Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.953
Filtrar
1.
Int Arch Allergy Immunol ; 181(1): 24-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31752003

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most prevalent causes of drug hypersensitivity reactions (DHRs), yet the underlying processes are far from clear. Despite the established role of histamine in allergic reactions, its precise implication in DHRs is elusive. OBJECTIVES: This study aimed to explore the connection of basal blood histamine levels to the reported NSAID hypersensitivity. METHODS: Sixteen patients reporting hypersensitivity reactions to a single or multiple NSAIDs and/or paracetamol and 18 healthy volunteers serving as the normal control group enrolled in the study. The medical history was recorded and histamine was quantified spectrophotofluorometrically in whole peripheral blood and plasma. RESULTS: Compared to the normal group, plasma but not whole blood histamine levels were significantly higher in patients (p < 0.001), mainly in the subgroup reporting hypersensitivity to a single agent (p < 0.001). Plasma histamine levels were significantly correlated with the culprit drug selectivity for cyclooxygenase (COX) isozymes (p < 0.001), with higher levels being obtained in patients reporting reactions to COX-1 than to COX-2 selective inhibitors (p < 0.05). CONCLUSIONS: The findings provide first evidence connecting basal blood histamine levels to the reported NSAID-triggered DHRs. Prospective studies are expected to decipher the contribution of histamine-associated parameters to the mechanisms underlying DHRs.


Assuntos
Acetaminofen/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Hipersensibilidade a Drogas/imunologia , Histamina/sangue , Acetaminofen/imunologia , Acetaminofen/uso terapêutico , Adulto , Idoso , Alérgenos/imunologia , Anti-Inflamatórios não Esteroides/imunologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores/sangue , Inibidores de Ciclo-Oxigenase 2/imunologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
2.
Clin Oral Investig ; 24(1): 79-96, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31016540

RESUMO

OBJECTIVES: To compare selective COX-2 inhibitors with ibuprofen in terms of analgesia, rescue medication consumption, and adverse effects after impacted third molar removal. MATERIALS AND METHODS: Electronic databases were searched. Single dose, double-blind, randomized, and controlled clinical trials comparing the analgesic effect of a selective COX-2 inhibitor versus at least one active control group using ibuprofen after impacted third molar removal were selected. RESULTS: Twelve studies were included for the qualitative synthesis and eight were included in the meta-analysis. No statistically significant differences were found between selective COX-2 inhibitors and ibuprofen in terms of pain relief after 6, 8, and 12 h. Rescue analgesia use after 24 h was significantly greater in the ibuprofen group than in the selective COX-2 inhibitor group. There were no statistically significant differences in the number of patients presenting one or more adverse events between the two groups, though ibuprofen intake was related with more nausea and vomiting. CONCLUSIONS: No statistically significant differences were found in terms of pain relief 6, 8, and 12 h post-medication between selective COX-2 inhibitors and ibuprofen following totally or partially impacted third molar removal. The patients who consumed selective COX-2 inhibitors needed less rescue analgesia after 24 h. The occurrence of one or more adverse events was similar in both groups, though patients who consumed ibuprofen had more nausea and vomiting. CLINICAL RELEVANCE: COX-2 inhibitors could be considered a suitable alternative to ibuprofen for pain relief after third molar extraction in patients at risk of developing nausea and vomiting. Also, COX-2 inhibitors seem to slightly reduce the need of rescue medication consumption.


Assuntos
Analgésicos/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Dente Serotino , Manejo da Dor/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Extração Dentária , Método Duplo-Cego , Humanos , Dor Pós-Operatória
3.
Drug Metab Rev ; 51(4): 498-523, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726891

