Meloxicam; Motor Activity; Pain Measurement; Pain, Postoperative; Random Allocation; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles; Treatment Outcome

To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity.. 21 healthy green iguanas (Iguana iguana).. To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg).. There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 μg•h/mL and 5.83 ± 2.49 μg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 μg/mL) versus PO (0.19 ± 0.07 μg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues.. Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 μg/mL for approximately 24 hours.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Blood Cells; Body Weight; Female; Iguanas; Injections, Intravenous; Kidney; Male; Meloxicam; Pain; Stomach; Thiazines; Thiazoles

This study evaluated whether the automated behaviour recognition software 'HomeCageScan' (HCS) could detect behaviour changes and any positive analgesic effects in two mouse strains undergoing vasectomy (C3H/HeNCrl and C57BL/6). Another objective was to test the effectiveness of HCS in differentiating between the effects of each treatment relative to conventional manual analysis. Each control (unoperated) group consisted of four mice of each strain. They were either untreated mice, mice given meloxicam alone (10 mg/kg) or mice given either saline or meloxicam (10 mg/kg) 30 min prior to isoflurane anaesthesia. The vasectomized mice received either saline or meloxicam at 5, 10 or 20 mg/kg, again, 30 min prior to isoflurane anaesthesia. Filming began one hour following surgery. Each mouse was filmed for 6 min for the manual analysis and then for a further 20 min for analysis with HCS. In a time-matched test, HCS and the manual analysis produced activity data that generated identical conclusions regarding treatment effects and strain differences. Both HCS and the manual analysis found the C57BL/6 controls were overall more active, but not following vasectomy, when both types of analysis detected markedly reduced activity. Low-dose meloxicam (5 mg/kg) had a positive effect on postoperative mobility in the C3H/HeNCrl mice; however, increasing the dose rate progressively reduced this. These effects were also detected with the manual analysis. Overall, HCS provided a sufficiently accurate and rapid method of analysing mouse behaviour encouraging more prolonged assessments in the future. This capability and the possibility of training the software to recognize a greater range of behaviours, including pain-specific indicators, should be of considerable value for assessing postoperative behaviour in both mice and rats. This would allow analgesic requirements to be investigated in a greater range of rodent models than is currently feasible with conventional analysis methods.

Topics: Analgesics; Animals; Behavior, Animal; Body Weight; Male; Meloxicam; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred Strains; Pain Measurement; Pain, Postoperative; Postoperative Period; Sensitivity and Specificity; Software; Thiazines; Thiazoles; Vasectomy

It is essential to identify objective and efficient methods of evaluating postoperative pain in rodents. The authors investigated whether postoperative changes in rates of body weight gain could serve as a measure of the efficacy of meloxicam or buprenorphine analgesia in growing rats. Young adult male Lewis rats underwent general endotracheal anesthesia and thoracotomy and were treated postoperatively for 3 d with saline (no analgesia), buprenorphine (six doses of 0.1 mg per kg) or meloxicam (three doses of 1 mg per kg). The authors evaluated rats' daily growth rates for 5 d after surgery and compared them with baseline (preoperative) growth rates. To discriminate between the effects of postoperative pain and other concurrent physiologic effects associated with anesthesia, thoracotomy or analgesia, the authors evaluated weight changes in multiple control groups. Treatment with buprenorphine in the absence of any other procedure or with anesthesia alone significantly affected rats' body weight. Notably, growth rate was maintained at near normal levels in rats treated postoperatively with meloxicam. These findings suggest that growth rate might serve as an efficient index of postoperative pain after major surgical procedures in young adult rats treated with meloxicam but not in rats treated with buprenorphine.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Intubation, Intratracheal; Meloxicam; Pain, Postoperative; Rats; Rats, Inbred Lew; Thiazines; Thiazoles; Thoracotomy; Weight Gain

Chronic arthritis leads to a decrease in body weight that is associated with a decrease in skeletal muscle and white adipose tissue mass. We have observed that overactivation of cyclooxygenase-2 (COX-2) is responsible for muscle wasting in arthritic rats. The aim of this work was to study the role of COX-2 in arthritis-induced white adipose tissue mass loss. Arthritis was induced in rats by Freund's adjuvant injection, and the effect of the COX-2 inhibitor meloxicam on serum concentrations of leptin, adiponectin, insulin and glycerol, as well as on gene expression of leptin, adiponectin, hormone-sensitive lipase (HSL), fatty acid synthase (FAS), tumour necrosis factor alpha (TNF) and insulin-like growth factor I (IGF-I) in white adipose tissue were determined. Arthritis decreased adipose tissue weight, serum leptin and adiponectin as well as their mRNAs in adipose tissue. Meloxicam administration to arthritic rats increased adipose tissue weight, serum concentrations of adiponectin and its mRNA in adipose tissue, but it did not modify leptin. Arthritis decreased serum insulin and FAS and IGF-I gene expression in adipose tissue. Meloxicam administration did not modify these effects. Serum concentrations of glycerol were decreased in arthritic rats. In control rats, meloxicam administration did not modify serum glycerol or adipose tissue gene expression of HSL. However, in arthritic rats HSL gene expression in adipose tissue was decreased by meloxicam. All these data indicate that COX-2 activation plays a role in the decrease in adiponectin secreted by adipocytes and in the loss in white adipose tissue mass in arthritic rats.

