Kinds Of Non-steroidal Anti-inflammatory Drugs Research Articles

NIR Absorbing Organic Chromophores Combination with NSAIDs for Remodeling of the Inflammatory Microenvironment to Amplify Tumor Ferroptosis-Photothermal Synergistic Therapy.

Photothermal therapy has emerged as a promising approach for cancer treatment, which can cause ferroptosis to enhance immunotherapeutic efficacy. However, excessively generated immunogenicity will induce serious inflammatory response syndrome, resulting in a discounted therapeutic effect. Herein, a kind of NIR absorption small organic chromophore nanoparticles (TTHM NPs) with high photothermal conversion efficiency (68.33%) is developed, which can induce mitochondria dysfunction, generate mitochondrial superoxide, and following ferroptosis. TTHM NPs-based photothermal therapy is combined with Sulfasalazine (SUZ), a kind of nonsteroidal anti-inflammatory drugs, to weaken inflammation and promote ferroptosis through suppressing glutamate/cystine (Glu/Cys) antiporter system Xc- (xCT). Additionally, the combination of SUZ with PTT can induce immunogenic cell death (ICD), followed by promoting the maturation of DCs and the attraction of CD8+ T cell, which will secrete IFN-γ and trigger self-amplified ferroptosis via inhibiting xCT and simulating Acyl-CoA synthetase long-chain family member 4 (ACSL4). Moreover, the in vivo results demonstrate that this combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation, facilitate T-cell infiltration, and realize effective thermal elimination of primary tumors and distant tumors. In general, this work provides an excellent example of combined medication and stimulates new thinking about onco-therapy and inflammatory response.

Eu3+ functionalized metal-organic framework for selective monitoring of emerging environmental pollutants non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs), as a new water pollutant emerging in recent years, has potential hazards to the environment. The difficult degradation characteristics of NSAIDs lead to long-term accumulation in the natural environment, which will inevitably cause incalculable damage to human health. In this work, for practical application considerations, MIL-53(Al) type MOF [Al(OH)(TDC)]‧1.5H2O‧0.7DMF (MIL-53-TDC, TDC = 2,5-thiophene dicarboxylic acid) with good water stability is selected as the sensing main body. The ligand TDC was chosen for two reasons: one is as an antenna ligand, which can sensitize Eu3+ ions to emit characteristic fluorescence; the other is as binding site that the sulfur atoms on the thiophene ring can introduce Eu3+ ions through coordination. Thus, Eu3+ functionalized MIL-53-TDC hybrid materials (Eu@MIL-53-TDC) were developed as a fluorescence sensor for the detection of two kinds of NSAIDs, S-ibuprofen (S-IBP) and diclofenac (DCF). The concentration range of S-IBP and DCF detected by the prepared sensors is 0.001–0.07 mM (LOD = 0.5 μM) and 0.0005–0.1 mM (LOD = 0.2 μM), respectively. Moreover, this sensor not only can achieve rapid (3 min) and sensitive analysis of these two NSAIDs but also has a satisfactory recovery for the detection of S-IBP and DCF in serum and tap water.

Deep eutectic solvent-imprinted polymer based on magnetic UiO-66-NH2 for fast and selective removal of benzydamine hydrochloride in environmental samples

Benzydamine hydrochloride (BDH) is a kind of nonsteroidal anti-inflammatory drugs for the treatment of inflammation. However, research on removing BDH from the environment has not attracted attention. Herein, a green deep eutectic solvent (DES) as functional monomer and magnetic metal organic frameworks (MUiO-66-NH2) as supporter help to form more effective recognition sites and easy separation properties in polymerization procedure of the surface imprinted polymer (DES-MMIP). The performance of novel DES-MMIP for the selective removal of the template (BDH) in water was characterized and evaluated. The equilibrium experiment results showed that the maximum adsorption capacity of BDH can reach 41.18 mg g−1, and fast adsorption equilibrium was obtained within 30 min. Due to the participation of magnetic MUiO-66-NH2 and DES, the prepared DES-MMIP had excellent separability, and the adsorption capacity towards template (BDH) was 1.4–2.6 times that of other commercial adsorbents (PS-DVB, HLB, silica and zeolite). The DES-MMIP combined with UV-via was successfully applied to remove BDH from eight environmental samples. Additionally, the DES-MMIP adsorbent can be reused 5 times and still maintain excellent recovery. This work provides a promising method for preparing an efficient adsorbent for the fast separation and selective removal of BDH in the environmental field.

