Development of nanostructured environmentally responsive system containing hydroxypropyl methylcellulose for nose-to-brain administration of meloxicam.

The intranasal administration of drugs using environmentally responsive formulations, employing a combination of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), can result in release systems that may assist in the treatment of neurological diseases. Meloxicam, considered a potential adjuvant in the treatment of Alzheimer's disease, could be used in these platforms. The aim of this work was to develop a mucoadhesive, thermoresponsive, and nanostructured system containing HPMC for nose-to-brain administration of meloxicam. The initially selected systems were investigated for their rheological, mechanical, and micellar size characteristics. The systems were dilatant at 25 °C and pseudoplastic with a yield value at 37 °C, showing viscoelastic properties at both temperatures. The platform containing HPMC (0.1%, w/w) and P407 (17.5%, w/w) was selected and demonstrated good mucoadhesive properties, along with an appropriate in vitro release profile. HPMC could form a binary system with P407, displaying superior mucoadhesive and thermoresponsive properties for nose-to-brain meloxicam administration, indicating that the selected formulation is worthy of clinical studies.

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

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

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

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

Oral meloxicam given as an ancillary treatment at respiratory disease diagnosis was not associated with growth, clinical scores, or ultrasound scores in preweaned dairy calves.

Objective: To assess the efficacy of a single dose of oral meloxicam as an ancillary therapy to an antibiotic given at the time of respiratory disease identification on average daily gain (ADG), behavioral attitude, clinical respiratory, and lung ultrasound scores in preweaned dairy calves. Animals: 215 male and female Holstein, Jersey, and crossbred preweaned calves enrolled between 1 and 14 days of age at study enrollment on a single commercial dairy in the western US. Methods: The study took place from March 4, 2021, to November 21, 2021. In this double-blind placebo-controlled study, calves were given an antibiotic (1.1 mL of tulathromycin/kg, SC, once) and either a placebo (1 mg of lactose monohydrate/kg, in a gelatin capsule) or oral meloxicam (1 mg/kg) at the time of respiratory disease identification. Behavioral attitude, clinical respiratory, and lung ultrasound scores and ADG were assessed in preweaned dairy calves at different time points including the next health examination, 1 week later, or at weaning. Results: There was no association between treatment (placebo vs meloxicam) on ADG or respiratory disease status at weaning (P > .05). There was no effect of treatment on behavioral attitude, clinical respiratory, or lung ultrasound scores at the next health examination or 1 week later (P > .05). Clinical Relevance: The present study did not provide evidence that oral meloxicam given once is beneficial for growth, behavioral attitude, or clinical or lung ultrasound scores.

Integrated analysis of marine biotoxins and contaminants of emerging concern in bivalve mollusks from Santa Catarina, Brazil.

Santa Catarina is the main producer state of oysters and mussels in Brazil, reaching 98 % of national production. To assure the safety of bivalve mollusks production, control programs of marine biotoxins (MBs) have been continuously performed. Herein, the co-occurrence of MBs and contaminants of emerging concern (CECs) in oyster and mussels from the main production sites of Santa Catarina was reported, covering 178 compounds. Samples of wild and non-cultivated oysters and mussels were also assessed. Chemometric tools were used to evaluate and optimize several sample preparation techniques such as solid-liquid, ultrasound assisted, and pressurized liquid extraction. The optimized protocol was based on ultrasound assisted extraction followed by liquid chromatography coupled to tandem mass spectrometry. The results showed the incidence of several CECs and MBs. In the case of MBs, all results were below the regulatory limits for both cultivated and non-cultivated samples. Wild mollusks have shown a higher number of compounds. Regarding CECs, the more frequent compounds were caffeine, diclofenac, meloxicam, and sertraline. Domoic acid and okadaic acid were the main toxins detected. The results highlighted the need of monitoring for MBs and the potential of oyster and mussels as sentinel organisms to risk analysis of CECs in coastal regions. To the best of our knowledge, this is the first method to describe a simultaneous sample preparation and analysis of CECs and MBs in bivalve mollusks, as well as the first report of meloxicam and florfenicol in mussels and oysters.

Use of meloxicam with or without dipyrone in non-surgical embryo recovery in hair sheep: Effects on animal welfare.

