BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review an...BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.展开更多
Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no prop...Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.展开更多
The goals of global vaccination are to control,eliminate,or eradicate infectious diseases in a sustainable way that strengthens public health systems.Although the use of vaccines is essential for the control of epidem...The goals of global vaccination are to control,eliminate,or eradicate infectious diseases in a sustainable way that strengthens public health systems.Although the use of vaccines is essential for the control of epidemics,the vaccines against coronavirus disease 2019(COVID-19)proved to be inadequate to end the pandemic and thus are considered incomplete.These vaccines failed to prevent infection,so their primary purpose has been shifted to prevent severe disease and reduce hospitalizations and deaths.Therefore,we believe that all the strategies available to reduce transmission,hospitalizations and deaths due to COVID-19 will be put in place.It is reported that uncontrolled inflammation and thrombosis are the principal mechanisms for aggravation and death in patients with COVID-19.Unlike corticosteroids that should not be administered at the beginning of the symptoms for their immunosuppressive action,which could worsen the evolution of the disease,the usefulness of non-steroidal anti-inflammatory drugs in the early at-home treatment of the disease is becoming evident.展开更多
BACKGROUND: The role of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) for reduction of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is debated. We performed a meta-analysis of ...BACKGROUND: The role of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) for reduction of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is debated. We performed a meta-analysis of all published randomized controlled trials to evaluate the efficacy of NSAIDs in the prevention of post-ERCP pancreatitis. DATA SOURCES: Searches were conducted in the databases PubMed, EMBASE and the Cochrane Library. Six randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. Data were extracted by two independent observers according to predetermined criteria. RESULTS: The risk of pancreatitis was lower in the NSAID group than in the placebo, group (OR: 0.46, 95% CI: 0.32 to 0.65, P < 0.0001). Two hours after ERCP, prophylactic administration of NSAIDs was associated with a lower serum amylase level (WMD: -91.09,95% CI: -149.78 to -32.40, P=0.002), but there was no difference in mean 24-hour serum amylase values (WMD: -379.00, 95% CI: -805.75 to 47.76, P=0.08). No deaths or NSAID-related complications were noted. CONCLUSIONS: Prophylactic administration of NSAIDs can reduce the incidence of post-ERCP pancreatitis; this administration in patients undergoing ERCP is recommended. Further randomized controlled trials are required before its introduction into routine care.展开更多
AIM:To investigate the effect of nonsteroidal antiinflammatory drugs(NSAIDs)on the incidence of postendoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP).METHODS:Two independent reviewers searched pub ...AIM:To investigate the effect of nonsteroidal antiinflammatory drugs(NSAIDs)on the incidence of postendoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP).METHODS:Two independent reviewers searched pub Med(1966 to October 2013),Embase(1984 to October2013)and the Cochrane Central Register of Controlled Trials(CENTRAL;Issue 4,2013)for relevant randomized controlled trials(RCTs)studying the effectiveness of prophylactic NSAID administration in the prevention of PEP.Using the Cochrane Collaboration Handbook,meta-analyses were conducted to evaluate the overall effect of NSAIDs in preventing the incidences of PEP and moderate to severe pancreatitis.RESULTS:Eight RCTs were identified from the literature search and included 1883 patients that underwent ERCP,with 971 patients in the NSAID group and 912patients in the placebo group.Sixty-nine out of 971(7.11%)patients developed PEP in the NSAID group in comparison to 143 out of 912(15.68%)patients in the placebo group.The pooled RR of PEP incidence with prophylactic NSAID administration was 0.43(95%CI:0.33-0.56),which demonstrates that NSAID administration after ERCP significantly reduced the incidence of PEP when compared to the placebo group(p<0.0001).Subgroup analysis was performed and revealed that the presence(NSAID group)or absence(placebo group)of NSAIDs had no significant effect on the development of moderate to severe pancreatitis(RR=0.79,95%CI:0.52-1.18).Moreover,the administration of NSAIDs as a rectal suppository(RR=0.35,95%CI:0.26-0.48;p<0.0001)was more effective than oral administration(RR=0.97,95%CI:0.53-1.80)or through infusion(RR=0.43,95%CI:0.12-1.54).CONCLUSION:NSAIDs effectively reduce the incidence of PEP but not of moderate to severe pancreatitis.展开更多
Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinf...Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinfectious agents, list on the top for causes of DrugInduced Liver Injury (DILI). The incidence of liver disease induced by NSAIDs reported in clinical studies is fairly uniform ranging from 0.29/100 000 [95% confidence interval (CI): 0.17-051] to 9/100 000 (95% CI: 6-15). However, compared with these results, a higher risk of liver-related hospitalizations was reported (3-23 per 100 000 patients). NSAIDs exhibit a broad spectrum of liver damage ranging from asymptomatic, transient, hyper-transaminasemia to fulminant hepatic failure. However, under-reporting of asymptomatic, mild cases, as well as of those with transient liver-tests alteration, in conjunction with reports non-compliant with pharmacovigilance criteria to ascertain DILI and flawed epidemiological studies, jeopardize the chance to ascertain the actual risk of NSAIDs hepatotoxicity. Several NSAIDs, namely bromfenac, ibufenac and benoxaprofen, have been withdrawn from the market due to hepatotoxicity; others like nimesulide were never marketed in some countries and withdrawn in others. Indeed, the contro-versy concerning the actual risk of severe liver disease persists within NSAIDs research. The present work intends (1) to provide a critical analysis of the dissimilar results currently available in the literature concerning the epidemiology of NSAIDS hepatotoxicity; and (2) to review the risk of hepatotoxicity for each one of the most commonly employed compounds of the NSAIDs family, based on past and recently published data.展开更多
Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the devel...Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.展开更多
AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and Januar...AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was needed.CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in展开更多
AIM: To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs(NSAIDs) on macular edema following cataract surgery in diabetic patients, and to compare between types o...AIM: To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs(NSAIDs) on macular edema following cataract surgery in diabetic patients, and to compare between types of NSAIDs(ketorolac tromethamine 0.4% and nepafenac 0.1%). METHODS: Group 1(control) received artificial tears substitute as a placebo group, group 2(nepafenac) received topical nepafenac 0.1%, and group 3(ketorolac) received topical ketorolac tromethamine 0.4%. Patients were examined postoperatively after completing one week, one month, two months and three months' intervals for evaluating cystoid macular edema(CME) development. The main study outcomes were achieving the best corrected visual acuity(BCVA) and change in the central macular thickness(CMT) measured with optical coherence topography(OCT).RESULTS: Eighty eyes of 76 patients were included in this study. BCVA showed a statistically significant difference at the third month postoperative follow up between the control group and the NSAIDs groups(P=0.04). There was an increase in the CMT in all cases starting from postoperative first week until third month. CMT showed a statistically significant difference between control group and NSAIDs groups from postoperative first month until third month(P=0.008, 0.027, 0.004). There was no statistically significant difference between nepafenac and ketorolac groups in BCVA and OCT CMT. CONCLUSION: Prophylactic preoperative and postoperative NSAIDs may have a role in reducing the frequency and severity of CME in diabetic eyes following cataract surgery.展开更多
BACKGROUND Non-steroidal anti-inflammatory drugs(NSAIDs)are among the most commonly prescribed medications in the United States.Although they are safe and effective means of analgesia for children with broken bones,th...BACKGROUND Non-steroidal anti-inflammatory drugs(NSAIDs)are among the most commonly prescribed medications in the United States.Although they are safe and effective means of analgesia for children with broken bones,there is considerable variation in their clinical use due to persistent concerns about their potentially adverse effect on fracture healing.AIM To assess whether NSAID exposure is a risk factor for fracture nonunion in children.METHODS We systematically reviewed the literature reporting the effect of NSAIDs on bone healing.We included all clinical studies that reported on adverse bone healing complications in children with respect to NSAID exposure.The outcomes of interest were delayed union or nonunion.Study quality was assessed using the Newcastle-Ottawa scale for non-randomized studies.A final table was constructed summarizing the available evidence.RESULTS A total of 120 articles were identified and screened,of which 