Silver Nanoparticles Embedded within a Silicon Photocathode for Photoelectrochemical Fixation of CO2 to Synthesize Intermediates of Profen Drugs

Photoelectrochemical (PEC) fixation of carbon dioxide (CO2) into intermediates of Profen drugs, a kind of nonsteroidal antiinflammatory drug, is a useful and important technology for the utilization of CO2. In this work, we successfully designed and prepared a silver nanoparticles (AgNPs)-embedded silicon photocathode for PEC-fixating CO2 to synthesize intermediates of Profen drugs with high efficiency and stability. AgNPs endow the photocathode with extremely high catalytic activity, the Schottky junction between Ag and Si promotes the separation and transfer of photogenerated carriers, the AgNPs-embedded structure greatly improves the stability of the photocathode, and the nanohole structure improves light absorption.

The regulation of electron distribution on Fe Lewis acidic sites within silicon skeleton and its contribution to Ketoprofen ozonation

Lewis acid site was vital center for activating O3 during catalytic ozonation process. Herein, we proposed a strategy to enhance the Lewis acid strength of Fe-MCM-48 (FeM) by fluorination. Fluorinated Fe-MCM-48 (FFeM) exhibited the better catalytic ozonation efficiency towards Ketoprofen (KET), a kind of nonsteroidal anti-inflammatory drug. 87.4 % TOC removal was obtained by F2.5Fe0.8M/O3 process, but only 27.5 % and 52.7 % were found by sole ozonation and Fe0.8M/O3 processes, respectively. Comparative characterizations, experiments and DFT calculations showed that fluorinated FFeM was regular sphere with three dimensional duct channel and large SBET. Doping of F reduced particle size, implanted electron withdrawing Si-F group and formed the electron poor center around Fe atom, which enhanced Lewis acid strength of FFeM. Protonated hydroxyl groups on Lewis acid sites were the main active sites for O3 activation. Greater amount of O3 were absorbed on the surface of FFeM and the greater O3 utilization rate, •OH and •O2– generation rates were obtained by FFeM/O3 process. Common anions such as Cl−, SO42− and NO3– and Humic acids (HA) had little effect on KET removal but inhibited TOC removal in FFeM/O3 process. •OH, •O2– and Fe(IV) = O oxidation were accounted for KET degradation. 16 kinds of intermediates generated from KET degradation and 4 pathways were deduced.

Underlying mechanisms of promoted formation of haloacetic acids disinfection byproducts after indometacin degradation by non-thermal discharge plasma

Indometacin (IDM), as a kind of non-steroidal anti-inflammatory drugs, has ecological and health risks, which is the potential precursor of chlorination disinfection byproducts (DBPs). Non-thermal discharge plasma was attempted to eliminate IDM and control subsequent DBPs formation. Satisfactory removal performance for IDM was realized by the plasma oxidation; almost 100% of IDM was removed within 2 min. Relatively greater removal efficiency was gained at a higher plasma voltage and a lower pH level. Electron paramagnetic resonance spectrometer revealed that reactive species ·OH, O2·−, and 1O2 were responsible for IDM decomposition. Based on analyses of Fourier transform infrared spectroscopy, two-dimensional correlation spectroscopy, three-dimensional fluorescence spectrum, and gas chromatography-mass spectrometer, attacks of reactive species resulted in sequence breakages in functional groups of IDM, leading to production of small molecular alcohols, acids, and amines. Possible decomposition pathways of IDM were proposed. The produced acetamide and 1H-indol-5-ol were important precursors of DBPs. Formation and toxicity of nitrogen-containing DBPs were dramatically inhibited after IDM degradation; however, those of haloacetic acids were strengthened. The relevant roadmaps among DBPs and degradation intermediates were figured out. This study revealed the underlying mechanisms of IDM degradation by discharge plasma and its potential risks in chlorination disinfection.

Combination of Photothermal Therapy with Anti-Inflammation Therapy Attenuates the Inflammation Tumor Microenvironment and Weakens Immunosuppression for Enhancement Antitumor Treatment.

