Search

The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major racetracks in Louisiana between 2016 and 2020.During this 5-year period, 27,237 blood samples and 25,672 urine samples collected during the course of normal race meeting activities were analysed by initial screening procedure utilizing Liquid Chromatography Mass Spectrometry (LC-MS/MS). Following initial screening, suspect samples were subject to quantitative or semi- quantitative confirmation analysis by LC-MS/MS.The total number of violations reported was 534 (1.01% of the total number of specimens analysed). The total number of violations reported in Thoroughbred horses was 210 while the total number of violations reported in Quarter Horses was 324. The percentage of total violations was %0.59 for all the specimens analysed in Thoroughbred horses while this percentage was %1.9 for all the specimens analysed in Quarter Horses during this 5-year period. The most frequent violations included the overages (concentrations of permitted medications equal to or exceeding the set threshold) of clenbuterol (165 violations), non-steroidal anti-inflammatory drugs (NSAIDs) such as phenylbutazone (73 violations), combination of phenylbutazone with flunixin (45 violations) and muscle relaxant methocarbamol (40 violations).The total number of violations were relatively low during 5-year period, but wide varieties of medications with different pharmacological actions were confirmed in performance horses in Louisiana. The most frequently reported violations in Louisiana were for permitted therapeutic medications (clenbuterol, phenylbutazone, flunixin methocarbamol) with established threshold and/or withdrawal guidelines in racehorses.

Southern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain-relieving medications. One of the preferred treatments is the nonsteroidal anti-inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood samples collected under voluntary behavioural restraint at up to four predetermined time points (0, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 30 and 48 h). Drug analysis was performed by high-performance liquid chromatography. The population pharmacokinetic parameters were calculated with nonlinear mixed-effects modelling, and analysis showed a peak concentration (C

Lameness is an important clinical sign for the problems of locomotor system. When, visual inspection and diagnostic analgesia are not enough for reaching out the accurate diagnosis of the lesion, diagnostic imaging including radiology helps to determine the problem in a specific area. This study investigated the role of radiography as a crucial step for clinical diagnosis of bone exostosis lesions in equines. Between July 2019 and December 2020, seventeen animals were involved in this study 10 horses and 7 donkeys. These animals (age, 4.1±3.8 years; weight, 199±98 Kg) were suffered from lameness with prominent bone exostosis on the distal limb, then were subjected to radiographic examination with lateromedial and dorsopalmar/dorsoplantar views. The most detected cases were more prevalent in the fore limb (76.5%) than the hind limb (23.5%). The most prevalent lesions recorded in this study were ring bone (9 cases; 52.9%), Degenerative joint disease of the carpal joint and sore shins (3 cases; 17.64%) for each, and then bone spavin and side bone were the lowest prevalent one (1 case; 5.88%) for each. There was no treatment for all cases except sore shins which was improved thoroughly by topical iodine compounds with systemic administration of phenylbutazone. X-ray radiography is still beneficial for equine industry especially in the lesions related to the joints and bone exostosis that appeared on the distal limb.

A 41-year-old woman with no significant past medical history presented to the hospital with complaints of nausea, vomiting, and generalized weakness over two weeks. The patient did not seek medical attention as she assumed that her symptoms willwould resolve. Following her initial denial of drug abuse and her abnormal urine drug screening, we discussed the findings with the patient. She later admitted to using both amphetamines and marijuana. This led us to take a detailed social history that revealed an unexpected event.

Background Gastrointestinal (GI) injury and dysbiosis are adverse events associated with nonsteroidal anti-inflammatory drug (NSAID) use in horses. Phenylbutazone has been shown to alter GI barrier function both in vitro and ex vivo, but its effects on barrier function have not been assessed in vivo. In addition, the ability of nutritional therapeutics to prevent these changes is not known. Objective Our objectives were to determine whether (a) phenylbutazone affected barrier function in vivo and (b) if phenylbutazone-induced GI injury could be ameliorated by the use of a nutritional therapeutic. Animals Thirty healthy horses were randomly assigned to 3 groups (n = 10 per group): control, phenylbutazone, or phenylbutazone plus nutritional therapeutic. Methods This study was conducted as a blinded, randomized block design. All horses were managed identically throughout the study period. Samples were collected throughout the study period to monitor fecal microbiota changes and gastric ulcers before and after treatment. Quantification of the bacterial 16S rRNA gene in blood was used as a marker of intestinal permeability. Results Phenylbutazone increased amounts of bacterial 16S rDNA in circulation 3.02-fold (95% confidence interval [CI], 0.1.89-4.17), increased gastric ulceration score by a mean of 1.1 grade (P = .02), and induced specific changes in the microbiota, including loss of Pseudobutyrivibrio of family Lachnospiraceae. These changes were attenuated by nutritional treatment. Conclusions and clinical importance Collectively, these findings suggest that phenylbutazone induces GI injury, including impaired barrier function, and that nutritional treatment could attenuate these changes.

The aim of this study was to correlate the serum levels of acute phase proteins (APPs) and cytokines in response to treatment by various antimicrobial agents in feedlots calves (FL) naturally infected with Mannheimia haemolytica (M. haemolytica) and Histophilus somni (H. somni). 840 feedlot calves in one farm in Al-Kharg region, Saudi Arabia were clinically examined for the presence of respiratory disease manifestations. The infection was confirmed using nasopharyngeal swabs. Blood samples from diseased animals were collected before and after (7 days) treatment for biochemical analysis of serum amyloid A (SAA), haptoglobin (HP) and cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-1 β (IL1β), and interleukin-8 (IL-8). FL that were positive for M. haemolytica and/or H. somni (n=69) received treatment with one antibiotic, including tulathromycin (Tula; n=26 cases), florfenicol (FFC; n=19), tilmicosin (Tm; n=13), or ceftiofur (CEF; n=11) and one non-steroidal anti-inflammatory drug (Flunixin meglumine (FM; n=43) or phenylbutazone (PBZ; n= 26). We demonstrated the selective potent inhibitory effect of the administrated anti-inflammatory agents either FM or PBZ on the production of APPs and pro-inflammatory cytokines in FL infected with bovine respiratory disease (BRD). Our findings showed the antibacterial efficacy of FFC and Tm for the treatment of infected FL when administrated with either FM or PBZ. However, Tula was preferable to administrate in combination with FM for the treatment of FL with respiratory manifestations. Importantly, monitoring the sera level of Hp, IL-1β, and interleukin-8 (IL-8) in feedlots treated with either FM combined with Tula, FFC, or Tm or PBZ combined with FFC, and Tm has been effective in predicting the disease prognosis

Background: A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. Methods: A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Results: Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring “R” played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Conclusion: Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

The crystal growth kinetics of piracetam, fenofibrate, phenylbutazone, acetaminophen, carbamazepine, and risperidone in methanol have been studied by two different methods; the isothermal seeded de...

Piperazine (PIP) is a pharmaceutically acceptable molecule and a good co-conformer in crystallographic engineering. Most of the non-steroidal anti-inflammatory drugs (NSAIDs) have poor aqueous solubility, which hinders their clinical application. The reports show that the solubility of many insoluble drugs can be significantly improved through salt formation with the PIP. In this work, we obtained a series of NSAIDs-PIP salts, such as ibuprofen-piperazine (IBU-0.5PIP) salt, indomethacin-piperazine (IND-0.5PIP) salt, sulindac-piperazine (SUL-0.5PIP) salt, phenylbutazone-piperazine (PBZ-0.5PIP) salt, ketoprofen-piperazine (KPF-0.5PIP) salt and flurbiprofen-piperazine (FLB-0.5PIP) salt. The spatial structure, arrangement, interaction and associations were expatiated by single crystal X-ray diffraction. Powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The six new salts had more than 10 folds of solubility and a faster dissolution rate improved corresponding to the bulk drugs in pure water, and the significant improvement of solubility is closely related to the structure of salts.

