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Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most commonly used classes of drugs in both human and veterinary medicine. However, many clinical side effects have been observed, especially when treatment has been prolonged. While the anti-inflammatory efficacy and safety of repeated administration of firocoxib (Previcox®), which is a selective NSAID COX-2 inhibitor, has been evaluated for short-term use (one to fourteen days), its clinical relevance for longer-term use is not known. As a preliminary study, healthy, adult male and female horses (n = 7) were treated with firocoxib for 40 days concomitant with the collection of blood samples encompassing treatment to assess hematological and biochemical endpoints. Daily oral administration of firocoxib was performed with one 57 mg tablet/animal (0.11-0.14 mg/kg), which was crushed and mixed with feed. Blood samples were collected one day before treatment (D0 or basal sample), during (D10, D20, D30, and D40), and after treatment (D55 and D70). Results indicated some hematological and biochemical effects were significantly reduced (p < 0.05) towards the end of treatment on D40 relative to pre-treatment or baseline values on D0. Post-treatment, all values returned to pre-treatment values within 30 days without any apparent clinical adversities. In conclusion, while these preliminary results are favorable for prolonged use of firocoxib in horses, future studies are required to evaluate the efficacy of prolonged use accompanied with other clinically relevant endpoints in healthy as well as injured or diseased animals.
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The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (µ3 - OH, and - OH2) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.
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Anti-Inflamatórios não Esteroides , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estruturas Metalorgânicas , Naproxeno , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/química , Estruturas Metalorgânicas/química , Naproxeno/administração & dosagem , Naproxeno/química , Naproxeno/farmacocinética , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Ibuprofeno/farmacocinética , Humanos , Adsorção , Portadores de Fármacos/química , Diclofenaco/administração & dosagem , Diclofenaco/química , Diclofenaco/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Ácidos FtálicosRESUMO
Naproxen reduces the production of prostaglandins via inhibition of the cyclooxygenase. Studies have shown that its administration in women can be related to failed ovulation. Therefore, preclinical investigations must be performed in order to investigate its effects in experimental models. Thus, the aim of this study was to evaluate the effects of naproxen on murine folliculogenesis, ovulation, and female fertility. Female C57BL/6 mice (n = 128 - 6 weeks old) were divided into Control, low (10 mg/kg), and high naproxen (50 mg/kg) groups, who were treated for 8 days and directed to morphofunctional analyses. Follicular quantification showed a reduced percentage of antral follicles in naproxen-treated animals. These treated animals also showed smaller oocytes included in secondary and antral follicles, and the diameter of secondary and antral follicles was also reduced. A reduction in the percentage of Ki67-positive granulosa cells was observed in treated animals that also showed down-regulation of Igf1r compared to control. After an ovarian stimulation protocol, naproxen-treated animals showed a reduction in the percentage of secondary and antral follicles, a reduced number of ovulated oocytes and, corpora lutea, and an increased number of failed ovulations. Finally, naproxen-treated animals also showed a reduction in mating index and pregnancy rate. Our findings suggested that, in mice, naproxen administration (eight days treatment) negatively affects molecular and morphological aspects related to late folliculogenesis, ovulation, and fertility.
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Naproxeno , Ovulação , Humanos , Feminino , Camundongos , Animais , Naproxeno/toxicidade , Camundongos Endogâmicos C57BL , Oócitos , Proliferação de CélulasRESUMO
Among the most recent proposals regarding the mechanism of action of dipyrone, the modulation of cannabinoid receptors CB1 and CB2 appears to be a promising hypothesis. In this context, the present work describes a series of five novel pyrazolamides (7-11) designed as molecular hybrids of dipyrone metabolites and NSAIDs, such as ibuprofen and flurbiprofen. Target compounds were obtained in good overall yields (50-80%) by classical amide coupling between 4-aminoantipyrine and arylacetic or arylpropionic acids, followed in some cases by N-methylation of the amide group. The compounds presented good physicochemical properties in addition to stability to chemical (pH 2 and 7.4) and enzymatic (plasma esterases) hydrolysis and showed medium to high gastrointestinal and BBB permeabilities in the PAMPA assay. When subjected to functional testing on CB1- or CB2-transfected cells, compounds demonstrated an inverse agonist profile on CB2 receptors and the further characterization of compound LASSBio-2265 (11) revealed moderate binding affinity to CB2 receptor (Ki = 16 µM) with an EC50 = 0.36 µM (Emax = 63%). LASSBio-2265 (11) (at 1, 3, and 10 mg/kg p.o.) was investigated in the formalin test in mice and a remarkable analgesic activity in the late inflammatory phase was observed, suggesting it could be promising for the treatment of pain syndromes associated with chronic inflammatory diseases.