Photothermal therapy has gained widespread attention in cancer treatment, although its efficacy is suppressed due to the inflammatory response and immunosuppression, resulting in a discounted therapeutic effect. In this contribution, a high-performance NIR absorption organic small chromophore is developed, which is encapsulated into Pluronic F-127 to fabricate NIR absorption organic nanoparticles (TTM NPs) with excellent photothermal conversion efficiency (51.49%) for photothermal therapy. TTM NPs based photothermal therapy are combined with Aspisol, a kind of nonsteroidal anti-inflammatory drug, to weaken the inflammation and immunosuppression tumor microenvironment and enhance the antitumor effect. The results prove that the combination therapy realizes effective thermal elimination of primary tumors, inhibition of distant tumors, and suppression of tumor metastasis. The data show that combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation and maturation, reverse the immunosuppression, facilitate T cell infiltration, and restore antitumor cytotoxic T lymphocyte activity. This study provides a paradigm to extend the development of photothermal therapy.

Van der Waals force-driven indomethacin-ss-paclitaxel nanodrugs for reversing multidrug resistance and enhancing NSCLC therapy

The high expression of multidrug resistance-associated protein 1 (MRP1) in cancer cells caused serious multidrug resistance (MDR), which limited the effectiveness of paclitaxel (PTX) in non-small cell lung cancer (NSCLC) chemotherapy. Indomethacin (IND), a kind of non-steroidal anti-inflammatory drugs (NSAIDs), which has been confirmed to be a potential MRP1 inhibitor. Taking into account the advantages of old drugs without extra controversial biosafety issue, in this manuscript, the disulfide bond (-S-S-) was employed for connecting IND and PTX to construct conjugate IND-S-S-PTX, which was further self-assembled and formed nanodrug (IND-S-S-PTX NPs). The particle size of IND-S-S-PTX NPs was ~160 nm with a narrow PDI value of 0.099, which distributed well in water and also exhibited a stable characteristic. Moreover, due to the existence of disulfide bond, the NPs were sensitive to the high level of glutathione (GSH) in tumor microenvironment. Molecular dynamics (MD) simulation presented the process of self-assembly in detail. Density functional theory (DFT) calculations revealed that the main driving force in self-assembly process was originated from the van der waals force. In addition, this carrier-free nano drug delivery systems (nDDs) could reverse the MDR by downregulating the expression of MRP1 protein in A549/taxol.

Improved performance of wrinkled CoNi-LDHs via in situ immobilization onto cotton gauze for solid phase extraction of non-steroidal anti-inflammatory drugs

Solid phase microextraction (SPME) based on advanced composites as stationary phase is an effective technical means to preconcentrate trace analytes from environment samples. Here, a wrinkled cobalt nickel-layered double hydroxide arrays was successfully fabricated via in situ growing on polydopamine-coated cotton gauze (CoNi-LDH@PDC). Thanks to the wrinkled morphology of CoNi-LDH, the anion exchange rate and adsorption capacity of the fabricated composite were remarkably improved. The morphology of the fabricated CoNi-LDH@PDC composite was characterized by scanning electron microscopy, and the interaction between the adsorbent and analytes were analyzed by Fourier transform infrared spectroscopy. Then, a piece of 2 × 3 cm modified cotton gauze was packed into a pipette tip for simultaneous extraction and concentration three kinds of non-steroidal anti-inflammatory drugs (NSAIDs) including ketoprofen, fenbufen and ibuprofen, following analysis through high-performance liquid chromatography. Potential factors affecting the SPME process were studied in detail. Under the optimized conditions, the developed method exhibited excellent performance as the detection limits of 0.075, 0.18 and 0.17 μg L−1, besides the linear range of 0.20–3000, 0.50–200 and 0.50–3000 μg L−1 for ketoprofen, fenbufen and ibuprofen, respectively. The recoveries for spiking 5, 20 and 100 μg L−1 NSAIDs in tap water and drinking water samples were 77.3–92.4% and 82.6–95.6%, respectively. Moreover, the proposed SPME column was stable enough for 30 days experiments of extraction and desorption without obvious loss of extraction efficiency.

