Carboxymethyl potato starch hydrogels encapsulated cyclodextrin metal-organic frameworks for enantioselective loading of S-naproxen and its programmed release.

A natural polysaccharide-based vehicle is facilely prepared for enantioselective loading of S-naproxen (S-NPX) and its programmed release. Cyclodextrin metal-organic frameworks (CD-MOF) are synthesized through the coordination of K+ with γ-cyclodextrin (γ-CD). Compared with R-NPX, the CD-MOF preferably combines with S-NPX, which can be confirmed by the thermodynamic calculations. The S-NPX loaded CD-MOF (CD-MOF-S-NPX) is grafted with disulfide bond (-S-S-) to improve its hydrophobicity, and the loaded S-NPX is further encapsulated in the chiral cavity of γ-CD by carboxymethyl potato starch (CPS) hydrogels. The intermolecular hydrogen bonding of the CPS hydrogels is prone to be destroyed in mildly basic media (∼pH 8.0), resulting in the swelling of the hydrogels; the -S-S- linkage in the vehicle can be cleaved in the presence of glutathione (GSH), leading to the collapse of the CD-MOF. Therefore, the programmed release of S-NPX can be achieved. Also in this work, the release kinetics is investigated, and the results indicate that the release of S-NPX is controlled by the Higuchi model.

Degradation characteristics of refractory organic matter in naproxen pharmaceutical secondary effluent using vacuum ultraviolet-ozone treatment.

Vacuum ultraviolet-ozone (VUV-O3) treatment was found to be superior to ultraviolet-ozone (UV-O3) treatment in terms of ozone utilization and hydroxyl radicals (·OH) generation when used to treat the secondary effluent (SE) from a naproxen pharmaceutical plant. VUV-O3 treatment was beneficial in terms of decolorization (100%), chemical oxygen demand removal (43.29%), and total organic carbon removal (54.81%). The VUV-O3 process was applicable over a wide pH range, and the presence of various anions had no significant influence on the oxidation efficiency. After treatment, the genotoxicity, unsaturation degree, and polarity of the SE decreased. In addition, the oxidation sensitivities of the fluorescent organic compounds were ranked as follows: humic acid-like > tyrosine-like > fulvic acid-like > tryptophan-like Moreover, the VUV-O3 process effectively converted refractory organic matter (molecular weights, MW > 2000 Da) into short-chain molecules with low MWs. The removal efficiency of dissolved organic matter (DOM) was 63.27%, and 77.27% of the DOM was found to be reactive to VUV-O3 oxidation. The unsaturation, polarity, and compositional complexity of the DOM decreased after VUV-O3 treatment. Finally, it was deduced that the direct O3 oxidation,·OH, O2·- and 1O2 played a role in the VUV-O3 oxidation process.

Effect of salinity on the toxicity of diclofenac, ibuprofen and naproxen toward cyanobacterium Synechocystis salina.

Aquatic species are continuously exposed to pharmaceuticals and changeable water conditions simultaneously, which can induce changes in the toxicity of pollutants. Cyanobacterium are an organism for which less ecotoxicological tests have been performed compared to green algae. In this study, we decided to check how selected non-steroidal anti-inflammatory drugs (NSAID) affect the grow of Synechocystis salina, picocyanobacterium isolated from the Baltic Sea, with salinity as potential modulator of toxicity. S. salina was exposed to diclofenac (DCF), ibuprofen (IBF) and naproxen (NPX) (nominal 100 mg L-1) in BG11 medium and sea salt supplemented BG11 medium (38 PSU) over 96 h in continuous light at 23 °C. No acute toxicity was found in both tested salinity levels. The comparable grow rate in exposed culture compared to control culture over 4 days indicate lack of stress for several generations which need to be overcome with substantial energy consumption. S. salina was found to be halotolerant and can be species for ecotoxicology test where salinity in an additional stressor. Furthermore, resistant of S. salina to target NSAIDs provide a competitive advantage over other phytoplankton species.

Dissemination of nonsteroidal anti-inflammatory drugs (NSAIDs) and metabolites from wastewater treatment plant to soils and agricultural crops via real-scale different agronomic practices.