The aim of this study was to determine the effectiveness of meloxicam with or without dipyrone on the welfare of ewes subjected to non-surgical embryo recovery (NSER). Two studies were carried out using 51 multiparous Santa Inês ewes. All animals received a standard oestrous synchronization treatment and a superovulatory protocol. In Study 1, 12 ewes received meloxicam (GM) before cervical transposition (1 mg kg-1 , i.v.), repeated 24 h after (1 mg kg-1 , i.m.), while the other 10 received a saline solution, remaining as a control group (GC1). In Study 2, ewes were allocated into a group of 15 ewes treated as GM of Study 1 associated with dipyrone (GMD; 50 mg kg-1 , i.m.) before cervical transposition, 12 h, and 24 h after, or a control group (GC2) of 14 ewes treated with saline solution. In both studies, heart and respiratory rates (RR), cortisol, glucose, total proteins, albumin and globulins blood concentration were recorded before sedation (BS), after sedation (AS), after cervical transposition, immediately after collection (IAC), and 0.5, 1.5, 3, 6, 12, 24 and 48 h after embryo collection (hAC). In Study 1, RR tended to be greater in GC1 (p = .08), serum total proteins and globulins values were lower and serum albumin values were greater in this group than GM (p = .003, p < .0001, and p < .0001, respectively). In Study 2, treatment of GMD tended to reduce the glycaemia at AS (p = .052) and reduced it at 3hAC (p < .0001), and 6hAC (p = .03). It also tended to reduce cortisol concentrations (p = .10). The other variables varied with NSER without interaction with the experimental treatments. In conclusion, in this study condition, NSER in sheep induced transient changes indicative of stress and possibly pain, therefore, affecting animal welfare. The administration of meloxicam was ineffective to reduce those responses, and the association of dipyrone had only slight effects without modifying the main welfare indicative responses in ewes subjected to NSER.

Influence of Constant Rate Infusions of Fentanyl Alone or in Combination With Lidocaine and Ketamine on the Response to Surgery and Postoperative Pain in Isoflurane Anesthetized Dogs Undergoing Unilateral Mastectomy: A Randomized Clinical Trial.

The aim of this study was to compare the effects of constant rate infusions (CRI) of fentanyl alone or combined with lidocaine and ketamine (FLK), on physiological parameters, isoflurane requirements and the number of postoperative analgesic rescues in dogs undergoing unilateral mastectomy. Twenty-two dogs were premedicated with acepromazine 0.02 mg/kg and morphine 0.5 mg/kg and anesthetized with propofol and isoflurane. Dogs were randomly assigned to 1 of 2 groups: Fentanyl group (fentanyl 5 µg/kg loading dose [LD] and 9 µg/kg/h CRI; n = 11); FLK group (fentanyl [same doses]; lidocaine 2 mg/kg LD and 3 mg/kg/h CRI; ketamine 1.0 mg/kg LD and 0.6 mg/kg/h CRI; = 11). Intraoperative evaluations were performed before the start of surgery and administration of the treatments (T0); three minutes after the LD (T1); during incision and tissue divulsion (T2); during closure of the surgical wound (T3). Meloxicam (0.1 mg/kg) was administered at T3. Blood samples were collected for determination of plasma concentrations of fentanyl, lidocaine and ketamine. Pain scores and the number of postoperative analgesic rescues with morphine (0.5 mg/kg) were evaluated for 24 hours postoperatively using the short form of the Glasgow Composite Measure Pain Scale. Compared to T0, significant decreases in heart rate (from 84 ± 28 to 53 ± 16 bpm in the Fentanyl group and from 93 ± 16 to 63 ± 15 bpm in FLK) and mean arterial pressure (from 61 ± 5 to 49 ± 10 mmHg in Fentanyl and from 59 ± 3 to 38 ± 6 mmHg in FLK) were observed at T1. Arterial hypotension was transient, with normalization of values at T2 and T3. The expired fraction of isoflurane did not differ significantly between the groups. Plasma concentrations of fentanyl, lidocaine and ketamine remained within the therapeutic range. Postoperatively, the number of dogs requiring analgesic rescue was significantly lower in the FLK (0/11, 0%) than in the Fentanyl group (5/11, 45%). In dogs administered morphine and meloxicam as part of the anesthesia protocol, an intraoperative CRI of FLK abolished the requirement for postoperative analgesic rescue for 24 hours in dogs undergoing mastectomy.

Identification of New Carbonic Anhydrase VII Inhibitors by Structure-Based Virtual Screening.