Expression of VEGF-A And COX-2 mRNA in non-steroidal anti-inflammatory drugs treated rat primary colonic fibroblast

Non-steroidal anti-inflammatory drugs (NSAIDs) is often used to shorten recovery time after surgery, including after colon anastomosis surgery. Studies showed that NSAIDs might involve in the development of colon anastomotic leakage. However, the effect of NSAIDs in colon anastomosis leakage is still a subject of controversy. Studies indicated that selectivity of COX-2 might have a role in the deleterious effect of NSAIDs in colon anastomosis. Disruption of VEGF-A by NSAIDs also suspected to be the culprit in the development of anastomosis leakage during NSAIDs treatment. This study aimed to investigate the NSAIDs effect toward VEGF-A and COX-2 mRNA in rat primary colonic fibroblast. The in vitro study was conducted using fibroblast isolated from rat colon. The isolated fibroblast was divided into 4 groups of treatment i.e.controlgroup, acetaminophen group, metamizole group, and ketorolacgroup. After 48 h of treatment, the cell was harvested and the RNA was isolated. The expression of VEGF-A and COX-2 mRNA was conducted using semi-quantitative PCR(sq-PCR). Both VEGF-A and COX-2 were not expressed in untreated rat colon fibroblast. However, VEGF-A mRNA washighly expressed in the ketorolacgroup. Interestingly, COX-2 mRNA couldbe seen in the ketorolac and metamizole groups but not in the acetaminophen group. The COX-2 mRNA expression wasthe highest in ketorolac treated rat colon fibroblast. It can be concluded that the effect of various kinds of NSAIDs towards VEGF-A and COX-2 mRNA expression of colon fibroblasts is different. This condition is duetotheir different inhibitory selectivity towards COX-1 and COX2.

Enantioseparation of flurbiprofen enantiomers using chiral ionic liquids by liquid-liquid extraction.

Flurbiprofen is a kind of nonsteroidal anti-inflammatory drug, which has been widely used in clinic for treatment of rheumatoid arthritis and osteoarthritis. It has been reported that S-flurbiprofen shows good performance on clinic anti-inflammatory treatment, while R-enantiomer almost has no pharmacological activities. It has important practical values to obtain optically pure S-flurbiprofen. In this work, chiral ionic liquids, which have good structural designability and chiral recognize ability, were selected as the extraction selector by the assistance of quantum chemistry calculations. The distribution behaviors of flurbiprofen enantiomers were investigated in the extraction system, which was composed of organic solvent and aqueous phase containing chiral ionic liquid. The results show that maximum enantioselectivity up to 1.20 was attained at pH2.0, 25°C using 1,2-dichloroethane as organic solvent, 1-butyl-3-methylimidazole L-tryptophan ([Bmim][L-trp]) as chiral selector. The racemic flurbiprofen initial concentration was 0.2mmolL-1 , and [Bmim][L-trp] concentration was 0.02molL-1 . Furthermore, the recycle of chiral ionic liquids has been achieved by reverse extraction process of the aqueous phase with chiral selector, which is significant for industrial application of chiral ionic liquids and scale-up of the extraction process.

Bromfenac Inhibits TGF-β1-Induced Fibrotic Effects in Human Pterygium and Conjunctival Fibroblasts.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown antifibrotic effects on several diseases. The aims of the present in vitro study were to investigate the antifibrotic effects of bromfenac (a kind of NSAID) on primary human pterygium fibroblasts (HPFs) and primary human conjunctival fibroblasts (HConFs), as well as to explore the possible mechanisms of these effects. The cells used in this study were primary HPFs and HConFs, and profibrotic activation was induced by transforming growth factor-beta1 (TGF-β1). Western blot, quantitative real-time PCR, and immunofluorescence (IF) assays were used to detect the effects of TGF-β1 and bromfenac on the synthesis of fibronectin (FN), type III collagen (COL3), and alpha-smooth muscle actin (α-SMA) in HPFs and HConFs; the changes of signaling pathways were detected by Western blot; cell migration ability was detected by wound healing assay; cell proliferation ability was detected by CCK-8 assay; and pharmaceutical inhibitions of the downstream signaling pathways of TGF-β1 were used to assess their possible associations with the effects of bromfenac. Bromfenac suppressed the TGF-β1-induced protein expression of FN (0.59 ± 0.07 folds, P = 0.008), COL3 (0.48 ± 0.08 folds, P = 0.001), and α-SMA (0.61 ± 0.03 folds, P = 0.008) in HPFs. Bromfenac also attenuated TGF-β1-induced cell migration (0.30 ± 0.07 folds, P < 0.001), cell proliferation (0.64 ± 0.03 folds, P = 0.002) and the expression levels of p-AKT (0.66 ± 0.08 folds, P = 0.032), p-ERK1/2 (0.69 ± 0.11 folds, P = 0.003), and p-GSK-3β-S9 (0.65 ± 0.10 folds, P = 0.002) in HPFs. PI3K/AKT inhibitor (wortmannin) and MEK/ERK inhibitor (U0126) reduced the TGF-β1-induced synthesis of FN, COL3, and α-SMA in HPFs. All the results were similar in HConFs. Bromfenac protects against TGF-β1-induced synthesis of FN, α-SMA, and COL3 in HPFs and HConFs at least in part by inactivating the AKT and ERK pathways.