RESUMO

Articular cartilage has a complex structure and metabolism which allow for a proper movement within joints. Nevertheless, several systemically administered pharmacological agents have been proved to improve the anabolic response in the case of cartilage lesions. Alendronate, glucosamine, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, vitamin C, vitamin D, aspirin and strontium ranelate have shown positive results in clinical trials. On the other hand, calcitonin, risedronate, doxycycline, and celecoxib did not slow the progression of cartilage lesions in clinical trials. Other systemic drugs or supplements such as teriparatide, leptin, zoledronic acid, bevacizumab, atorvastatin, omega-3 fatty acid, naringin, MSM, selenium, zinc, magnesium, resveratrol, donepezil, naproxen, etodolac, ursodeoxycholic acid (UDCA), lithium chloride, and rebamipide showed positive results in in vitro and animal studies but clinical trials are needed to confirm the positive impact on cartilage repair. A number of molecules, not currently available on the market, have also shown promising results in cartilage healing, such as licofelone, sclerostin, cyclopamine, cyclodextrin polysulfate, AG-041R, osteoprotegerin, rhMK, ß-cryptoxanthine, NF-κb essential modulator binding domain (NBD), TGF-ß-neutralizing antibody, osteogenic protein-1 (BMP-7), fibroblast growth factor 2 (FGF2), and RhBMP-2. Currently available systemic drugs that impair cartilage healing are represented by corticosteroids, vitamin A, and fluoroquinolones.


Assuntos
Osteoartrite/tratamento farmacológico , Acetaminofen/uso terapêutico , Analgésicos não Entorpecentes/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Capsaicina/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Suplementos Nutricionais , Humanos , Osteoartrite/metabolismo , Osteoartrite/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Int J Nanomedicine ; 14: 7561-7581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571864

RESUMO

Introduction: This study was conducted to elucidate the chemopreventive potential, cytotoxic, and suppression of cellular metastatic activity of etodolac (ETD)-loaded nanocarriers. Methods: To esteem the effect of charge and composition of the nanovectors on their performance, four types of vectors namely, negative lipid nanovesicles; phosalosomes (N-Phsoms), positive phosalosomes (P-Phsoms), nanostructured lipid carriers (NLCs) and polymeric alginate polymer (AlgNPs) were prepared and compared. ETD was used as a model cyclo-oxygenase-2 (COX-2) inhibitor to evaluate the potency of these nanovectors to increase ETD permeation and retention through human skin and cytotoxicity against squamous cell carcinoma cell line (SCC). Moreover, the chemopreventive activity of ETD nanovector on mice skin cancer model was evaluated. Results: Among the utilized nanovectors, ETD-loaded N-Phsoms depicted spherical vesicles with the smallest particle size (202.96±2.37 nm) and a high zeta potential of -24.8±4.16 mV. N-Phsoms exhibited 1.5, and 3.6 folds increase in the ETD amount deposited in stratum corneum, epidermis and dermis. Moreover, cytotoxicity studies revealed a significant cytotoxic potential of such nanovector with IC50=181.76 compared to free ETD (IC50=982.75), correlated to enhanced cellular internalization. Its efficacy extended to a reduction in the relative tumor weight with 1.70 and 1.51-fold compared to positive control and free ETD, that manifested by a 1.72-fold reduction in both COX-2 and proliferating cell nuclear antigen mRNA (PCNA-mRNA) levels and 2.63-fold elevation in caspase-3 level in skin tumors relative to the positive control group with no hepato-and nephrotoxicity. Conclusion: Encapsulation of ETD in nanovector enhances its in-vitro and in-vivo anti-tumor activity and opens the door for encapsulation of more relevant drugs.


Assuntos
Quimioprevenção , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Nanoestruturas/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/enzimologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/toxicidade , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Etodolac/farmacologia , Etodolac/uso terapêutico , Feminino , Humanos , Concentração Inibidora 50 , Lipídeos/química , Camundongos , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Estudos Prospectivos , Absorção Cutânea/efeitos dos fármacos , Neoplasias Cutâneas/patologia , Eletricidade Estática , Resultado do Tratamento
5.
Int J Mol Sci ; 20(16)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405112

RESUMO

Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant efficacy, but also considerable toxicity. This study addresses the chemopreventive effect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16-/-, n = 10, parecoxib-treated); II (HPV16-/- n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/-, n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn't modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive effects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.