Human carbonic anhydrase VII (hCA VII) constitutes a promising molecular target for the treatment of epileptic seizures and other central nervous system disorders due to its almost exclusive expression in neurons. Achieving isoform selectivity is one of the main challenges for the discovery of new hCA inhibitors, since nonspecific inhibition may lead to tolerance and side effects. In the present work, we report the development of a molecular docking protocol based on AutoDock4Zn for the search of new hCA VII inhibitors by virtual screening. The docking protocol was applied to the screening of two sets of compounds: a ZINC15 subset of sulfur-containing structures and an in-house library consisting of synthetic and commercial candidates (including approved drugs). Five compounds were selected from the first screening campaign and three from the second one, and they were tested in vitro against the enzyme. Among the eight selected structures, four showed Ki values in the low nanomolar range. These confirmed hits include three approved drugs: meloxicam, piroxicam, and nitrofurantoin, which also showed good selectivity for hCA VII versus hCA II.

Protocolo de sedação visando a castração química em cães / Sedation protocol aiming to chemical castration in dogs

A castração química é utilizada para castrar cães machos a um custo mais baixo que o procedimento cirúrgico, que é o método mais aplicado para castrar cães e gatos. A castração química é um procedimento mais simples que a castração cirúrgica e pode ser realizada a nível ambulatorial, sem necessidade de anestesia geral. Entretanto, devido ao estresse pela manipulação e ao desconforto produzido pela injeção de uma substância no interior dos testículos, faz-se necessária uma sedação para que a castração química seja efetuada de um modo que proporcione o bem-estar do animal. Assim, este artigo tem como objetivo propor um protocolo inovador para sedação de cães submetidos à castração química. Para isso, foram utilizados 12 cães submetidos à administração de xilazina em subdose no acuponto yin tang. Após o estabelecimento da sedação, os cães foram castrados quimicamente. O protocolo proposto permitiu que a castração química fosse realizada com conforto para o paciente e para a equipe de médicos veterinários. Desta forma, concluiu-se que o protocolo de sedação é seguro e pode ser empregado em cães para procedimentos não invasivos, como exames, coleta de material e outros processos ou técnicas semelhantes.

Chemical castration is used to spay male dogs at a lower cost than the surgical procedure, which is the most applied method to spay dogs and cats. Chemical castration is a simpler procedure than surgical castration and can be performed on an outpatient basis, without the need for general anesthesia. However, due to the stress caused by manipulation and the discomfort produced by the injection of a substance into the testicles, sedation is necessary so that chemical castration is to be carried out in a way that provides the animal's welfare. Thus, this article aims to propose an innovative protocol for sedation of dogs submitted to chemical castration. For this purpose, twelve dogs submitted to the administration of xylazine in subdosis in the yin-tang acupoint were used. After the establishment of sedation, the dogs were chemically neutered. The proposed protocol allowed chemical castration to be performed with comfort for the patient and the team of veterinarians. Therefore, it is concluded that the sedation protocol is safe and can be used in dogs for non-invasive procedures such as exams, material collection, and other similar processes or techniques.

Postoperative Acupuncture is as Effective as Preoperative Acupuncture or Meloxicam in Dogs Undergoing Ovariohysterectomy: a Blind Randomized Study.

Background: Acupuncture has the same analgesic effect as non-steroidal antiinflammatory drugs and opioids. It is challenging to perform preoperative acupuncture in unmanageable animals, while the residual postoperative anesthetic effect facilitates the performance of acupuncture postoperatively. Objectives: To compare preoperative acupuncture or meloxicam versus postoperative acupuncture for postoperative analgesia after ovariohysterectomy. Methods: This is a horizontal prospective positive control blind randomized experimental study. Thirty-six dogs were randomly divided into three groups: GA (preemptive acupuncture), GPA (postoperative acupuncture), and GM (meloxicam 0.2 mg/kg IV preoperatively). After sedation with acepromazine (0.05 mg/kg IM), anesthesia was induced with propofol (5.3 ± 0.3 mg/kg) and maintained with isoflurane/O2. Fentanyl (2 µg/kg, IV) was administered immediately before surgery. Bilateral acupuncture was performed at acupoints Large intestine 4, Spleen 6, and Stomach 36 for 20 minutes, before (GA) or immediately after surgery (GPA). Pain was evaluated by an observer blind to the treatment using the Glasgow scale before and for 24 hours after ovariohysterectomy. Dogs with a score ≥ 6 received rescue analgesia with morphine (0.5 mg/kg IM). Nonparametric data were analyzed by the Kruskal-Wallis test, followed by Dunn's test and parametric data by ANOVA followed by Tukey's test. Results: Two GA and one GPA dogs received rescue analgesia once. Two GM dogs received rescue analgesia and one of those was treated again twice. There were no differences in the number of dogs receiving rescue analgesia between groups (p = 0.80). Conclusion: Postoperative acupuncture was as effective as preoperative acupuncture or meloxicam in female dogs undergoing ovariohysterectomy.