Pharmacokinetics Interaction of Non-Steroid Anti Inflammatory Drugs to &lt;sup&gt;99m&lt;/sup&gt;Tc-MDP Radiopharmaceuticals for Bone Imaging and Its Biodistribution

99m Tc-MDP has been developed as a radiopharmaceutical for bone imaging in nuclear medicine. A drug therapy can alter the pharmacokinetic profiles and biodistribution patterns of radiopharmaceuticals. To achieve an optimum diagnostic outcome, this research focused on pharmacokinetics interaction between two kinds of nonsteroidal anti-inflammatory drugs ( NSAID ) drugs , meloxicam and sodium diclofenac with 99m Tc-MDP using mice ( Mus musculus ) . There were five groups of animal model and each group consists of three mice except for group II and III which consists of six mice . The groups were classified as untreated mice (I) , mice treated with meloxicam for 3 days ( II) , treated with sodium diclofenac for 3 days (III), treated with meloxicam once or at onset (IV), and mice with sodium diclofenac once or at onset (V). Pharmacokinetics interaction and biodistribution test were conducted by injecting 1 00 µCi/ 1 00 µL 99m Tc-MDP intravenously. Blood samples were withdrawn from each mouse which were then weighted and counted using single channel analyzer. The %ID/g of 99m Tc-MDP in blood of untreated mice (I), mice treated with meloxicam (II) and sodium diclofenac (III) 5 minutes post injection were 3.71, 8.96 and 9.15 % respectively, then decrease to 0.12, 0.01, and 0.01 %, respectively, 24 hours post injection. The results of T-test showed there were no significan t differences in distribution of 99m Tc-MDP in untreated mice (I) and in treated mice either with meloxicam (II) or sodium diclofenac (III). However, there was significant difference in elimination of 99m Tc-MDP in untreated mice (I) and in treated mice either with meloxicam (II) or sodium diclofenac (III). T he bone uptakes of 99m Tc-MDP were 9.03 ± 0.41, 3.52 + 0.52, 3.62 + 0.45, 8.44 + 1.39, and 8.09 ± 0.86 % in group I, II, III, IV, and V, respectively. T-test showed there were significant differences in bone uptake of 99m Tc-MDP in mice with previously treated with meloxicam and sodium diclofenac for 3 days. From th ese result, it can be concluded that an administration of meloxicam and sodium diclofenac could accelerate elimination half-life that cause low uptake of 99m Tc-MDP radiopharmaceuticalon the bone as the primary target. Therefore, it is necessary to follow up using image study to determine the significance of the effects on image quality.

Clinical characteristics of peptic ulcer perforation in Korea.

