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The Science of the Total Environment Aug 2024Developing cost-efficient wastewater treatment technologies for safe reuse is essential, especially in developing countries simultaneously facing water scarcity. This...
Developing cost-efficient wastewater treatment technologies for safe reuse is essential, especially in developing countries simultaneously facing water scarcity. This study developed and evaluated a hybrid constructed wetlands (CWs) approach, incorporating tidal flow (TF) operation and utilising local Jordanian zeolite as a wetland substrate for real pharmaceutical industry wastewater treatment. Over 273 days of continuous monitoring, the results revealed that the first-stage TFCWs filled with either raw or modified zeolite performed significantly higher reductions in Chemical Oxygen Demand (COD, 58 %-60 %), Total Nitrogen (TN, 32 %-37 %), and Phosphate (PO, 46 %-64 %) compared to TFCWs filled with normal sand. Water quality further improved after the second stage of horizontal subsurface flow CWs treatment, achieving log removals of 1.09-2.47 for total coliform and 1.89-2.09 for E. coli. With influent pharmaceutical concentrations ranging from 275 to 2000 μg/L, the zeolite-filled hybrid CWs achieved complete removal (>98 %) for ciprofloxacin, ofloxacin, erythromycin, and enrofloxacin, moderate removal (43 %-81 %) for flumequine and lincomycin, and limited removal (<8 %) for carbamazepine and diclofenac. The overall accumulation of pharmaceuticals in plant tissue and substrate adsorption accounted for only 2.3 % and 4.3 %, respectively, of the total mass removal. Biodegradation of these pharmaceuticals (up to 61 %) through microbial-mediated processes or within plant tissues was identified as the key removal pathway. For both conventional pollutants and pharmaceuticals, modified zeolite wetland media could only slightly enhance treatment without a significant difference between the two treatment groups. The final effluent from all hybrid CWs complied with Jordanian treated industry wastewater reuse standards (category III), and systems filled with raw or modified zeolite achieved over 95 % of samples meeting the highest water reuse category I. This study provides evidence of using hybrid CWs technology as a nature-based solution to address water safety and scarcity challenges.
Topics: Wetlands; Wastewater; Waste Disposal, Fluid; Water Pollutants, Chemical; Jordan; Drug Industry; Zeolites; Biological Oxygen Demand Analysis
PubMed: 38823717
DOI: 10.1016/j.scitotenv.2024.173634 -
International Journal of Pharmaceutics Jun 2024Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is...
Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is one of the most significant areas of clinical medicine and basic research. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. A medicinal preparation is required that relieves the neuropathic pain and prolongs action time, which has not yet been discovered. In this study, MIL-101 (Fe) was employed as a drug carrier to regulate the release of diclofenac sodium, thereby achieving the effect of analgesia and sustained release. The release curves demonstrated that diclofenac sodium could be continuously released from MIL-101 (Fe) for more than 48 h. There was no toxicity in vitro and in vivo, and the safety of MIL-101 (Fe) was confirmed by hematoxylin and eosin as well as ELISA tests in vivo. The results of behavioral testing, pharmacokinetics, and RNA sequencing analysis showed that MIL-101 (Fe) loaded with diclofenac sodium could enhance the mechanical withdrawal threshold and alleviate cold allodynia induced by Spared Nerve Injury, prolonging the work time by three days. The results indicated that MIL-101 (Fe) exhibited excellent biocompatibility, while the MIL-101 (Fe)-DS demonstrated analgesic and controlled-release properties. These findings provide a scientific foundation for the clinical management of neuropathic pain and the development of a novel formulation.
Topics: Animals; Diclofenac; Neuralgia; Male; Rats, Sprague-Dawley; Spinal Cord; Transcriptome; Nanomedicine; Rats; Drug Carriers; Anti-Inflammatory Agents, Non-Steroidal; Drug Liberation; Delayed-Action Preparations; Disease Models, Animal; Hyperalgesia
PubMed: 38821436
DOI: 10.1016/j.ijpharm.2024.124276 -
Chemosphere Aug 2024This study investigated the occurrence, removal rate, and potential risks of 43 organic micropollutants (OMPs) in four municipal wastewater treatment plants (WWTPs) in...