Topics: Adiponectin; Adipose Tissue, White; Animals; Arthritis, Experimental; Body Weight; Chronic Disease; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Insulin-Like Growth Factor I; Male; Meloxicam; Rats; Rats, Wistar; RNA, Messenger; Severity of Illness Index; Thiazines; Thiazoles; Tumor Necrosis Factor-alpha

One of the challenges facing veterinarians and investigators who use rabbits (Oryctolagus cuniculus) as a surgical model in biomedical research is choosing an appropriate and efficacious postoperative analgesic without systemic complications and side effects. The objective of this study was to evaluate the gastrointestinal side effects associated with the postoperative use of buprenorphine in Dutch Belted rabbits. We also evaluated the analgesic meloxicam as an alternative to opioid administration during the postoperative period. Rabbits were assigned to 1 of 3 treatment groups during the postoperative period after routine ovariohysterectomy: buprenorphine (n = 10), meloxicam (n = 10), and incisional infiltration with bupivicaine (no treatment control; n = 10). Feed intake, fecal production, weight loss, urine output, and other physiologic parameters were monitored and behavior and pain assessments were performed for 7 d after surgery and compared with baseline values collected before surgery. All rabbits showed decreased pellet consumption, fecal production, and weight on day 1 after surgery. This effect was severe in some rabbits that received bupivicaine; therefore treatment of this entire group with metoclopramide, fluids, and hay was instituted to reverse gut stasis. No significant difference in feed consumption and fecal production was present between the buprenorphine- and meloxicam-treated groups. On the basis of these results, meloxicam appears to be a suitable alternative or adjunct to buprenorphine for alleviating postoperative pain with minimal risk of anorexia and gastrointestinal ileus.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Chemical Analysis; Body Temperature; Body Weight; Buprenorphine; Cyclooxygenase Inhibitors; Meloxicam; Postoperative Period; Rabbits; Thiazines; Thiazoles; Treatment Outcome

Behaviour was assessed in 32 C57BL/6JCrl and 32 C3H/HeN male mice 1 h following vasectomy; saline or meloxicam was administered 30 min prior to surgery at 5, 10, or 20 mg kg(-1). Faeces were collected 24 h prior to, and 3, 6, 9, 12, 24 h following, vasectomy for measurement of faecal corticosterone. Peak corticosterone levels were significantly higher in mice that underwent vasectomy and received saline (p<0.001) or meloxicam at 5 or 10 mg kg(-1) (p=0.021, and p<0.001, respectively) compared with normal un-operated controls. Mice that underwent vasectomy and received 20 mg kg(-1) meloxicam had peak corticosterone levels that were not different from normal un-operated mice (p=0.254). Discriminant analysis was used to identify behaviours responsible for group separation; these were summed to create two behaviour scores. Score 2 (the frequency of flinching, writhing, rear leg lift and press 2) was thought to be pain related; mice that underwent vasectomy and received saline exhibited significantly more of these behaviours than the normal controls (p=0.032), and the mice that received meloxicam (at any dose). Strain differences were observed in both the stress response to vasectomy and the behavioural changes; the C3H/HeN mice had higher pain scores (behaviour Score 2) and peak corticosterone responses than the C57BL/6JCrl mice. We have demonstrated that significant changes occur in the behaviour of mice following vasectomy, and these changes are reduced by use of meloxicam. Vasectomy elicits a rise in corticosterone levels that was only reduced by the highest dose of meloxicam.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Weight; Corticosterone; Feces; Male; Meloxicam; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Pain Measurement; Pain, Postoperative; Species Specificity; Stress, Physiological; Thiazines; Thiazoles; Vasectomy