Meloxicam versus Celecoxib for Postoperative Analgesia after Total Knee Arthroplasty: Safety, Efficacy and Cost.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2 inhibitors (e.g., celecoxib) are believed to have fewer gastrointestinal (GI) adverse effects than nonselective NSAIDS. Meloxicam is less selective for COX-2 than celecoxib is and partially inhibits COX-1 at higher doses. Nonetheless, some surgeons prefer using nonselective NSAIDs because of their lower expense. METHODS: Four thousand nine hundred ninety-four patients who underwent TKA between January 2015 and February 2020 and took either celecoxib (n = 3,174), meloxicam 15 mg/d (n = 1,819), or meloxicam 7.5 mg/d (n = 451) were studied. Mutlimodal postoperative analgesia protocols were otherwise similar. GI bleeding and wound complication incidence were determined, as well as average 30-day prescription costs. RESULTS: GI bleeding incidence was similar in the three cohorts (P = 0.4). The incidence of wound complications did not significantly differ between the groups: 0.06%, 0.07%, and 0.22% in the celecoxib, meloxicam 15 mg/d, and meloxicam 7.5 mg/d groups, respectively (P = 0.06). Subsituting meloxicam for celecoxib results in an average savings of $183 per prescription. DISCUSSION: Meloxicam used at higher doses (15 mg/d) does not markedly increase the risk of GI or wound complications associated with COX-1 inhibition and is less costly for multimodal analgesia after TKA.

Administration of meloxicam to improve the welfare of mice in research: a systematic review (2000 - 2020).

Although laboratory animals experience pain as a necessary component of the objectives of experimental protocols, the level of pain should be minimized through use of an adequate analgesic regimen. The non-steroidal anti-inflammatory drug meloxicam may be beneficial in alleviating post-operative pain in mice, although no regimen has been demonstrated as universally efficacious owing to differences in experimental protocols, strain, sex, and incomplete descriptions of methodology in the literature. The aim of this systematic literature review was to identify potential applications of meloxicam for pain management in experimental mice and to evaluate the general quality of study design. Searches of MEDLINE, Scopus and CAB Direct databases elicited 94 articles published between January 2000 and April 2020 that focused on the analgesic efficacy of meloxicam in the management of momentary or persistent pain in mice. The extracted data showed that most articles were deficient in descriptions of housing, husbandry, group size calculation and humane endpoint criteria, while few described adverse effects of the drug. A wide range of dosages of meloxicam was identified with analgesic efficiencies that varied considerably according to the different models or procedures studied. It was impossible to correlate the extracted data into a single meta-analysis because of the differences in experimental protocols and strains employed, the low representation of female mice in the studies, and incomplete descriptions of the methodology applied. We conclude that meloxicam has potential application for pain management in mice but that the dosage must be adjusted carefully according to the experimental procedures. Moreover, authors must take more care in designing their studies and in describing the methodology employed.

Risperidone in analgesia induced by paracetamol and meloxicam in experimental pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain. Their use in combination with other drugs may broaden their applicability in analgesia if their ceiling and adverse effects are reduced. The aim of this study was to evaluate the pharmacological interaction of two NSAIDs, paracetamol and meloxicam, with the antipsychotic drug risperidone in mice, in several experimental tests of nociceptive and inflammatory pain. Antinociception was assessed by dose-response curves to paracetamol and meloxicam before and after the i.p. administration of 0.5 mg/kg of risperidone. Results are presented as means ± SEM and differences were calculated by one-way ANOVA followed by Tukey's post-test. Paracetamol and meloxicam produced a dose-related antinociceptive effect with diverse potencies. Risperidone increased the analgesia mediated by paracetamol and meloxicam only in the tonic tests that detected inflammatory pain. This suggests that COX inhibition is only a partial explanation of the increased analgesic potency of paracetamol and meloxicam since the effects of NSAIDs in the CNS are mediated by multiple mechanisms. These results indicate that the combination of risperidone with paracetamol or meloxicam could be a new and effective alternative for the management of inflammatory pain.