6 articles were included for final review.Nonunion in children is extremely rare;among the studies included,there were 2011 nonunions among 238822 fractures(0.84%).None of the included studies documented an increased risk of nonunion or delayed bone healing in those children who are treated with NSAIDs in the immediate post-injury or peri-operative time period.Additionally,children are likely to take these medications for only a few days after injury or surgery,further decreasing their risk of adverse side-effects.CONCLUSION This systematic review suggests that NSAIDS can be safely prescribed to pediatric orthopaedic patients absent other contraindications without concern for increased risk of fracture non-union or delayed bone healing.Additional prospective studies are needed focusing on higher risk fractures and elective orthopaedic procedures such as osteotomies and spinal fusion.展开更多
Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our...Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.展开更多
<strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) use is very common. NSAIDs use could be associated with elevated eosinophil count which could be a class effect or patient-rela...<strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) use is very common. NSAIDs use could be associated with elevated eosinophil count which could be a class effect or patient-related. Inflammation could be the link between NSAIDs use and eosinophilia. <strong>Aims: </strong>To compare the pattern of eosinophil count in the peripheral blood of frequent users of NSAIDs and healthy controls. <strong>Methodology: </strong>Two hundred (one hundred frequent users of NSAIDs and 100 healthy controls) participants who had no known risk factor for kidney disease and had given informed consent were recruited. Blood was taken to determine the white cell count and differentials, serum electrolyte and creatinine, and random blood sugar. <strong>Results:</strong> The mean age of NSAIDs users was not significantly different from controls, P = 0.3. The mean eosinophil count was higher in males than females. The incidence of eosinophilia in NSAIDs users was 4%. The mean Eosinophil count of NSAIDs users was insignificantly higher than controls, 164.3 ± 51 6 vs 135. 6 ± 53.4, P = 0.4. The mean platelet count of NSAIDs users was significantly higher compared to controls, P = 0.04. The mean hematocrit of NSAIDs users was significantly lower than the controls, P = 0.02. Propionic acid derivatives were associated with the highest eosinophil count. Eosinophil count was positively related to age and serum creatinine and inversely related to blood glucose, hematocrit and glomerular filtration rate.<strong> Conclusion: </strong>The incidence of eosinophilia was 4%. The eosinophil count was higher in frequent NSAIDs users than occasional and non-users, in males than females and with use propionic acid derivatives compared to other NSAIDs. The Eosinophil count was positively related to age and platelet count. Being commoner in inflammatory states, the tissue destruction associated with elevated EC can be avoided by the prevention and prompt treatment of inflammatory conditions.展开更多
Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial i...Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.展开更多
Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was c...Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.展开更多
Increased risk due to nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been observed in patients. Although diaphragm-like stricture in the small bowel and colon induced by NSAIDs therapy has been rarely repor...Increased risk due to nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been observed in patients. Although diaphragm-like stricture in the small bowel and colon induced by NSAIDs therapy has been rarely reported, gastric body diaphragm-like stricture has not been reported. We describe the first case of gastric body diaphragm-like stricture due to NSAIDs in a 44-year-old male patient who was successfully treated by an endoscopic approach to avoid complicated surgery. This case highlights new insight into the disadvantages of NSAIDs and provides new data for future clinical studies.展开更多
Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (...Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.展开更多
The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. In fact, recovery after brain artery occlusion is dramatically worsened by aging,...The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. In fact, recovery after brain artery occlusion is dramatically worsened by aging, even normal aging is associated with neuron damage and cognitive decline. Mechanisms involved in aging-related, cognitive decline and susceptibility to neuron damage in stroke and neurode- generation are largely unknown. One of the most important mech- anisms contributing to neural dysfunction and death is excitotox- icity. This process is based on the fact that the excessive glutamate receptor stimulation may lead to neuronal damage. This overstim- ulation may be due to increased concentration of glutamate, or the prolonged activation of receptors.展开更多
Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of i...Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.展开更多
Non-steroidal anti-inflammatory drugs (NSAIDs) are classified as Class 4 agents by the Association of Racing Commissioners International and are banned in racehorses during competition in Pennsylvania (PA). To control...Non-steroidal anti-inflammatory drugs (NSAIDs) are classified as Class 4 agents by the Association of Racing Commissioners International and are banned in racehorses during competition in Pennsylvania (PA). To control the abuse of these agents in racehorses competing in PA, a forensic method for screening and confirmation of the presence of these agents is needed. Equine plasma (0.5 mL) was acidified with 75 μL 1M H3PO4 to increase recovery of the analytes by liquid-liquid extraction using methyl tert-butyl ether (MTBE). Extracted analytes were separated by reversed-phase liquid chromatography using a C8 column under gradient condition. All 16 analytes were detected, quantified and confirmed using a triple quadrupole tandem mass spectrometry with selected reaction monitoring (SRM) in both negative and positive electrospray ionization modes. The limit of detection, quantification and confirmation of the analytes were 1.0 - 5.0 ng/mL, 1.0 - 5.0 ng/mL and 1.0 - 20 ng/mL, respectively. The linear dynamic range of quantification was 5.0 - 200 ng/mL. The method is routinely used in anti-doping analysis to control the abuse of NSAIDs in racehorses competing in PA.展开更多
<strong>Aims:</strong> The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still accountable for millions of deaths wor...<strong>Aims:</strong> The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still accountable for millions of deaths worldwide and declared as a global pandemic by the World Health Organisation. Despite efforts, there is still limited evidence available on a successful potent inhibitor with a low toxicity profile that can aid in the prevention and/or treatment of COVID-19. This study will focus on four main aspects: 1) screening 19 Food Drug and Administration (FDA) approved drugs using computational molecular docking;2) assessing drug toxicity profiles using biological data;3) recommending potential therapies against COVID-19 and 4) supplementing currently used therapies. <strong>Methods:</strong> 19 FDA approved drugs were investigated against the crystal structure of SARS-CoV-2 protease (6LU7) and SARS-CoV-2 glycoprotein (6VXX) using a computational molecular docking software, Molecular Operating Environment (MOE). Separately, on MOE, 6LU7 and 6VXX were loaded, prepared, and the binding pockets located. The drug’s canonical SMILES were imported, minimised, and docked on the prepared proteins using a search algorithm to establish the highest stability conformation. Drugs were ranked depending on binding properties and biological data to assess safety;steric clashes and voids in the binding site were also analysed. <strong>Results and discussion:</strong> Out of the nineteen (19) FDA approved drugs, 18 inhibited 6LU7 and 13 inhibited 6VXX. High-ranked drugs based on binding properties for 6LU7 were hydroxychloroquine, dexamethasone, naproxen, etoricoxib, and ibuprofen. For 6VXX were hydroxychloroquine, celecoxib, etoricoxib, meloxicam, and parecoxib. Considering safety profile, the top 3 drugs in descending order for 6LU7 were etoricoxib, naproxen and dexamethasone and for 6VXX were etoricoxib, meloxicam, and parecoxib. Compared to the literature, the results were consistent for dexamethasone which was effective against 6LU7. However, for hydroxychloroquine and ibuprofen, there was conflicting literature regarding safety and efficacy. <strong>Conclusion and future work:</strong> The findings suggest that against COVID-19 etoricoxib might be effective as a therapeutic and prophylactic measure. Naproxen and dexamethasone would be more effective as treatment only while meloxicam and parecoxib as prophylaxis. However, future studies are needed to validate these findings. Compared to previous literature, the findings in this study also support the use of dexamethasone over hydroxychloroquine and ibuprofen for COVID-19 based on the binding and safety properties. Despite this, future research should explore the impressive binding properties displayed by hydroxychloroquine and ibuprofen to aid in developing a new drug against COVID-19.展开更多
基金Supported by the Science and Technology Plan Project of Jingmen Science and Technology Bureau,No.2018YFZD025。
文摘BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.