This study investigated the occurrence, removal rate, and potential risks of 43 organic micropollutants (OMPs) in four municipal wastewater treatment plants (WWTPs) in Korea. Results from two-year intensive monitoring confirmed the presence of various OMPs in the influents, including pharmaceuticals such as acetaminophen (pain relief), caffeine (stimulants), cimetidine (H-blockers), ibuprofen (non-steroidal anti-inflammatory drugs- NSAIDs), metformin (antidiabetics), and naproxen (NSAIDs) with median concentrations of >1 μg/L. Some pharmaceuticals (carbamazepine-anticonvulsants, diclofenac-NSAIDs, propranolol-β-blockers), corrosion inhibitors (1H-benzotriazole-BTR, 4-methyl-1H-benzotriazole-4-TTR), and perfluorinated compounds (PFCs) were negligibly removed during WWTP treatment. The OMP concentrations in the influents and effluents were mostly lower in August than those of other months (p-value <0.05) possibly due to wastewater dilution by high precipitation or enhanced biodegradation under high-temperature conditions. The anaerobic-anoxic-oxic process (A2O) with a membrane bioreactor exhibited higher OMP removal than other processes, such as A2O with sedimentation or the conventional activated sludge process (p-value <0.05). Pesticides (DEET and atrazine), corrosion inhibitors (4-TTR and BTR), and metformin were selected as priority OMPs in toxicity-driven prioritization, whereas PFCs were determined as priority OMPs given their persistence and bioaccumulation properties. Overall, our results contribute to an important database on the occurrence, removal, and potential risks of OMPs in Korean WWTPs.
Topics: Wastewater; Republic of Korea; Water Pollutants, Chemical; Waste Disposal, Fluid; Environmental Monitoring; Pharmaceutical Preparations; Metformin; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38821128
DOI: 10.1016/j.chemosphere.2024.142460 -
Journal of Biomaterials Applications May 2024Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into...
BACKGROUND
Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into extended-release versions can effectively address the issue of multiple daily doses. In this study, we designed and synthesized a novel poly(lactic-co-glycolic acid) (PLGA) nanoliposome as a dual-drug delivery sustained-release formulation (PPLs-DS-CEL) to achieve long-lasting synergistic treatment of OA with both DS and CEL.
METHODS
PPLs-DS-CEL was synthesized by the reverse evaporation method and evaluated for its physicochemical properties, encapsulation efficiency, drug release kinetics and biological properties. A rat OA model was established to assess the therapeutic efficacy and biosafety of PPLs-DS-CEL.
RESULTS
The particle size of PPLs-DS-CEL was 218.36 ± 6.27 nm, with a potential of 32.56 ± 3.28 mv, indicating a homogeneous vesicle size. The encapsulation of DS and CEL by PPLs-DS-CEL was 95.18 ± 4.43% and 93.63 ± 5.11%, with drug loading of 9.56 ± 0.32% and 9.68 ± 0.34%, respectively. PPLs-DS-CEL exhibited low cytotoxicity and hemolysis, and was able to achieve long-lasting synergistic analgesic and anti-inflammatory therapeutic effects in OA through slow release of DS and CEL, demonstrating good biosafety properties.
CONCLUSION
This study developed a novel sustained-release nanoliposomes formulation capable of co-loading two drugs for the long-acting synergistic treatment of OA. It offers a new and effective therapeutic strategy for OA treatment in the clinic settings and presents a promising approach for drug delivery systems.
PubMed: 38820587
DOI: 10.1177/08853282241258311 -
Toxicology Letters May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) may cause drug-induced liver injury (DILI). However, the molecular mechanisms underlying NSAIDs hepatotoxicity remain...
Non-steroidal anti-inflammatory drugs (NSAIDs) may cause drug-induced liver injury (DILI). However, the molecular mechanisms underlying NSAIDs hepatotoxicity remain elusive. Dysregulations of bile acids (BAs) have been implicated in various DILI. In this study, we systematically investigated the effects of ibuprofen, the most commonly used NSAID, on BA metabolism and signaling in adult male C57/BL6 mice after oral administration of ibuprofen (IBU) at clinically relevant doses (30, 100, and 200 mg/kg) for one week. Notably, IBU significantly decreased BA concentrations in the liver in a dose-dependent manner, with a concomitant increase in both mRNA and protein expression of cholesterol 7alpha-hydoxylase (CYP7A1), the rate-limiting enzyme for BA synthesis. Mechanically, IBU altered the composition of gut microbiota and increased cecal BAs, leading to reduced intestinal absorption of BAs and thus deactivated ileal farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling. Additionally, diclofenac and indomethacin also induced hepatic Cyp7a1 expression in mice via their effects on gut microbiota and intestinal BA signaling. To conclude, the current findings suggest that NSAIDs-induced liver injury could be at least partially attributable to the dysregulation of BA metabolism and signaling.
PubMed: 38815664
DOI: 10.1016/j.toxlet.2024.05.015 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
Environmental Science and Pollution... Jun 2024This study presents a theoretical analysis of the adsorption process of pharmaceutical pollutants, specifically acetaminophen (ATP) and diclofenac (DFC), onto activated...