The effective concentration of a drug in the blood, i.e. the concentration of a free drug in the blood, is influenced by the strength of drug binding onto plasma proteins. Besides its efficacy, these interactions subsequently influence the liberation, absorption, distribution, metabolism, excretion, and toxicological properties of the drug. It is important to not only determine the binding strength and stoichiometry, but also the binding site of a drug on the plasma protein molecule, because the co-administration of drugs with the same binding site can affect the above-mentioned concentration and as a result the pharmacological behavior of the drugs and lead to side effects caused by the change in free drug concentration, its toxicity. In this study, the binding characteristics of six drugs with human serum albumin, the most abundant protein in human plasma, were determined by capillary electrophoresis-frontal analysis, and the obtained values of binding parameters were compared with the literature data. The effect of several drugs and site markers on the binding of l-tryptophan and lidocaine to human serum albumin was investigated in subsequent displacement studies which thus demonstrated the usability of capillary electrophoresis as an automated high-throughput screening method for drug-protein binding studies.

Responding to concerns about the potential for increased risk of adverse cardiovascular outcomes, specifically myocardial infarction, associated with certain glucose-lowering therapies, the US Food and Drug Administration and the Committee for Medicinal Products for Human Use of the European Medicines Agency issued guidance to the pharmaceutical industry in 2008. Glucose-lowering therapies were granted regulatory approval primarily from smaller studies that have demonstrated reductions in glycated hemoglobin concentration. Such studies were overall underpowered and of insufficient duration to show any effect on cardiovascular outcomes. The 2008 guidance aimed to ensure the cardiovascular safety of new glucose-lowering therapies to treat patients with type 2 diabetes mellitus. This resulted in a plethora of new cardiovascular outcome trials, most designed primarily as placebo-controlled noninferiority trials, but with many also powered for superiority. Several of these outcome trials demonstrated cardiovascular benefits of the newer agents, resulting in the first-ever cardiovascular protection indications for glucose-lowering therapies. Determining whether the guidance continues to have value in its current form is critically important as we move forward after the first decade of implementation. In February 2018, a think tank comprising representatives from academia, industry, and regulatory agencies convened to consider the guidance in light of the findings of the completed cardiovascular outcome trials. The group made several recommendations for future regulatory guidance and for cardiovascular outcome trials of glucose-lowering therapies. These recommendations include requiring only the 1.3 noninferiority margin for regulatory approval, conducting trials for longer durations, considering studying glucose-lowering therapies as first-line management of type 2 diabetes mellitus, considering heart failure or kidney outcomes within the primary outcome, considering head-to-head active comparator trials, increasing the diversity of patients enrolled, evaluating strategies to streamline registries and the study of unselected populations, and identifying ways to improve translation of trial results to general practice.

Muscleblind-like 1 (MBNL1) is a ubiquitously expressed RNA-binding protein, which is highly expressed in skeletal muscle. Abnormally expanded CUG-repeats in the DMPK gene cause myotonic dystrophy type 1 (DM1) by sequestration of MBNL1 to nuclear RNA foci and by upregulation of another RNA-binding protein, CUG-binding protein 1 (CUGBP1). We previously reported that a nonsteroidal anti-inflammatory drug (NSAID), phenylbutazone, upregulates MBNL1 expression in DM1 mouse model by demethylation of MeR2, an enhancer element in Mbnl1 intron 1. NSAIDs inhibit cyclooxygenase (COX), which is comprised of COX-1 and COX-2 isoforms. In this study, we screened 29 NSAIDs in C2C12 myoblasts, and found that 13 NSAIDs enhanced Mbnl1 expression, where COX-1-selective NSAIDs upregulated Mbnl1 more than COX-2-selective NSAIDs. Consistently, knockdown of COX-1, but not of COX-2, upregulated MBNL1 expression in C2C12 myoblasts and myotubes, as well as in myotubes differentiated from DM1 patient-derived induced pluripotent stem cells (iPSCs). Luciferase assay showed that COX-1-knockdown augmented the MeR2 enhancer activity. Furthermore, bisulfite sequencing analysis demonstrated that COX-1-knockdown suppressed methylation of MeR2. These results suggest that COX-1 inhibition upregulates Mbnl1 transcription through demethylation of the MeR2 enhancer. Taken together, our study provides new insights into the transcriptional regulation of Mbnl1 by the COX-1-mediated pathway.

The high level of nuclear radiation threats in the modern world determines the need to find new means of pharmacological protection of the health of military personnel and civilians from the effects of ionizing radiation. Of particular scientific interest in this aspect are natural polyphenols as a promising basis for the development of newdrugs, radiomodifiers.Justification of the prospects of creating radioprotective agents based on compositions of plantpolyphenolic substances (PPS) and polysaccharides.The experiments were performed on 130 laboratory white rats-male of Wistar line sexually mature weighting 180-240 g. Animals once received a total X-ray dose equivalent to 4.25 Gy. The effects ofquercetin and patulaten to the processes of reparative regeneration under conditions of X-ray irradiation andagainst the background of butadione suppression were investigated. Indicators in the study groups were compared using the Student's t-test for independent samples; the differences were considered statistically significantat p0.05.The various biological properties of quercetin, in particular, the ability to bind hydroxyl radicals, is thepotential for developing radioprotective agents based on it. At the first stage of the study, the effect of PPS andtheir compositions with polysaccharides on reparative regeneration was studied against the background of its suppression in intact and irradiated animals. With the oral administration of PPS and their compositions with pectin towhite rats, 30 minutes before the administration of butadion, an increase in the processes of reparative regeneration in the cells of the covering epitheliumof the esophagus was observed. At the same time, quercetin granulescaused the most expressive effect, which increased the statistically significant value of the mitotic index by 78.5 %in relation to the group of animals injected with butadion. At the second stage of the study, the effect of polyphenolic substances and their compositions with pectin on the processes of reparative regeneration in intact and irradiated white rats was studied on a model of linear skin wounds. The prophylactic administration of quercetin granules and the treatment of wounds with 20 % sterile quercetin gel significantly accelerated the healing process.Experimental data indicate that quercetin granules have the ability to stimulate the processes of reparative regeneration, quercetin showed the greatest efficiency with simultaneous use inside and topically.The research results indicate the promise of developing radioprotective drugs that can stimulatereparative regeneration processes based on compositions of plant polyphenolic substances and polysaccharides invarious qualitative and quantitative ratios.Vysokyĭ riven' radiatsiĭno-iadernykh zagroz v suchasnomu sviti vyznachaie neobkhidnist' poshuku diievykh zasobiv farmakologichnogo zakhystu zdorov’ia viĭs'kovosluzhbovtsiv i tsyvil'nogo naselennia vid diï ionizuiuchogo vyprominiuvannia. Osoblyvyĭ naukovyĭ interes v ts'omu aspekti predstavliaiut' pryrodni polifenoly iak perspektyvni spolukydlia rozrobky farmpreparativ radiozakhysnoï diï.Meta. Obґruntuvannia perspektyv stvorennia zasobiv radiozakhysnoï diï na osnovi kompozytsiĭ roslynnykh polifenol'nykh spoluk (PFS)i polisakharydiv.Material ta metody. Eksperymenty provedeno na 130 laboratornykh bilykh statevozrilykh shchurakh-samtsiakh liniïWistar masoiu 180–240 g. Tvaryny odnorazovo otrymaly zagal'ne rentgenivs'ke oprominennia v dozi, ekvivalentniĭ 4,25 Gr. Doslidzhuvaly vplyv kvertsetynu i patulatenu na reparatyvnu regeneratsiiu na modeli liniĭnykhran shkiry na foni oprominennia ta na foni prygnichennia Butadionom. Pokaznyky v grupakh doslidzhennia porivniuvaly za dopomogoiu t-kryteriiu St'iudenta dlia nezalezhnykh vybirok; vidminnosti vvazhaly statystychno znachushchymy pry0,05.Rezul'taty doslidzhennia. Riznomanitni biologichni vlastyvosti kvertsetynu, zokrema spromozhnist' zv’iazuvatygidroksyl'ni radykaly, ie potentsialom dlia rozrobky na ĭogo osnovi radiozakhysnykh zasobiv. Pry peroral'nomuvvedenni polifenol'nykh spoluk ta ïkh kompozytsiĭ z pektynom bilym shchuram za 30 khv do vvedennia butadionu sposterigaly posylennia protsesiv reparatyvnoï regeneratsiï v klitynakh pokryvnogo epiteliiu stravokhodu. Pry ts'omunaĭbil'sh vyrazhenu diiu chynyly kvertsetynu granuly, iaki zbil'shuvaly statystychno dostovirnu velychynu mitotychnogo indeksu na 78,5 % porivniano z grupoiu tvaryn, iakym vvodyly butadion (kontrol'). Na drugomu etapidoslidzhennia vyvchavsia vplyv polifenol'nykh spoluk (PFS) ta ïkh kompozytsiĭ z pektynom na protsesy reparatyvnoï regeneratsiï u intaktnykh i oprominenykh bilykh shchuriv na modeli liniĭnykh ran shkiry. Profilaktychne vvedenniakvertsetynu granul i obrobka ran 20 % steryl'nym gelem kvertsetynu znachno pryskoriuvalo protses zagoienniaran. Eksperymental'ni dani svidchat' pro zdatnist' kvertsetynu granul posyliuvaty protsesy reparatyvnoï regeneratsiï, osoblyvo pry odnochasnomu zastosuvanni peroral'no i mistsevo.Vysnovky. Rezul'taty doslidzhen' vkazuiut' na perspektyvnist' rozrobky radiozakhysnykh preparativ, zdatnykhstymuliuvaty protsesy reparatyvnoï regeneratsiï na osnovi kompozytsiĭ roslynnykh polifenol'nykh spoluk ipolisakharydiv u riznykh iakisnykh i kil'kisnykh spivvidnoshenniakh.

