RESUMO
Ketoprofen (KET), as a non-steroidal anti-inflammatory drug frequently detected in aqueous environments, is a threat to human health due to its accumulation and low biodegradability, which requires the transformation and degradation of KET in aqueous environments. In this paper, the reaction process of ozone-initiated KET degradation in water was investigated using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The detailed reaction path of KET ozonation is proposed. The thermodynamic results show that ozone-initiated KET degradation is feasible. Under ultraviolet irradiation, the reaction of ozone with water can also produce OH radicals (HO·) that can react with KET. The degradation reaction of KET caused by HO· was further studied. The kinetic calculation illustrates that the reaction rate (1.99 × 10-1 (mol/L)-1 sec-1) of KET ozonation is relatively slow, but the reaction rate of HO· reaction is relatively high, which can further improve the degradation efficiency. On this basis, the effects of pollutant concentration, ozone concentration, natural organic matter, and pH value on degradation efficiency under UV/O3 process were analyzed. The ozonolysis reaction of KET is not sensitive to pH and is basically unaffected. Finally, the toxicity prediction of oxidation compounds produced by degradation reaction indicates that most of the degradation products are harmless, and a few products containing benzene rings are still toxic and have to be concerned. This study serves as a theoretical basis for analyzing the migration and transformation process of anti-inflammatory compounds in the water environment.
Assuntos
Cetoprofeno , Ozônio , Poluentes Químicos da Água , Cetoprofeno/química , Ozônio/química , Poluentes Químicos da Água/química , Cinética , Anti-Inflamatórios não Esteroides/química , Modelos Químicos , Purificação da Água/métodosRESUMO
We sought to examine whether scheduled intravenous (IV) ketorolac decreased post-operative narcotic utilization and changed peri-operative outcomes (including complications) in patients undergoing robotic-assisted simple prostatectomy (RASP). An IRB-approved, retrospective chart review was performed of all patients undergoing RASP at a single institution from November 2017 to July 2019. Patient demographic, peri-operative, and post-operative data, including morphine equivalent use (MEU), were collected. Scheduled ketorolac use was implemented at the surgeon's discretion for up to 5 days post-operatively. The primary outcome was MEU in the post-operative stay. Two hundred seven men underwent RASP during the study period, of which 143 (69%) received scheduled ketorolac. No differences in patient demographics, prostate size, prior opioid utilization, or operative characteristics were identified between groups. Median MEU was significant less (5 vs 15, p < 0.001) in patients receiving scheduled ketorolac. Significantly more patients receiving scheduled ketorolac did not require the use of any narcotic during hospitalization (30% vs 11%, p = 0.005). On multivariable linear regression adjusted for age, BMI, prior opioid use, and length of stay, ketorolac use independently associated with decreased narcotic use (p = 0.003). No significant difference in transfusion rates were identified (3.5% vs. 1.6%, p = 0.44). Scheduled ketorolac is effective in reducing post-operative, in-hospital opioid utilization without increasing morbidity after RASP. Almost a third of patients on scheduled ketorolac did not require any opioids post-operatively.
Assuntos
Anti-Inflamatórios não Esteroides , Cetorolaco , Dor Pós-Operatória , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Cetorolaco/administração & dosagem , Cetorolaco/uso terapêutico , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Masculino , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Administração Intravenosa , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Entorpecentes/administração & dosagem , Entorpecentes/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Neoplasias da Próstata/cirurgiaRESUMO
BACKGROUND: This study aimed to identify and describe links between pain medication use and self-reported pain among people aged ≥ 50 years with osteoarthritis (OA) in an Irish population, and to examine the relationships between pain, medication usage and socioeconomic and clinical characteristics. METHODS: Secondary data analysis of wave 1 cross-sectional data from The Irish Longitudinal Study on Ageing (TILDA) was undertaken of 1042 people with self-reported doctor-diagnosed OA. We examined use of medications typically included in OA clinical guidelines, including non-opioid analgesics (e.g. paracetamol), topical and oral non-steroidal anti-inflammatory drugs (NSAIDs), opioids and nutraceuticals. Latent Class Analysis (LCA) was used to identify underlying clinical subgroups based on medication usage patterns, and self-reported pain severity. Multinomial logistic regression was used to explore sociodemographic and clinical characteristic links to latent class membership. RESULTS: A total of 358 (34.4%) of the 1042 people in this analysis were taking pain medications including oral NSAIDs (17.5%), analgesics (11.4%) and opioids (8.7%). Nutraceutical (glucosamine/chondroitin) use was reported by 8.6% and topical NSAID use reported by 1.4%. Three latent classes were identified: (1) Low medication use/no pain (n = 382, 37%), (2) low medication use/moderate pain (n = 523, 50%) and (3) moderate medication use/high pain (n = 137, 13%). Poorer self-rated health and greater sleep disturbance were associated with classes 2 and 3; depressive symptoms and female gender were associated with class 2, and retirement associated with class 3. CONCLUSIONS: Whilst pain medication use varied with pain severity, different medication types reported broadly aligned with OA guidelines. The two subgroups exhibiting higher pain levels demonstrated poorer self-rated health and greater sleep disturbance.