Assuntos
Anticarcinógenos/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Papillomavirus Humano 16/isolamento & purificação , Isoxazóis/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/virologia , Animais , Anticarcinógenos/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Feminino , Papillomavirus Humano 16/genética , Isoxazóis/efeitos adversos , Camundongos , Camundongos Transgênicos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Pele/efeitos dos fármacos , Pele/patologia , Pele/virologia , Neoplasias Cutâneas/patologia
6.
J Med Life ; 12(2): 150-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31406516

RESUMO

Pain control during and after any surgical procedure, is extremely essential for the comfort of patients. Pain killers used routinely act by inhibiting cyclooxygenase to control pain and inflammation. Cox-1 is constitutively expressed in most cell types, including platelets, whereas Cox-2 is absent from most healthy tissues but is induced by pro-inflammatory or proliferative stimuli. Cox-1 plays a role in the production of prostaglandins involved in protection of the gastric mucosal layer and thromboxanes (TX) in platelets. Cox-2 generally mediates elevations of prostaglandins associated with inflammation, pain, and pyresis. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are generally nonselective inhibitors of Coxs. This lack of selectivity has been linked to their propensity to cause gastrointestinal side effects. The new Cox-2 selective inhibitors, or coxibs, show the same anti-inflammatory, analgesic, and antipyretic effects as nonselective NSAIDs but are supposed to have reduced side-effect profiles. This study evaluates whether rofecoxib (50 mg) given one hour pre-operatively or the same drug given one hour post-operatively is more effective in controlling the pain and swelling in mandibular third molar surgery.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Mandíbula/cirurgia , Dente Serotino/cirurgia , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Proteína C-Reativa/metabolismo , Feminino , Humanos , Lactonas/farmacologia , Masculino , Cuidados Pós-Operatórios , Sulfonas/farmacologia , Adulto Jovem
7.
J Dairy Sci ; 102(11): 10277-10290, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31447141

RESUMO

Nonsteroidal anti-inflammatory drugs are used as supportive therapy with antimicrobial treatments for mastitis in cows to alleviate pain of the inflamed mammary gland. They act mainly by inhibition of cyclooxygenases. Meloxicam (MEL) is a drug designed for cyclooxygenase-2 selectivity, which is upregulated upon inflammation, acting as a key enzyme for the conversion of arachidonic acid to prostaglandins. Although some studies in dairy cows showed positive results in recovery from mastitis when MEL was added to the treatments, direct effects of MEL on the immune system of mastitic cows are unknown. The aim of this study was to investigate effects of MEL on the immune response of bovine mammary epithelial cells (MEC) with or without simultaneous immune stimulation by pathogen-associated molecular patterns of common mastitis pathogens. Mammary epithelial cells from 4 cows were isolated and cultured. To evaluate dose effects of MEL, MEC were challenged with or without 0.2 µg/mL lipopolysaccharide (LPS; serotype O26:B6 from Escherichia coli) with addition of increasing concentrations of MEL (0, 0.25, 0.5, 1.0, 1.5, or 2.0 mg/mL). The addition of MEL prevented the increase of mRNA expression of key inflammatory factors in LPS-challenged MEC in a dose-dependent manner. To investigate the effects of MEL on pathogen-specific immune responses of MEC, treatments included challenges with LPS from E. coli and lipoteichoic acid from Staphylococcus aureus with or without 1.5 mg/mL MEL for 3, 6, and 24 h. Meloxicam prevented the increase of mRNA abundance of key inflammatory mediators in response to LPS and lipoteichoic acid, such as tumor necrosis factor, serum amyloid A, inducible nitric oxide synthase, and the chemokines IL-8 and CXC chemokine ligands 3 and 5. The prostaglandin E2 synthesis in challenged and nonchallenged cells was reduced by MEL within 24 h. Furthermore, MEL reduced the viability and consequently the total RNA yield of the cells. However, mRNA abundance of apoptosis-related enzymes was not affected by any treatment. Meloxicam had clear dose-dependent effects on the immune response of MEC to pathogen-associated molecular patterns of common mastitis pathogens by preventing increased expression of important factors involved in inflammation. This nonsteroidal anti-inflammatory drug also has detrimental effects on cell viability. How these effects would influence the elimination of pathogens from an infected mammary gland during mastitis therapy with meloxicam needs to be further investigated.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inflamação/veterinária , Mastite Bovina/tratamento farmacológico , Meloxicam/uso terapêutico , Animais , Biomarcadores/análise , Bovinos , Células Epiteliais/patologia , Escherichia coli/química , Feminino , Lipopolissacarídeos/efeitos adversos , Glândulas Mamárias Animais/patologia , Mastite Bovina/patologia , Staphylococcus aureus/química , Ácidos Teicoicos/efeitos adversos
8.
Pediatrics ; 144(3)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31462447