Improvement of the bioavailability of poorly soluble medicinal substances is currently one of the major challenges for pharmaceutical industry. Enhancing the dissolution rate of those drugs using novel methods allows to increase their bioavailability. In recent years, silica-based mesoporous materials have been proposed as drug delivery systems that augment the dissolution rate. The aim of this study was to analyse the influence of phenylbutazone adsorption on SBA-15 on its dissolution rate. Moreover, we examined the cytotoxicity of the analyzed silica. The material was characterized by SEM, TEM, DSC, 1H-NMR, XRD, and FT-IR. The phenylbutazone did not adsorb on unmodified SBA-15, while the adsorption on APTES-modified SBA-15 resulted in 50.43 mg/g of loaded phenylbutazone. Phenylbutazone adsorbed on the APTES-modified SBA-15 was then released in the hydrochloric acidic medium (pH 1.2) and phosphate buffer (pH 7.4) and compared to the dissolution rate of the crystalline phenylbutazone. The release profiles of the amorphous form of adsorbed phenylbutazone are constant in different pH, while the dissolution rate of the crystalline phenylbutazone depends on the pH. The cytotoxicity assays were performed using the Caco-2 cell line. Our results indicate that the analyzed material ensured phenylbutazone adsorption in an amorphous state inside the mesopores and increased its dissolution rate in various pH levels. Furthermore, the cytotoxicity assay proved safety of studied material. Our study demonstrated that APTES-modified SBA-15 can serve as a non-toxic drug carrier that improves the bioavailability of phenylbutazone.

Apoptosis is an important mechanism underlying chondrocyte loss in osteoarthritis that could be affected by modulation of lipid signaling via inhibition of cyclooxygenases (COX) and soluble epoxide hydrolase (sEH).To determine the impact of inhibiting COX and sEH alone or in combination on apoptosis of equine chondrocytes.Cultured primary equine chondrocytes were subjected to serum deprivation or incubation with 1 μg/ml tunicamycin for 24 h to induce apoptosis via caspase activation and endoplasmic reticulum (ER) stress, respectively. Cells were treated with the non-selective COX inhibitor phenylbutazone, the COX-2 selective inhibitor firocoxib and the sEH inhibitor t-TUCB alone or in combination. The inhibitors were used at half-maximal (ICIn the caspase model, 10xICIn vitro findings that will need to be verified in vivo.Chondrocyte apoptosis caused by ER stress can be enhanced by COX inhibition but prevented by concurrent inhibition of sEH.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), like phenylbutazone (PBZ), are prescribed to treat pain and inflammation in the equine. However, experimentally their use has been associated with the development of Equine Glandular Gastric Disease (EGGD). To evaluate the prophylactic effects of Glycyrrhiza glabra root extracts (GGRE) on EGGD induction following oral administration of PBZ, 12 donkeys were used. Animals were divided into three equal groups (A, B and C) in a randomized block design. A: placebo, B: PBZ (4.4 mg/kg PO q 12 h) and C: PBZ plus GGRE (17.6 mg/kg PO q 24h). Gastroscopy and blood sampling for CBC, biochemical tests and antioxidant status were performed days 0 and 7. All but 1 animal had no EGGD lesions on day 0, but on day 7, severe EGGD lesions were seen in group B animals (grade 1/4 (× 1), grade 2/4 (× 2), and grade 3/4 (× 1)). Only mild changes were seen in group C animals, the most severe lesions being grade 1/4 lesions in 2 animals. No change was observed in Group A. Hematology and serum antioxidant status did not change significantly in any group. In group B glucose decreased and ALT and ALP increased, while in group C only ALP increased. In conclusion, GGRE reduced the severity of EGGD caused by PBZ. Further, GGRE prevented PBZ induced hypoglycemia and might reduce the possible hepatic injury of PBZ.

Made available in DSpace on 2022-04-29T08:32:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 Proper pain therapy requires adequate pain assessment. This study evaluated the reliability and validity of the Unesp-Botucatu horse acute pain scale (UHAPS), the Orthopedic Composite Pain Scale (CPS) and unidimensional scales in horses admitted for orthopedic and soft tissue surgery. Forty-two horses were assessed and videotaped before surgery, up to 4 hours postoperatively, up to 3 hours after analgesic treatment, and 24 hours postoperatively (168 video clips). After six evaluators viewing each edited video clip twice in random order at a 20-day interval, they chose whether analgesia would be indicated and applied the Simple Descriptive, Numeric and Visual Analog scales, CPS, and UHAPS. For all evaluators, intraobserver reliability of UHAPS and CPS ranged from 0.70 to 0.97. Reproducibility was variable among the evaluators and ranged from poor to very good for all scales. Principal component analysis showed a weak association among 50% and 62% of the UHAPS and CPS items, respectively. Criterion validity based on Spearman correlation among all scales was above 0.67. Internal consistency was minimally acceptable (0.51-0.64). Item-total correlation was acceptable (0.3-0.7) for 50% and 38% of UHAPS and CPS items, respectively. UHAPS and CPS were specific (90% and 79% respectively), but both were not sensitive (43 and 38%, respectively). Construct validity (responsiveness) was confirmed for all scales because pain scores increased after surgery. The cut-off point for rescue analgesia was ≥ 5 and ≥ 7 for the UHAPS and CPS, respectively. All scales presented adequate repeatability, criterion validity, and partial responsiveness. Both composite scales showed poor association among items, minimally acceptable internal consistency, and weak sensitivity, indicating that they are suboptimal instruments for assessing postoperative pain. Both composite scales require further refinement with the exclusion of redundant or needless items and reduction of their maximum score applied to each item or should be replaced by other tools. Department of Surgical Specialties and Anesthesiology Medical School São Paulo State University (Unesp), São Paulo Department of Clinical Studies New Bolton Center School of Veterinary Medicine University of Pennsylvania, Kennett Square Dipartimento di Scienze Veterinarie Università degli Studi di Torino The Royal (Dick) School of Veterinary Studies Roslin Institute The University of Edinburgh, Midlothian Department of Veterinary Clinical Sciences Section of Medicine and Surgery Faculty of Health and Medical Sciences University of Copenhagen Department of Veterinary Surgery and Animal Reproduction School of Veterinary Medicine and Animal Science São Paulo State University (Unesp), São Paulo Department of Veterinary Medicine MaringáState University, Paraná Faculty of Animal Science and Food Engineering Sao Paulo State University Department of Anesthesiology and Domestic Animal Surgery Faculty of Veterinary Medicine Ghent University Department of Surgical Specialties and Anesthesiology Medical School São Paulo State University (Unesp), São Paulo Department of Veterinary Surgery and Animal Reproduction School of Veterinary Medicine and Animal Science São Paulo State University (Unesp), São Paulo Faculty of Animal Science and Food Engineering Sao Paulo State University