AIMTo elucidate the epidemiological characteristics and associated risk factors of perforated peptic ulcer (PPU).METHODSWe retrospectively reviewed medical records of patients who were diagnosed with benign PPU from 2010 through 2015 at 6 Hallym university-affiliated hospitals.RESULTSA total of 396 patients were identified with postoperative complication rate of 9.1% and mortality rate of 0.8%. Among 174 (43.9%) patients who were examined for Helicobacter pylori (H. pylori) infection, 78 (44.8%) patients were positive for H. pylori infection, 21 (12.1%) were on non-steroidal anti-inflammatory drugs (NSAIDs) therapy, and 80 (46%) patients were neither infected of H. pylori nor treated by any kinds of NSAIDs. Multivariate analysis indicated that older age (OR = 1.09, 95%CI: 1.04-1.16) and comorbidity (OR = 4.11, 95%CI: 1.03-16.48) were risk factors for NSAID-associated PPU compared with non-H. pylori, non-NSAID associated PPU and older age (OR = 1.04, 95%CI: 1.02-1.07) and alcohol consumption (OR = 2.08, 95%CI: 1.05-4.13) were risk factors for non-H. pylori, non-NSAID associated PPU compared with solely H. pylori positive PPU.CONCLUSIONElderly patients with comorbidities are associated with NSAIDs-associated PPU. Non-H. pylori, non-NSAID peptic ulcer is important etiology of PPU and alcohol consumption is associated risk factor.

PEG-Fmoc-Ibuprofen Conjugate as a Dual Functional Nanomicellar Carrier for Paclitaxel.

Ibuprofen is a kind of nonsteroidal anti-inflammatory drug (NSAIDs), and it is considered to possess some antitumor effect. In this study, a novel nanomicellar carrier based on PEG-derivatized ibuprofen, PEG2K-Fmoc-Ibuprofen (PEG2K-FIbu), was developed for delivery of anticancer agents such as paclitaxel (PTX). This conjugate readily forms stable mixed micelles with PTX with a relatively high PTX loading capacity of 67%. The release of PTX from PTX-loaded PEG2K-FIbu micelles was significantly slower than that from Taxol formulation. PTX-loaded PEG2K-FIbu micelles and Taxol showed a comparable in vitro cytotoxicity. Importantly, PTX-loaded PEG2K-FIbu micelles demonstrated a much more pronounced in vivo therapeutic efficacy compared with Taxol with respect to both inhibition of tumor growth and animal survival. Our system may represent an attractive dual-functional delivery system to achieve synergistic activity with PTX while minimizing the carrier-associated toxicity.

Photodegradation of ibuprofen by TiO2 co-doping with urea and functionalized CNT irradiated with visible light – Effect of doping content and pH

Ibuprofen (IBP) is one kind of non-steroidal anti-inflammatory drugs (NSAIDs), which are classified as Pharmaceuticals and Personal Care Products (PPCPs). IBP possesses bioactive property and the substantial use of IBP results in a harmful impact on bioreceptors even in small concentrations. Accordingly, the treatment of these wastewaters is important before discharging them into the ecosystem. The photodegradation of IBP with TiO2 co-doped with functionalized CNTs (CNT-COOH and CNT-COCl) and urea, named as N-doping CNT/TiO2, irradiated with visible light of 410 nm was investigated in this study. The titanium tetrachloride was used as the precursor of Ti. The N-doping CNT-COCl/TiO2 photocatalysts exhibited a better crystalline structure and smaller crystal size than the N-doping CNT-COOH/TiO2 photocatalyst. It might largely ascribe to strong binding between acyl chloride functional group and TiO2. About 85.0%–86.0% of IBP was degraded with N-doping CNT/TiO2 within 120 min at natural condition, which obeyed the pseudo first order reaction and the rate constant was 4.45 × 10−3–1.22 × 10−2 min−1 and 5.03 × 10−3–1.47 × 10−2 min−1 for N-doping CNT-COOH/TiO2 and N-doping CNT-COCl/TiO2, respectively. The best IBP degradation of 87.9%–89.0% was found at pH 5, which indicated superoxide radicals (O2−) played a key role. The optimal pH was majorly dominated by the nature of IBP and N-doping CNT/TiO2. A successful synergy effect of TiO2 and dopants was exhibited and this mainly attributed to the strong binding strength by functional group of acyl chloride (COCl) and carboxylic acid (COOH). In summary, IBP could be effectively photodegraded by the fabricated N-doping CNT/TiO2 photocatalysts.

Postoperative nonsteroidal antiinflammatory drugs and the prevention of heterotopic ossification after cervical arthroplasty: analysis using CT and a minimum 2-year follow-up.

OBJECT Heterotopic ossification (HO) after cervical arthroplasty is not uncommon and may cause immobility of the disc. To prevent HO formation, study protocols of clinical trials for cervical arthroplasty undertaken by the US FDA included perioperative use of nonsteroidal antiinflammatory drugs (NSAIDs). However, there are few data supporting the use of NSAIDs to prevent HO after cervical arthroplasty. Therefore, this study aimed to evaluate the efficacy of NSAIDs in HO formation and clinical outcomes. METHODS Consecutive patients who underwent 1- or 2-level cervical arthroplasty with a minimum follow-up of 24 months were retrospectively reviewed. All patients were grouped into 1 of 2 groups, an NSAID group (those patients who had used NSAIDs postoperatively) and a non-NSAID group (those patients who had not used NSAIDs postoperatively). The formation of HO was detected and classified using CT in every patient. The incidence of HO formation, disc mobility, and clinical outcomes, including visual analog scale (VAS) scores of neck and arm pain, neck disability index (NDI) scores, and complications were compared between the two groups. Furthermore, a subgroup analysis of the patients in the NSAID group, comparing the selective cyclooxygenase (COX)-2 to nonselective COX-2 NSAID users, was also conducted for each of the above-mentioned parameters. RESULTS A total of 75 patients (mean age [± SD] 46.71 ± 9.94 years) with 107 operated levels were analyzed. The mean follow-up duration was 38.71 ± 9.55 months. There were no significant differences in age, sex, and levels of arthroplasty between the NSAID and non-NSAID groups. There was a nonsignificantly lower rate of HO formation in the NSAID group than the non-NSAID group (47.2% vs. 68.2%, respectively; p = 0.129). During follow-up, most of the arthroplasty levels remained mobile, with similar rates of immobile discs in the NSAID and non-NSAID groups (13.2% and 22.7%, respectively; p = 0.318). Furthermore, there was a nonsignificantly lower rate of HO formation in the selective COX-2 group than the nonselective COX-2 group (30.8% vs 52.5%, respectively; p = 0.213). The clinical outcomes, including VAS neck, VAS arm, and NDI scores at 24 months postoperatively, were all similar in the NSAID and non-NSAID groups, as well as the selective and nonselective COX-2 groups (all p > 0.05). CONCLUSIONS In this study there was a trend toward less HO formation and fewer immobile discs in patients who used postoperative NSAIDs after cervical arthroplasty than those who did not, but this trend did not reach statistical significance. Patients who used selective COX-2 NSAIDs had nonsignificantly less HO than those who used nonselective COX-2 NSAIDs. The clinical outcomes were not affected by the use of NSAIDs or the kinds of NSAIDs used (selective vs nonselective COX-2). However, the study was limited by the number of patients included, and the efficacy of NSAIDs in the prevention of HO after cervical arthroplasty may need further investigation to confirm these results.

Colonic diverticular hemorrhage associated with the use of nonsteroidal anti‐inflammatory drugs, low‐dose aspirin, antiplatelet drugs, and dual therapy

The effects of various medications on lower gastrointestinal tract remains unknown. Here, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, and antiplatelet drugs associated with diverticular bleeding. This prospective study involved patients with diverticulosis who underwent colonoscopy. Alcohol and smoking, medications, and Charlson comorbidity index and Gastrointestinal Symptom Rating Scale scores were assessed. The medications evaluated were nine kinds of NSAIDs, two kinds of low-dose aspirin, 10 kinds of nonaspirin antiplatelet drugs, three kinds of anticoagulants, acetaminophen, and corticosteroids. Adjusted odds ratios (aOR) were estimated by a logistic regression model. A total of 911 patients with non-bleeding diverticula (n = 758) and bleeding diverticula (n = 153) were enrolled. Independent risk factors were alcohol consumption (light drinker, aOR 3.4; ≥ moderate drinker, aOR 3.3), smoking index (≥ 400, aOR 2.0), NSAIDs (aOR 4.6), low-dose aspirin (aOR 1.9), and nonaspirin antiplatelet drugs (aOR 2.2). The drugs significantly associated with bleeding were loxoprofen (aOR 5.0), diclofenac (aOR 3.1), diclofenac suppository (aOR 8.0), etodolac (aOR 4.9), enteric-coated aspirin (aOR 3.9), buffered aspirin (aOR 9.9), clopidogrel (aOR 2.5), and cilostazol (aOR 7.3). Dual therapy carried a higher risk than monotherapy (single NSAID, aOR 3.6, P < 0.01; dual, aOR 23, P < 0.01; single antiplatelet drug, aOR 2.0, P < 0.01; dual, aOR 4.1, P < 0.01). Besides alcohol and smoking, NSAIDs, low-dose aspirin, and antiplatelet drugs are risk factors for diverticular bleeding. The magnitude of risk may differ between different kinds of NSAIDs and antiplatelet drugs, and dual therapy with NSAIDs or antiplatelet drugs increases the risk of bleeding.