RESUMO

Lymphatic malformation (LM) is a congenital disorder resulting from an abnormal development of lymphatic vessels. LM may result in problems of cosmesis and functional impairment, including airway compression. An 11-year-old girl was referred to our department with increasing dysphagia caused by a large left cervical LM with a long history of treatment. Because of the LM location, surgical resection was not an option, and various therapies, including use of picibanil, had proven ineffective. Celecoxib treatment (100 mg/day) was initiated for local pain management. Softening of the lesion was observed 2 weeks after treatment initiation, and the dose was increased to 200 mg/day with additional shrinking of the LM over the next 2 weeks. With parental consent, celecoxib was continued, with a 65% reduction in volume achieved at 6 months. The patient discontinued treatment at 12 months, and the LM volume increased. Control over the LM was achieved with resumption of celecoxib treatment. After 2 years of treatment, the LM persists, but the size of the malformation is significantly smaller. No adverse effects of celecoxib treatment were observed. The anti-cyclooxygenase-2 effect of celecoxib prevented lymphatic vessel growth through an inhibition of cyclooxygenase-2 activity in the conversion of prostaglandin to prostaglandin E2. In conclusion, celecoxib may be a promising therapeutic agent for LM management.


Assuntos
Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Anormalidades Linfáticas/tratamento farmacológico , Obstrução das Vias Respiratórias/etiologia , Criança , Transtornos de Deglutição/etiologia , Feminino , Humanos , Anormalidades Linfáticas/complicações , Anormalidades Linfáticas/diagnóstico por imagem , Imagem por Ressonância Magnética , Adesão à Medicação , Recidiva
9.
Int J Clin Pharmacol Ther ; 57(11): 531-541, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397273

RESUMO

OBJECTIVE: Osteoarthritis is highly prevalent in older adults and often treated with nonsteroidal anti-inflammatory drugs (NSAIDs). COX-2-selective NSAIDs have been shown to offer better gastrointestinal (GI) safety benefits than non-selective NSAIDs (ns-NSAIDs). However, most COX-2-selective NSAIDs have not been comprehensively evaluated for use in combination with gastroprotective agents (GPAs). This study compared the risk of adverse GI events in patients treated with COX-2-selective NSAIDs and ns-NSAIDs alone, or in combination with GPAs. MATERIALS AND METHODS: We utilized National Health Insurance Claim Data collected from 2012 to 2015. Newly diagnosed patients with osteoarthritis (60 years or older) were included in this study. The study population was divided into two groups: 1) COX-2-selective NSAID treatment and 2) ns-NSAIDs treatment. Patients were followed-up for up to 6 months to determine whether GI events occurred. The Cox proportional hazards model was used to identify differences in risk. Subgroup analyses were conducted for monotherapies and combination treatments with GPAs. RESULTS: The number of subjects prescribed COX-2-selective NSAID and ns-NSAIDs were 20,868 (5.6%) and 353,494 (94.4%), respectively. After adjustment for confounding factors, COX-2-selective NSAID were safer than ns-NSAIDs (adjusted hazard ratio (aHR) = 0.80, 95% confidence interval (CI): 0.77 - 0.82). Use of GPAs with COX-2-selective NSAID was associated with a lower risk of GI events than use of ns-NSAIDs (aHR = 0.92, 95% CI: 0.87 - 0.97). CONCLUSION: Use of COX-2-selective NSAID was associated with a lower risk of GI adverse events than use of ns-NSAIDs as a monotherapy. Furthermore, COX-2-selective NSAID were safer than ns-NSAIDs in combination with GPAs.
.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Gastroenteropatias/induzido quimicamente , Osteoartrite/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Humanos , Estudos Retrospectivos
10.
Biol Pharm Bull ; 42(7): 1120-1127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257288

RESUMO

Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1ß, resulting in reduced nitric oxide and prostaglandin E2 production. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Edema/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Úlcera Gástrica/tratamento farmacológico , Estômago/efeitos dos fármacos , Animais , Aspirina , Carragenina , Celecoxib , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Indometacina , Masculino , Olea , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Ratos Sprague-Dawley , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo
11.
Cancer Sci ; 110(10): 3018-3026, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31361372

RESUMO

Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer-related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well-established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of CRC. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non-steroidal anti-inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first-line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel "post-aspirin" agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger CRC prevention, but also to improvement of other obesity-related diseases.


