With an increasing focus on sustainable technologies in the pharmaceutical industry, milling provides a solvent-free approach to improve drug dissolution. Milling of drugs with an excipient offers additional opportunities to achieve supersaturation kinetics. Therefore, this work aims to present insights of co-milling fenofibrate and apremilast, two good glass formers with low and high glass transition temperatures (Tgs) respectively. Drugs were co-milled with croscarmellose sodium for various process durations followed by thermal analysis, investigation of crystallinity, surface area and dissolution. The dissolution enhancement of the low-Tg glass former fenofibrate highly correlated with the process-induced increase in surface area of co-milled systems (R2 = 0.96). In contrast, the high-Tg glass former apremilast lost its crystalline order gradually after ≥ 10 min of co-milling, and favourable supersaturation kinetics during biorelevant dissolution testing were observed. Interestingly, the melting point of co-milled apremilast decreased and linearly correlated with the highest measured drug concentration (cmax) during in vitro dissolution (onset temperature R2 = 0.98; peak temperature R2 = 0.96). The melting point depression remained stable after 90 days for apremilast, whereas fenofibrate co-milled for 20 min or more showed an increase in melting point upon storage. This study demonstrated that co-milling with croscarmellose sodium is ideally suited to good glass formers with a high Tg. The melting point depression is thereby proposed as an easily accessible critical quality attribute to estimate likely dissolution performance of drugs in dry co-milled formulations.
- MeSH
- Aspirin chemistry analogs & derivatives MeSH
- Fenofibrate * chemistry MeSH
- Excipients chemistry MeSH
- Drug Compounding methods MeSH
- Solubility MeSH
- Glass * chemistry MeSH
- Thalidomide analogs & derivatives MeSH
- Transition Temperature MeSH
- Drug Liberation MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
OBJECTIVE: Emergence delirium (ED) is a postoperative complication in pediatric anesthesia characterized by a perception and psychomotor disorder, with a negative impact on postoperative recovery. As the use of inhalation anesthesia is associated with a higher incidence of ED, we investigated whether titrating the depth of general anesthesia with BIS monitor can reduce the incidence of ED. DESIGN: Randomized, prospective, and double-blind. SETTING: Patients undergoing endoscopic adenoidectomy under general anesthesia according to a uniform protocol. PATIENTS: A total of 163 patients of both sexes aged 3-8 years were enrolled over 18 months. INTERVENTIONS: Immediately after the induction of general anesthesia, a bispectral index (BIS) electrode was placed on the patient's forehead. In the study group, the depth of general anesthesia was monitored with the aim of achieving BIS values of 40-60. In the control group, the dose of sevoflurane was determined by the anaesthesiologist based on MAC (minimum alveolar concentration) and the end-tidal concentration. MEASUREMENTS: The primary objective was to compare the occurrence of ED during the PACU (post-anesthesia care unit) stay in both arms of the study. The secondary objective was to determine the PAED score at 10 and 30 min in the PACU and the need for rescue treatment of ED. MAIN RESULTS: 86 children were randomized in the intervention group and 77 children in the control group. During the entire PACU stay, 23.3% (38/163) of patients developed ED with PAED score >10: 35.1% (27/77) in the control group and 12.8% (11/86) in the intervention group (p = 0.001). Lower PAED scores were also found in the intervention group at 10 (p < 0.001) and 30 (p < 0.001) minutes compared to the control group. The need for rescue treatment did not differ between groups (p = 0.067). CONCLUSION: Individualization of the depth of general anesthesia with BIS monitoring is an effective method of preventing ED in children. CLINICAL TRIAL REGISTRATION: NCT04466579.