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Evaluate the anti-inflammatory activity in vivo and in vitro of cis-(±)-acetate of 4-chloro-6-(naphtalene-1-yl)-tetrahydro-2H-pyran-2-yl) methyl 2-(2-(2,6-diclorofenylamine) phenyl (LS19). Male Swiss mice were analyzed in the paw edema, ear edema, and air pouch tests, and in vitro COX inhibition, cytotoxicity evaluation, and cytokine and nitric oxide determination tests. The compound showed effect on the carrageenan- and bradykinin-induced paw edema and capsaicin-induced ear edema tests. In addition, the compound was able to inhibit leukocyte migration to decrease the levels of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) and to increase the levels of the anti-inflammatory cytokine IL-10. The compound was also able to reduce levels of TNF-α, IL-6, and nitric oxide in the RAW 264.7 cell line and to inhibit COX activity. LS19 did not induce any significant changes in the viability of RAW 264.7 cells, demonstrating safety for these cell lines. The compound LS19 did not reduce the production of gastric mucus and induced a smaller increase in the extent of gastric lesions than that developed by the administration of diclofenac. In summary, the new compound proved to be safer and it had additional mechanisms compared to diclofenac.
Assuntos
Anti-Inflamatórios não Esteroides , Anti-Inflamatórios , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Masculino , Camundongos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Pain is responsible for inducing physical and mental stress, interfering negatively in patients' quality of life. Classic analgesic drugs, such as opioids and non-steroidal anti-inflammatory drugs, are known for their wide range of adverse effects, making it important to develop new drugs. Thus, this study aimed to analyse the action of the hybrid compound cis- (±) -acetate of 4-chloro-6- (naphthalene-1-yl) -tetrahydro-2h-pyran -2-yl) methyl2- (2- [2,6-dichlorophenylamine] phenyl (LS19) under acute nociceptive conditions, and deepened the understanding of the responsible mechanisms. Male Swiss mice were evaluated in the acetic acid-induced abdominal writhing, formalin, tail flick, capsaicin- and glutamate-induced nociception, thermal stimulation in animals injected with capsaicin and rotarod tests besides the acute and subchronic toxicological evaluation. The compound showed effect on the acetic acid-induced abdominal writhing, formalin (both phases), tail flick, thermal stimulation in animals injected with capsaicin and capsaicin-induced nociception tests. In the study of the mechanism of action was observed reversion of the antihyperalgesic effect of the compound from the previous intraperitoneal and intrathecal administration of naloxone, nor-binaltorphimine, naltrindole, methylnaltrexone, 7-nitroindazole, L-NAME, ODQ, glibenclamide on the tail flick test. In the thermal stimulation in animals injected with capsaicin, the compound showed antinociceptive effect by oral and intraplantar routes, besides to reducing the levels of TNF-α, IL-1ß and PGE2 in the paws previously administered with capsaicin. There were no signs of acute and subchronic intoxication with the compound. In summary, the compound LS19 presented spinal and local antihyperalgesic effect, demonstrating participation of the opioid/NO/cGMP/K+ ATP pathway and TRPV1 receptors and it demonstrated safety in its use in mice.
Assuntos
Anti-Inflamatórios não Esteroides , Dor , Piranos , Animais , Humanos , Masculino , Camundongos , Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Capsaicina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/toxicidade , Temperatura Alta/efeitos adversos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Piranos/química , Piranos/farmacologiaRESUMO
ABSTRACT Objective: To investigate the effectiveness of pharmacological interventions in the treatment of delayed onset muscle soreness (DOMS). Design: A systematic review and meta-analysis of randomized controlled clinical trials (RCTs). Data sources: The PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs published prior to August 3, 2020. Eligibility criteria for selecting studies: Studies that 1) used an RCT design; 2) evaluated the effectiveness of steroidal or nonsteroidal anti-inflammatory drugs (NSAIDs) in treating DOMS; and 3) therapeutically used drugs after exercise were included. Results: In total, 26 studies (patients = 934) were eligible for inclusion in the qualitative analysis on the treatment of DOMS. The results of the meta-analysis showed no superiority between the use and non-use of NSAIDs in the improvement of late muscle pain, as no statistically significant differences were verified (21 studies, n= 955; standard mean difference (SMD)= 0.02; 95% confidence interval (CI) −0.58, 0.63; p=0.94; I2=93%). The quality of the synthesized evidence was very low according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and there was significant heterogeneity among the included studies. Conclusion: The results demonstrate that NSAIDs are not superior to controls/placebos in treating DOMS. The inclusion of both studies with dose-response protocols and those with exercise protocols may have influenced the results. In addition, the high risk of bias identified reveals that limitations need to be considered when interpreting the results. Level of evidence I; ystematic review of RCT (Randomized and Controlled Clinical Trials).