Assuntos
Antineoplásicos/uso terapêutico , Quimioprevenção/métodos , Neoplasias Colorretais/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Comitês Consultivos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/efeitos adversos , Cardiotoxicidade , Doenças Cardiovasculares/induzido quimicamente , Quimioprevenção/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Eur J Clin Pharmacol ; 75(10): 1355-1360, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31243478

RESUMO

OBJECTIVE: Renal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively. METHODS: This was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group, n = 12; healthy control group, n = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib and its two metabolites (M1 and M2) were determined by the liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters (clearance [CL], apparent volume of distribution [Vd], maximum (or peak) serum concentration [Cmax], amount of time drug is present in serum at Cmax [Tmax], area under the curve [AUC; total drug exposure across time], mean residence time [MRT] and elimination half-life [t1/2]) were calculated. RESULTS: The demographic characteristics of the two groups were not significantly different, with the exception of renal function. The mean Cmax and AUC0-t (AUC from time 0 to the last measurable concentration) of imrecoxib in the renal insufficiency group were 59 and 70%, respectively, of those of the healthy control volunteers with normal renal function, indicating a significant decline in the former group (P < 0. 05). The mean pharmacokinetic parameters of Ml in the renal insufficiency and healthy control groups did not significantly differ. In contrast, the mean Cmax and AUC0-t of M2 in the renal insufficiency group were 233 and 367%, respectively, of those of the normal renal function group, indicating a significant increase in the former group (P < 0.05). The mean CL/F (clearance/bioavailability) of M2 of the renal insufficiency group was 37% of that of the normal renal function group, indicating a notable reduction in the former group (P < 0.05). CONCLUSION: The exposure of imrecoxib in OA patients with renal insufficiency showed a decline compared to that in healthy subjects. However, in patients with renal insufficiency the exposure of M2 was markedly increased and the CL was noticeably reduced. These results indicate that the dosage of imrecoxib should be reduced appropriately in patients with renal insufficiency.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacocinética , Pirróis/farmacocinética , Insuficiência Renal/metabolismo , Sulfetos/farmacocinética , Adulto , Idoso , Inibidores de Ciclo-Oxigenase 2/sangue , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Interações de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Pirróis/sangue , Pirróis/uso terapêutico , Insuficiência Renal/tratamento farmacológico , Sulfetos/sangue , Sulfetos/uso terapêutico
13.
Cerebrovasc Dis Extra ; 9(1): 31-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31039577

RESUMO

BACKGROUND: Saccular intracranial aneurysms (IAs) are outpouchings of the vessel wall of intracranial arteries. Rupture of IAs results in subarachnoid hemorrhage which is associated with high morbidity and mortality. Surgical interventions, such as clipping and coiling, have associated risks. Currently, there are no proven pharmacological treatments to prevent the growth or rupture of IAs. Infiltration of proinflammatory cytokines in response to increased wall sheer stress is a hallmark of IA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are being investigated as potential therapeutic agents for reduction in growth and/or prevention of IA through inhibition of inflammatory pathways. SUMMARY: This review will discuss the role of NSAIDs in attenuating the inflammation that drives IA progression and rupture. There are two main subtypes of NSAIDs, nonselective COX and selective COX-2 inhibitors, both of which have merit in treating IA. Evidence will be presented which shows that NSAIDs inhibit several key inflammatory mediators involved in IA progression including nuclear factor-κB, tumor necrosis factor-α, and matrix metalloproteinases. In addition, the role of NSAIDs in limiting inflammatory cell adhesion to endothelial cells and attenuating endothelial cell senescence will be discussed. Key Messages: There is an abundance of basic science and preclinical data that support NSAIDs as a promising treatment for IA. Additionally, a combination treatment strategy of low-dose aspirin given concomitantly with a selective COX-2 inhibitor may result in a reduced side effect profile compared to aspirin or selective COX-2 inhibitor use alone. Several large clinical trials are currently planned to further investigate the efficacy of NSAIDs as an effective nonsurgical treatment for IAs.