One of the most consumed pharmaceutical subgroups across the world is nonsteroidal anti-inflammatory drugs (NSAIDs). However, the dissemination of these compounds to the natural environments through agronomic practices is a serious global problem. The hypothesis of this study is to reveal the transition of selected NSAIDs, paracetamol (PAR), diclofenac (DCF), ibuprofen (IBU), and naproxen (NAP) together with six main metabolites, detected in raw/treated wastewater (RWW/TWW) and sewage sludge generated in an urban wastewater treatment plant (WWTP) to soils and agricultural crops (corn, barley, sunflower, and sugar beet) through two widely applied agronomic practices, irrigation with TWW and application of sewage sludge as soil amendment. In other words, the cycles of 10 NSAIDs have been evaluated by simultaneously monitoring their concentrations in RWW/TWW, sewage sludge, soils, and crops. It was determined that the parent compounds and detected metabolites were treated at quite higher removal efficiencies (93.4 - >99.9%) in the studied WWTP, while DCF was eliminated poorly (7.9-52.2%). However, although it changes seasonally for some compounds, it was determined that the concentrations of almost all investigated NSAIDs increased at the determined irrigation points in the discharge channel (DC) where agricultural irrigations were performed. Apart from that, DCF, NAP, and 2-hydroxyibuprofen (2-OH-IBU) were always detected in sewage sludge seasonally up to about 20.5, 11.3, and 3.7 ng/g, respectively. While 2-OH-IBU was determined as the dominant metabolite in RWW, TWW, and sewage sludge, the metabolite of 1-hydroxyibuprofen (1-OH-IBU) was determined as the dominant compound in soils. Although 1-OH-IBU was not detected in TWW and sewage sludge in any season, detecting this metabolite as a common compound in all investigated soils (up to 60.1 ng/kg) reveals that this compound is the primary transformation product of IBU in soils. It was observed that at least one of the metabolites of IBU (1-OH-IBU and/or 2-OH-IBU) was detected in all plants grown (up to 0.75 ng/g), especially during the periods when both agricultural practices were applied. In addition, the detection of 1-OH-IBU with increasing concentrations from root to shoots in corn grown as a result of both agronomic practices shows that this compound has a high translocation potential in the corn plant. Apart from this, it was determined that PAR was detected in corn (up to 43.3 ng/kg) and barley (up to 16.8 ng/kg) within the scope of irrigation with TWW, and NAP was detected in sugar beet (up to 11.2 ng/kg) through sewage sludge application.

Pharmacokinetic and pharmacodynamic herb-drug interactions of common over-the-counter pain medications.

Pain is one of the most common reasons for seeking medical intervention, and self-medication with over-the-counter medications and/or traditional herbal remedies has become increasingly popular. In this review, original articles on understanding possible herb-drug interactions between traditional herbs and four major pain medications-acetaminophen, aspirin, ibuprofen and naproxen-are compiled and analyzed. In terms of analytical methods, high-performance liquid chromatography using an isocratic eluent system coupled to biological sample clean-up is the most common, while a wide variety of detectors have been observed, including a photodiode array, variable wavelength detector, electrochemical detector and tandem mass spectrometer. Both synergistic and anti-synergistic effects were observed for acetaminophen and aspirin, while only synergistic effects have been found for naproxen. Currently, no interactions have been reported for ibuprofen.

2022 Taiwan Guidelines for Acute Treatment of Migraine.

The Taiwan Headache Society published its guidelines for acute migraine treatment in 2017. Since then, emerging drugs and treatment options have developed rapidly. The migraine-specific drugs gepants and ditans and several noninvasive neuromodulation devices have been approved for use in Europe and the United States. Although not all emerging drugs and treatment options have been approved for use in Taiwan, keeping pace with international trends and updating treatment guidelines are imperative. Therefore, the Treatment Guideline Subcommittee of the Taiwan Headache Society reviewed the quality of recent trials, evaluated the corresponding grade of evidence, and appraised the reported clinical efficacy to reach a new consensus. To ensure that the updated Taiwan guidelines are appropriate and feasible, the subcommittee also referred to the guidelines from the United States, Europe, Canada, and other countries concerning the main roles, recommendation levels, clinical efficacy, and adverse reactions of drugs for the acute migraine treatment. Several types of drugs are currently available for acute migraine treatment in Taiwan. These drugs can be categorized into migraine-specific and migraine-non-specific. Among them, migraine-specific triptans (oral or nasal spray formulations) and migraine-nonspecific acetaminophen and NSAIDs (diclofenac, ibuprofen, naproxen) are highly recommended because they are supported by strong evidence and demonstrate high efficacy. Prochlorperazine injection has been upgraded to a highly recommended level because of the rich clinical experience for this treatment. Ergotamine/caffeine remains a second-line drug because of its lower specificity and efficacy compared with triptans. High-dose aspirin was downgraded to rescue treatment because of potential gastrointestinal side effects. Although evidence supports the combination of oral tramadol and acetaminophen, this combination should be used as a rescue treatment due to concerns about dependence. Evidence supporting the use of intravenous tramadol or morphine is insufficient; therefore, their use is not recommended. As for non-pharmacological approaches, there are only limited controlled data. The choice of treatment for acute migraine attacks should follow the concept of "stratified care." For mild to moderate migraine attacks, oral NSAIDs are the first choice, with combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplements to alleviate nausea and vomiting. Other emerging migraine-specific drugs, such as gepants or ditans, may also have a role in the future. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroids and fluid supply are the first-line treatment for status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. To prevent medication overuse headache, the use of acute treatment should be limited to a maximum of 2 days per week. Key words: acute migraine treatment, evidence-based medicine, treatment guidelines, triptans, ergotamine, neuromodulation.

Fecal indicator bacteria levels at a marine beach before, during, and after the COVID-19 shutdown period and associations with decomposing seaweed and human presence.

Studies are limited that evaluate seaweed as a source of bacteria to beach waters. The objective of the current study was to evaluate whether seaweed, along with humans and other animals, could be the cause of beach advisories due to elevated levels of enterococci. The monitoring period occurred a year prior to and through the COVID-19 beach shutdown period, which provided a unique opportunity to evaluate bacteria levels during prolonged periods without recreational activity. Samples of water, sediment, and seaweed were measured for enterococci by culture and qPCR, in addition to microbial source tracking by qPCR of fecal bacteria markers from humans, dogs, and birds. During periods of elevated enterococci levels in water, these analyses were supplemented by chemical source tracking of human-associated excretion markers (caffeine, sucralose, acetaminophen, ibuprofen, and naproxen). Results show that enterococci with elevated levels of human fecal markers persist in the seaweed and sediment and are the likely contributor to elevated levels of bacteria to the nearshore waters. During the shutdown period the elevated levels of enterococci in the sediment were isolated to the seaweed stranding areas. During periods when the beaches were open, enterococci were distributed more uniformly in sediment across the supratidal and intertidal zones. It is hypothesized from this study that human foot traffic may be responsible for the spread of enterococci throughout these areas. Overall, this study found high levels of enterococci in decomposing seaweed supporting the hypothesis that decomposing seaweed provides an additional substrate for enterococci to grow.

Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.

BACKGROUND: Heavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual bleeding, whereas levonorgestrel IUD (LNG IUD) users tend to have irregular menstruation. Medical therapies used to reduce heavy menstrual bleeding or pain associated with Cu and LNG IUD use include non-steroidal anti-inflammatory drugs (NSAIDs), anti-fibrinolytics and paracetamol. We analysed treatment and prevention interventions separately because the expected outcomes for treatment and prevention interventions differ. We did not combine different drug classes in the analysis as they have different mechanisms of action. This is an update of a review originally on NSAIDs. The review scope has been widened to include all interventions for treatment or prevention of heavy menstrual bleeding or pain associated with IUD use. OBJECTIVES: To evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021. SELECTION CRITERIA: We included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random-effects model in all meta-analyses. Review authors assessed the certainty of evidence using GRADE. MAIN RESULTS: This review includes 21 trials involving 3689 participants from middle- and high-income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding. Treatment of heavy menstrual bleeding Cu IUD Vitamin B1 resulted in fewer pads used per day (mean difference (MD) -7.00, 95% confidence interval (CI) -8.50 to -5.50) and fewer bleeding days (MD -2.00, 95% CI -2.38 to -1.62; 1 trial; 110 women; low-certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low-certainty evidence). Treatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD -64.26, 95% CI -105.65 to -22.87; 1 trial, 94 women; low-certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI -0.27 to 0.42, 2 trials, 152 women; low-certainty evidence). LNG IUD The use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD -9.30 days, 95% CI -26.76 to 8.16; 1 trial, 24 women; low-certainty evidence). Unknown IUD type Mefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD -2.40, 95% CI -13.77 to 8.97; 1 trial; 84 women; low-certainty evidence). Treatment of pain Cu IUD Treatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low-certainty evidence). Unknown IUD type Naproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low-certainty evidence). Prevention of heavy menstrual bleeding Cu IUD We found very low-certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD -14.11, 95% CI -36.04 to 7.82) and duration of bleeding (MD -0.2 days, 95% CI -1.40 to 1.0; 1 trial, 28 women, low-certainty evidence). Aspirin may not prevent heavy bleeding in comparison to paracetamol (MD -0.30, 95% CI -26.16 to 25.56; 1 trial, 20 women; very low-certainty evidence). LNG IUD Ulipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low-certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B. There were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol. Prevention of pain Cu IUD There was low-certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low-certainty evidence). AUTHORS' CONCLUSIONS: Findings from this review should be interpreted with caution due to low- and very low-certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.

An active tumor-targeting organic photochemotherapy agent with naproxen for enhanced cancer therapy.

An active tumor-targeting organic photochemotherapy agent via the combination of a an organic photothermal material and a naproxen prodrug was developed to precisely kill cancer cells and suppress the inflammatory response induced by cell necrosis; in vitro, and in vivo experiments illustrated its low cytotoxicity and excellent tumor inhibitory effect.

The Effects of Ibuprofen, Naproxen and Diclofenac on cell Apoptosis, Cell Proliferation and Histology Changes in Human Cholangiocarcinoma Cell Lines.

OBJECTIVE: To examine the effects of ibuprofen, naproxen and diclofenac, non-steroidal anti-inflammatory drugs (NSAIDs) on cell proliferation activity of the human CCA cell lines. METHODS: KKU-M139 and KKU-213B cell lines were used in this study. The cell viability was assessed by the MTT assay. Lipid synthesis determined by Oil red O staining and colorimetric assay. An inverted phase-contrast light microscope was used to investigate the histological change of the cells. Caspases 3/7 activity and AnnexinV/PI were used to assess apoptosis by multiple microplate reader. RESULTS: The results showed that ibuprofen, naproxen and diclofenac suppressed the viability of the KKU-M139 and KKU-213B cells in a dose-dependent manner, as measured especially diclofenac. However, these three NSAIDs slightly decreased lipid synthesis determined by Oil red O staining and colorimetric assay. The histological change observations showed the shrinking cell and become star-shaped in high dose treated groups. Interestingly, these NSAIDs exhibited in both of KKU-M139 and KKU-213B cell lines, the diclofenac-treated cells had the most injury cells. The cells exhibited cell injury features. In addition, the detection of caspase 3/7 and AnnexinV/PI in this investigation revealed early cell apoptotic characteristics. CONCLUSION: These finding suggest that ibuprofen, naproxen and diclofenac suppress cell viability. The results reveal that ibuprofen, naproxen and diclofenac, which induce the histological change and apoptosis. This study indicates that these NSAIDs may be used as an anti-proliferation agent for the treatment of CCA in the future.

Weak electrostimulation enhanced the microbial transformation of ibuprofen and naproxen.

Ibuprofen (IBU) and naproxen (NPX) are commonly used non-steroidal anti-inflammatory drugs (NSAIDs) with high-risk quotients and are frequently detected in various aquatic environments. A weak electrostimulated biofilm not only had improved removal efficiencies to IBU and NPX, but also transformed different enantiomers with comparable efficiency and without configuration inversion. IBU was transformed mainly by oxidation (hydroxyl-IBU, carboxy-IBU), while NPX was mainly detoxified. The microbial analysis of IBU and NPX biofilm showed that the shared core consortia (> 1%) contained typical electro-active bacteria (Geobacter, Desulfovibrio), fermenters (Petrimonas, Acetobacterium) and potential degraders (Pandoraea, Nocardiaceae), which exhibited synergistic interactions by exchanging the additional electrons, H+, coenzyme NAD(H) or NAD(P) (H) and energy. The fungal community has a significant correlation to those core bacteria and they may also play transformation roles with their diverse enzymes. Plenty of nonspecific oxidoreductase, decarboxylase, hydrolase, cytochrome P450, and other enzymes relating to xenobiotic degradation were high-abundance encoded by the core consortia and could potentially participate in IBU and NPX biotransformation. This study offers new insights into the functional microbes and enzymes working on complex NSAIDs biotransformation and provided a feasible strategy for the enhanced removal of NSAIDs (especially IBU and NPX).

Evidence for antioxidant and anti-inflammatory potential of mango (Mangifera indica L.) in naproxen-induced gastric lesions in rat.

This study investigated the anti-inflammatory and antioxidant effects of hydroalcoholic extracts of mango peel and pulp on oxidative damage in a naproxen-induced gastric injury rat model. The extracts were assessed for antioxidant activity (ABTS and FRAP methods), and the phenolic profile was investigated with UPLC-QToF-MSE . Gastric damage was evaluated in vivo by assessing the membrane lipid peroxidation (malondialdehyde (MDA) content), myeloperoxidase (MPO) enzyme activity, and glutathione (GSH) content. Mango peel and pulp contained high contents of bioactive compounds, particularly phenolics (69.50-5.287.70 mg gallic acid equivalents/100 g), carotenoids (651.30-665.50 µg/100 g), and vitamin C (21.59-108.19 mg/100 g). UPLC-QToF-MSE analysis identified 17 phenol compounds, including gallotannins, glycosylated flavonoids, and xanthone. The hydroalcoholic extracts of mango peel and pulp (LPe and LPu, respectively) significantly reduced the MPO activity and MDA content. In addition to preventing naproxen-induced GSH decline, LPe (30 mg/kg) and LPu (10 mg/kg) restored its content to normal levels. LPe and LPu neutralized the oxidizing agents triggered by naproxen and reduced the severity of gastric lesions owing to their antioxidant properties.

In Vitro Assessment of the Antiviral Activity of Ketotifen, Indomethacin and Naproxen, Alone and in Combination, against SARS-CoV-2.

The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and indomethacin, alone or in combination, in reducing SARS-CoV-2 replication. In addition, the cytotoxicity of the drugs was evaluated. The findings showed that the combination of ketotifen with indomethacin (SJP-002C) or naproxen both reduce viral yield. Compared to ketotifen alone (60% inhibition at EC50), an increase in percentage inhibition of SARS-CoV-2 to 79%, 83% and 93% was found when co-administered with 25, 50 and 100 µM indomethacin, respectively. Compared to ketotifen alone, an increase in percentage inhibition of SARS-CoV-2 to 68%, 68% and 92% was found when co-administered with 25, 50 and 100 µM naproxen, respectively. For both drug combinations the observations suggest an additive or synergistic effect, compared to administering the drugs alone. No cytotoxic effects were observed for the administered dosages of ketotifen, naproxen, and indomethacin. Further research is warranted to investigate the efficacy of the combination of ketotifen with indomethacin (SJP-002C) or naproxen in the treatment of SARS-CoV-2 infection in humans.

Comparative Effectiveness of Thai Herbal Formula (Thor-Ra-Nee-San-Tha-Kat) Versus Naproxen for Chronic Myofascial Pain: A Pilot Randomized-Controlled Trial.

Background: Myofascial pain syndrome (MPS) is a painful musculoskeletal condition. The prevalence of MPS ranges from 5.9% to 38.7% in the general population. "Thor-ra-nee-san-tha-kat" (TRK) is a traditional formula included in the Thailand National List of Essential Medicines for the treatment for muscle pain caused by abdominal rigidity and for severe constipation. Objectives: The authors employed a pilot single-blind, randomized-controlled trial to compare the effectiveness of TRK and naproxen for the treatment of chronic upper trapezius MPS. Materials and Methods: Seventy-six male and female subjects, ages 25-55 years, who met the inclusion criteria were equally randomized into two groups to receive either two 500 mg capsules of TRK once daily before bed or two 250 mg naproxen tablets twice a day after meals for 14 days. Subjects assessed their level of pain using the numerical rating scale. Cervical range of motion (CROM) was determined using a goniometer, and pressure pain threshold (PPT) was assessed using an algometer. Adverse drug reactions were recorded and all items were compared within and between groups, before and after treatment. Results: The results revealed that patient pain scores after 14 days of treatment were much improved with mean differences exceeding the reference minimum clinically important difference (MCID) in both groups. However, the changes in CROM and PPT values were small and did not surpass their respective reference MCIDs except for the right lateral bending CROM for naproxen treatment. The adverse drug reactions were mild, with watery stools reported by 47% of patients in the TRK-treated group and constipation reported by 24% of those in the naproxen group. Conclusion: The administration of TRK formula for 14 days was safe and as effective as naproxen at providing short-term relief of pain in patients with chronic upper trapezius pain.

cPLA2α Enzyme Inhibition Attenuates Inflammation and Keratinocyte Proliferation.

As a regulator of cellular inflammation and proliferation, cytosolic phospholipase A2 α (cPLA2α) is a promising therapeutic target for psoriasis; indeed, the cPLA2α inhibitor AVX001 has shown efficacy against plaque psoriasis in a phase I/IIa clinical trial. To improve our understanding of the anti-psoriatic properties of AVX001, we sought to determine how the compound modulates inflammation and keratinocyte hyperproliferation, key characteristics of the psoriatic epidermis. We measured eicosanoid release from human peripheral blood mononuclear cells (PBMC) and immortalized keratinocytes (HaCaT) and studied proliferation in HaCaT grown as monolayers and stratified cultures. We demonstrated that inhibition of cPLA2α using AVX001 produced a balanced reduction of prostaglandins and leukotrienes; significantly limited prostaglandin E2 (PGE2) release from both PBMC and HaCaT in response to pro-inflammatory stimuli; attenuated growth factor-induced arachidonic acid and PGE2 release from HaCaT; and inhibited keratinocyte proliferation in the absence and presence of exogenous growth factors, as well as in stratified cultures. These data suggest that the anti-psoriatic properties of AVX001 could result from a combination of anti-inflammatory and anti-proliferative effects, probably due to reduced local eicosanoid availability.

Solubility of Pharmaceutical Ingredients in Natural Edible Oils.

Natural edible oils (NEOs) are common excipients for lipid-based formulations. Many of them are complex mixtures comprising hundreds of different triglycerides (TGs). One major challenge in developing lipid-based formulations is the variety in NEO compositions affecting the solubility of active pharmaceutical ingredients. In this work, solubilities of indomethacin (IND), ibuprofen (IBU), and fenofibrate (FFB) in soybean oil and in coconut oil were measured via differential scanning calorimetry, high-performance liquid chromatography, and Raman spectroscopy. Furthermore, this work proposes an approach that mimics NEOs using one key TG and models the API solubilities in these NEOs based on perturbed-chain statistical associating fluid theory (PC-SAFT). Key TGs were determined using the 1,2,3-random hypothesis, and PC-SAFT parameters were estimated via a group-contribution method. Using the proposed approach, the solubility of IBU and FFB was modeled in soybean oil and coconut oil. Furthermore, the solubilities of five more APIs (IND, cinnarizine, naproxen, griseofulvin, and felodipine) were modeled in soybean oil. All modeling results were found in very good agreement with the experimental data. The influence of different NEO kinds on API solubility was examined by comparing FFB and IBU solubilities in soybean oil and refined coconut oil. PC-SAFT was thus found to allow assessing the batch-to-batch consistency of NEO batches in silico.

An Experimental Comparison of the Analgesic and Anti-Inflammatory Effects of Safflower Oil, Benzydamine HCl, and Naproxen Sodium.

The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1-physiological saline 0.9%; Group No. 2-safflower oil 100 mg/kg; Group No. 3-safflower oil 300 mg/kg; Group No. 4-benzydamine HCl 30 mg/kg; Group No. 5-benzydamine HCl 100 mg/kg; and Group No. 6-naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7-10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7-physiological saline 0.9%; Group No. 8-safflower oil 300 mg/kg; Group No. 9-benzydamine HCl 100 mg/kg; and Group No. 10-naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro-Wilk, Kruskal-Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic-anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.

Herbal formulation "turmeric extract, black pepper, and ginger" versus Naproxen for chronic knee osteoarthritis: A randomized, double-blind, controlled clinical trial.

Osteoarthritis is the most common articular disease that can lead to chronic pain and severe disability. Curcumin-an effective ingredient in turmeric with anti inflammatory property-plays an important role in protecting the joints against destructive factors. Gingerols and piperine, are the effective ingredients of ginger and black pepper, which may potentially enhance and sustain the effect of curcumin in this direction. To determine the effect of cosupplementation with turmeric extract, black pepper, and ginger on prostaglandin E2 (PGE2 ) in patients with chronic knee osteoarthritis, compared with Naproxen. Sixty patients with two different levels of knee osteoarthritis (Grade 2 and 3) were studied. Individuals were randomly assigned to receive daily turmeric extract, ginger, and black pepper together or Naproxen capsule for 4 weeks. PGE2 was evaluated by ELISA method. 24-hr recall was also assessed. All of participants completed the study. PGE2 decreased significantly in both groups (p < .001), but there was no significant differences between groups. The results of this study indicated that intake of the selected herbs twice a day for 4 weeks may improve the PGE2 levels in patients with chronic knee osteoarthritis similar to Naproxen drug.

A comparative study of the efficacy of NAXOZOL compared to celecoxib in patients with osteoarthritis.

OBJECTIVE: Selective cyclooxygenase-2 inhibitors (celecoxib) can minimize the gastrointestinal complications related to non-steroidal anti-inflammatory drug (NSAID) use. NAXOZOL is a new combination formulation designed to provide sequential delivery of a non-enteric-coated, immediate-release esomeprazole strontium tetrahydrate 20 mg mantle followed by an enteric-coated naproxen 500 mg core. However, there have been no studies comparing NAXOZOL to celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis. This study was undertaken to compare the effects of NAXOZOL and celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis. METHODS: The randomized enrolled patients were divided into two treatment groups: a NAXOZOL group and a celecoxib group. All participants received treatments (NAXOZOL, 500/20 mg (naproxen 500 mg, esomeprazole strontium tetrahydrate 20 mg) twice per day versus celecoxib, 200 mg daily) on a 1:1 allocation basis for 12 weeks. The primary outcome was the Leeds Dyspepsia Questionnaire (LDQ) score used for non-inferiority testing. Secondary outcome measures included the Gastrointestinal Symptom Rating Scale (GSRS) score, Visual Analogue Scale (VAS) score, European Quality of Life-5 dimensions (EQ-5D) scale and the EQ-5D Visual Analogue Scale (EQ VAS). Other outcome measures included the use of supplementary or rescue drugs, and the incidence of adverse events. RESULTS: The baseline-adjusted LDQ scores immediately after 12 weeks of treatment in NAXOZOL group were not inferior to those in celecoxib group. The overall change in the baseline-adjusted GSRS score, VAS score, EQ-5D, and EQ VAS was not different between the two groups. The usage of supplementary drugs and the drug-related incidence of adverse events were not different. However, the days to use rescue drug were longer in celecoxib group than in NAXOZOL group. CONCLUSION: NAXOZOL was not inferior to celecoxib in protecting the gastrointestinal tract and providing pain relief in patients with osteoarthritis.

Central nervous system evaluation of an ethanol extract of Bidens odorata Cav (Asteraceae) leaves, and its antinociceptive interaction with paracetamol and naproxen.

INTRODUCTION: Bidens odorata Cav (Asteraceae) is a medicinal plant employed for the treatment of pain, anxiety, and depression. This study aimed to evaluate some neuropharmacological effects of an ethanol extract of B. odorata (BOE) and assess its antinociceptive interaction with naproxen and paracetamol. MATERIALS AND METHODS: The following neuropharmacological effects were evaluated with the ethanolic extract of B. odorata leaves (BOE) (10-200 mg/kg p.o.): the strychnine-induced-convulsion assay (anticonvulsant effect), rotarod test (locomotor activity), tail suspension test (anti-depressant-like activity), cylinder exploratory test (anxiolytic-like actions), and pentobarbital-induced sleep test (sedative effect). The interaction of the BOE-paracetamol and BOE-naproxen combinations were evaluated with the acetic acid-induced writhing test. The ED50 value of each drug was estimated and the combinations of paracetamol and naproxen with BOE were calculated. RESULTS: BOE (100-200 mg/kg) showed anti-convulsant activity by increasing the latency to occurrence of strychnine-induced convulsions, antidepressant-like effects by 28% and 33%, respectively, exerted anxiolytic actions (ED50 = 125 mg/kg), but did not affect motor locomotion. The pre-treatment with 2 mg/kg flumazenil or 20 mg/kg pentylenetetrazol partially reverted the anxiolytic activity shown by BOE alone. BOE (200 mg/kg) prolonged the duration of sleep with similar effect in comparison to clonazepam (1.5 mg/kg). The combinations of BOE-paracetamol (1:1) and BOE-naproxen (1:1) showed antinociceptive synergism. CONCLUSION: BOE induces sedative and anticonvulsant effects. The anxiolytic actions shown by BOE are probably induced by the participation of the GABAergic system. BOE exerts antinociceptive synergistic interaction with paracetamol and naproxen probably by the participation of nitric oxide and ATP-sensitive K+ channels, respectively.