Humans ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects* ; Aspirin/therapeutic use* ; Respiration Disorders ; Respiratory Tract Diseases

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.
Animals ; Rats ; Anti-Inflammatory Agents ; Bleomycin/toxicity* ; Fibronectins/metabolism* ; Fibrosis ; Inflammasomes/metabolism* ; Ivermectin/adverse effects* ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pulmonary Fibrosis/drug therapy*

OBJECTIVE: To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD). METHODS: The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction. RESULTS: Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01). CONCLUSION RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.
Animals ; Zebrafish ; Lipopolysaccharides ; Disease Models, Animal ; Inflammatory Bowel Diseases/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Trinitrobenzenesulfonic Acid/adverse effects* ; Colitis/drug therapy*

PURPOSE: Eperisone is an oral muscle relaxant used in musculoskeletal disorders causing muscle spasm and pain. For more effective pain control, eperisone is usually prescribed together with nonsteroidal anti-inflammatory drugs (NSAIDs). As such, eperisone may have been overlooked as the cause of anaphylaxis compared with NSAIDs. This study aimed to analyze the adverse drug reaction (ADR) reported in Korea and suggest an appropriate diagnostic approach for eperisone-induced anaphylaxis. METHODS: We reviewed eperisone-related pharmacovigilance data (Korea Institute of Drug Safety-Korea Adverse Event Reporting System [KIDS-KAERS]) reported in Korea from 2010 to 2015. ADRs with causal relationship were selected. Clinical manifestations, severity, outcomes, and re-exposure information were analyzed. For further investigation, 7-year ADR data reported in a single center were also reviewed. Oral provocation test (OPT), skin prick test (SPT) and basophil activation test (BAT) were performed in this center. RESULTS: During the study period, 207 patients had adverse reactions to eperisone. The most common ADRs were cutaneous hypersensitive reactions (30.4%) such as urticaria, itchiness or angioedema. Fifth common reported ADR was anaphylaxis. There were 35 patients with anaphylaxis, comprising 16.9% of the eperisone-related ADRs. In the single center study, there were 11 patients with eperisone-induced anaphylaxis. All the patients underwent OPT and all the provoked patients showed a positive reaction. Four of the 11 patients with anaphylaxis also underwent SPT and BAT, which were all negative. CONCLUSIONS: Incidence of eperisone-induced anaphylaxis calculated from the KIDS-KAERS database was 0.001%. Eperisone can cause hypersensitive reactions, including anaphylaxis, possibly by inducing non-immunoglobulin E-mediated immediate hypersensitivity.
Anaphylaxis ; Angioedema ; Anti-Inflammatory Agents, Non-Steroidal ; Basophils ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Incidence ; Korea ; Pharmacovigilance ; Skin ; Spasm ; Urticaria

Endoscopic retrograde cholangiopancreatography (ERCP) is an irreplaceable measure with minimally invasive diagnosis and treatment of endoscopy for biliary and pancreatic diseases, but the related complications associated with ERCP are the highest among the endoscopic procedures. Post-ERCP pancreatitis (PEP) is one of the most common complications with life-threatening in severe cases. Early active prevention can effectively reduce the incidence of post-ERCP pancreatitis. At present, measures including preoperative rectal non-steroidal anti-inflammatory drugs and prophylactic pancreatic stent placement, have definite effective strategy in clinic. Aggressive hydration with lactated Ringer's solution is also a safe and effective way to prevent PEP.
Anti-Inflammatory Agents, Non-Steroidal ; Cholangiopancreatography, Endoscopic Retrograde ; adverse effects ; Humans ; Incidence ; Pancreatitis ; etiology ; Risk Factors ; Stents

In the present study, we investigated anti-inflammatory effect of Cardamine komarovii flower (CKF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We determined the effect of CKF methanolic extracts on LPS-induced pro-inflammatory mediators NO and prostaglandin E2 (PGE2), production of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), and related protein expression levels of MyD88/TRIF signaling pathways in peritoneal macrophages (PMs). Nuclear translocation of NF-κB-p65 was analyzed by immunofluorescence. For the in vivo experiments, an ALI model was established to detect the number of inflammatory cells and inflammatory factors (IL-1β, TNF-α, and IL-6) in bronchoalveolar lavage fluid (BALF) of mice. The pathological damage in lung tissues was evaluated through H&E staining. Our results showed that CKF can decrease the production of inflammatory mediators, such as NO and PGE2, by inhibiting their synthesis-related enzymes iNOS and COX-2 in LPS-induced PMs. In addition, CKF can downregulate the mRNA levels of IL-1β, TNF-α, and IL-6 to inhibit the production of inflammatory factors. Mechanism studies indicated that CKF possesses a fine anti-inflammatory effect by regulating MyD88/TRIF dependent signaling pathways. Immunocytochemistry staining showed that the CKF extract attenuates the LPS-induced translocation of NF-kB p65 subunit in the nucleus from the cytoplasm. In vivo experiments revealed that the number of inflammatory cells and IL-1β in BALF of mice decrease after CKF treatment. Histopathological observation of lung tissues showed that CKF can remarkably improve alveolar clearance and infiltration of interstitial and alveolar cells after LPS stimulation. In conclusion, our results suggest that CKF inhibits LPS-induced inflammatory response by inhibiting the MyD88/TRIF signaling pathways, thereby protecting mice from LPS-induced ALI.
Acute Lung Injury ; chemically induced ; drug therapy ; genetics ; metabolism ; Adaptor Proteins, Vesicular Transport ; genetics ; metabolism ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; Cardamine ; chemistry ; Cyclooxygenase 2 ; genetics ; metabolism ; Female ; Flowers ; chemistry ; Humans ; Lipopolysaccharides ; adverse effects ; Male ; Mice ; Myeloid Differentiation Factor 88 ; genetics ; metabolism ; NF-kappa B ; genetics ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Plant Extracts ; administration & dosage ; chemistry ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Although a variety of regimens are available for the treatment of atopic dermatitis (AD), severe adverse reactions and unpopular costs often limit their usage. In contrast, certain inexpensive, naturally-occurring ingredients are proven effective for AD with fewer side effects. The beneficial effects of these ingredients can be attributed to inhibition of cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or the enhancement of epidermal permeability barrier function. Since herbal medicines are widely available, inexpensive and generally safe, they could be valuable alternatives for the treatment of AD, particularly for those patients who are not suitable for the utilization of immune modulators. In this review, we summarize the therapeutic benefits of natural ingredients for the treatment of AD and the mechanisms of their actions.
Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Biological Products ; adverse effects ; therapeutic use ; Dermatitis, Atopic ; drug therapy ; Humans ; Permeability ; Treatment Outcome

BACKGROUND: Adverse cutaneous drug reactions (ACDRs) are common and are responsible for increased morbidity, mortality, and socioeconomic costs. OBJECTIVE: The purpose of our study was to investigate the common drugs and clinical patterns related to ACDRs using an electronic drug adverse reaction reporting system at a single secondary referral center. METHODS: We conducted a retrospective analysis of the ACDR database between January 2014 and April 2016 at the Ilsan Paik Hospital. RESULTS: The study analyzed 320 patients with ACDRs (male:female ratio=93:227; mean age 50.8±17.8 years). Using a Korean causality evaluation algorithm, the percentage of drugs with a possible relationship with ACDRs was calculated to be 50.6%, while the percentage with a probable relationship was 44.7%. Antibiotics (44.0%), radiocontrast media (15.1%), and non-steroidal anti-inflammatory drugs (NSAIDs) (14.3%) were the most commonly implicated drugs. Antibiotics, including cephalosporins (30.6%) and quinolones (10.2%), were responsible for the majority of the ACDRs. Acetic acid (5.9%) and propionic acid (5.9%) derivatives of NSAIDs were also common causative agents. The most common clinical presentations were maculopapular exanthema (33.4%), pruritus (30.9%), and urticaria (25.7%). Severe ACDRs were significantly associated with older age, eosinophilia, and underlying heart and renal diseases (p<0.05). CONCLUSION: Antibiotics, radiocontrast media, and NSAIDs were identified as common causes of ACDRs. Older age, eosinophilia, heart disease, and renal disease were associated with severe ACDRs.
Acetic Acid ; Adverse Drug Reaction Reporting Systems ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Cephalosporins ; Contrast Media ; Diethylpropion ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia ; Exanthema ; Heart ; Heart Diseases ; Humans ; Mortality ; Pruritus ; Quinolones ; Retrospective Studies* ; Secondary Care Centers* ; Urticaria

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in various clinical situations, with excellent analgesic, anti-pyretic and anti-inflammatory effects. In addition to gastrointestinal bleeding, which was the first adverse effect to be reported, myriad adverse effects from the digestive system, cardiovascular system, renal system and hematology have been also reported. In early 2000s, a few new cyclooxygenase (COX)-2 selective inhibitors were developed with the expectation of better gastrointestinal safety profile, most of them were withdrawn from the market due to various adverse effects, and interest in safety of NSAIDs has been increased again. Over the past two decades, research on the safety and adverse effects of NSAIDs has accumulated. In brief, celecoxib is associated with fewer gastrointestinal adverse events compared to non-selective NSAIDs. In patients receiving aspirin, the use of non-selective NSAIDs should be avoided, and if an anti-inflammatory drug is required, a COX-2 selective inhibitor should be considered. Celecoxib has been shown to have similar or better safety profile than other non-selective COX inhibitors. Additionally, the new COX-2 selective inhibitors of etorixocib and polmacoxib have been approved. Many factors should be considered when prescribing NSAIDs, as the safety profile of indivisual NSAIDs vary, and NSAIDs have a high risk of duplicate prescription because of the variety of indications and over-the-counter products. Physicians should comprehend the updated guidelines and the results of new clinical studies, and the risk factors for each individual patient should also be reviewed. Physicians should therefore contemplate new prescription strategies.
Anti-Inflammatory Agents, Non-Steroidal ; Aspirin ; Cardiovascular System ; Celecoxib ; Digestive System ; Drug-Related Side Effects and Adverse Reactions ; Hematology ; Hemorrhage ; Humans ; Medication Therapy Management ; Prescriptions ; Prostaglandin-Endoperoxide Synthases ; Risk Factors

OBJECTIVE: To investigate the effectiveness of preemptive analgesia with loxoprofen sodium orally, which was a kind of non-steroid anti-inflammatory drugs, in extractions of mandibular impacted third teeth. METHODS: There were questionnaires about postoperative pain for patients whose mandibular impacted third teeth were extracted from July 2017 to August 2017 in First Clinical Division of Peking University School and Hospital of Stomatology. All the patients did their routine clinical examinations and imaging examinations. After their mandibular impacted third teeth were extracted, the questionnaires were sent to them. The questionnaires were filled in by the patients on their own and returned one week later. There were 120 questionnaires that were sent and 105 questionnaires returned, of which 98 questionnaires were filled in completely. According to the inclusive criteria and exclusion criteria, 66 questionnaires were totally selected in this study. According to the time when the patients took their loxoprofen sodium orally firstly, the patients were divided into 3 groups. The first group was for patients who didn't take loxoprofen sodium during their extractions (non-medicine group). The second group was for patients who took 60 mg loxoprofen sodium 30 min before their extractions (preoperative group). The third group was for patients who took 60 mg loxoprofen sodium 30 min after their extractions (postoperative group). The operation time among the 3 groups was analyzed by Kruskal-Wallis method. The postoperative time points were 2, 4, 12,24 and 48 h after operation. The scores of visual analogue scales (VAS) for postoperative pain in each group at different postoperative time points were analyzed by Friedman method. At each postoperative time point, VAS scores in the different groups were analyzed by Kruskal-Wallis me-thod. The numbers of the patients taking loxoprofen sodium home and drug adverse reactions were also analyzed. RESULTS: The operation time of the 3 groups was 15.0 (5.0,30.0) min and had no significant differences (P=0.848).VAS scores of non-medicine group 2,4, 12,24 and 48 h after operation were 1.75 (0.1,10.0), 6.25 (1.5,10.0), 2.00 (0.1,8.0), 2.00 (0.1,6.0) and 0.5 (0.1,5.5) separately and had significant differences (P<0.001).The VAS score at 4 h after operation was higher than the VAS scores at other time points after operation (P<0.005). Four hours after the operations, the VAS scores of preoperative group [2.0 (0.1,10.0)] and postoperative group [2.0 (0.1,5.0)] were lower significantly than those of non-medicine group [6.25 (1.5,10.0)] (P<0.001).The numbers of the patients taking loxoprofen sodium home were 9(40.9%) in non-medicine group,5(21.8%) in preoperative group and 7(33.3%) in postoperative group. The number of the patients who had drug adverse reactions in preoperative group (n=3,13.0%) and in postoperative group (n=4,19.0%) was less than the number of the patients who had drug adverse reactions in non-medicine group (n=8,36.4%). CONCLUSION There were two protocols of preemptive analgesia with loxoprofen sodium orally in extractions of mandibular impacted third teeth, which were taking 60 mg loxoprofen sodium orally 30 min before the extractions and taking 60 mg loxoprofen sodium orally 30 min after the extractions. Both of the two preemptive analgesia protocols could decrease the postoperative pain significantly.
Analgesia ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage* ; Humans ; Pain, Postoperative/prevention & control* ; Phenylpropionates/administration & dosage* ; Tooth Extraction/adverse effects* ; Tooth, Impacted