Repeated dose of meloxicam induces genotoxicity and histopathological changes in cardiac tissue of mice.

Meloxicam is the non-steroidal anti-inflammatory drug most used in small animals; however, studies on genotoxicity, oxidative stress, and histopathologic alterations in cardiac tissue are limited, especially at therapeutical doses used in these animals. This study evaluated the toxic effects caused by the treatment involving repeated low at higher doses of meloxicam in mice, by genotoxicity, oxidative stress, and histopathological parameters. Mice (CF1, male) received, by gavage, meloxicam at the therapeutic dose indicated for small animals (0.1 mg/kg) and at higher doses (0.5 and 1 mg/kg) for 28 days. Later, they were euthanized for blood and organ analysis. Oxidative stress was analyzed by the plasma ferric reduction capacity (FRAP) and catalase, and genotoxicity, by the comet assay and the micronucleus test. Heart, liver, lung, and kidney tissues were analyzed by the histology, and stomach and duodenum were analyzed with a magnifying glass. The relative weight of organs did not present significant alterations. However, congestion of duodenum vessels was observed at the three tested doses and caused hyperemia of stomach mucosa at 1 mg/kg. In the heart histology there was a reduction in the number of cardiomyocytes, accompanied by an increase in cell diameter (possible cell hypertrophy) dose-dependent. The highest tested dose of meloxicam also increased the DNA damage index, without alterations in the micronucleus test. Meloxicam did not affect the catalase activity but increased the FRAP (1 mg/kg). Meloxicam at the dose prescribed for small animals could potentially cause cardiac histopathologic alterations and genotoxic effects.

Synergistic anti-inflammatory effect of NSAIDs plus B vitamins administered pre and postoperatively in third molar surgery: randomized clinical trial / Efeito anti-inflamatório sinérgico da associação de AINEs e vitaminas do complexo B administrada no pré e pós-operatório de cirurgia de terceiros molares: ensaio clínico randomizado

Objective : The aim of the present study was to evaluate the synergistic anti-inflammatory effect of Non-steroidal anti-inflammatory drugs (NSAIDs) plus B vitamins administered pre and postoperatively in surgeries of impacted mandibular third molars. Material and Methods : Double-blind randomized clinical trial, sixty-six patients participated and were randomized into 2 groups. The control group was administered meloxicam 15 mg intramuscularly plus placebo orally and to the experimental group, meloxicam 15 mg intramuscularly plus vitamins B [B1, B6, and B12] orally; both treatments were administered preoperatively. The anti-inflammatory effect was evaluated by pain intensity, facial swelling (facial contour measurements), and mouth opening (distance between the upper and lower incisors) during the post-surgical phase. Student's t-test was performed for independent samples. Results : In all the evaluated times (1 hour, 6 hours, 12 hours, 24 hours, 2 days, and 3 days after the end of the surgery) the experimental group presented a significantly lower intensity of pain compared to the control group (p<0.05). The highest pain intensity was recorded at 6 hours (17.7 ± 9.1 mm in the experimental group and 34.5 ± 21.3 mm in the control group). Swelling and mouth opening were similar in both groups, at all times evaluated (p>0.05). Conclusion : In the present study, the administration of NSAIDs plus B vitamins (B1, B6, B12) produced lower intensity of pain compared to the administration of only NSAIDs. Nevertheless, swelling and mouth opening were similar in all evaluations for both study groups (AU)