Assuntos
Análise de Classes Latentes , Osteoartrite , Autorrelato , Humanos , Masculino , Feminino , Idoso , Estudos Longitudinais , Pessoa de Meia-Idade , Irlanda/epidemiologia , Estudos Transversais , Osteoartrite/tratamento farmacológico , Osteoartrite/epidemiologia , Osteoartrite/diagnóstico , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor/tratamento farmacológico , Dor/epidemiologia , Medição da Dor , Analgésicos Opioides/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: Evaluation of the analgesic, opioid-sparing, anti-inflammatory and adverse effects of the diclofenac and orphenadrine (Neodolpasse) fixed combination for analgesia in the postoperative period of surgical cancer patients. MATERIAL AND METHODS: A randomized, single-center, prospective, comparative study evaluated two analgesic regimens in 40 cancer patients undergoing various open cavity surgeries, including extensive combined interventions associated with the resection of 3 or more organs. The study was conducted following the transfer from the ICU to the surgical department during the early activation period, within the first two postoperative days. In the first group N (n=20), "Neodolpasse" (a fixed combination of 75 mg Diclofenac and 30 mg Orphenadrine) was administered as an infusion, twice daily. In the second group K (n=20) analgesia was performed with ketoprofen as an intravenous infusion at a daily dose of 200 mg. Patients in both groups received scheduled prolonged epidural analgesia with 0.2% ropivacaine, and when the severity of pain in a visual analogue scale (VAS) increased to more than 40 mm, so an additional dose of 100 mg tramadol was administered intramuscularly. Daily measurments of blood creatinine level and C-reactive protein were taken, postoperative blood loss was accounted for, as well as postoperative complications according to the Clavien-Dindo classification. RESULTS: The comparative analysis of the indicators of pain syndrome severity showed that the patients in group N exhibited a more pronounced analgesic effect, so on the second postoperative day 30% of patients reported moderate pain (from 50 to 60 mm on the pain scale), on the third day - 15%, and by the fourth day - all 100% of patients experienced pain of low intensity. The additional analgesia with tramadol in group N was required twice less than in the comparison group, and such adverse effects as nausea, drowsiness, and weakness were significantly more common in the ketoprofen group. In both groups, the average blood creatinine level did not exceed permissible values, and the C-reactive protein was elevated at all stages of the study but tended to decrease by the fourth day. The analysis of postoperative complications according to the Clavien-Dindo scale at the time of discharge did not reveal a direct correlation between the occurred complications and the use of NSAIDs. Adverse effects such as anastomotic failure, gastrointestinal complications, or other hemorrhagic manifestations were not recorded. CONCLUSION: The inclusion of Neodolpasse into multimodal analgesic regimens resulted in the most pronounced analgesic and opioid-sparing effects in surgical cancer patients using laparotomy access. Additionally, the application of short courses of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a favorable safety profile.