A 38-year-old white rhinoceros bull (Ceratotherium simum) was treated with phenylbutazone over a period of four years for chronic osteoarthritic and neuropathic pain of the thoracic limbs. Initially the lameness was sporadic and responded well to phenylbutazone (4 mg/kg PO SID). The lameness increased in severity during the winter months. Four years after treatment was initiated, there was an increase in the severity and incidence of the lameness. Analgesia was augmented by the addition of non-conventional analgesic drugs. Pentosan polysulfate was administered IM at 3 mg/kg once a week for two treatments and thereafter monthly when possible. Gabapentin was used at 8 mg/kg but produced ataxia and anorexia. The dose was reduced to 4-5 mg/kg PO SID. Amantadine (3 mg/kg PO BID) was added to the multimodal analgesia and produced a significant improvement in the clinical lameness. Chronic inflammation was monitored using both automated and manual fibrinogen methods. Eventually the rhinoceros was euthanized on humane grounds when treatment was unable to produce suitable clinical relief.

Equine Glandular Gastric Disease (EGGD) is a common disease in sport horses. This disease might be associated with usage of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating inflammatory diseases. Although gastroscopy has been an effective method for diagnosis, but a less invasive, and inexpensive method is preferred. This study used proteomic technology to identify candidate serum proteins that might be used as markers of NSAIDs induced EGGD. Five Thoroughbred horses were given high doses of NSAID, phenylbutazone to treat lameness. The experiment was divided into three periods: (i) Pre-EGGD period, (ii) during EGGD period, and (iii) Post-EGGD period. Gastroscopy were used to diagnose EGGD, serum was collected to perform gel electrophoresis (1D SDS-PAGE) and mass spectrometry (LC-MS) in order to identify serum proteins in each group. The candidate serum proteins were computationally predicted for the interaction between phenylbutazone and proteins, tissue specific expression, and association to gastric ulceration. After EGGD induction, all horses showed clinical signs of colic with marked congestion and erosion appearing in the mucosa of the glandular stomach whereas no change was observed in the mucosa of non-glandular stomach. Our proteomic results identified 14 proteins that might be used as EGGD markers. These proteins were highly expressed in the glandular stomach and some proteins were associated with phenylbutazone or ulcer development. However, confirmation of these candidate marker proteins is required with specific antibodies in the larger horse population before they can be considered for application in the field.

Phenylbutazone (PBZ) is a potent mon-steroidal anti-inflammatory drug used commonly in performance horses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics of PBZ and its metabolites following intravenous (IV) and oral administration and to describe the duration of pharmacodynamic effect. To that end, 17 horses received an IV administration and 18 horses an oral administration of 2 g of PBZ. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of PBZ and eicosanoids were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and non-compartmental pharmacokinetic analysis performed on concentration data from IV and oral administration. Serum concentrations of PBZ and its metabolites were below the limit of quantitation at 96 hours post administration. The volume of distribution at steady state, systemic clearance, and terminal half-life was 0.194 ± 0.019 L/kg, 23.9 ± 4.48 mL/h/kg, and 10.9 ± 5.32 hours, respectively. The terminal half-life following oral administration was 13.4 ± 3.01 (paste) and 15.1 ± 3.96 hours (tablets). Stimulation of PBZ treated whole blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2 , PGE2 , LTB4 and 15-HETE production for a prolonged period of time post drug administration. The results of this study suggest that PBZ has a prolonged anti-inflammatory following IV or oral administration of 2 g to horses.

Pazopanib (PZP) is a multi-targeting tyrosine kinase inhibitor and is currently approved by FDA for the treatment of soft tissue sarcoma and renal cancer. Molecular interaction mechanism of PZP with human serum albumin (HSA) was explored under simulated physiological conditions (pH = 7.4), using fluorescence and UV absorption spectroscopy along with computational methods. Based on the inverse correlation between the Stern-Volmer constant (

Flunixin meglumine is the most commonly used nonsteroidal anti-inflammatory drug used to treat elephants; however, no pharmacokinetic study for flunixin has yet been conducted in these species, and dosages used range widely. Pharmacokinetic parameters of flunixin were determined in African (Loxodonta africana) and Asian (Elephas maximus) elephants after single-dose oral administration of 0.8 and 1.5 mg/kg flunixin paste in each species. Elephant compliance to oral administration of banamine was occasionally challenging, especially among older, female African elephants. After administration of 0.8 mg/kg flunixin, mean serum concentrations peaked in approximately 1.3 hr at 2.1 ± 0.8 µg/ml for Asian (n = 8) and 2.8 hr at 2.5 ± 0.7 µg/ml for African (n = 8) elephants. Dosages of 1.5 mg/kg flunixin resulted in mean serum concentration peaks of 7.2 ± 1.5 µg/ml in Asian elephants (n = 7) and 4.4 ± 0.7 µg/ml in African elephants (n = 6). However, multiple-dose trials using 1.1 mg/kg flunixin resulted in peak serum concentrations that were again less in Asian than African elephants (2.7 µg/ml versus 4.4 µg/ml, respectively). Asian elephants consistently had lower time to maximal concentration, greater area under the curve, and longer mean residence times compared with African elephants. In other species, flunixin is excreted unchanged primarily via hepatic routes with small amounts in the urine. Asian elephants may engage in some level of enterohepatic recycling of flunixin, as was previously reported for phenylbutazone. This study supports that different oral dosing regimens should be used for Asian (1.0 mg/kg SID) and African (1.2 mg/kg SID) elephants, and oral administration techniques used should ensure complete dosage delivery.