Objetivo : O objetivo do presente estudo foi avaliar o efeito anti-inflamatório sinérgico de anti-inflamatórios não esteroidais (AINEs) com vitaminas do complexo B administrados no pré e pós-operatório de cirurgias de terceiros molares inferiores impactados. Material e Métodos: Ensaio clínico randomizado duplo-cego, 66 participantesque foram randomizados em 2 grupos. O grupo controle recebeu Meloxicam 15 mg por via intramuscular + placebo por via oral e o grupo experimental, Meloxicam 15 mg por via intramuscular + vitaminas B [B1, B6 e B12] por via oral; ambos os tratamentos foram administrados no pré-operatório. O efeito anti-inflamatório foi avaliado pela intensidade da dor, edema facial (medidas do contorno facial) e abertura da boca (distância entre os incisivos superiores e inferiores) durante a fase pós-cirúrgica. Foi aplicado o teste t de Student para amostras independentes. Resultados: Em todos os tempos avaliados (1 hora, 6 horas, 12 horas, 24 horas, 2 dias e 3 dias após o término da cirurgia) o grupo experimental apresentou uma intensidade de dor significativamente menor em relação ao grupo controle (p <0,05). A maior intensidade de dor foi registrada em 6 horas (17,7 ± 9,1 mm no grupo experimental e 34,5 ± 21,3 mm no grupo controle). Edema e abertura bucal foram semelhantes nos dois grupos, em todos os momentos avaliados (p>0,05). Conclusão: No presente estudo, a administração de AINEs com vitaminas do complexo B (B1, B6, B12) resultou em menor intensidade de dor em comparação com a administração apenas de AINEs. No entanto, o edema e a abertura da boca foram semelhantes em todas as avaliações para ambos os grupos de estudo (AU).

Assessment of general activity and anxiety-like behavior in mice following tramadol and meloxicam administration for managing immediate post-operative pain

After analgesic administration, we evaluated general activity in the Open-Field and anxiety-like behavior in the Elevated Plus Maze of vasectomized mice. We divided C57BL/6J male mice into eight groups: saline, three non-operated control groups treated with 10 mg/kg meloxicam, 20 mg/kg tramadol, or both intraperitoneally, and four vasectomized mice groups treated with the same analgesic protocol as the control groups. One group of vasectomized mice received both treatments and an additional 10 mg/kg lidocaine at the incision site. We conducted the vasectomy via scrotal approach under isoflurane inhalation anesthesia and performed behavioral tests after full anesthesia recovery. Mice treated with meloxicam demonstrated low ambulation, spontaneous activity, and rearing frequency. Mice treated with tramadol showed spontaneous behavior compared with the saline control. Due to behavior changes demonstrated by meloxicam controls, we were unable to identify whether meloxicam provided adequate analgesia. Vasectomized mice treated with tramadol showed general activity behavior similar to their control but displayed significantly less rearing, suggesting that they were under potential signs of pain or discomfort. In conclusion, the Open Field test and the Elevated Plus Maze can usefully pre-evaluate analgesic protocols to identify possible interference caused by adverse drug effects. For future directions, an appropriate regimen of meloxicam and tramadol for enhancing mice welfare post vasectomy should be better investigated.

The analgesic effect of preventive administration of meloxicam in calves submitted to hot-iron dehorning / Efeito analgésico da administração preventiva de meloxicam em bezerros submetidos à descorna com ferro quente

Dehorning is a zootechnical practice that causes severe pain in cattle. Although there are several studies evaluating the effects of analgesics in calf dehorning, none of them used validated pain assessment instruments. We evaluated the analgesic effectiveness of meloxicam administered before dehorning, compared to a control group, using the Unesp-Botucatu, numerical, simple descriptive, and visual analogue scales for pain assessment before and 4, 8, and 24 hours after the dehorning in 44 female calves. All calves received 0.04 mg/kg of xylazine IM 20 minutes before dehorning and local anesthetic block with 2% lidocaine with a vasoconstrictor. Calves were divided into two groups: without (GX; n = 22) or with 0.5 mg/kg of meloxicam (GXM; n = 22) administered intravenously before the procedure. Dehorning was performed through the section of the base of the horn bud, followed by thermocautery disbudding. For comparisons over time, mixed linear or generalized mixed linear model were used. The interaction between groups and study phases was used as fixed effects and each calf as a random effect. Bonferroni post hoc test was used. There was an increase in the pain scores at 4h compared to baseline in both groups (GX and GXM) for the four scales. The scores at 4h were higher in GX compared to GXM for all scales. Meloxicam reduced, but did not eliminate, behavioral expressions of pain in calves submitted to hot-iron dehorning. Therefore, it should be included in the analgesic protocol to improve welfare in calves undergoing dehorning.