This study presents a theoretical analysis of the adsorption process of pharmaceutical pollutants, specifically acetaminophen (ATP) and diclofenac (DFC), onto activated carbon (AC) derived from avocado biomass waste. The adsorption isotherms of ATP and DFC were analyzed using a multilayer model, which revealed the formation of two to four adsorption layers depending on the temperature of the aqueous solution. The saturation adsorption capacities for ATP and DFC were 52.71 and 116.53 mg/g, respectively. A steric analysis suggested that the adsorption mechanisms of ATP and DFC involved a multi-molecular process. The calculated adsorption energies (ΔE and ΔE) varied between 12.86 and 22.58 kJ/mol, with the highest values observed for DFC removal. Therefore, the adsorption of these organic molecules was associated with physisorption interactions: van der Waals forces and hydrogen bonds. These findings enhance the understanding of the depollution processes of pharmaceutical compounds using carbon-based adsorbents and highlight the potential of utilizing waste biomass for environmental remediation.
Topics: Adsorption; Charcoal; Water Pollutants, Chemical; Diclofenac; Pharmaceutical Preparations; Carbon; Acetaminophen
PubMed: 38814558
DOI: 10.1007/s11356-024-33806-9 -
Annals of Medicine Dec 2024Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.
METHODS
We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.
RESULTS
We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity between the studies was low.
CONCLUSIONS
Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
Topics: Humans; Tension-Type Headache; Analgesics; Adult; Network Meta-Analysis; Ibuprofen; Acetaminophen; Bayes Theorem; Treatment Outcome; Diclofenac; Randomized Controlled Trials as Topic; Naproxen; Ketoprofen; Anti-Inflammatory Agents, Non-Steroidal; Female; Male
PubMed: 38813682
DOI: 10.1080/07853890.2024.2357235 -
Cureus Apr 2024In a rural Japanese setting, this case report delves into managing a post-partum woman diagnosed with ankylosing spondyloarthritis (AS), showcasing the complexities of...
In a rural Japanese setting, this case report delves into managing a post-partum woman diagnosed with ankylosing spondyloarthritis (AS), showcasing the complexities of balancing effective pain relief with breastfeeding. The study highlights a multifaceted approach that incorporates medical treatment, psychosocial support, and comprehensive patient education, which are essential in rural healthcare where resources may be scarce. Initially managed with diclofenac due to its safer profile for breastfeeding, the patient's treatment was eventually escalated to adalimumab, aligning with improved circumstances regarding breastfeeding. This case emphasizes the critical role of holistic, patient-centered care in family medicine, particularly for managing maternal and child health chronic conditions. It illustrates how integrating mental health support, acknowledging patient fears, and educating families can significantly enhance patient care and outcomes. Through this approach, the report advocates for a broader application of family medicine principles to improve maternal and child health services in rural settings, demonstrating the importance of tailored healthcare strategies that consider patients' medical and emotional needs.
PubMed: 38807812
DOI: 10.7759/cureus.59187 -
Environmental Toxicology and Chemistry May 2024Pharmaceuticals have been classified as an environmental concern due to their increasing consumption globally and potential environmental impact. We examined the...
Pharmaceuticals have been classified as an environmental concern due to their increasing consumption globally and potential environmental impact. We examined the toxicity of sediment-associated diclofenac and citalopram administered as both single compounds and in a mixture to the sediment-living amphipod Corophium volutator. This laboratory-based study addressed the following research questions: (1) What is the toxicity of sediment-associated diclofenac and citalopram to C. volutator? (2) Can the mixture effect be described with either of the two mixture models: concentration addition (CA) or independent action (IA)? (3) What is the importance of the choice of (i) exposure measure (start concentration, time-weighted average [TWA], full exposure profile) and (ii) effect model (concentration-response vs. the toxicokinetic-toxicodynamic model general unified threshold model for survival in its reduced form [GUTS-RED]) for the derived effect concentration values? Diclofenac was more toxic than citalopram to C. volutator as a single compound (10-day exposure). Diclofenac exposure to C. volutator provided median lethal concentrations (LC50s) within the same range (11 µg g dry wt sediment) using concentration-response based on TWA and both GUTS-RED models. However, concentration-response based on measured start concentrations provided an approximately 90% higher LC50 (21.6 ± 2.0 µg g dry wt sediment). For citalopram, concentration-response parameters were similar regardless of model or concentration used (LC50 85-97 µg g dry wt sediment), however, GUTS-RED with the assumption of individual tolerance resulted in a lower LC50 (64.9 [55.3-74.8] µg g dry wt sediment). The mixture of diclofenac and citalopram followed the CA quite closely, whereas the result was synergistic when using the IA prediction. In summary, concentration-response based on TWA and GUTS-RED provided similar and reasonably good fits compared to the data set. The implications are that GUTS-RED will provide a more flexible model, which, in principle, can extend beyond the experimental period and make predictions based on variable exposure profiles (toxicity at different time frames and at different variable exposure scenarios) compared to concentration-response, which provides contaminant toxicity at one point in time. Environ Toxicol Chem 2024;00:1-11. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
PubMed: 38804665
DOI: 10.1002/etc.5894