Assuntos
Diclofenaco , Orfenadrina , Medição da Dor , Dor Pós-Operatória , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Masculino , Feminino , Pessoa de Meia-Idade , Diclofenaco/administração & dosagem , Orfenadrina/administração & dosagem , Orfenadrina/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Resultado do Tratamento , Combinação de Medicamentos , Manejo da Dor/métodos , Neoplasias Abdominais/cirurgia , Estudos Prospectivos , Idoso , Tramadol/administração & dosagem , Tramadol/efeitos adversos , Adulto , Analgésicos Opioides/administração & dosagemRESUMO
Introduction: Endometriosis is delineated as a benign yet steroid-dependent disorder characterized by the ectopic presence of endometrial glandular and stromal cells outside the uterine cavity, affecting estimated 10%-15% of women of reproductive age, 20%-50% of all women with infertility and costing a great economic burden per-patient. Endometriosis exerts pervasive influence on multiple facets of female reproductive physiology. Given its characterization as a chronic inflammatory disorder, escalated levels of pro-inflammatory cytokines were unequivocally recognized as well-established characteristics of endometriosis, which might attribute to mechanisms like retrograde menstruation, progesterone receptor resistance, and immune dysregulation. Therapeutic utilization of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, analgesic agent for reducing pain, inflammation, and fever, could be holding promise in augmenting reproductive outcomes of endometriosis women. Therefore, the objective of this comprehensive review is to elucidate the intricate interplay between endometriosis and aspirin, both within the context of infertility and beyond. We meticulously explore potential pharmacological agents targeting endometriosis, which may concurrently optimize the efficacy of reproductive interventions, while also delving into the underlying mechanistic pathways linking endometriosis with inflammatory processes. Methods: We conducted a comprehensive search in the data available in PubMed and the Web of Science using the terms 'endometriosis' and 'aspirin'. Then analyzed the identified articles based on established inclusion and exclusion criteria independently by three reviewers. Results: The survey of the chosen terms revealed 72 articles, only 10 of which were considered for review. Discussion: Based on the research available currently, it is not substantial enough to address the conclusion that aspirin shall be an effective therapeutic choice for endometriosis, further studies are needed to elucidate the efficacy, safety profile, and optimal dosing regimens of aspirin in the context of endometriosis treatment.
Assuntos
Anti-Inflamatórios não Esteroides , Aspirina , Endometriose , Endometriose/tratamento farmacológico , Humanos , Feminino , Aspirina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Infertilidade Feminina/tratamento farmacológicoRESUMO
INTRODUCTION: Osteoarthritis is a prevalent degenerative joint disorder associated with pain and functional impairment. Curcumin, a natural anti-inflammatory compound, has garnered attention for its potential therapeutic benefits in osteoarthritis management.
Assuntos
Anti-Inflamatórios não Esteroides , Curcumina , Osteoartrite , Curcumina/uso terapêutico , Humanos , Bulgária , Osteoartrite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos de CoortesRESUMO
Inflammation is a hallmark of many diseases, including cancer, neurodegenerative diseases like Alzheimer's, type II diabetes, rheumatoid arthritis, and asthma. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been a cornerstone in the management of various inflammatory, pain, and fever-related conditions. As a result, NSAIDs have found their applications in new therapeutic areas. NSAIDs are known to act by inhibiting the cyclooxygenase (COX) pathway. In recent years, new strategies have been proposed to counter inflammation and develop safer COX inhibitors. This review discusses the design of new COX inhibitors, the derivatization of conventional NSAIDs, and their biological applications. The review also presents an integrated classification of NSAIDs incorporating both traditional chemical-based and function-based approaches, including a brief overview of the NSAIDs of natural origins. Additionally, the review addresses adverse effects associated with different NSAIDs, including effects associated with cardiovascular, renal, and hepatic complications emphasizing the need for the development of new and safer COX inhibitors.
Assuntos
Anti-Inflamatórios não Esteroides , Inibidores de Ciclo-Oxigenase , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/efeitos adversos , Desenho de Fármacos , Estrutura Molecular , Animais , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamenteRESUMO
Groundwater harbours unique species adapted to perpetual darkness. Groundwater fauna plays a crucial role in global ecosystem services, but contamination poses a threat to this keystone ecosystem. Diclofenac is a common non-steroidal anti-inflammatory drug of particular concern, due to its presence in both surface and groundwater. We assess the environmental risk of diclofenac in European groundwaters using different scenarios, analyzing Measured Environmental Concentrations (MECs) of diclofenac and estimating the Predicted No Effect Concentration (PNECs) through two approaches: considering the sensitivity of the groundwater crustacean Proasellus lusitanicus (Isopoda: Asellidae), and using surface water species as proxies. Our results show that scenarios based on surrogate species predict that groundwater ecosystems are at risk due to diclofenac contamination. On the other hand, the MECs of diclofenac were consistently lower than the PNEC of P. lusitanicus, suggesting that the current MECs do not pose a significant threat to this groundwater-adapted species. However, risk scenarios differ considering the sensitivity of other groundwater species, emphasizing the importance of considering multiple species' sensitivities in risk assessment. Therefore, we recommend establishing an environmental quality standard for diclofenac in groundwater at 5 ng/L, a value that accounts the need for precautionary measures to safeguard groundwater ecosystems, essential for preserving their unique biota and services.
Assuntos
Diclofenaco , Monitoramento Ambiental , Água Subterrânea , Poluentes Químicos da Água , Diclofenaco/análise , Água Subterrânea/química , Água Subterrânea/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos adversos , Animais , Monitoramento Ambiental/métodos , Europa (Continente) , Medição de Risco , Isópodes/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/efeitos adversos , EcossistemaRESUMO
Gynecologic surgery with minimally invasive method using robotic or laparoscopic techniques has gained popularity for reducing perioperative discomfort and length of hospital stay. However, the debate over postoperative pain superiority between traditional laparoscopy and robotic surgery persist. This study compared the postoperative pain of patients within 24 h of robotic (RM) and laparoscopic myomectomy (LM). This retrospective cohort study included 24 and 53 patients who underwent RM and LM, respectively, between January 2019 and July 2023. The primary outcomes were the postoperative pain levels of patients within 24 h and the use and dosage of postoperative analgesia. Additional perioperative analgesia, including long-acting non-steroidal anti-inflammatory drugs (Dynastat) and abdominal nerve block, was also recorded. The secondary outcomes were blood loss and hospitalization duration. The patient characteristics were similar between the groups. Factors that could potentially increase pain, such as the number of ports (p < 0.0001), additional procedures (p = 0.0195), operative time (p < 0.0001), number of myomas (p = 0.0057), and the largest myoma size (p = 0.0086), were significantly higher in the RM group than in the LM group. However, there were no significantly different in the postoperative visual analog scale pain scores, use and dosage of ketorolac and opioid, and use of Dynastat and nerve block between the groups. Hospitalization duration and intraoperative blood loss were similar between the groups. RM and LM offer comparable postoperative pain outcomes, emphasizing the importance of patient-specific factors in decision-making regarding myomectomy techniques.
Assuntos
Laparoscopia , Dor Pós-Operatória , Procedimentos Cirúrgicos Robóticos , Miomectomia Uterina , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos Retrospectivos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Miomectomia Uterina/métodos , Miomectomia Uterina/efeitos adversos , Feminino , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Adulto , Pessoa de Meia-Idade , Neoplasias Uterinas/cirurgia , Estudos de Coortes , Duração da Cirurgia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Medição da Dor , Tempo de Internação/estatística & dados numéricos , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Leiomioma/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricosRESUMO
BACKGROUND: The aim of this trial was to evaluate the effect of a preoperative, single dose sublingual fast-dissolving piroxicam (20 mg) compared to placebo on postoperative pain at rest (POP), on biting (POPB) and on percussion (POPer) after single-visit endodontic treatment of asymptomatic mandibular molars with non-vital pulp. METHODS: Seventy patients randomly received either piroxicam or placebo 1 h before treatment (n = 35). Patients recorded their pain (POP and POPB) level 6 h, 12 h, 24 h, 48 h, 72 h and 7 days postoperatively using an 11-point numerical rating scale; POPer was assessed after 7 days. Resuce-analgesic intake (RAI) and flare-up incidence (FUI) were recorded. Data were statistically analyzed. RESULTS: Both groups had similar baseline characteristics (P > 0.05). Piroxicam showed less POP intensity and incidence than placebo at 6, 12 and 24 h, less POPB intensity and incidence at all timepoints, less POPer intensity and incidence and less RAI (p > 0.05), but similar FUI (P > 0.05). A significant rise in pain compared to baseline occurred with placebo from 6 to 72 h for POP and to 7 days with POPB (p > 0.05); such rise was not detected with piroxicam. POPB showed higher pain intensity than POP at all time points (p < 0.05). No swelling or adverse effects occured. CONCLUSIONS: A preoperative single dose of sublingual fast-dissolving piroxicam can be effective in reducing spontaneous pain up to 24 h, stimulated pain up to 7 days, and RAI incidence in asymptomatic mandibular molars with non-vital pulp; it can prevent rise in POP and POPB postoperatively. Stimulated postoperative pain can be more severe and longer lasting than spontaneous pain. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03998826 (2019).