A descorna é uma prática zootécnica que causa dor intensa em bovinos. Há na literatura diversos estudos sobre os efeitos de analgésicos para mitigar a dor frente a descorna, mas nenhum usando escalas validadas. Avaliamos a eficácia do meloxicam administrado previamente à descorna, comparado a um grupo controle, utilizando-se as escalas Unesp-Botucatu, numérica, simples descritiva e analógica visual para avaliação da dor antes e 4, 8 e 24 horas após a descorna em 44 bezerros fêmeas tratadas com 0,04 mg/kg de xilazina IM 20 minutos antes da descorna e bloqueio anestésico local com lidocaína a 2% com vasoconstritor. Os bezerros foram alocados em dois grupos: sem (GX; n=22) ou com 0.5 mg/kg de meloxicam (GXM; n=22) administrado por via intravenosa antes do procedimento. Realizou-se a descorna por secção da base do botão cornual seguido de termocauterização. Para as comparações ao longo do tempo, empregou-se o modelo linear ou linear misto. Considerou-se a interação entre grupos e momentos como efeito fixo e cada bezerro como efeito aleatório. As alterações foram inferidas de acordo com o pós-teste de Bonferroni. Para as quatro escalas houve aumento dos escores às 4h comparado ao basal em ambos os grupos (GX e GXM). Os escores de todas as escalas às 4h foram maiores em GX que em GXM. O meloxicam reduziu, mas não aboliu, a expressão comportamental da dor em bezerros submetidos à descorna com ferro quente, o que sugere o uso de terapia antálgica multimodal para realizar tal procedimento e garantir o bem-estar animal.

Desenvolvimento de organogel injetável subcutâneo de Pluronic®-F127 e lecitina de soja (OPL) contendo meloxicam para uso veterinário / Development of a veterinary organogel formulation containing soy lecithin, Pluronic® F-127 and meloxicam for the treatment of acute and chronic pain in small animals

O organogel é formado por uma matriz tridimensional composta de filamentos que se auto-organizam em uma rede entrelaçada e que, por seu tipo de estrutura, pode ser utilizado com o objetivo de atuar como um implante que se forma in situ, sendo capaz de se comportar como uma forma farmacêutica de liberação prolongada. Esse trabalho tem, por tanto, o objetivo desse trabalho foi desenvolver, caracterizar, quantificar e traçar perfis de dissolução para formulações de organogel contendo meloxicam como principio ativo. O material está dividido em quatro capítulos, sendo apresentada inicialmente (I) revisão da literatura a respeito da lecitina de origem vegetal, com suas principais fontes de obtenção, como soja, girassol e colza, e também seu uso farmacêutico na obtenção de formulações como organogéis, microemulsões e lipossomas. Os demais capítulos abordam (II) desenvolvimento e otimização de uma formulação de organogel contendo lecitina de soja e Pluronic® F-127 como formadores da matriz tridimensional e meloxicam como principio ativo. (III) Desenvolvimento e validação de um método de quantificação do teor de meloxicam por cromatografia líquida de alta eficiência (CLAE). (IV) Desenvolvimento de um método de dissolução para formulações de organogel, que fosse capaz de ser utilizado na caracterização do perfil de dissolução de diferentes formulações. Com os resultados obtidos, foi possível desenvolver formulações de organogel contendo lecitina de soja, Pluronic® F-127 e meloxicam, assim como um método analítico validado para as analises de teor. Por fim, foram obtidos também os perfis de dissolução de duas formulações mais promissoras

Organogels are formed by a three-dimensional matrix composed of filaments that selforganize in an interlaced network and that, due to its type of structure, can be used with the objective of acting as an implant that forms in situ, being able to behave as an extendedrelease dosage form. This work has, therefore, the objective of this work was to develop, characterize, quantify and trace dissolution profiles for organogel formulations containing meloxicam as active ingredient. The material is divided into four chapters, initially presented (I) review of the literature on lecithin of plant origin, with its main sources of production, such as soybean, sunflower and rapeseed, and also its pharmaceutical use in obtaining formulations such as organogels , microemulsions and liposomes. The remaining chapters address (II) development and optimization of an organogel formulation containing soy lecithin and Pluronic® F-127 as three-dimensional matrix formers and meloxicam as an active ingredient. (III) Development and validation of a method for quantification of meloxicam content by high performance liquid chromatography (HPLC). (IV) Development of a dissolution method for organogel formulations, capable of being used to characterize the dissolution profile of different formulations. With the results obtained, it was possible to develop organogel formulations containing soy lecithin, Pluronic® F-127 and meloxicam, as well as a validated analytical method for content analysis. Finally, the dissolution profiles of two more promising formulations were also obtained