Compensatory Cellular Reactions to Nonsteroidal Anti-Inflammatory Drugs on Osteogenic Differentiation in Canine Bone Marrow-Derived Mesenchymal Stem Cells

ABSTRACTThe suppressive effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the bone healing process have remained controversial, since no clinical data have clearly shown the relationship between NSAIDs and bone healing. The aim of this study was to assess the compensatory response of canine bone marrow-derived mesenchymal stem cells (BMSCs) to several classes of NSAIDs, including carprofen, meloxicam, indomethacin and robenacoxib, on osteogenic differentiation. Each of the NSAIDs (10 µM) was administered during 20 days of the osteogenic process with human recombinant IL-1β (1 ng/ml) as an inflammatory stimulator. Gene expression of osteoblast differentiation markers (alkaline phosphatase and osteocalcin), receptors of PGE2 (EP2 and EP4) and enzymes for prostaglandin (PG) E2 synthesis (COX-1, COX-2, cPGES and mPGES-1) was measured by using quantitative reverse transcription-polymerase chain reaction. Protein production levels of alkaline phosphatase, osteocalcin and PGE2 were quantified using an alkaline phosphatase activity assay, osteocalcin immunoassay and PGE2 immunoassay, respectively. Histologic analysis was performed using alkaline phosphatase staining, von Kossa staining and alizarin red staining. Alkaline phosphatase and calcium deposition were suppressed by all NSAIDs. However, osteocalcin production showed no significant suppression by NSAIDs. Gene expression levels of PGE2-related receptors and enzymes were upregulated during continuous treatment with NSAIDs, while certain channels for PGE2 synthesis were utilized differently depending on the kind of NSAIDs. These data suggest that canine BMSCs have a compensatory mechanism to restore PGE2 synthesis, which would be an intrinsic regulator to maintain differentiation of osteoblasts under NSAID treatment.

The effects of celecoxib on proliferation of human bone mesenchymal stem cells and differentiation into osteoblasts

Objective To investigate the effects of celecoxib,a kind of nonsteroidal anti-inflammatory drugs,on the proliferation of human bone mesenchymal stem cells (hBMSCs) and their differentiation into osteoblasts.Methods The bone marrow was harvested from a healthy male volunteer.hBMSCs were isolated by density gradient centrifugation with Ficoll-Paque and expanded in vitro.Celecoxib was added at the concentrations ranging from 10 μmol/L to 100 μmol/L in the process of cellular proliferation and induction.The effect of celecoxib on the proliferation of hBMSCs was evaluated by CCK8 assay.hBMSCs were induced to differentiate into osteoblasts by dexamethasone ascorbic acid and β-glycerophosphate.hBMSCs were treated with 100 μmol/L of celecoxib in the process of osteogenesis before alkaline phosphatase (ALP) activities and calcium deposition were analyzed to determine the effect of celecoxib on the differentiation into osteoblasts.The expression of Runx2,a critical transcription factor of osteogenesis,was analyzed by Western blot.Results Celecoxib inhibited the hBMSCs proliferation in a dose-dependent manner.Such an inhibiting effect of celecoxib was observed at concentrations of 12.5 μmol/L to 100 μmol/L,intensified with the increased concentration.The ALP activities and calcium deposition were reduced by a high dose of Celecoxib and the expression level of Runx2 was also suppressed.Conclusions Celecoxib can suppress the proliferation and osteogenesis of hBMSCs in a dose-dependent manner.Long term administration of celecoxib,particularly high dose usage,should arouse concerns from both the patients and medical staff about the effect of celecoxib on the osteogenesis of hBMSCs. Key words: Bone marrow cells; Mesenchymal stem cells; Osteoblasts; Transcription factors; Celecoxib