We have recently demonstrated dose-related analgesic-induced reductions in the occurrence of 7 behavioural activities following midline laparotomy in rats. For these behaviours to be useful in evaluating pain in laboratory rats they must be shown to occur after different types of surgery, and frequently enough to allow rapid scoring of animals. Here, the relevant behaviours were used to test the analgesic efficacy of meloxicam with a variation of our previous laparotomy model. As part of an unrelated project, 57 male Fischer rats were divided into groups to receive either saline (0.2 ml/100g s.c.), meloxicam (0.5, 1 or 2 mg/kg s.c.) or carprofen (2.5, 5, or 10 mg/kg s.c.) 1h before surgery. Behaviour data were collected for 10 min following 25 min of recovery from isoflurane anaesthesia. The cumulative frequencies of back arching, fall/stagger, writhe and poor gait were used to compute a composite behaviour score. Irrespective of whether analyses included only 5 or all 10 min of the observation period, the relevant behaviours occurred significantly more often in rats given saline or low dose meloxicam than in those given 1 or 2 mg/kg of meloxicam, or any dose of carprofen. We conclude that this technique of quantifying post-surgery behaviour is an effective pain scoring method following abdominal surgery in rats, and that 1 mg/kg meloxicam significantly attenuates laparotomy induced pain. Since only a short observation period is required, this approach represents an important practical advance in assessing abdominal pain severity and clinical drug potency.

Topics: Abdominal Pain; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Weight; Carbazoles; Disease Models, Animal; Exploratory Behavior; Male; Meloxicam; Motor Activity; Pain Measurement; Pain, Postoperative; Rats; Rats, Inbred F344; Thiazines; Thiazoles; Time Factors

The effects of the cyclooxygenase-2 (COX-2) inhibitor, meloxicam, on tumour growth and cachexia have been determined in 2 established murine adenocarcinomas (MAC). At a dose level of 2.5 and 5.0 mgkg(-1), meloxicam produced pronounced inhibition of the growth of the MAC13 tumour, increasing the tumour volume doubling time from 2 to 5 days. Meloxicam also suppressed growth of the MAC16 tumour, which is generally refractory to standard cytotoxic agents, increasing the tumour volume doubling time from 1.5 to 2.5 days at dose levels of 0.5 and 1.0 mgkg(-1). Cachexia was also effectively attenuated at these dose levels. To investigate whether meloxicam exerted a direct effect on the cachectic process, studies on protein degradation were carried out using C(2)C(12) mouse myoblasts in response to a proteolysis-inducing factor (PIF). PIF produced maximum protein degradation at a concentration of 4.2 nM, and this was effectively attenuated by meloxicam at concentrations greater than 1 microM. This suggests that meloxicam may be capable of directly antagonizing the process of muscle catabolism in cachexia.

Topics: Adenocarcinoma; Animals; Body Weight; Cachexia; Colonic Neoplasms; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Isoenzymes; Male; Meloxicam; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles; Time Factors

Prostaglandins are implicated in periodontal bone destruction. We investigated the effect of a non-selective cyclooxygenase (COX) inhibitor (indomethacin-IND) or a type 2 COX inhibitor (meloxicam-MLX) in an experimental periodontal disease (EPD) model.. Wistar rats were subjected to placement of a nylon thread ligature around the maxillary molars and sacrificed after 7 days. Alveolar bone loss (ABL) was measured in one quadrant as the distance between the cemento-enamel junction and the alveolar bone. The other quadrant was processed for histopathologic analysis. Daily weight and white blood cell count were recorded. Groups were treated subcutaneously for 7 days with either IND (0.5, 1, or 2 mg/kg) or MLX (0.75, 1.5, or 3 mg/kg). Controls received no treatment. Macroscopic analysis of the gastric mucosa was done. The control group did not receive any manipulation, and a non-treated group consisted of rats subjected to periodontitis that received no pharmacological treatment.. In the non-treated (NT) group, there was significant ABL, severe mononuclear influx, and an increase in osteoclast numbers. Significant neutrophilia and lymphomonocytosis occurred at 6 hours and at 7 days, respectively, as compared to controls. Significant weight loss persisted until the seventh day in the NT group. Both IND and MLX reduced ABL and histopathologic changes. Neutrophilia and lymphomonocytosis were also significantly reversed. Both IND and MLX induced earlier weight recovery. The stomachs of the IND (1 and 2 mg/kg) groups presented hemorrhage and ulcers, whereas in the MLX-treated groups, there were mild petechiae just in the 3 mg/kg group.. COX inhibition prevented ABL in this experimental periodontal disease model. MLX displays similar efficacy and less gastric damage than IND. MLX may provide a better risk/benefit ratio in the treatment of human periodontitis than non-selective COX inhibitors.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cell Count; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Disease Models, Animal; Indomethacin; Injections, Subcutaneous; Isoenzymes; Leukocyte Count; Leukocytes, Mononuclear; Leukocytosis; Male; Meloxicam; Molar; Neutrophils; Osteoclasts; Periodontitis; Peroxidases; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Stomach; Thiazines; Thiazoles; Tooth Cervix