Background: Complete avulsion of the hoof in horses, also known as exungulation, is not a commonly reported injury and usually leads to euthanasia due to the great amount of tissue loss, intense pain, secondary complications, expensive and lengthy treatment. It can involve deep structures and cause different complications leading to chronic lameness. In stallions affected by such injury, the reproductive tract and performance may also be affected. The aim of this study was to report a case of complete avulsion of the right front hoof in a Criollo stallion and subsequent bilateral testicular degeneration. Case: A 10-year-old Criollo stallion was referred to the Veterinary Clinical Hospital of the Federal University of Pelotas (HCV- UFPel) with a complete avulsion of the left front hoof. At admission, the stallion had clinical parameters compatible with intense pain and blood loss. Evaluation of the wound demonstrated that the distal end of the third phalanx (P3) was exposed but no fracture was detected on radiological evaluation. No other structure was apparently affected. Initially, anti-inflammatory (phenylbutazone) and opioid (morphine) was given for pain control and supportive fluid therapy was started to restore hydration. Antibiotic (Sulfamethoxazole with trimethoprim) were administered for 10 days. Continued therapy with phenylbutazone, pentoxifylline, omeprazole and supplementation with methionine, biotin and zinc was also given. Local treatment was carried out by cleaning the wound, applying an antimicrobial ointment and dressing it with a bandage. Wound management was adapted according to the evolution and healing process. The stallion was kept in stall rest during its hospitalization time. In the second month after the injury, accumulation of liquid in the scrotum was observed. Clinical and ultrasound evaluation lead to a presumptive diagnosis of testicular degeneration. The stallion was discharged after three months when the wound was almost healed and the hoof had started to grow. Six month later, a follow up by the referring vet showed that the hoof was almost completely grown and the x-ray assessment demonstrated a cranial rotation and resorption of the distal end of the third phalanx. Discussion: The stallion of this report had a complete avulsion of the hoof capsule caused by trauma. Conservative treatment was established including wound cleaning and dressing to avoid contamination, control of pain and inflammation, antimicrobial care and supplementation to support hoof growth. Time period for wound healing and hoof growth was in agreement with other cases described previously. Bone sequestrum of the distal end of the third phalanx, and detachment of a fragment were observed in this case, followed by bone resorption. The stallion was closely monitored to prevent laminitis in the contralateral limb and no alterations were detected during the treatment period. Testicular degeneration was observed, probably caused as a consequence of hoof avulsion and due to a long period of stall rest. Degenerative alterations in testicles interfere with thermoregulation and spermatogenesis, affecting semen quality and reproductive performance. Rotation of the third phalanx was also observed six months later caused by the hoof loss. In conclusion, the patient of this report had a complete regrowth of the hoof capsule although a long intensive treatment was necessary to achieve this result. As a consequence, testicles degeneration may happen impairing its function as a stallion. Keywords: exungulation, hoof trauma, degenerative changes.

The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s. Incubation of phenylbutazone in microsomes generated oxyphenbutazone and gamma-hydroxy phenylbutazone. Microsomal incubations with flunixin meglumine generated 5-OH flunixin, with a kinetic profile suggestive of substrate inhibition. In recombinant P450 assays, equine CYP3A97 was the only enzyme capable of generating oxyphenbutazone while several members of the equine CYP3A family and CYP1A1 were capable of catalyzing the biotransformation of flunixin to 5-OH flunixin. Flunixin meglumine metabolism by CYP1A1 and CYP3A93 showed a profile characteristic of biphasic kinetics, suggesting two substrate binding sites. The current study identifies specific enzymes responsible for the metabolism of two NSAIDs in horses and provides the basis for future study of drug-drug interactions and identification of reasons for varying pharmacokinetics between horses.

BackgroundAcute kidney injury (AKI) in horses may develop as a complication of a primary disease or following the administration of nephrotoxic drugs, and may pose a diagnostic challenge. Hence, the main objective of this study was to evaluate the concentrations and diagnostic significance of serum symmetric dimethylarginine (SDMA) and conventional renal dysfunction biomarkers in healthy horses, horses at risk of developing AKI, and horses with clinically evident AKI. A second aim was to assess how gastrointestinal disease and exposure to potentially nephrotoxic drugs affected SDMA levels. Thirty healthy horses, 30 horses with gastrointestinal disease and/or receiving phenylbutazone or gentamicin (risk group) and 11 horses with AKI were included in the study. Serum SDMA levels were measured using commercially available enzyme immunoassay tests.ResultsSDMA levels in healthy horses, horses at risk of AKI and horses with AKI were 12 µg/dL (11–14), 12 µg/dL (11–13) and 20 µg/dL (20–37), respectively (all results presented as a median (quartile 1–quartile 3)). There was a significant difference in SDMA concentration between the healthy horses and those with AKI, whereas the SDMA levels in healthy horses and those at risk of AKI were comparable. A SDMA cut-off value of 19 µg/dL was established. Horses from the risk group had higher urine protein concentration and urine protein to creatinine ratio compared with healthy horses. Furthermore, horses with colic from the risk group presented with elevated urine γ-glutamyl transpeptidase to creatinine ratio.ConclusionThe SDMA cut-off value established in healthy horses was higher than previously reported. The SDMA level correlated with the azotaemia levels. Horses from the AKI risk group had normal SDMA levels but single urine parameters was abnormal indicating their higher sensitivity in assessing subclinical kidney dysfunction.

OBJECTIVE To examine the association between prerace administration of phenylbutazone and the risk of musculoskeletal injury (MSI) and fatal injury in Thoroughbred racehorses that raced between 2006 and 2015 at 2 of the 4 official racetracks in Argentina. SAMPLE Data from racetrack databases and veterinary reports on 283,193 race starts. PROCEDURES Data were collected relating to race performance and injury outcomes for starts at these tracks. The incidence of MSI and fatal injury was calculated for each year, stratified by the declared prerace administration of phenylbutazone. Univariable logistic regression, followed by multivariable logistic regression, was used to identify significant risk factors for both MSI and fatal injury. RESULTS Analyses identified associations between the declared prerace administration of phenylbutazone and the risk of MSI and fatal injury during racing. Horses with declared prerace phenylbutazone administration had greater odds of MSI (OR, 1.45 [95% CI, 1.03 to 2.04]) and fatal injury (OR, 1.59 [95% CI, 1.1 to 2.27]) than did horses racing without prerace phenylbutazone administration. These associations remained significant when other risk factors were accounted for in both multivariable models. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested an association between the prerace administration of phenylbutazone and the risk of MSI and fatal injury in Thoroughbred racehorses during racing. Although these results did not imply a direct causal relationship between prerace phenylbutazone administration and injury, they may be considered in the development of more conservative medication policies to optimize racehorse welfare in North and Latin America.

An extract from Eisenia bicyclis containing -principally a polyphenolic polymer was examined for pharmacological activity. The investi gat ion centered around the established activity of a model polyphenolic compound, phloroglucinol. Studies on inflammation and alteration of hepatic microsomal enzyme activity were also performed. Heat denat uration of a 0.15 % bovine serum albumin solution was inhibited 96% by the addition of the material at a final concentration of 0.32 mg/ml. Since stabilization of such solutions is often indicative 9f anti-inflammatory activity, direct me asurements of this. activity were made . The inhibition of formation of carageenin-induced rat paw edema was utilized as a test system. As determined by paw volume changes, administration of a dose of 75 mg/kg (ip) one hour prior to carrageenin injection inhibited edema production by 88%. The potent anti-inflammatory agent phenylbutazone, at a dose of 90 mg/kg (ip), provided 100% protection. The protection given by the Eisenian extract apparently was not due to pituitary-adrenal stimulation, since the protection is 4· fold better than that given by a dose of 50 mg/kg ( ip ) of cortisone. The effect cannot be attributed to changes in body temperature, which r emains unchanged . The effect can be partially but not completely attributed to the irr·itant

This study aimed to evaluate the efficacy of flunixin, ketoprofen and phenylbutazone on serum biochemistry, plasma catecholamines and serum cortisol in Delman horses with mild colic. During the study period, 32 horses were evaluated due to mild colic. Flunixin, ketoprofen, and phenylbutazone were administered intravenously at the recommended dose rates of 1.0; 2.2 and 4.4 mg/kg, respectively. Administration of the NSAIDs commenced on Day 1 and continued every 12 h for 12 days. Blood samples collected between days 2, 5, 9 and 13 to evaluate AST, ALP, GGT, creatinine, urea, epinephrine, norepinephrine, and cortisol level. The data analysis performed using Multivariate analysis of variance (Manova) followed by Duncan multiple range test. The results showed a significant alleviation in all observed variables on Day 13, although the use of various NSAIDs showed no significant difference.