RESUMEN Objetivo: Investigar la efectividad de las intervenciones farmacológicas en el tratamiento del dolor muscular de aparición tardía (DOMS). Metodología: Revisión sistemática y metanálisis de ensayos clínicos controlados aleatorios (RCT). Fuentes de datos: Se realizaron búsquedas en las bases de datos de PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo y Cochrane Central Register of Controlled Trials (CENTRAL) para ECA publicados antes del 3 de agosto de 2020. Criterios de elegibilidad para la selección de estudios: Estudios en los que 1) se utilizó un diseño de RCT; 2) se evaluó la eficacia de los fármacos antiinflamatorios no esteroideos (AINE) y esteroideos en el tratamiento de DOMS; y 3) se incluyó el uso terapéutico de medicamentos para dolor después del ejercicio. Resultados: En total, 26 estudios (pacientes = 934) fueron elegibles para su inclusión en el análisis cualitativo sobre el tratamiento de DOMS. Los resultados encontrados en el metanálisis no demostraron superioridad entre el uso y no uso de AINE para mejorar el dolor muscular tardío cuando se comparó con una condición de control, ya que no hubo diferencias estadísticamente significativas (21 estudios, n = 955; media estándar diferencia = 0,02; intervalo de confianza (IC) del 95% −0,58, 0,63; p = 0,94; I2 = 93%). La calidad de la evidencia encontrada se clasificó como muy baja según los criterios del "Grading of Recommendations Assessment, Development and Evaluation" (GRADE), principalmente porque existe una heterogeneidad significativa entre los estudios incluidos. Conclusión: Los resultados demuestran que los AINE no son superiores a los controles o placebos en el tratamiento de DOMS. La inclusión de ambos modelos de estudio con protocolos de dosis-respuesta y protocolos de ejercicio puede haber influido en los resultados. Además, el alto riesgo de sesgo identificado revela que la interpretación de los resultados debe verse con limitaciones. Nivel de evidencia: I; Revisión sistemática de ECRC (Ensayos clínicos aleatorizados y controlados).
RESUMO Objetivo: Investigar a eficácia das intervenções farmacológicas no tratamento da dor muscular de início tardio (DOMS). Desenho: Revisão sistemática e metanálise de estudos clínicos randomizados e controlados (RCTs). Fontes de dados: Os bancos de dados PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo e Cochrane Central Register of Controlled Trials (CENTRAL) foram pesquisados em busca de RCTs publicados antes de 3 de agosto de 2020. Critérios de elegibilidade para selecionar estudos: Estudos que 1) usaram um desenho de RCT; 2) avaliaram a eficácia de anti-inflamatórios esteroides ou não esteroides (AINEs) no tratamento de DOMS e 3) incluíram tratamento medicamentoso depois de exercício. Resultados: No total, 26 estudos (pacientes = 934) foram elegíveis para inclusão na análise qualitativa do tratamento de DOMS. Os resultados da metanálise não mostraram superioridade entre o uso e não uso de AINEs na melhora da dor muscular tardia, pois não foram verificadas diferenças estatisticamente significativas (21 estudos, n = 955; diferença média padronizada (SMD) = 0,02; Intervalo de confiança (IC) de 95% −0,58, 0,63; p = 0,94; I2 = 93%). A qualidade da evidência encontrada foi muito baixa de acordo com os critérios da Grading of Recommendations Assessment, Development and Evaluation (GRADE), e verificou-se heterogeneidade significante entre os estudos incluídos. Conclusão: Os resultados demonstram que os AINEs não são superiores aos controles ou placebos no tratamento de DOMS. A inclusão de estudos com protocolos de dose-resposta e com protocolos de exercícios podem ter influenciado os resultados. Além disso, o alto risco de viés identificado revela que as limitações devem ser consideradas na interpretação dos resultados. Nível de evidência I; Revisão sistemática de ECRC (Estudos clínicos randomizados e controlados).
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ABSTRACT BACKGROUND: Endoscopic retrograde cholangiopancreatography is a widely used therapeutic modality for the pancreaticobiliary tree. However, it is responsible for the highest rates of complications among the endoscopic procedures, especially post-endoscopic retrograde cholangiopancreatography pancreatitis. The preventive methods include mechanical and pharmacological approaches, such as the use of non-steroidal anti-inflammatory drugs. OBJECTIVE: To compare the efficacy of two different strategies using non-steroidal anti-inflammatory drugs for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis, and to clarify the uncertainty about the route of administration of non-steroidal anti-inflammatory drugs in the prevention of this complication. METHODS: This was a prospective trial. Two therapeutic groups were compared with a control group that was composed of patients who underwent endoscopic retrograde cholangiopancreatography, performed in the same service and by the same team in the period preceding the study (historical series), without the administration of any type of prophylaxis. The first group received 100 mg rectal diclofenac. The second group received 100 mg intravenous ketoprofen. Both groups were compared, separately and jointly, with the control group. RESULTS: Post-endoscopic retrograde cholangiopancreatography pancreatitis occurred in 4.39% (12/273) of the participants. In the group without prophylaxis, the incidence was 6.89% (10/145). Among those who received intravenous ketoprofen, the incidence was 2.56% (2/78). No cases of acute post-procedural pancreatitis were observed in the group that received rectal diclofenac (0/52). Although there was no statistical difference between the therapeutic groups when they were separately analyzed, a statistical difference in the prevention of post-procedural pancreatitis was observed when they were analyzed together (P=0.037). CONCLUSION: This study provides evidence for the efficacy of non-steroidal anti-inflammatory drugs in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis.
RESUMO CONTEXTO: A colangiopancreatografia retrógrada endoscópica (CPRE) é uma modalidade terapêutica amplamente utilizada para vias biliopancreáticas, responsável pelas taxas mais elevadas de complicações entre os procedimentos endoscópicos, especialmente a pancreatite pós-CPRE (PPC). Os métodos preventivos incluem abordagens mecânicas e farmacológicas, entre elas, a utilização de antinflamatórios não esteroidais (AINEs). OBJETIVO: Comparar a eficácia de duas estratégias diferentes utilizando AINEs para a prevenção de PPC. Elucidar o cenário incerto sobre a via de administração do AINEs na prevenção da PPC. MÉTODOS - Ensaio clínico prospectivo. Duas estratégias terapêuticas foram comparadas a um grupo controle, composto por pacientes submetidos a CPRE no mesmo serviço e com a mesma equipe no período anterior ao estudo (série histórica), que não recebeu qualquer tipo de profilaxia. O primeiro grupo experimental recebeu 100 mg de diclofenaco via retal, o segundo grupo recebeu 100 mg de cetoprofeno endovenoso. Ambos os grupos foram comparados separadamente e em associação com o grupo de controle. RESULTADOS: A PPC ocorreu em 4,39% (12/273) dos participantes. No grupo sem profilaxia, esta incidência foi de 6,89% (10/145); entre os que receberam cetoprofeno endovenoso foi de 2,56% (2/78). Não houve casos de pancreatite aguda após o procedimento no grupo que recebeu diclofenaco via retal (0/52). Apesar de não haver diferença estatística entre estes grupos analisados separadamente, quando os dois grupos terapêuticos são analisados em conjunto estes apresentam diferenças estatísticas na prevenção da PPC (P=0,037). CONCLUSÃO: Este estudo foi capaz de corroborar a eficácia da utilização de AINEs para a profilaxia de pancreatite pós-CPRE.
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Humanos , Pancreatite/etiologia , Pancreatite/prevenção & controle , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Anti-Inflamatórios não Esteroides , Diclofenaco , Estudos ProspectivosRESUMO
Patients with urticaria and angioedema often have triggers that cause an outbreak or a swelling episode or worsen their chronic condition. Exploring these factors with each patient may result in better understanding and control of their disease. Patients should be advised to avoid known triggers, if feasible, or prepare to prevent or control an exacerbation with appropriate pretreatment if avoidance is not possible. In this review, we describe and discuss a variety of factors for which there is evidence that they cause or exacerbate chronic spontaneous urticaria and angioedema. These potentially exacerbating factors include drugs, food additives, and naturally occurring pseudoallergens, mental stress, and trauma.
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Angioedema , Urticária Crônica , Urticária , Angioedema/epidemiologia , Doença Crônica , Humanos , Prevalência , Urticária/epidemiologiaRESUMO
This investigation focuses on the development and optimization of cashew gum polysaccharide (CGP) nanoparticles grafted with polypropylene glycol (PPG) as carriers for diclofenac sodium. The optimization of parameters affecting nanoparticles formulation was performed using a central composite rotatable design (CCRD). It was demonstrated that the best formulation was achieved when 10 mg of CGP was mixed with 10 µL of PPG and homogenized at 22,000 rpm for 15 min. The physicochemical characterization evidenced that diclofenac was efficiently entrapped, as increases in the thermal stability of the drug were observed. The CGP-PPG@diclofenac nanoparticles showed a globular shape, with smooth surfaces, a hydrodynamic diameter around 275 nm, a polydispersity index (PDI) of 0.342, and a zeta potential of -5.98 mV. The kinetic studies evidenced that diclofenac release followed an anomalous transport mechanism, with a sustained release up to 68 h. These results indicated that CGP-PPG nanoparticles are an effective material for the loading/release of drugs with similar structures to diclofenac sodium.
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Because ibuprofen is a high consumption drug, which has the waters as its final destination, causing alterations in the aquatic environment, specifically in fish. However, there is not enough knowledge about the effect it can have on neotropical fish. This study aimed to evaluate the impact of different concentrations of ibuprofen on sperm quality, both in vivo and in vitro, of the striped catfish Pseudoplatystoma magdaleniatum, and analyze its effects on the reproduction of this critical extinction endangered species. For this purpose, three groups of fish, with a mean weight of 2.3 ± 0.6 kg and mean total length of 62.9 ± 6.1 cm, were placed in tanks (3 fish/tank) with water at concentrations of 0 (control), 25, and 50 µg/L of ibuprofen for 4 months. For the analysis of sperm quality for each treatment (in vivo), the males were selected in the spermiation phase. Also, the semen from the control group was used for in vitro tests and activated with type I water solutions containing 0, 25, and 50 µg/L of ibuprofen. In the in vivo and in vitro tests, when fish and semen were treated to 50 µg/l, the seminal quality of striped catfish was statistically different from the other treatments. For this study, it was shown that ibuprofen at concentrations of 50 µg/L can cause a significant reduction in sperm quality and, therefore, a threat to the reproduction of P. magdaleniatum.
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Peixes-Gato , Animais , Ibuprofeno , Masculino , Reprodução , Sêmen , EspermatozoidesRESUMO
Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a twofold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤ 15 days in 12 patients (21%) and one patient developed ALF within 7 days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤ 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Falência Hepática Aguda/induzido quimicamente , Sulfonamidas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Bilirrubina/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Criança , Colestase/induzido quimicamente , Colestase/epidemiologia , Estudos de Coortes , Feminino , Humanos , Icterícia/induzido quimicamente , Icterícia/epidemiologia , América Latina/epidemiologia , Falência Hepática Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , Espanha/epidemiologia , Sulfonamidas/administração & dosagem , Fatores de Tempo , Adulto JovemRESUMO
Abstract Saliva is widely used for clinical and laboratory analysis. This study proposed to use DNA extracted from saliva for genotyping and pharmacokinetics of piroxicam. A fast and efficient genotyping method was used to determine relevant allelic variants of CYP2C9 (*2 and *3), since genetic factors can influence in non-steroidal anti-inflammatory drugs (NSAIDs) metabolization. DNA Extract All Reagents Kit® was used for DNA extraction and genotyping was performed using TaqMan® GTXpress™ Master Mix, SNP genotyping assays and a Viia7 Real-Time PCR system. Volunteers performed sequential collections of saliva samples before and after taking a single dose of piroxicam (0.25 to 72 h) which were used for pharmacokinetics assays. Piroxicam concentrations were analyzed using LC-MS/MS. Sixty-six percent of volunteers were ancestral homozygous (CYP2C9*1/*1), and 34% showed one or both polymorphisms. Of these 34%, 22 individuals showed CYP2C9*2 polymorphism, 8 CYP2C9*3, and 4 CYP2C9*2/*3. Piroxicam pharmacokinetics were performed in 5 subjects. Areas under the curve (AUC0-t(h*ng/mL)) for CYP2C9*1/*1, *1/*2 and *1/*3 were, respectively, 194.33±70.93, 166 and 303. Maximum concentrations (Cmax(ng/mL)) for these genotypes were respectively 6.46±2.56, 4.3 and 10.2. Saliva sampling was a very effective matrix for both pharmacogenetic and pharmacokinetic tests, ensuring the speed of the procedure and the well-being and agreement of the participants. Once having the knowledge about the slow and fast metabolizers, it is possible to make an adequate prescription in order to avoid the adverse effects of the medication and to guarantee greater analgesic comfort to the patients respectively.
Resumo Saliva é amplamente utilizada para análises clínicas e laboratoriais. Este estudo propôs o uso de DNA extraído da saliva para genotipagem e farmacocinética do piroxicam. Um método de genotipagem rápido e eficiente foi usado para determinar as variantes alélicas clinicamente relevantes de CYP2C9 (* 2 e * 3), uma vez que fatores genéticos podem influenciar nas respostas metabólicas individuais a medicamentos como anti-inflamatórios não esteroides (AINEs). DNA Extract All Reagents Kit® foi usado para extração de DNA e a genotipagem foi realizada usando TaqMan® GTXpress ™ Master Mix, ensaios de genotipagem SNP e um sistema Viia7 Real-Time PCR. Os voluntários realizaram coletas sequenciais de amostras de saliva antes e após a ingestão de uma única dose de piroxicam (0,25 a 72 h) que foram utilizadas para ensaios farmacocinéticos. As concentrações de piroxicam foram analisadas usando LC - MS / MS. Sessenta e seis por cento dos voluntários eram homozigotos ancestrais (CYP2C9 * 1 / * 1) e 34% apresentaram um ou ambos os polimorfismos. Destes 34%, 22 indivíduos apresentaram polimorfismo CYP2C9 * 2, 8 CYP2C9 * 3 e 4 CYP2C9 * 2 / * 3. A farmacocinética do piroxicam foi realizada em 5 indivíduos. As áreas sob a curva (AUC0-t (h * ng / mL)) para CYP2C9 * 1 / * 1, * 1 / * 2 e * 1 / * 3 foram, respectivamente, 194,33±70,93, 166 e 303. Concentrações máximas (Cmax (ng / mL)) para esses genótipos foram, respectivamente, 6,46±2,56, 4,3 e 10,2. A amostra de saliva foi uma matriz muito eficaz tanto para os testes farmacogenéticos quanto para os farmacocinéticos, garantindo a agilidade do procedimento e o bem-estar e concordância dos participantes. Com o conhecimento dos metabolizadores lentos e rápidos, é possível fazer uma prescrição adequada para evitar os efeitos adversos da medicação e garantir maior conforto analgésico aos pacientes respectivamente.
Assuntos
Humanos , Farmacogenética , Saliva , Prescrições de Medicamentos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Citocromo P-450 CYP2C9/genéticaRESUMO
PURPOSE: To evaluate the effect of preoperative 0.09% bromfenac ophthalmic solution for the reduction of intraoperative miosis and pain in patients who have undergone femtosecond laser-assisted cataract surgery. METHODS: This prospective randomized clinical study included 65 patients with senile cataracts in the absence of significant ocular comorbidity. The patients received 0.09% bromfenac ophthalmic solution or control placebo twice a day for 3 days before surgery. Pupil diameter was measured at the initiation and finalization of femtosecond laser-assisted cataract surgery, and pain quantification was assessed by an analogous pain scale after one day of follow-up. RESULTS: A total of 65 patients were randomly divided into two groups. Five patients were excluded due to defective coupling with the laser interface. Each of the 60 patients was randomized to receive preoperative topical treatment with either 0.09% bromfenac or 0.1% sodium hyaluronate. Baseline characteristics were similar between groups for age and gender. The mean change in horizontal and vertical pupil diameter from the preoperative to post-femtosecond laser measurements were significantly less in the bromfenac group than in the placebo group (0.43 ± 0.6 vs. 1.71 ± 0.9, P < 0.001 and 0.40 ± 0.6 vs. 1.78 ± 0.9, P < 0.001, respectively). Compared with untreated patients, the quantification of pain one day after the procedure was significantly lower in the 0.09% bromfenac group (46.7% with a score of 3 vs. 50% with a score of 1, P < 0.001, respectively). CONCLUSIONS: The maintenance of pupil dilation and the prevention of miosis were more effective in the 0.09% bromfenac group than in the control group. Likewise, the greater control of postoperative pain represented an additional significant benefit.
RESUMO
Background: Inappropriate use of drugs for veterinary patients represents a common problem at clinical practice. Nonsteroidal anti-inflammatories are one of these misused drugs and may lead to clinical status of challenging diagnosis. Adverseeffects for patients submitted to its incorrect use may include simple cases such as pharmacological gastroenteritis to severeacute renal failure or perforated gastroenteric ulcers with no pathognomonic clinical signs. The objective of this reportwas to describe a case of a perforated pyloric ulcer secondary to prolonged use of meloxicam in a cat with its clinical,laboratorial and image aspects from the moment of suspicion until the diagnosis.Case: An 8-year-old female feline was attended at the Veterinary Hospital of the Dom Bosco Catholic University, withmain complaint being a mammary nodule with recent ulceration. Tumor staging and pre-surgical blood analysis wereperformed previous to total unilateral mastectomy. Eleven days post-surgery the patient was brought for suture removal,but it was observed stupor, moderate dehydration (estimated 10%), 36.7ºC rectal temperature, heart rate at 100 beats/min,respiratory rate at 60 breaths/min, 40 mg/dL blood glucose, icterus and abdominal distension with tympany at percussion(fluid wave test was negative). Anamnesis revealed the possible use of meloxicam for 10 days. The first suspicion wassepsis, with enteric gas secondary to infection. Due to no classical signs of peritoneum effusion and possible severe entericdistension, abdominocentesis was not immediate performed. Complete blood count and serum biochemistry revealed amarked band leukocytosis associated with renal injury, supporting the first sepsis suspicion. Abdominal radiography revealedradiodensity of diffuse aspect at ventral topography but no evidence of marked...(AU)
Assuntos
Animais , Gatos , Anti-Inflamatórios não Esteroides/efeitos adversos , Mucosa Gástrica/lesões , Úlcera Gástrica/veterináriaRESUMO
Ibuprofen (IBU) is a non-steroidal anti-inflammatory (NSAIDs) that is used in various conditions. The prescriptions and the global consumption of this drug are very high and its annual production oscillates in millions of tons, this generates that the IBU is present in many waterbodies because it is discharged through the municipal, hospital and industrial effluents. For the above, the purpose of this work was to determine if IBU at environmentally relevant concentrations was capable of inducing alterations to embryonic development, teratogenic effects and oxidative stress in oocytes and embryos of Cyprinus carpio. Oocytes of common carp were exposed to IBU concentrations between 1.5 and 11.5⯵gâ¯L-1 (environmentally relevant). LC50 and EC50 of malformations were determined to calculate the teratogenic index (TI). Also, main alterations to embryonic development and teratogenic effects were evaluated. Oxidative stress was evaluated by determining biomarkers of cellular oxidation and antioxidation using the same concentrations at 72 and 96â¯hpf in embryos of Cyprinus carpio. The results showed a LC50 of 4.17⯵gâ¯L-1, EC50 of 1.39⯵gâ¯L-1 and TI of 3.0. The main embryonic development disorders and teratogenic effects were delayed hatching, hypopigmentation, pericardial edema, yolk deformation, and developmental delay. Biomarkers of cellular oxidation and antioxidants were increased with respect to the control in a concentration-dependent manner. The results of the study allow us to conclude that IBU at environmentally relevant concentrations is capable of inducing embryotoxicity and teratogenicity in a fish of commercial interest like Cyprinus carpio.
Assuntos
Carpas , Teratogênese , Animais , Desenvolvimento Embrionário , Ibuprofeno , Estresse Oxidativo , Poluentes Químicos da ÁguaRESUMO
This study aimed to identify dogs with presumptive diagnosis of cervical intervertebral disc disease (IVDD) submitted to clinical management and to evaluate the outcomes. Data were obtained from the medical records of patients with neurological dysfunction assisted at a University Veterinary Hospital from 2006 to 2017. In addition to the patients' records, dog owners responded to a questionnaire on the success of therapy. Four hundred and thirteen neurological records were evaluated, and 164 met the inclusion criteria of the study. The most common breed was Dachshund, followed by mongrels. Classification of neurological dysfunction in the study sample was as follows: 15.9% with grade I, 25.6% with grade II, 26.8% with grade III, 8.5% with grade IV, and 23.2% with grade V. Outcome was satisfactory in 71.6% of the dogs and unsatisfactory in 28.4% of them. Recurrence was observed in 27.7% of those with satisfactory outcomes. The clinical treatment of dogs with thoracolumbar IVDD is satisfactory, particularly for animals with milder disease grades (I, II, and III). There is possibility of recurrence with conservative therapy and clinical signs may be more severe.(AU)
O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar submetidos ao tratamento clínico, a fim de avaliar a resposta à terapia instituída. Foram revisados os registros neurológicos de cães atendidos pelo Serviço de Neurologia e Neurocirurgia Veterinária no período de 2006 a 2017 de um Hospital Veterinário Universitário. Foi realizada coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Foram avaliadas 413 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 164 delas. As raças mais frequentes foram dachshunds, seguido de cães sem raça definida. Quanto ao grau de disfunção neurológica foi definido como grau I para 15,9% dos cães, grau II para 25,6%, grau III para 26,8%, grau IV para 8,5% e grau V para 23,2%. A recuperação foi satisfatória em 71,6% dos cães e insatisfatória em 28,4%. Dos que se recuperaram satisfatoriamente, 27,7% tiveram recidivas. Com base nos resultados obtidos pode-se concluir que o tratamento clínico em repouso absoluto e administração de anti-inflamatórios e analgésicos opióides para cães com DDIV toracolombar é efetivo, principalmente para cães em graus mais leves da doença (grau I, II e III). Há possibilidade de recidiva com esse tipo de terapia cujos sinais clínicos poderão ser mais graves.(AU)
Assuntos
Animais , Cães , Compressão da Medula Espinal/tratamento farmacológico , Compressão da Medula Espinal/terapia , Compressão da Medula Espinal/veterinária , Doenças da Coluna Vertebral/tratamento farmacológico , Doenças da Coluna Vertebral/terapia , Doenças da Coluna Vertebral/veterinária , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/veterinária , Disco Intervertebral/patologiaRESUMO
Background: Inappropriate use of drugs for veterinary patients represents a common problem at clinical practice. Nonsteroidal anti-inflammatories are one of these misused drugs and may lead to clinical status of challenging diagnosis. Adverseeffects for patients submitted to its incorrect use may include simple cases such as pharmacological gastroenteritis to severeacute renal failure or perforated gastroenteric ulcers with no pathognomonic clinical signs. The objective of this reportwas to describe a case of a perforated pyloric ulcer secondary to prolonged use of meloxicam in a cat with its clinical,laboratorial and image aspects from the moment of suspicion until the diagnosis.Case: An 8-year-old female feline was attended at the Veterinary Hospital of the Dom Bosco Catholic University, withmain complaint being a mammary nodule with recent ulceration. Tumor staging and pre-surgical blood analysis wereperformed previous to total unilateral mastectomy. Eleven days post-surgery the patient was brought for suture removal,but it was observed stupor, moderate dehydration (estimated 10%), 36.7ºC rectal temperature, heart rate at 100 beats/min,respiratory rate at 60 breaths/min, 40 mg/dL blood glucose, icterus and abdominal distension with tympany at percussion(fluid wave test was negative). Anamnesis revealed the possible use of meloxicam for 10 days. The first suspicion wassepsis, with enteric gas secondary to infection. Due to no classical signs of peritoneum effusion and possible severe entericdistension, abdominocentesis was not immediate performed. Complete blood count and serum biochemistry revealed amarked band leukocytosis associated with renal injury, supporting the first sepsis suspicion. Abdominal radiography revealedradiodensity of diffuse aspect at ventral topography but no evidence of marked...