Assuntos
Artérias Cerebrais/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/uso terapêutico , Mediadores da Inflamação/metabolismo , Aneurisma Intracraniano/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos , Animais , Aspirina/uso terapêutico , Artérias Cerebrais/metabolismo , Artérias Cerebrais/patologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Ciclo-Oxigenase/efeitos adversos , Dilatação Patológica , Quimioterapia Combinada , Humanos , Aneurisma Intracraniano/metabolismo , Aneurisma Intracraniano/patologia , Transdução de Sinais , Resultado do Tratamento
14.
Drugs Aging ; 36(Suppl 1): 25-44, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31073922

RESUMO

OBJECTIVE: Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. METHODS: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). RESULTS: Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09-1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03-1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08-1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01-2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80-1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22-2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21-2.29; 0%). CONCLUSIONS: In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.


Assuntos
Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Lactonas/efeitos adversos , Osteoartrite/tratamento farmacológico , Sulfonas/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Lactonas/administração & dosagem , Lactonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfonas/administração & dosagem , Sulfonas/uso terapêutico , Resultado do Tratamento
15.
Ter Arkh ; 91(1): 108-113, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090381

RESUMO

The review presents current information on the role of NSAIDs in the development of cardiovascular disasters. The development of non-desirable cardiovascular effects and an increase in cardiovascular risk with the administration of NSAIDs, most experts assess in terms of the antagonistic effect on the platelet-vascular homeostasis of metabolites of COX-thromboxane A2 and prostaglandin I2 (prostacyclin). All the presented reviews confirming an increase in the risk of MI complications in the administration of NSAIDs, indicate the class-specificity of this undesirable effect, not homogeneous for different representatives of the group. Important clinical aspects of prescribing NSAIDs for patients with low and moderate cardiovascular risk are the clinical features of the patient and the individual set of risk factors for CVD. Such pharmacokinetic characteristics of NSAIDs as a short half-life, a high degree of binding to blood plasma albumins are indicative of greater safety of NSAIDs, but the final decision must be made based on the accumulated data of clinical trials and meta-analyzes. Keywords: nonsteroidal anti-inflammatory drugs, cardiovascular diseases, cardiovascular risk, lornoxicam, diclofenac sodium, thrombo-elastogram, myocardial infarction, stroke.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Diclofenaco/administração & dosagem , Diclofenaco/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Humanos , Fatores de Risco
16.
Pak J Pharm Sci ; 32(1(Special)): 391-396, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30852475

RESUMO

The aim of this study is to determine the effects of alone or combined usage of doxycycline and meloxicam on brain superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and matrix metalloproteinase (MMP)-9 levels of lipopolysaccharide (LPS)-induced brain inflammation. Totally 78 rats were divided into 5 groups; Healthy control (n=6), LPS (n=18, 0.05µg/µL/rat, intracranially), LPS+D (n=18, LPS 0.05µg/µL/rat, intracranially and doxycycline 40 mg/kg, intraperitoneally), LPS+M (n=18, LPS 0.05 µg/µL/rat, intracranially and meloxicam 2 mg/kg, intraperitoneally), LPS+Combination (n=18, LPS 0.05 µg/µL/rat, intracranially and simultaneously both drug combination) groups. Animals were euthanized at 1, 3 and 6 hours following injections and the brains were removed. Brain SOD, CAT, MDA and MMP-9 levels were determined by ELISA reader. Parameters of LPS groups generally different from Healthy control group. When compared to LPS group, increased SOD level of LPS+D at 3 hours and CAT levels of LPS+M and LPS+D groups were determined (P<0.05) at 3 and 6 hours, respectively. In addition, all treatments statistically significantly (P<0.05) decreased MMP-9 levels at 6 hours. In conclusion, doxycycline and meloxicam may show antioxidant effect via increasing antioxidant enzyme production in the brain; however combined usage of drugs may show more beneficial effect for neuroinflammation. .