- MeSH
- Anesthesia, General * adverse effects MeSH
- Child MeSH
- Anesthesia, Inhalation * adverse effects MeSH
- Humans MeSH
- Emergence Delirium * epidemiology prevention & control etiology MeSH
- Child, Preschool MeSH
- Anesthesia Recovery Period MeSH
- Prospective Studies MeSH
- Sevoflurane MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Electronic waste (e-waste) poses significant environmental and health risks in Thailand due to both domestic production and international imports. A notable portion of this waste is processed in small-scale, community-based workshops, often located in poorer regions, where safety regulations are improperly enforced or entirely ignored. This study focuses on the Kalasin province in Northern Thailand, a region with numerous such workshops, where no comprehensive analysis of exposure to polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DP) has been conducted. The study's objective was to quantify these toxic substances in environmental and biological samples to assess its contamination and human health risks. Environmental samples, including soil, dust, sediment, ash, eggs, crabs, snails, fish, and rice, were collected from e-waste processing sites and compared with control areas. Blood samples from e-waste workers and a control group were also analysed. Gas chromatography coupled with mass spectrometry operated in negative ion chemical ionization (GC-NCI-MS) was used to quantify PBDEs and DP isomers. Results showed significantly higher concentrations of these toxic compounds in e-waste sites compared to control areas. E-waste workers also had elevated levels of these substances in their blood, suggesting exposure through contaminated dust and food. These findings underscore the severe environmental contamination and health risks associated with improper e-waste management, highlighting the urgent need for regulatory measures and improved recycling practices to safeguard both environmental and public health.
- MeSH
- Hydrocarbons, Chlorinated * analysis blood MeSH
- Electronic Waste * analysis MeSH
- Halogenated Diphenyl Ethers * analysis toxicity blood MeSH
- Risk Assessment MeSH
- Environmental Pollutants analysis blood MeSH
- Humans MeSH
- Environmental Monitoring methods MeSH
- Polycyclic Compounds * analysis MeSH
- Dust analysis MeSH
- Occupational Exposure analysis MeSH
- Recycling * MeSH
- Environmental Exposure adverse effects analysis MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Thailand MeSH
Globin adducts of various chemicals, persisting in organism over the whole lifetime of erythrocytes, have been used as biomarkers of cumulative exposures to parent compounds. After removal of aged erythrocytes from the bloodstream, cleavage products of these adducts are excreted with urine as alternative, non-invasively accessible biomarkers. In our biomonitoring studies on workers exposed to ethylene oxide, its adduct with globin, N-(2-hydroxyethyl)valine, and the related urinary cleavage product N-(2-hydroxyethyl)-L-valyl-L-leucine have been determined. To describe a toxicokinetic relationship between the above types of biomarkers, a general compartmental model for simulation of formation and removal of globin adducts has been constructed in the form of code in R statistical computing environment. The essential input variables include lifetime of erythrocytes, extent of adduct formation following a single defined exposure, and parameters of exposure scenario, while other possible variables are optional. It was shown that both biomarkers reflect the past exposures differently as the adduct level in globin is a mean value of adduct levels across all compartments (subpopulations of erythrocytes of the same age) while excretion of cleavage products reflects the adduct level in the oldest compartment. Application of the model to various scenarios of continuous exposure demonstrated its usefulness for human biomonitoring data interpretation.
- MeSH
- Biomarkers * urine blood MeSH
- Models, Biological MeSH
- Biological Monitoring * MeSH
- Erythrocytes * metabolism drug effects MeSH
- Ethylene Oxide toxicity pharmacokinetics urine MeSH
- Globins metabolism MeSH
- Humans MeSH
- Computer Simulation MeSH
- Occupational Exposure * MeSH
- Toxicokinetics MeSH
- Valine analogs & derivatives pharmacokinetics urine blood MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The present study was conducted to scrutinize the pharmacological effect of Estragole (ESG) against CFA-induced arthritis in rats. The rats underwent induction of arthritis using the administration of CFA and after that, the rats were randomly divided into five different groups, where three groups correspond to diverse dosages of ESG, and the other two were control and CFA-arthritic control. Results of the study suggested that ESG in a dose-dependent manner, improves body weight and arthritis score of rats as evidenced by reduction of hind-paw volume. ESG also improved the antioxidant status of rats by reducing MDA levels and enhancing the concentration of endogenous antioxidants SOD and GPx. The level of pro-inflammatory cytokines was also found to be reduced in the case of ESG treated group as compared to CFA-group. In a western blot analysis, ESH showed downregulation of p-JAK-2/STAT-3. The study provided concrete evidence for the protective effect of ESG against rheumatoid arthritis in rats.