Mammary fibroepithelial hyperplasia in a male cat

Background: Feline mammary hyperplasia (FMH) is a benign disease that commonly affects young females, once it iscaused by the exaggerated stimulation of endogenous or exogenous progestogen. FMH leads to acute edema and inflammation of the mammary glands and frequently evolve to ulcerations, secondary infections, and systemic clinical signs.Even though it is rare in male cats, progesterone therapy or an unknown endogenous source of hormone can cause thedisease. This report aims to describe a case of FMH in a male feline with no history of hormonal treatment and treatedwith radical surgical resection.Case: A 7-month-old intact male domestic shorthair cat was presented due to acute onset of generalized mammary tumorswhich had progressed for 18 days. Tumors size had 5 cm large in diameter, symmetric, bilateral, and affected all mammaryglands. The tissue was firm, hyperemic, and ulcerated. FMH was initially suspected but with a differential diagnosis formammary adenocarcinoma. Except for pain on tumor palpation, there was no other clinical abnormality. Survey thoracicradiographs and abdominal ultrasound did not find signs of metastasis or hermaphroditism. Fine-needle aspirate biopsy andfurther cytological examination were inconclusive. Surgical resection through a single-stage bilateral total mastectomy andreconstruction using a left flank fold flap was elected. There were no intraoperative complications and the cat recoveredwell, with good healing and no clinical signs 21 days after the surgery. Histological examination of the mammary glandsconfirmed the diagnosis of FMH due to the non-neoplastic characteristics and tissues benign biological behavior. Elevenmonths after diagnosis, the cat was asymptomatic.Discussion: The FMH frequently affects young females and is associated with gestational periods, the end of the estrouscycle, and, most commonly, hormonal therapy with synthetic progesterone. Male cats are rarely affected with or...(AU)

Unveiling meloxicam monohydrate process of dehydration by an at-line vibrational multi-spectroscopy approach.

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug, extensively used for inflammatory diseases and pain treatments, which exhibits five known solids forms. Form IV of MLX, a zwitterionic monohydrate (MH), is an emblematic hydrate case with promissory dissolution properties in a poorly soluble drug. However, the lack of information about MH stability regarding the dehydration process and phase transition impedes the development of further stability studies. A multi-spectroscopic/chemometric approach was implemented coupling middle- (MIR), near-infrared (NIR) and Raman spectroscopies to monitor the heat-mediated dehydration process of MH. The application of multivariate curve resolution-alternating least squares (MCR-ALS) to multi-source spectra by data fusion allow a complete view of the phenomena, improving the selectivity and precision to establish the transition temperatures and to identify involved species. It was revealed a two-step mechanism, where MH changes to Form V at 90 °C obtaining its complete dehydration at 130 °C, Form V remains unchanged during the temperature range 130-190 °C and then the polymorphic conversion to Form I starts, which reaches 100 % at 230 °C before melting MLX (248 °C). The findings of this work allow set targets in the process control of products using MH. Additionally, MCR-ALS detected an event not evidenced by conventional thermal analysis, the transformation of Form V to Form I.

Meloxicam and/or Etoricoxib Could Be Administered Safely in Two Equal Doses during an Open Oral Challenge in Patients with Nonsteroidal Anti-Inflammatory Drug Hypersensitivity.

BACKGROUND: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative. OBJECTIVE: The aim of the study was to demonstrate the safety of meloxicam and etoricoxib administered by open oral challenge in 2 equal steps in patients with NSAID hypersensitivity. METHODS: A cross-sectional, descriptive study of patients with a diagnosis of NSAID hypersensitivity who underwent an oral drug provocation test (DPT) with meloxicam or etoricoxib between January 2011 and August 2017 was conducted. The analysis was performed from a database in BD Clinic. RESULTS: Two hundred and twenty-eight oral provocations were performed with an alternative NSAID (203 with meloxicam and 25 with etoricoxib) in 217 patients with hypersensitivity to NSAIDs. The median age was 38 years. Ninety-eight percent of meloxicam and 100% of etoricoxib DPTs were performed in 2 steps (without previous placebo), and 52% and 64% of meloxicam and etoricoxib DPTs, respectively, were performed with 50% of the therapeutic dose in each step. Tolerance to meloxicam was demonstrated in 192 patients (94.5%) and in 100% of patients receiving etoricoxib. CONCLUSIONS: Open oral provocation with meloxicam and etoricoxib carried out in 2 steps without placebo seems to be safe and implies less costs and less time expenditure. Also, it could be performed with 2 equal doses.