Assuntos
Antibacterianos/uso terapêutico , Antioxidantes/metabolismo , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Doxiciclina/uso terapêutico , Encefalite/tratamento farmacológico , Meloxicam/uso terapêutico , Animais , Antibacterianos/administração & dosagem , Catalase/metabolismo , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Modelos Animais de Doenças , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Encefalite/enzimologia , Inflamação , Lipopolissacarídeos , Masculino , Meloxicam/administração & dosagem , Ratos Wistar , Superóxido Dismutase/metabolismo
17.
Curr Med Sci ; 39(1): 94-98, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868497

RESUMO

Using anesthetic gel may not sufficiently exclude pain perception during and after cystoscopy in male patients. To evaluate the analgesic efficacy and safety of intramuscular parecoxib (40 mg) for outpatient-based rigid cystoscopy, we performed a prospective, randomized and controlled study. Consecutive male patients requiring diagnostic cystoscopy in our hospital were divided into group A (1% tetracaine gel, n=50) and group B (parecoxib, n=51) at random. Patients received intramuscular injections of either 2 mL sterile saline in group A or 40 mg parecoxib in group B 30 min before the procedure. Tetracaine gel was injected into the urethra 3 min before the procedure in group A, with patients receiving plain lubricant gel in group B at the same time. Cystoscopy-associated pain levels were evaluated using the Visual Analog Score (VAS) during the procedure. Post-procedure urethral pain and complications were recorded and analyzed. The results showed that male patients experienced significantly less pain in group B than in group A (2.70±1.36 vs. 3.56±1.74, P=0.008). The percentage of patients with dysuria pain was not significantly different between the two groups. In addition, 24 h after cystoscopy, the patients with no previous experience of cystoscopy were more likely to declare urethral pain (59.2% vs. 33.3%, P=0.012, relative risk=1.78). No difference was observed in analgesic-related complications between the two groups. We conclude that intramuscular injection of 40 mg parecoxib may improve comfort for male patients undergoing rigid cystoscopy.


Assuntos
Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Cistoscopia/efeitos adversos , Isoxazóis/administração & dosagem , Dor/tratamento farmacológico , Tetracaína/administração & dosagem , Instituições de Assistência Ambulatorial , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Cistoscopia/instrumentação , Método Duplo-Cego , Humanos , Injeções Intramusculares , Isoxazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Manejo da Dor , Medição da Dor , Estudos Prospectivos , Tetracaína/uso terapêutico , Resultado do Tratamento
18.
J Med Case Rep ; 13(1): 39, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30786934

RESUMO

BACKGROUND: Pachydermoperiostosis (PDP) is a rare disorder characterized by clubbing of the fingers, thickening of the skin (pachyderma), and excessive sweating (hyperhidrosis). It typically appears during childhood or adolescence, often around the time of puberty, and progresses slowly. Clinical presentations of PDP can be confused with secondary hypertrophic osteoarthropathy, psoriatic arthritis, rheumatoid arthritis, thyroid acropachy, and acromegaly. CASE PRESENTATION: A Mongolian male, aged 19 years, resident of a hilly district of Nepal, with history of consanguinity, presented to our outpatient department with chief complaints of pain and swelling in both hands and feet for 6 years. The pain was insidious in onset, throbbing in nature, and not relieved by over-the-counter medications. The patient also complained of profuse sweating, progressive enlargement of hands and feet, and gradual coarsening of facial features. On examination there were marked skin folds in the forehead, face, and eyelids. Clubbing and swelling of bilateral knee joints and ankle joints was also evident. He was subsequently investigated extensively for acromegaly. Insulin-like growth factor-1 level and oral glucose tolerance test were normal. Radiography of various bones showed periosteal hypertrophy with subperiosteal bone formation. CONCLUSIONS: PDP should be considered as a differential diagnosis when a patient presents with hypertrophic osteoarthropathy and acromegalic features.