文摘Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.
文摘The goals of global vaccination are to control,eliminate,or eradicate infectious diseases in a sustainable way that strengthens public health systems.Although the use of vaccines is essential for the control of epidemics,the vaccines against coronavirus disease 2019(COVID-19)proved to be inadequate to end the pandemic and thus are considered incomplete.These vaccines failed to prevent infection,so their primary purpose has been shifted to prevent severe disease and reduce hospitalizations and deaths.Therefore,we believe that all the strategies available to reduce transmission,hospitalizations and deaths due to COVID-19 will be put in place.It is reported that uncontrolled inflammation and thrombosis are the principal mechanisms for aggravation and death in patients with COVID-19.Unlike corticosteroids that should not be administered at the beginning of the symptoms for their immunosuppressive action,which could worsen the evolution of the disease,the usefulness of non-steroidal anti-inflammatory drugs in the early at-home treatment of the disease is becoming evident.
文摘BACKGROUND: The role of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) for reduction of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is debated. We performed a meta-analysis of all published randomized controlled trials to evaluate the efficacy of NSAIDs in the prevention of post-ERCP pancreatitis. DATA SOURCES: Searches were conducted in the databases PubMed, EMBASE and the Cochrane Library. Six randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. Data were extracted by two independent observers according to predetermined criteria. RESULTS: The risk of pancreatitis was lower in the NSAID group than in the placebo, group (OR: 0.46, 95% CI: 0.32 to 0.65, P < 0.0001). Two hours after ERCP, prophylactic administration of NSAIDs was associated with a lower serum amylase level (WMD: -91.09,95% CI: -149.78 to -32.40, P=0.002), but there was no difference in mean 24-hour serum amylase values (WMD: -379.00, 95% CI: -805.75 to 47.76, P=0.08). No deaths or NSAID-related complications were noted. CONCLUSIONS: Prophylactic administration of NSAIDs can reduce the incidence of post-ERCP pancreatitis; this administration in patients undergoing ERCP is recommended. Further randomized controlled trials are required before its introduction into routine care.
文摘AIM:To investigate the effect of nonsteroidal antiinflammatory drugs(NSAIDs)on the incidence of postendoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP).METHODS:Two independent reviewers searched pub Med(1966 to October 2013),Embase(1984 to October2013)and the Cochrane Central Register of Controlled Trials(CENTRAL;Issue 4,2013)for relevant randomized controlled trials(RCTs)studying the effectiveness of prophylactic NSAID administration in the prevention of PEP.Using the Cochrane Collaboration Handbook,meta-analyses were conducted to evaluate the overall effect of NSAIDs in preventing the incidences of PEP and moderate to severe pancreatitis.RESULTS:Eight RCTs were identified from the literature search and included 1883 patients that underwent ERCP,with 971 patients in the NSAID group and 912patients in the placebo group.Sixty-nine out of 971(7.11%)patients developed PEP in the NSAID group in comparison to 143 out of 912(15.68%)patients in the placebo group.The pooled RR of PEP incidence with prophylactic NSAID administration was 0.43(95%CI:0.33-0.56),which demonstrates that NSAID administration after ERCP significantly reduced the incidence of PEP when compared to the placebo group(p<0.0001).Subgroup analysis was performed and revealed that the presence(NSAID group)or absence(placebo group)of NSAIDs had no significant effect on the development of moderate to severe pancreatitis(RR=0.79,95%CI:0.52-1.18).Moreover,the administration of NSAIDs as a rectal suppository(RR=0.35,95%CI:0.26-0.48;p<0.0001)was more effective than oral administration(RR=0.97,95%CI:0.53-1.80)or through infusion(RR=0.43,95%CI:0.12-1.54).CONCLUSION:NSAIDs effectively reduce the incidence of PEP but not of moderate to severe pancreatitis.
文摘Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinfectious agents, list on the top for causes of DrugInduced Liver Injury (DILI). The incidence of liver disease induced by NSAIDs reported in clinical studies is fairly uniform ranging from 0.29/100 000 [95% confidence interval (CI): 0.17-051] to 9/100 000 (95% CI: 6-15). However, compared with these results, a higher risk of liver-related hospitalizations was reported (3-23 per 100 000 patients). NSAIDs exhibit a broad spectrum of liver damage ranging from asymptomatic, transient, hyper-transaminasemia to fulminant hepatic failure. However, under-reporting of asymptomatic, mild cases, as well as of those with transient liver-tests alteration, in conjunction with reports non-compliant with pharmacovigilance criteria to ascertain DILI and flawed epidemiological studies, jeopardize the chance to ascertain the actual risk of NSAIDs hepatotoxicity. Several NSAIDs, namely bromfenac, ibufenac and benoxaprofen, have been withdrawn from the market due to hepatotoxicity; others like nimesulide were never marketed in some countries and withdrawn in others. Indeed, the contro-versy concerning the actual risk of severe liver disease persists within NSAIDs research. The present work intends (1) to provide a critical analysis of the dissimilar results currently available in the literature concerning the epidemiology of NSAIDS hepatotoxicity; and (2) to review the risk of hepatotoxicity for each one of the most commonly employed compounds of the NSAIDs family, based on past and recently published data.
文摘Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.
文摘AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was needed.CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in
文摘AIM: To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs(NSAIDs) on macular edema following cataract surgery in diabetic patients, and to compare between types of NSAIDs(ketorolac tromethamine 0.4% and nepafenac 0.1%). METHODS: Group 1(control) received artificial tears substitute as a placebo group, group 2(nepafenac) received topical nepafenac 0.1%, and group 3(ketorolac) received topical ketorolac tromethamine 0.4%. Patients were examined postoperatively after completing one week, one month, two months and three months' intervals for evaluating cystoid macular edema(CME) development. The main study outcomes were achieving the best corrected visual acuity(BCVA) and change in the central macular thickness(CMT) measured with optical coherence topography(OCT).RESULTS: Eighty eyes of 76 patients were included in this study. BCVA showed a statistically significant difference at the third month postoperative follow up between the control group and the NSAIDs groups(P=0.04). There was an increase in the CMT in all cases starting from postoperative first week until third month. CMT showed a statistically significant difference between control group and NSAIDs groups from postoperative first month until third month(P=0.008, 0.027, 0.004). There was no statistically significant difference between nepafenac and ketorolac groups in BCVA and OCT CMT. CONCLUSION: Prophylactic preoperative and postoperative NSAIDs may have a role in reducing the frequency and severity of CME in diabetic eyes following cataract surgery.
文摘BACKGROUND Non-steroidal anti-inflammatory drugs(NSAIDs)are among the most commonly prescribed medications in the United States.Although they are safe and effective means of analgesia for children with broken bones,there is considerable variation in their clinical use due to persistent concerns about their potentially adverse effect on fracture healing.AIM To assess whether NSAID exposure is a risk factor for fracture nonunion in children.METHODS We systematically reviewed the literature reporting the effect of NSAIDs on bone healing.We included all clinical studies that reported on adverse bone healing complications in children with respect to NSAID exposure.The outcomes of interest were delayed union or nonunion.Study quality was assessed using the Newcastle-Ottawa scale for non-randomized studies.A final table was constructed summarizing the available evidence.RESULTS A total of 120 articles were identified and screened,of which 6 articles were included for final review.Nonunion in children is extremely rare;among the studies included,there were 2011 nonunions among 238822 fractures(0.84%).None of the included studies documented an increased risk of nonunion or delayed bone healing in those children who are treated with NSAIDs in the immediate post-injury or peri-operative time period.Additionally,children are likely to take these medications for only a few days after injury or surgery,further decreasing their risk of adverse side-effects.CONCLUSION This systematic review suggests that NSAIDS can be safely prescribed to pediatric orthopaedic patients absent other contraindications without concern for increased risk of fracture non-union or delayed bone healing.Additional prospective studies are needed focusing on higher risk fractures and elective orthopaedic procedures such as osteotomies and spinal fusion.
文摘Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.
文摘<strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) use is very common. NSAIDs use could be associated with elevated eosinophil count which could be a class effect or patient-related. Inflammation could be the link between NSAIDs use and eosinophilia. <strong>Aims: </strong>To compare the pattern of eosinophil count in the peripheral blood of frequent users of NSAIDs and healthy controls. <strong>Methodology: </strong>Two hundred (one hundred frequent users of NSAIDs and 100 healthy controls) participants who had no known risk factor for kidney disease and had given informed consent were recruited. Blood was taken to determine the white cell count and differentials, serum electrolyte and creatinine, and random blood sugar. <strong>Results:</strong> The mean age of NSAIDs users was not significantly different from controls, P = 0.3. The mean eosinophil count was higher in males than females. The incidence of eosinophilia in NSAIDs users was 4%. The mean Eosinophil count of NSAIDs users was insignificantly higher than controls, 164.3 ± 51 6 vs 135. 6 ± 53.4, P = 0.4. The mean platelet count of NSAIDs users was significantly higher compared to controls, P = 0.04. The mean hematocrit of NSAIDs users was significantly lower than the controls, P = 0.02. Propionic acid derivatives were associated with the highest eosinophil count. Eosinophil count was positively related to age and serum creatinine and inversely related to blood glucose, hematocrit and glomerular filtration rate.<strong> Conclusion: </strong>The incidence of eosinophilia was 4%. The eosinophil count was higher in frequent NSAIDs users than occasional and non-users, in males than females and with use propionic acid derivatives compared to other NSAIDs. The Eosinophil count was positively related to age and platelet count. Being commoner in inflammatory states, the tissue destruction associated with elevated EC can be avoided by the prevention and prompt treatment of inflammatory conditions.
基金support from the National Natural Science Foundation of China(Nos.52073230,62204204,and 62288102)the Shaanxi Provincial Science Fund for Distinguished Young Scholars(No.2023-JC-JQ-32)+2 种基金the Science and Technology Innovation 2030-Major Project(No.2022ZD0208601)the Shanghai Sailing Program(No.21YF1451000)the China National Postdoctoral Program for Innovative Talents(No.BX20230494).
文摘Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.
基金funded by The National Key Research and Development Program(2022YFC2603500,2022YFC2603505)Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26+2 种基金Beijing Hospitals Authority Clinical medicine Development of special funding support(XMLX202127)The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(XXZ0302)The capital health research and development of special(2022-1-2172)。
文摘Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.
文摘Increased risk due to nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been observed in patients. Although diaphragm-like stricture in the small bowel and colon induced by NSAIDs therapy has been rarely reported, gastric body diaphragm-like stricture has not been reported. We describe the first case of gastric body diaphragm-like stricture due to NSAIDs in a 44-year-old male patient who was successfully treated by an endoscopic approach to avoid complicated surgery. This case highlights new insight into the disadvantages of NSAIDs and provides new data for future clinical studies.
基金supported by the grant from Georgian National Science Foundation,No.GNSF/ST07/6-234
文摘Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs (NSAIDs), or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic (intraperitoneal) administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.
基金supported by grants VA145U13,BIO/VA33/13,BIO103/VA45/11 from Junta de Castillay León,SpainBFU2012-37146 from Ministerio de Economíay Competitividad,Spainsupported by a pre-doctoral fellowship from Junta de Castillay León,Spain and The European Social Fund
文摘The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. In fact, recovery after brain artery occlusion is dramatically worsened by aging, even normal aging is associated with neuron damage and cognitive decline. Mechanisms involved in aging-related, cognitive decline and susceptibility to neuron damage in stroke and neurode- generation are largely unknown. One of the most important mech- anisms contributing to neural dysfunction and death is excitotox- icity. This process is based on the fact that the excessive glutamate receptor stimulation may lead to neuronal damage. This overstim- ulation may be due to increased concentration of glutamate, or the prolonged activation of receptors.
文摘Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.
文摘Non-steroidal anti-inflammatory drugs (NSAIDs) are classified as Class 4 agents by the Association of Racing Commissioners International and are banned in racehorses during competition in Pennsylvania (PA). To control the abuse of these agents in racehorses competing in PA, a forensic method for screening and confirmation of the presence of these agents is needed. Equine plasma (0.5 mL) was acidified with 75 μL 1M H3PO4 to increase recovery of the analytes by liquid-liquid extraction using methyl tert-butyl ether (MTBE). Extracted analytes were separated by reversed-phase liquid chromatography using a C8 column under gradient condition. All 16 analytes were detected, quantified and confirmed using a triple quadrupole tandem mass spectrometry with selected reaction monitoring (SRM) in both negative and positive electrospray ionization modes. The limit of detection, quantification and confirmation of the analytes were 1.0 - 5.0 ng/mL, 1.0 - 5.0 ng/mL and 1.0 - 20 ng/mL, respectively. The linear dynamic range of quantification was 5.0 - 200 ng/mL. The method is routinely used in anti-doping analysis to control the abuse of NSAIDs in racehorses competing in PA.
文摘<strong>Aims:</strong> The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still accountable for millions of deaths worldwide and declared as a global pandemic by the World Health Organisation. Despite efforts, there is still limited evidence available on a successful potent inhibitor with a low toxicity profile that can aid in the prevention and/or treatment of COVID-19. This study will focus on four main aspects: 1) screening 19 Food Drug and Administration (FDA) approved drugs using computational molecular docking;2) assessing drug toxicity profiles using biological data;3) recommending potential therapies against COVID-19 and 4) supplementing currently used therapies. <strong>Methods:</strong> 19 FDA approved drugs were investigated against the crystal structure of SARS-CoV-2 protease (6LU7) and SARS-CoV-2 glycoprotein (6VXX) using a computational molecular docking software, Molecular Operating Environment (MOE). Separately, on MOE, 6LU7 and 6VXX were loaded, prepared, and the binding pockets located. The drug’s canonical SMILES were imported, minimised, and docked on the prepared proteins using a search algorithm to establish the highest stability conformation. Drugs were ranked depending on binding properties and biological data to assess safety;steric clashes and voids in the binding site were also analysed. <strong>Results and discussion:</strong> Out of the nineteen (19) FDA approved drugs, 18 inhibited 6LU7 and 13 inhibited 6VXX. High-ranked drugs based on binding properties for 6LU7 were hydroxychloroquine, dexamethasone, naproxen, etoricoxib, and ibuprofen. For 6VXX were hydroxychloroquine, celecoxib, etoricoxib, meloxicam, and parecoxib. Considering safety profile, the top 3 drugs in descending order for 6LU7 were etoricoxib, naproxen and dexamethasone and for 6VXX were etoricoxib, meloxicam, and parecoxib. Compared to the literature, the results were consistent for dexamethasone which was effective against 6LU7. However, for hydroxychloroquine and ibuprofen, there was conflicting literature regarding safety and efficacy. <strong>Conclusion and future work:</strong> The findings suggest that against COVID-19 etoricoxib might be effective as a therapeutic and prophylactic measure. Naproxen and dexamethasone would be more effective as treatment only while meloxicam and parecoxib as prophylaxis. However, future studies are needed to validate these findings. Compared to previous literature, the findings in this study also support the use of dexamethasone over hydroxychloroquine and ibuprofen for COVID-19 based on the binding and safety properties. Despite this, future research should explore the impressive binding properties displayed by hydroxychloroquine and ibuprofen to aid in developing a new drug against COVID-19.