Assuntos
Animais , Gatos , Anti-Inflamatórios não Esteroides/efeitos adversos , Mucosa Gástrica/lesões , Úlcera Gástrica/veterináriaRESUMO
This study aimed to identify dogs with presumptive diagnosis of cervical intervertebral disc disease (IVDD) submitted to clinical management and to evaluate the outcomes. Data were obtained from the medical records of patients with neurological dysfunction assisted at a University Veterinary Hospital from 2006 to 2017. In addition to the patients' records, dog owners responded to a questionnaire on the success of therapy. Four hundred and thirteen neurological records were evaluated, and 164 met the inclusion criteria of the study. The most common breed was Dachshund, followed by mongrels. Classification of neurological dysfunction in the study sample was as follows: 15.9% with grade I, 25.6% with grade II, 26.8% with grade III, 8.5% with grade IV, and 23.2% with grade V. Outcome was satisfactory in 71.6% of the dogs and unsatisfactory in 28.4% of them. Recurrence was observed in 27.7% of those with satisfactory outcomes. The clinical treatment of dogs with thoracolumbar IVDD is satisfactory, particularly for animals with milder disease grades (I, II, and III). There is possibility of recurrence with conservative therapy and clinical signs may be more severe.(AU)
O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar submetidos ao tratamento clínico, a fim de avaliar a resposta à terapia instituída. Foram revisados os registros neurológicos de cães atendidos pelo Serviço de Neurologia e Neurocirurgia Veterinária no período de 2006 a 2017 de um Hospital Veterinário Universitário. Foi realizada coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Foram avaliadas 413 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 164 delas. As raças mais frequentes foram dachshunds, seguido de cães sem raça definida. Quanto ao grau de disfunção neurológica foi definido como grau I para 15,9% dos cães, grau II para 25,6%, grau III para 26,8%, grau IV para 8,5% e grau V para 23,2%. A recuperação foi satisfatória em 71,6% dos cães e insatisfatória em 28,4%. Dos que se recuperaram satisfatoriamente, 27,7% tiveram recidivas. Com base nos resultados obtidos pode-se concluir que o tratamento clínico em repouso absoluto e administração de anti-inflamatórios e analgésicos opióides para cães com DDIV toracolombar é efetivo, principalmente para cães em graus mais leves da doença (grau I, II e III). Há possibilidade de recidiva com esse tipo de terapia cujos sinais clínicos poderão ser mais graves.(AU)
Assuntos
Animais , Cães , Compressão da Medula Espinal/tratamento farmacológico , Compressão da Medula Espinal/terapia , Compressão da Medula Espinal/veterinária , Doenças da Coluna Vertebral/tratamento farmacológico , Doenças da Coluna Vertebral/terapia , Doenças da Coluna Vertebral/veterinária , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/veterinária , Disco Intervertebral/patologiaRESUMO
The crystal structure is reported of sodium 2-[2-(2,6-di-chloro-anilino)phen-yl]acetate 3.5-hydrate or tetra-µ-aqua-κ8 O:O-deca-aqua-bis-{µ3-2-[2-(2,6-di-chloro-anilino)phen-yl]acetato-κ3 O:O:O}tetra-sodium(I) bis-{2-[2-(2,6-di-chloro-anil-ino)phen-yl]acetate}, {[Na4(C14H10Cl2NO2)2(H2O)14](C14H10Cl2NO2)2} n , which re-presents a new hydrate form of the NSAID sodium diclofenac (SD). The triclinic unit cell contains one ionic compound with formula Na4(C14H10Cl2NO2)4(H2O)14, in which two symmetry-related carboxyl-ate anions C14H10Cl2NO2 - are bonded to a centrosymmetric [Na4]4+ core cationic cluster, while the others are only hydrogen bonded to the cationic cluster. The conformation for the anions is similar to that found in other diclofenac compounds, and the [Na4(Ocarbox)2(H2O)14]4+ cluster displays an unprecedented geometry, which can be described as an incomplete dicubane cluster formed by face-sharing incomplete cubes. A complex framework of O-Hâ¯O hydrogen bonds stabilizes the crystal structure. The herein reported crystal structure for SD·3.5H2O in space group P is different from those previously reported for other hydrates, namely SD·4.75H2O (P21) and SD·5H2O (P21/m).