Assuntos
Dente Molar , Medição da Dor , Dor Pós-Operatória , Piroxicam , Pré-Medicação , Humanos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Método Duplo-Cego , Masculino , Feminino , Piroxicam/administração & dosagem , Adulto , Pré-Medicação/métodos , Administração Sublingual , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Mandíbula/cirurgia , Adulto Jovem , Resultado do TratamentoRESUMO
Oxymatrine (OMT) as a quinazine alkaloid extracted from matrine has been shown to exhibit anti-inflammatory and anti-tumour effects. However, the protective mechanism of OMT on NSAID-associated small bowel mucosal injury remains unreported. We found that OMT could improve the clinical symptoms and pathological inflammation scoring, reduce the secretion of proinflammatory cytokines IL-1ß, IL-6 and TNF-α and cell apoptosis, promote cell proliferation and protect intestinal mucosal barrier as compared with the Diclofenac Sodium (DS) group. Further RNA-seq and KEGG analysis uncovered that the differentially expressed genes between DS and control groups were mainly enriched in immune regulation, of which MIP-1γ and its receptor CCR1 expression were validated to be repressed by OMTH. MAPK/NF-κB as the MIP-1 upstream signalling was also inactivated by OMT treatment. In this study, OMT regulated gut microbiota. Venn diagrams visualized and identified 1163 shared OTUs between DS group and OMTH group. The results showed that the α diversity index in the DS group was lower than that in the OMTH group, indicating that the complexity of the flora was reduced in the intestinal inflammatory state. ß diversity mainly includes Principal Component Analysis (PCA) and Principal Co-ordinates Analysis (PCoA). The differences between groups can be observed through PCA. The more similar the composition of the flora, the closer the samples are. We found that the difference was smaller in the DS group than in the OMTH group. The results of PcoA showed that the sample similarity between OMTH groups was the highest. Moreover, gut microbiota analysis unveiled that the abundances of Ruminococcus 1, Oscillibacter and Prevotellaceae at the genus level as well as Lactobacillus SP-L-Yj at the species level were increased in OMTH group as compared with the DS group but the abundance of Allobaculum, Ruminococceos-UCG-005, Ruminococceos-NK4A214 and Clostridium associated with DS-induced small bowel mucosal injury could be decreased by OMTH. MIP-1α and CCR1 were upregulated in human small bowel injury samples as compared with the normal ileal mucosa tissues. In conclusion, our findings demonstrated that OMT could alleviate NSAID-associated small bowel mucosal injury by inhibiting MIP-1γ/CCR1 signalling and regulating gut microbiota.
Assuntos
Alcaloides , Anti-Inflamatórios não Esteroides , Microbioma Gastrointestinal , Mucosa Intestinal , Quinolizinas , Receptores CCR1 , Transdução de Sinais , Quinolizinas/farmacologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Alcaloides/farmacologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Animais , Masculino , Receptores CCR1/metabolismo , Receptores CCR1/genética , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/microbiologia , Intestino Delgado/metabolismo , Diclofenaco/efeitos adversos , Apoptose/efeitos dos fármacos , Humanos , Citocinas/metabolismo , Citocinas/genética , MatrinasRESUMO
Targeting neutrophil function has gained attention as a propitious therapeutic strategy for diverse inflammatory diseases. Accordingly, a series of enone-based derivatives were developed to inhibit neutrophil-mediated inflammation, showing promise for treating inflammatory diseases. These compounds fall into two clusters with distinct effects: one inhibits neutrophilic superoxide (SO) anion production and elastase release triggered by N-formyl-Met-Leu-Phe (fMLF), with compound 6a being most effective (IC50 values of 1.23 and 1.37 µM, respectively), affecting c-Jun N-terminal kinase (JNK) and Akt phosphorylation. The second cluster suppresses formation of SO anion without affecting elastase levels, surpassed by compound 26a (IC50 of 1.56 µM), which attenuates various mitogen-activated protein kinases (MAPKs) with minimal Akt impact. Notably, none of the tested compounds showed cytotoxicity in human neutrophils, underscoring their potential as therapeutic agents against inflammatory diseases.