Background: Phenylbutazone is a class of non-steroidal anti-inflammatory drugs (NSAIDs) used in the treatment of rheumatoid arthritis. Phenylbutazone is used by the transdermal route to reduce the irritating effect on the gastrointestinal tract. Purpose: This study aims to obtain phenylbutazone suspensions with optimal levels in the ethosome vesicular carrier. Methods: Preparation was carried out by the hot method (40oC) and cold method (30oC) as well as variations in the concentration of phosphatidylcholine (2% and 3%) and ethanol (30%, 35%, and 40%). Characterization of vesicles, namely the shape and size of vesicles using optical microscopy and entrapment efficiency using the spectrophotometer method with λ maks 266.6 nm. Optimization of phenylbutazone levels was carried out at a concentration of 0.1%; 0.15%; 0.2%; and 0.25%. The optimum formula was obtained at a concentration of phosphatidylcholine 3% and ethanol 35% prepared by the hot method. Results:. The form of a Small Unilamellar Vesicle (SUV), a size of 23.7 nm, and entrapment efficiency is 88.358%. Optimization of phenylbutazone levels was obtained at a concentration of 0.1% with entrapment efficiency of 88.358%. Conclusion: The optimum level of phenylbutazone in the vesicular carrier ethosome was 0.1%.Keywords: ethosome, optimation, phenylbutazone, transdermal ABSTRAKLatar Belakang: Fenilbutazon merupakan golongan obat antiinflamasi non stroid (AINS) yang digunakan pada pengobatan penyakit rheumatoid arthritis. Fenilbutazon digunakan melalui rute transdermal untuk mengurangi efek iritasi pada saluran cerna. Tujuan: Penelitian ini bertujuan memperoleh suspensi fenilbutazon dengan kadar yang optimal dalam pembawa vesikular etosom. Metode: Preparasi dilakukan dengan metode panas (40oC) dan metode dingin (30oC) serta variasi konsentrasi fosfatidilkolin (2% dan 3%) dan etanol (30%, 35%, dan 40%). Karakterisasi vesikel yaitu bentuk dan ukuran vesikel menggunakan mikroskop optik serta efisiensi penjerapan menggunakan metode spektrofotometer pada λmaks 266,6 nm. Optimasi kadar fenilbutazon dilakukan pada konsentrasi 0,1%; 0,15%; 0,2%; dan 0,25%. Diperoleh formula optimum pada konsentrasi fosfatidilkolin 3% dan etanol 35% yang dipreparasi dengan metode panas Hasil: Vesikel yang diperoleh berbentuk Small Unilamellar Vesicle (SUV), ukuran 23,7 nm, dan efisiensi penjerapan 88,358%. Optimasi kadar fenilbutazon diperoleh pada konsentrasi 0,1% dengan efisiensi penjerapan 88,358%. Kesimpulan: Disimpulkan bahwa kadar optimum fenilbutazon dalam pembawa vesikular etosom adalah 0,1%.Kata kunci: etosom, optimasi, fenilbutazon, transdermal

Background Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown. Objectives To evaluate the effect of omeprazole on phenylbutazone-induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD). Study design Randomised block experimental design. Methods Twenty-two horses with EGGD and ESGD scores ≤2 were included. Horses were assigned to treatment groups: phenylbutazone (4.4 mg/kg PO q 12 h; PBZ), phenylbutazone plus omeprazole (4 mg/kg PO q. 24 h; PBZ/OME) or placebo (CON) in a randomised block design based upon initial EGGD score. Horses were treated for up to 14 days. Gastroscopy was performed weekly; CBC and biochemistry were performed at Day 0 and study end. Horses were monitored for signs of colic and/or diarrhoea. Results EGGD score increased in PBZ (median change 1, inter-quartile range, [IQR], 0-2) compared to PBZ/OME (median change 0, IQR -1 to 0; P = .05). PBZ/OME (6/8) had more intestinal complications than CON (0/6; difference between proportions = 75%; 95% CI, 23%-93%; P = .03). Plasma protein concentrations decreased in PBZ, compared to CON (mean difference between groups, 14 g/L; 95% CI, 1.04-27; P = .03). Five horses were withdrawn from the study due to intestinal complications (n = 3 PBZ/OME and n = 2 PBZ); one horse (PBZ) was withdrawn due to severe grade 4 EGGD. Main limitations Small sample size and changes in management for the 2-3 days prior to study initiation; variable treatment duration among groups due to development of complications. Conclusions Administration of omeprazole ameliorated PBZ-induced EGGD, but was associated with an increase in intestinal complications. Caution should be exercised when co-prescribing NSAIDs and omeprazole in horses, particularly in association with change in management.

The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s. Incubation of phenylbutazone in microsomes generated oxyphenbutazone and gamma-hydroxy phenylbutazone. Microsomal incubations with flunixin meglumine generated 5-OH flunixin, with a kinetic profile suggestive of substrate inhibition. In recombinant P450 assays, equine CYP3A97 was the only enzyme capable of generating oxyphenbutazone while several members of the equine CYP3A family and CYP1A1 were capable of catalyzing the biotransformation of flunixin to 5-OH flunixin. Flunixin meglumine metabolism by CYP1A1 and CYP3A93 showed a profile characteristic of biphasic kinetics, suggesting two substrate binding sites. The current study identifies specific enzymes responsible for the metabolism of two NSAIDs in horses and provides the basis for future study of drug-drug interactions and identification of reasons for varying pharmacokinetics between horses.

Cnidoscolus tehuacanensis is an endemic medicinal species used to treat some inflammatory diseases, and biosynthesizes triterpenes and sterols, being Lupeol Acetate (LuAc) the main compound. It was submitted to biological assay to determine the anti-inflammatory and leishmanicidal potential. Anti-inflammatory effect was determined on acute (12-O-tetradecanoylphorbol-13-acetate -TPA- and Carragenan models) and chronic inflammatory models (induce with Complet Freud´s Adjuvant -CFA-) using Indomethacin and Phenylbutazone (PBZ) as reference drugs. In vitro leishmanicidal activity was determined on Leishmania mexicana promastigotes and amastigotes, Miltefosine and amphotericin B were used as reference drugs. In TPA assay, LuAc showed an ED50=1.79 mg/ear (Ind, ED50=0.91 mg/ear) and on Carragenan model, the antiinflammatory effect was not dose-dependent, in this case LuAc at 100, 150 and 250 mg/kg showed 43.31, 40.22 and 51.25% of inhibition, respectively at 5 h. On CFA chronic inflammatory model, LuAc and PBZ groups showed similar anti-inflammatory effect and similar Body Weight (BW) gain although this value was less respect to healthy and CFA groups. Also, inhibited the COX-2 activity being this effect slightly better that PBZ, and the joints and soft tissue from LuAc and PBZ groups did not show any alteration with respect to CFA group. In soft tissue, CFA group showed a significant increase size and leukocyte infiltrate as a result of the chronic inflammatory process; it group also showed sinusoidal hyperplasia in the joint. In liver histological analysis, the healthy and LuAc groups showed no alteration, and the CFA group showed a slight microabscess and scarce hematopoiesis, while the PBZ group presented scarce steatosis. The fraction (rich in LuAc) and LuAc pure were less active that extract against L. mexicana promastigotes. C. tehuacanesis is a potential source of LuAc. This natural compound showed a good anti-inflammatory activity (similar effect to PBZ) and did not cause liver damage.