Assuntos
Osteoartropatia Hipertrófica Primária/diagnóstico por imagem , Osteoartropatia Hipertrófica Primária/patologia , Adulto , Anti-Inflamatórios/uso terapêutico , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Diagnóstico Diferencial , Humanos , Masculino , Nepal , Osteoartropatia Hipertrófica Primária/tratamento farmacológico , Prednisolona/uso terapêutico , Radiografia/métodos , Retinoides/uso terapêutico , Síndrome , Adulto Jovem
19.
Bioorg Chem ; 85: 541-557, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30807897

RESUMO

New thiophene and annulated thiophene pyrazole hybrids were synthesized and screened for their in vitro COX-1/COX-2 enzymatic inhibition and in vivo anti-inflammatory activities. All compounds were more COX-2 selective inhibitors than COX-1 with compound 13 exhibiting the highest COX-2 selectivity index. Compounds 3, 6a, 9 and 11 were the most promising in the acute anti-inflammatory assay while compounds 3, 5, 6a, 6c, 9, 10, 11 and 13 exerted promising anti-inflammatory activity in the sub-acute anti-inflammatory assay. Compounds 3, 6a, 6c, 9, 10 and 11 were evaluated for their ED50 values and were more potent than diclofenac sodium while compounds 6a, 6c and 9 were of greater potency than celecoxib with compound 6a being the most potent showing ED50 = 0.033 mmol/kg. These compounds were non-toxic and proved to be gastrointestinal safe compared to indomethacin, diclofenac sodium and celecoxib. Docking studies into COX-2 active site (PDB code 3LN1) revealed that compounds 3, 6a, 6c, 9, 10, 11 and 13 had binding modes and energies comparable to that of celecoxib. Compounds 3, 9, 10 and 11 complied with Lipinski's RO5 while compounds 6a and 6c showed one violation whereas compound 13 deviated by 2 violations. Compounds 6a, 6c and 13 showed 100% plasma protein binding (PPB) and showed no aqueous solubility while compounds 3, 10 and 11 demonstrated the best drug likeness model scores. Therefore, the thiophene analog 3 and the thienopyrimidine derivatives 10 and 11 are promising anti-inflammatory candidates that exert moderate selective COX-2 inhibition with acceptable physicochemical properties.


Assuntos
Anti-Inflamatórios/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Tiofenos/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/toxicidade , Sítios de Ligação , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/toxicidade , Desenho de Drogas , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/toxicidade , Pirimidinas/síntese química , Pirimidinas/toxicidade , Ratos , Úlcera Gástrica/induzido quimicamente , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/toxicidade
20.
J Photochem Photobiol B ; 192: 90-96, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30710830

RESUMO

Radiotherapy is considered as a primary modality for cancer treatment which accompanied by several side effects. Protection of normal tissues from radiation effects is one of the most significant concerns for researchers. Although many compounds acting as radio protectors, only two compounds were licensed clinically. Cyclooxygenase-2 (COX-2), as an inflammatory mediator is associated with ROS production with a NF-κB gene up regulation dependent manner in normal tissues. To that extend, his study was designed to target COX-2 and NF-κB by a newly synthesized benzopyran-4-one or chromone derivative; (2E)-2-((4-oxo-4H-chromen-3-yl) methylene amino-4- nitrobenzoic acid (Ch). Exposure of mice to IRR significantly induced intestinal inflammation via overexpression of COX-2 and NF-κB which is accompanied by an increase in the levels of MDA and iNOS in tissue homogenate and in the production of TNF-α and IL-6 as inflammatory signs. Moreover, the apoptotic effect of IRR was manifested by obvious elevation in caspase-3. Interapretonial injection of Ch significantly controls the inflammatory response by blocking the COX-2 and decrease the expression NF-κB which subsequently decreases other inflammatory parameters. Thus Ch compound might be a promising nonsteroidal anti-inflammatory drug (NSAID) against radiation-induced inflammation with a specific mode of COX-2 inhibition. Further researches are needed to elucidate its molecular mechanism and its combination with radiotherapy as a protector.


Assuntos
Benzopiranos/farmacologia , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Animais , Benzopiranos/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Raios gama/efeitos adversos , Inflamação/etiologia , Mediadores da Inflamação/farmacologia , Enteropatias/patologia , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA