The Association of Tumor Necrosis Factor Inhibitor Use With Incident Hypertension in Ankylosing Spondylitis: Data From the PSOAS Cohort

Objective Individuals with ankylosing spondylitis (AS) have a greater cardiovascular (CV) risk than those in the general population. The effect of tumor necrosis factor inhibitors (TNFis) on CV risk, including on the development of hypertension (HTN), remains unclear, with some data suggesting higher risk. We assessed the association of TNFi use with incident HTN in a longitudinal AS cohort. Methods Adults with AS enrolled in a prospective cohort in 2002–2018 were examined every 4–6 months. TNFi use during the preceding 6 months was ascertained at each study visit. We defined HTN by patient-reported HTN, antihypertensive medication use, or, on 2 consecutive visits, systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. We evaluated the association between TNFi use and the development of HTN with marginal structural models, estimated by inverse probability-of-treatment weighting, to account for time-dependent confounders and informative censoring. Potential confounders included age, sex, race, site, nonsteroidal antiinflammatory drug use, and disease activity. Results We included 630 patients without baseline HTN and with at least 1 year of follow-up. Of these, 72% were male, mean age was 39 ± 13 years, and 43% used TNFi at baseline. On follow-up (median 5 yrs), 129 developed incident HTN and 163 started on TNFi during follow-up. TNFi use was not associated with incident HTN (adjusted HR 1.10, 95% CI 0.83–1.37). Conclusion In our prospective AS cohort, TNFi use was not significantly associated with incident HTN.

Effects of tetracycline and ibuprofen on the relative abundance of protozoan and bacterial populations in wastewater treatment semi-batch reactors

The activated sludge process in Wastewater Treatment Plant (WWTPs) relies on the activities of microbes to reduce the organic and inorganic matter and produce effluent that is safe to discharge into receiving waters. This research examined the effects of non-steroidal antiinflammatory drug (NSAID) ibuprofen and the antibiotic tetracycline on the microbial population in activated sludge from the Humber WWTP. The current investigation was designated to observe the impact of these contaminants, at low (environmentally relative concentrations) as well as extremely high concentrations of tetracycline and ibuprofen. Using 16S and 18S rRNA gene primer sets, and qPCR the abundance of each population was monitored as well as the relative abundance of two populations under the various conditions. It was found that current environmental concentrations of ibuprofen stimulated protozoan growth but higher concentrations reduced their numbers especially in the presence of tetracycline. Finally using DGGE, the identity for some of the more abundant protozoa were identified and it was noted that high ibuprofen and tetracycline concentrations favored the abundance of some genera.

Effects of tetracycline and ibuprofen on the relative abundance of protozoan and bacterial populations in wastewater treatment semi-batch reactors

The activated sludge process in Wastewater Treatment Plant (WWTPs) relies on the activities of microbes to reduce the organic and inorganic matter and produce effluent that is safe to discharge into receiving waters. This research examined the effects of non-steroidal antiinflammatory drug (NSAID) ibuprofen and the antibiotic tetracycline on the microbial population in activated sludge from the Humber WWTP. The current investigation was designated to observe the impact of these contaminants, at low (environmentally relative concentrations) as well as extremely high concentrations of tetracycline and ibuprofen. Using 16S and 18S rRNA gene primer sets, and qPCR the abundance of each population was monitored as well as the relative abundance of two populations under the various conditions. It was found that current environmental concentrations of ibuprofen stimulated protozoan growth but higher concentrations reduced their numbers especially in the presence of tetracycline. Finally using DGGE, the identity for some of the more abundant protozoa were identified and it was noted that high ibuprofen and tetracycline concentrations favored the abundance of some genera.

TN HYDROGELS AS A POTENTIAL ANTI-INFLAMMATORY DRUG DELIVERY SYSTEM TARGETED TO OSTEOARTHRITIC KNEES

Arthritis affects 26.3% of adults and approximately 50,000 children in the United States [1]. Hydrogel drug-delivery systems have been considered as a viable option for drug delivery to arthritic articular cartilage in the knee. To determine physiologically relevant loading, a Qualisys motion capture system was used to analyze the gait of college-aged females as they took several steps on a flat surface, then stepped onto a force plate. The motion capture and force plate data was used to determine maximum force exerted on the knee during normal gait. Three different alginate-based hydrogels, where the superior one had a triple interpenetrating graphene oxide network (TN hydrogels), were investigated for use as an antiinflammatory drug delivery system in a human knee joint. Physiologically relevant cyclic loading was performed to ensure that the TN hydrogel could withstand the force exerted in the knee. The TN hydrogel experienced a change in energy of 50% after cyclic loading (10.6 ± 15.0 Pa) and survived high stresses of 4 kPa, which is 80 magnitudes larger than observable gait forces as measured in this study. From a mechanical perspective, TN hydrogel appears to be mechanically viable for arthritis drug delivery. In addition, based on calculations and Flory-Rehner equations, the pore size of the TN hydrogel is adequate for encapsulating most NSAIDs, which have a molecule size ≤ 5μm.

Development of Fourier transform infrared spectrophotometric method for identification and determination of marketed metamizole tablet preparation

Metamizole is a nonsteroidal antiinflammatory drug (NSAID) that functions as an analgesic, antipyretic, and antiinflammatory. Examination of active substance contents is a requirement that must be met to ensure the quality of drug preparations. The aims of this study were to develop and validate the Fourier Transform Infrared spectrophotometric method for the quantitation of metamizole content in marketed tablet preparation. Identification and determination of metamizole contents by Fourier Transform Infrared spectrophotometric method used methanol solvent in the wavenumber range 4000 cm–1 to 650 cm–1. The results showed that the specific wavenumbers of metamizole were 1649.3 cm–1; 1623.3 cm–1; and 1589.7 cm–1; and the contents metamizole in marketed tablet preparation ranged from (97.954 ± 0.121)% to (104.541 ± 0.257)%. From the validation method, the recovery result is 100.129%; the relative standard deviation is 0.057%; the limit of detection is 2.09526 mg/mL; the limit of quantitation is 6.34928 mg/mL; and the range 40 mg/mL to 60 mg/mL. The quantitation of metamizole contents can be carried out by Fourier Transform Infrared spectrophotometric method with accurate and precise quantitation results.

Strength and Sterility of Stock and Diluted Carprofen Over Time

Carprofen, a nonsteroidal antiinflammatory drug, is a commonly used analgesic for laboratory animals. The manufacturerlabeling indicates the stock bottle may be stored and used for up to 28 d under refrigeration. However, institutional guidelines may vary in how long diluted carprofen solutions can be stored before they must be discarded. When administered to laboratory rodents, small volumes of the stock solution are diluted to provide accurate dosing and ease of administration. Because carprofen is formulated for use in companion animals (for example, dogs) and comes in larger volume multidose vials, the majority of carprofen at our institution is discarded before it can be used. In this study, we evaluated the amount of target ingredient present (strength), sterility, and endotoxin levels of both stock and diluted carprofen when stored in a variety of containers and at multiple temperature settings for up to 180 d, mimicking facets of typical use in laboratory animal research and medicine. We demonstrated that when refrigerated and stored in sterile vials, stock and diluted carprofen can be kept and used for up to 180 d while retaining strength and sterility. For short-term use, diluted carprofen can also be stored for up to 60 d at room temperature in conical tubes. These results will help establish scientifically justified storage conditions for carprofen to ensure that these agents remain appropriately potent and sterile for therapeutic use in laboratory animals.

ROS Inhibitory Activity and Cytotoxicity Evaluation of Benzoyl, Acetyl, Alkyl Ester, and Sulfonate Ester Substituted Coumarin Derivatives

Background: A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. Methods: A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Results: Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring “R” played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Conclusion: Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

In silico and in vitro Study of the Inhibitory Effect of Antiinflammatory Drug Betamethasone on Two Lipases

Background: For the first time, the anti-inflammatory drug betamethasone is investigated for its inhibitory activity against lipase. Objective: This work aims to demonstrate the in vitro and in silico inhibitory effect of the anti-inflammatory drug betamethasone on the enzymatic activity of two lipases. Methods: In vitro study using p-nitrophenyllaurate as lipase substrate is used to determine inhibition potency. Molecular Docking is performed using the Autodock Vina for drug molecule and two enzymes Candida rugosa lipase and human pancreatic lipase. Results: Betamethasone represents a moderate inhibition effect with a value of IC50 of 0.36±0.01 mg/ml. Molecular docking allowed us to understand inhibitory – enzyme interactions and to confirm in vitro obtained results. Conclusion: These experiments showed that betamethasone can be used in the treatment of diseases related to lipase activity.