In this study, concentrations of analgesics including acetaminophen (ACETAM), indomethacin (INDO), acetylsalicylic acid (ACETYL ACID), phenylbutazone (PHENYL) and codeine (CO) were determined in wastewaters and risk assessment for organisms in the receiving environment was carried out. The analytical method for determination of analgesics in wastewater was optimized. The detection of analgesics was carried out by HPLC-MS/MS. Limit of detection (LOD) values for studied compounds were determined between 0.017 and 0.197 µg/L. Wastewater samples were taken from Konya Urban Wastewater Treatment Plant influent and effluent. ACETAM, CO, and INDO compounds were determined as 13000, 150, 80 ng/L in influent samples, respectively. ACETYL ACID and PHENYL were determined below limit of detection in influent samples. While INDO was determined about 84ng/L in effluent samples, ACETAM and CO were determined up to 25ng/L. The analgesic compounds indicated insignificant risk for algae, Daphnia magna and fish in the receiving environment

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in therapeutic doses in human and veterinary medicine for the treatment of inflammation, pain, and fever. A method for the simultaneous determination of nine NSAIDs, known as therapeutic prohibited substances, in equine urine was developed and fully validated according to the European Commission Decision 2002/657/EC and Association of Official Racing Chemists criteria. The validation was performed for naproxen, flunixin, ketoprofen, diclofenac, eltenac, meclofenamic acid, phenylbutazone, vedaprofen, and carprofen in equine urine in accordance with the International Screening Limits (ISL) regulated by International Federation of Horseracing Authorities. After basic hydrolysis, samples were extracted with a C18 cartridge using automated solid-phase extraction. Several derivatization reagents were investigated, and trimethylphenylammonium hydroxide/methanol (20/80, v/v) was selected. Analyses were carried out using gas chromatography-mass spectrometry with selected ion monitoring mode, but the method can be applied to a large number of analytes. The within-laboratory reproducibility was not more than 12.8% (≤15%), and mean relative recoveries ranged from 91.1% to 104.1% for inter-day and intra-day precision. The decision limits (CCα) and detection capabilities (CCβ) were evaluated at concentrations near the ISL for each therapeutic substance. The validation results demonstrated that the method is highly reproducible, easily applicable, and suitable for the analysis of some NSAIDs in equine urine that have not been previously published. Finally, the method was also applied to known positive samples.

Background Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects. Objectives Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators. Study design Two-way randomised balanced crossover experiment. Methods Twelve Thoroughbred exercised horses received 500 mg FM IV alone or in combination with 2 g of IV PBZ 24 hours later. Blood and urine samples were collected prior to and for up to 120 hours post-drug administration. Whole blood samples were collected at various times and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of FM, PBZ and eicosanoids were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis performed on concentration data. Results Flunixin meglumine clearance was significantly increased when horses received PBZ 24 hours post-administration (P = .03). No other differences in pharmacokinetic parameters were noted between groups. Thromboxane B2 was significantly suppressed, relative to baseline for 96 hours post-FM administration. Subsequent administration of PBZ prolonged the suppression. Prostaglandin E2 was decreased for 24 hours following administration of FM with subsequent administration of PBZ prolonging the suppression until 120 hours. PGF2alpha concentrations were decreased for up to 168 hours post-FM administration. FM administration significantly decreased 15-HETE. Main limitations Small sample size and lack of a phenylbutazone-only treatment group. Conclusions Administration of PBZ post-FM administration increased FM clearance. The anti-inflammatory effects of FM appear to be prolonged when PBZ is administered 24 hours post-administration.

BACKGROUND: There is little knowledge of the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) and whether their prescription varies between countries. OBJECTIVE: To describe prescription practices of NSAIDs in equids in the United Kingdom (UK), United States of America (USA) and Canada. STUDY DESIGN: Descriptive observational study. METHODS: Free-text electronic medical records from 141,543 equids from 10 equine practices in the UK, 255,777 equids from 7 equine practices with 20 branches from the USA and 2 practices with 7 branches from Canada were evaluated. A validated text-mining technique was used to describe the proportion of equids prescribed NSAIDs at least once in these countries. The choice of NSAIDs in orthopaedic and colic cases was evaluated. RESULTS: The prescription of NSAIDs is more common in the USA (42.4%) and Canada (34.2%) than in the UK (28.6%). Phenylbutazone and flunixin meglumine were the drugs mostly prescribed in all countries. While flunixi meglumine was most prescribed with colic cases in all countries, a proportion received phenylbutazone despite this drug being licensed for use only with musculoskeletal disease. Phenylbutazone was the most commonly prescribed drug in cases with orthopaedic disease followed by flunixin meglumine in all countries. Only a small proportion of cases received meloxicam, ketoprofen or firocoxib. MAIN LIMITATIONS: The retrospective design might have resulted in an unknown number of incomplete records, particularly in the reporting of colic and orthopaedic disease. Although the data set is large, the relatively small number of practices recruited from each country may introduce bias. CONCLUSIONS: Clinical practice can differ between countries although the influence of individual practitioners and practice-specific policy on apparent intercountry differences requires further research. Despite several other NSAIDs being available and a substantial effort being made to evaluate their efficacy, the prescription of NSAIDs other than phenylbutazone and flunixin meglumine remains rather limited.

Previous report described that CHCl3:MeOH extract ofC. chayamansaleaves and pure compounds (moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3′,4′-trimethoxyflavanone) showed important topical and systemic anti-inflammatory activity in acute model, as well asin vitroantimycobacterial and antiprotozoal activities. In this paper, we describe thein vivohepatoprotective and anti-inflammatory effects of the CHCl3:MeOH extract in chronic model and the isolation of additional compounds (moretenone and lupeol acetate). The hepatoprotective activity was determined at 39 days using Balb/c mice with liver damage induced with an antitubercular drug (RIF/INH/PZA). The anti-inflammatory activity was evaluated in a chronic model induced with CFA and in two acute models (TPA and carrageenan). In addition, moretenone and lupeol acetate were isolated and identified by spectroscopic data. Lupeol acetate is a main compound present in fractions 14-42, and this fraction was the majority fraction from the extract; from this moretenone was obtained. In animals with liver damage, the extract at 200 and 400 mg/kg induced better body weight gain with respect to positive control (Silymarin); in addition, the mice that received the extract at 200 mg/kg and Silymarin exhibited slight steatosis; however, the animals’ livers at 400 mg/kg did not show steatosis. The extract and fractions 14-42 showed a good anti-inflammatory activity by TPA model (DE50= 1.58 and 1.48 mg/ear) and by carrageenan model (DE50= 351.53 and 50.11 mg/kg). In the chronic inflammatory test, the extract at three doses revealed a similar effect to that of phenylbutazone, although the body weight gain was better in animals that received the extract at 900 mg/kg.Conclusion. The CHCl3:MeOH extract showed significant anti-inflammatory and good hepatoprotective effect on chronic models. The fraction containing moretenone and lupeol acetate as main compounds was more active than extract in both acute models of inflammation.

Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent and rate of drug release for all three forms of Syloid® silica at a 1:1 drug:silica ratio over a period of 30 min. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas were concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid® silica based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility such as phenylbutazone. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile. Keywords: Dissolution, Syloid® silicas, Drug-loading, Phenylbutazone, Solubility

Objective To determine the influence of epidural detomidine and morphine on serum corticosteroid concentrations and pain-related behavioral responses in mares during and after ovariectomy via colpotomy. Study design Blinded prospective study. Animals Nine university-owned mares. Methods Five of 9 horses received caudal epidural detomidine hydrochloride (0.01 mg/kg) and morphine sulfate (0.1 mg/kg) prior to surgery. All horses received local anesthetic around the ovarian pedicle, 0.02 mg/kg butorphanol IV at the start of the procedure and after first ovary removal, were sedated as required throughout the procedure, and were monitored for leg lifting, grunting, and abdominal tensing. Horses were monitored hourly for pain postoperatively. Heart rate was recorded every 4 hours, and photographs were taken to assess pain according to the horse grimace scale (HGS). Control group horses (n = 4) were treated with butorphanol (0.02 mg/kg IV) every 4 hours for 24 hours postoperatively. All horses received oral phenylbutazone 18 hours postoperatively. Serum cortisol was measured prior to the procedure, after first and second ovary removal, and 8 and 24 hours postoperatively. Results No differences were detected between horses receiving caudal epidural detomidine and morphine and those that received systemic opioids. A decrease in HGS score occurred after phenylbutazone administration. Conclusion Administration of caudal epidural detomidine and morphine resulted in similar pain-related behavior and corticosteroid concentrations as did administration of systemic butorphanol every 4 hours for 24 hours postoperatively. Clinical significance Caudal epidural detomidine and morphine may mitigate the requirement for frequent systemic opioid administration after a potentially painful procedure.