Assuntos
Relação Dose-Resposta a Droga , Inflamação , Neutrófilos , Proteínas Proto-Oncogênicas c-akt , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Relação Estrutura-Atividade , Estrutura Molecular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Descoberta de Drogas , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese químicaRESUMO
Loxoprofen has been widely used as a non-steroidal anti-inflammatory drug globally and it can also persist in the environment. Although it is known to be a non-toxic drug, its presence may still pose a potential risk to organisms in the environment. Here, the hyper lignin-degrading fungus Phanerochaete sordida YK-624 was used to study the degradation of loxoprofen. This fungus showed excellent loxoprofen biodegradation ability with 90.4% and 93.4% after one day of incubation at lower concentrations of 0.01 and 0.005 mM, respectively. And at a higher concentration of 0.1 mM, a significant removal of 94.2% was also observed after 10 days of incubation. In this study, four metabolites were isolated and determined by HR-ESI-MS and NMR. Furthermore, LC/MS analysis suggested the presence of intermediate hydroxy loxoprofen. In addition, loxoprofen-OH was also identified as a metabolite of loxoprofen through comparison with the synthesized compounds. In this metabolism of loxoprofen, cytochrome P450 may play a significant role. Interestingly, P. sordida YK-624 showed enantioselectivity in the degradation process of loxoprofen. By these results, three degradation pathways of loxoprofen by P. sordida YK-624 were hypothesized. To the best of our knowledge, this is the first report describing the potential degradation mechanisms of loxoprofen by a white-rot fungus.
Assuntos
Anti-Inflamatórios não Esteroides , Biodegradação Ambiental , Lignina , Phanerochaete , Fenilpropionatos , Fenilpropionatos/metabolismo , Anti-Inflamatórios não Esteroides/metabolismo , Phanerochaete/metabolismo , Lignina/metabolismoRESUMO
BACKGROUND: This study aimed to clarify serum salicylic acid (SA) levels in patients with Kawasaki disease (KD) after the administration of moderate-dose acetylsalicylic acid (ASA) and their relationship with the therapeutic effect. METHODS: We retrospectively analyzed the clinical data of 142 children with KD. We measured serum SA trough levels during the acute and recovery periods and determined their relationship with clinical and laboratory parameters. RESULTS: The median age of patients was 2.4 years. Thirty-one patients had incomplete KD, 29 were intravenous immunoglobulin (IVIG) non-responders, and one patient had coronary artery lesions. The median ASA dose was 49.7 mg/kg/day. The median serum SA level was 22 µg/mL in the acute period and 15 µg/mL in the recovery period, with 45 (33%) in the acute period and 60 (44%) in the recovery period below the limit of measurement (< 10 µg/mL). Serum SA levels during the recovery period were significantly lower in patients who received steroids. There were no significant differences in IVIG responsiveness based on serum SA levels. CONCLUSIONS: Serum SA trough levels in KD patients treated with moderate-dose ASA were highly variable and did not reach sufficient levels. Serum SA levels were not associated with IVIG responsiveness.
Assuntos
Aspirina , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Ácido Salicílico , Humanos , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estudos Retrospectivos , Masculino , Aspirina/uso terapêutico , Feminino , Pré-Escolar , Lactente , Imunoglobulinas Intravenosas/uso terapêutico , Ácido Salicílico/sangue , Criança , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Resultado do TratamentoRESUMO
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP. As the clinical effectiveness of topical epinephrine in preventing PEP is elusive, this work attempts to assess its impact on PEP prevention. The databases Embase, Web of Science, PubMed, and Cochrane Library were searched for randomized controlled trials (RCTs) and retrospective cohort studies (RCSs) on topical epinephrine in PEP prevention (data cutoff, November 2022). This study included a total of 10 research articles, involving 5683 patients, comprising 7 RCTs and 3 RCSs. The results of the meta-analysis indicated that epinephrine had no significant effect on preventing PEP or improving its severity. The meta-analysis results of RCTs subgroup revealed no significant difference in the incidence of PEP between patients receiving epinephrine treatment [alone/in combination with nonsteroidal anti-inflammatory drugs (NSAIDs)] vs. without epinephrine treatment (control group) (P = .23). However, patients treated with epinephrine alone experience a lower incidence of PEP compared to the control group (risk ratio [RR] = 0.28, 95% CI = 0.14-0.56, P = .0004). The treatment with epinephrine+NSAIDs vs. NSAIDs showed no significant difference (P = .95). The meta-analysis results of RCSs subgroup demonstrated a significant reduction in the incidence of PEP with the epinephrine+NSAIDs vs. NSAIDs (P < .05). Regarding the severity of PEP [mild, and moderate to severe (M-S)] in the RCT subgroup, the incidence of PEP was not reduced with epinephrine treatment (alone/in combination with NSAIDs) vs. control group. In the RCS subgroup, receiving epinephrine (alone/in combination with NSAIDs) reduced the incidence of mild PEP, while it had no effect on the incidence of M-S PEP. Epinephrine was not significantly effective in preventing PEP and improving its severity. The combined use of NSAIDs and epinephrine as a possible preventive measure requires further investigation into its efficacy.
Assuntos
Administração Tópica , Colangiopancreatografia Retrógrada Endoscópica , Epinefrina , Pancreatite , Humanos , Pancreatite/prevenção & controle , Pancreatite/etiologia , Epinefrina/administração & dosagem , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Masculino , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Pessoa de Meia-Idade , IncidênciaRESUMO
OBJECTIVE: This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. METHODS: We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. RESULTS: We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. CONCLUSIONS: The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.
Assuntos
Antirreumáticos , Aleitamento Materno , Guias de Prática Clínica como Assunto , Complicações na Gravidez , Espondilartrite , Humanos , Gravidez , Feminino , Antirreumáticos/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Espondilartrite/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Reumatologia/normas , Sociedades Médicas , Resultado da Gravidez , Glucocorticoides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêuticoAssuntos
Administração Retal , Anti-Inflamatórios não Esteroides , Colangiopancreatografia Retrógrada Endoscópica , Quimioterapia Combinada , Pancreatite , Ensaios Clínicos Controlados Aleatórios como Assunto , Somatostatina , Humanos , Somatostatina/administração & dosagem , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Pancreatite/prevenção & controle , Pancreatite/etiologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversosRESUMO
Purpose: This study aimed to investigate the relationship between diclofenac sodium ophthalmic solution (DFNa) and corneal epithelial cell damage and to evaluate the preventive effect of rebamipide (RBM) on it. Methods: DFNa, DFNa/preservative-free (PF), or 0.5% chlorobutanol (CB) solution was instilled into the conjunctival sac of a normal rabbit eye, and corneal resistance measurement (using a corneal resistance device [CRD]) was performed 120 min after the end of instillation. Then, fluorescent staining (FL), corneal tissue staining (hematoxylin and eosin [H&E]), and immunostaining (zona occlusion-1) were performed (RBM-untreated group). However, RBM was instilled into the eyes of another group of normal rabbits, followed by each of the solutions; 120 min after the end of instillation, all evaluations were performed for this group (RBM treatment group). Results: Using the CRD method, in the RBM-untreated group, corneal resistance (CR; %) was found to be significantly reduced in DFNa (79.9 ± 19.4%), DFNa/PF (89.1 ± 17.3%), and 0.5% CB (83.8 ± 10.6%). In addition, DFNa and 0.5% CB solutions showed positive staining in the FL staining method. In the H&E staining method, some clear voids were observed in the outermost layer of the cornea using DFNa and 0.5% CB solutions. However, corneal epithelial damage was suppressed in the RBM treatment group. ZO-1 immunostaining in DFNa and 0.5% CB solutions revealed discontinuous localization of ZO-1 at the cell periphery. Conclusions: RBM eye drops were effective in preventing corneal epithelial damage caused by DFNa eye drops, and CB was considered to be the main causative agent of this damage.