- MeSH
- Allylbenzene Derivatives * MeSH
- Anisoles * MeSH
- Antioxidants pharmacology therapeutic use MeSH
- Arthritis, Experimental * chemically induced drug therapy MeSH
- Cytokines metabolism MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Arthritis, Rheumatoid * chemically induced drug therapy MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
A miniature probe for electromembrane extraction is developed and constructed. The tubular probe with an internal volume of 1.1 μL is made of polypropylene hollow fiber with a supported liquid membrane of 85% nitrophenyloctyl ether (NPOE) with 15% bis(2-ethylhexyl)phosphonic acid (DEHP). The probe is connected on-line to the electrophoresis with short separation capillary via an air assisted flow gating interface cast from poly (dimethylsiloxane). The compact instrument is computer controlled via LabView. The probe parameters are tested for extraction of creatinine and basic amino acids from artificial solution and human urine. The sensitivity of the electrophoretic determination after 300 s extraction at 150 V compared to the sensitivity without extraction is 4.9-fold and 2.6-fold higher for creatinine and arginine, respectively. The RSDs for peak area measured from 5 repeated extractions of 50 μM solutions are 7.5%, 7.2%, 8.6% and 9.2% for Crea, Lys, Arg and His, respectively. The probe can be used for all-day measurements. The preparation of the probe is simple and requires no special tool.
- MeSH
- Electrophoresis, Capillary * methods MeSH
- Ethers * chemistry MeSH
- Creatinine MeSH
- Humans MeSH
- Membranes, Artificial MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Many legacy and emerging flame retardants (FRs) have adverse human and environmental health effects. This study reports legacy and emerging FRs in children from nine European countries from the HBM4EU aligned studies. Studies from Belgium, Czech Republic, Germany, Denmark, France, Greece, Slovenia, Slovakia, and Norway conducted between 2014 and 2021 provided data on FRs in blood and urine from 2136 children. All samples were collected and analyzed in alignment with the HBM4EU protocols. Ten halogenated FRs were quantified in blood, and four organophosphate flame retardants (OPFR) metabolites quantified in urine. Hexabromocyclododecane (HBCDD) and decabromodiphenyl ethane (DBDPE) were infrequently detected (<16% of samples). BDE-47 was quantified in blood from Greece, France, and Norway, with France (0.36 ng/g lipid) having the highest concentrations. BDE-153 and -209 were detected in <40% of samples. Dechlorane Plus (DP) was quantified in blood from four countries, with notably high median concentrations of 16 ng/g lipid in Slovenian children. OPFR metabolites had a higher detection frequency than other halogenated FRs. Diphenyl phosphate (DPHP) was quantified in 99% of samples across 8 countries at levels ∼5 times higher than other OPFR metabolites (highest median in Slovenia of 2.43 ng/g lipid). FR concentrations were associated with lifestyle factors such as cleaning frequency, employment status of the father of the household, and renovation status of the house, among others. The concentrations of BDE-47 in children from this study were similar to or lower than FRs found in adult matrices in previous studies, suggesting lower recent exposure and effectiveness of PBDE restrictions.
Advanced solid phase extraction (SPE) fibrous sorbents including polyethylene, polypropylene poly (hydroxybutyrate), and polyamide 6 nanofibers, polycaprolactone microfibers/nanofibers, polycaprolactone microfibers/polyvinylidene difluoride nanofibers, and poly (hydroxybutyrate) microfibers/polypropylene microfibers composites, as well as commercial molecularly imprinted polymers and restricted access media sorbent were compared in terms of bisphenols extraction from milk and their clean-up efficiency. Three on-line SPE-HPLC methods were completely validated for the extraction and detection of bisphenols A, AF, C, A diglycidyl ether, and F diglycidyl ether in bovine milk. Polycaprolactone composite nanofibers compared favorably to restricted access media, enabled excellent clean-up of bisphenols from the proteinaceous matrix, and yielded recoveries 98.0-124.5% and 93.0-115.0%, respectively, with RSD less than 10%. Total analysis time including on-line SPE step lasted only 12 min, which represents a significant reduction in time compared with previously reported as well as official European Union and AOAC methods defined for the determination of bisphenols in various matrices.
- MeSH
- Adsorption MeSH
- Ethers MeSH
- Solid Phase Extraction methods MeSH
- Hydroxybutyrates MeSH
- Milk MeSH
- Molecularly Imprinted Polymers MeSH
- Molecular Imprinting * methods MeSH
- Nanofibers * chemistry MeSH
- Polypropylenes MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