What is known and objective Drug-induced parotitis is a rare adverse drug reaction (ADR). A comprehensive literature review identified only three clearly associated medications: L-asparaginase, clozapine and phenylbutazone. Case description We describe a novel case of drug-induced parotitis attributed to doxorubicin and cyclophosphamide chemotherapy for breast cancer. What is new and conclusion Using general and parotitis-specific tools for assessing the probability of an ADR, we estimate the association of doxorubicin and cyclophosphamide with parotitis in this case as 'probable'. To our knowledge, this represents the first reported case of parotitis attributable to these medications and provides a valuable learning tool for the assessment of previously unrecognized ADRs.

The distributions of eight drugs (acetaminophen, acetylsalicylic acid/salicylic acid, ciprofloxacin, clarithromycin, flunixin, phenylbutazone, praziquantel, and thiamphenicol) were determined in milk products (skim milk, milk fat, curd, whey, and whey protein) and used to expand a previous model (from 7 drugs to 15 drugs) for predicting drug distribution. Phenylbutazone and praziquantel were found to distribute with the lipid and curd phases (≥50%). Flunixin distribution was lower but similar in direction (12% in milk fat, 39% in curd). Acetaminophen, ciprofloxacin, and praziquantel preferentially associated with casein proteins, whereas thiamphenicol and clarithromycin associated preferentially to whey proteins. Regression analyses for log [milk fat]/[skim milk] and log [curd]/[whey] had r2 values of 0.63 and 0.67, respectively, with p of

El presente trabajo describe el caso de una potranca de dos años que desarrolló graves lesiones gastrointestinales después de recibir dosis prolongadas de fenilbutazona al tratar una fractura en el miembro anterior derecho. Los hallazgos de necropsia revelaron una severa gastritis catarro- hemorrágico-ulcerativa difusa aguda y edema submucoso y severa enterocolitis mucohemorrágica difusa aguda y esplenomegalia con severa congestión pasiva aguda. La causa de muerte se debió a un paro cardio-respiratorio y coagulopatía con disturbio circulatorio y proceso ulcerogénico gástrico asociado a shock iatrogénico por fenilbutazona., The present paper describes the case of a two-year-old filly who developed severe gastrointestinal lesions after receiving prolonged doses of phenylbutazone when treating a fracture in the right forelimb. Necropsy findings revealed severe acute diffuse catarrahhemorrhagic-ulcerative gastritis and submucosal edema and severe diffuse acute mucohemorrhagic enterocolitis and splenomegaly with severe acute passive congestion. The cause of death was due to cardio-respiratory arrest and coagulopathy with circulatory disturbance and gastric ulcerogenic process associated with iatrogenic shock by phenylbutazone.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause right dorsal colitis, but longitudinal clinical studies are lacking. This study investigates whether NSAID treated horses develop right dorsal colonic pathology in a clinical setting. Non-gastrointestinal hospitalized horses treated with NSAIDs >4 days, and untreated hospital-owned teaching horses and non-gastrointestinal client-owned hospitalized horses were included. All horses were monitored over time with clinical examinations (focusing on presence of colic, depression, reduced appetite, unstructured feces), ultrasonographic intestinal wall measurements, fecal occult blood tests (semi-quantitative results), and blood analysis (total protein and albumin concentrations, white blood cell and neutrophil counts). Outcomes were recorded as “ultrasonographically thickened right dorsal colon (RDC) walls”, “colitis” and “right dorsal colitis”. Findings over time were compared to baseline values and to control horses. Seventeen NSAID treated horses and 5 controls were included. NSAID treated horses developed thickened RDC walls (4/9), and subclinical and mild colitis (9/11) and right dorsal colitis (4/10), whereas all control horses remained healthy. The first changes were identified on treatment day 2. RDC walls of treated horses were significantly thicker compared to their own baseline values and compared to control horses. In conclusion, presumptive colon pathology was identified with a high incidence, starting early in the course of treatment, but with low severity. Appropriate monitoring should be advised throughout NSAID treatment. Additional research for noninvasive diagnostic tests for colon pathology is required.

There are a limited number of published objective assessments of the orthopaedic efficacy of various non-steroidal anti-inflammatory drugs (NSAIDs) in horses. Several different models of pain in horses have been used, but the least invasive orthopaedic model is the reversible foot lameness model using a shoe with either a mechanical heart bar or an eccentrically-placed threaded nut accommodating a bolt, with both models allowing variable levels of lameness after tightening of the bar or bolt against the solar surface of the foot. These and other models have yielded objective data, reviewed here, on NSAID efficacy in orthopaedic conditions. Phenylbutazone and flunixin are of comparable efficacy, and each is superior to ketoprofen, in the reversible model of foot pain, evidenced at rest, during treadmill exercise, and during recovery after exercise. The selective cyclooxygenase (COX)-2 inhibitor firocoxib, given either orally or intravenously, appears to be an effective alternative to traditional pan-COX-inhibiting NSAIDs, but an initial three-fold loading dose is necessary with intravenous firocoxib to achieve steady state and full efficacy faster than the label dose allows. Meloxicam has also been shown to be effective in two published orthopaedic studies. Acetaminophen/paracetamol has shown some initial promise in preliminary studies using the reversible model of foot pain. Combination therapy should involve appropriately-dosed NSAIDs with differing onsets and durations, whereas drugs with similar onsets and durations may not be synergistic. Sanctioning bodies and local or federal laws may restrict or prohibit the use of NSAIDs before or during equestrian competition.

Background Guggul, the gum resin obtained from Commiphora mukul, is one of the components of various formulations of traditional Ayurvedic medicine to treat inflammation, atherosclerosis, and weight loss. This research work describes Guggul lipid as a carrier and synergistic effect for anti-inflammatory drugs. Method Guggulosomes prepared by trituration method was further incorporated into carbopol gel, developed for the enhanced topical drug delivery system for the phenylbutazone. This preparation was characterized by using Attenuated total reflection- Fourier transform infrared spectroscopy (ATR-FTIR), Scanning electron microscopy (SEM), Atomic force microscopy (AFM), Differential scanning calorimeter (DSC), Thermogravimetric analysis (TGA), Particle size & Zeta potential and further guggulosomes was tested for Anti-inflammatory activity and % cumulative drug release. All these study was carried out by using standard protocol. Results The guggulosomes shows all the characteristic peaks in ATR-FTIR. The optimized formulation was spherical in shape having diameter >200 nm. The % entrapment efficiency was 77.2 ± 0.212 with good % Cumulative drug release 60.80 ± 0.707%. The anti-inflammatory activity of the optimized formulation was found satisfactory (89%). Conclusion The guggulosomes prepared by trituration method was found to give a synergistic effect along with the phenylbutazone when incorporated into the carbopol gel. Thus, this present research shows that it can be good perspective for enhanced topical drug delivery system.

Sialosis is observed in relation to diabetes, alcoholism, and malnutrition. An assumed relation between gout and sialosis is probably based on confusion that originated from the therapeutic use of phenylbutazone for gout and the sialadenitis that the medication caused. This report describes a case of sialosis in a patient with a longstanding history of gout that was idiopathic in origin.