An optimization approach based on full factorial design was employed for developing an HPLC-UV method for simultaneous determination of a quaternary mixture used for the treatment of symptoms related to common cold and COVID-19. The quaternary mixture is composed of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride. The developed technique is a green, fast and simple method that uses isocratic elution of mobile phase consisting of 20:5:75 (v/v) of ethanol: acetonitrile: 2.5 mM heptane-1-sulphonic acid sodium salt at pH 6.5 [Formula: see text] 0.02. The chromatographic separation was carried out using Hypersil BDS Cyano LC Column (250 × 4.6 mm, 5 μm) with 230 nm UV detection and 1.0 mL/min. flow rate. Avoiding the routine methodology and resorting to the modern technology-represented in the usage of experimental design-allows rapid determination of the four drugs using the optimum quantity of chemicals to avoid any waste of resources. The quaternary mixture was eluted in less than 9 min., where retention times of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride were found to be 2.2, 3.8, 6.6 and 8.8 min., respectively. The calibration graphs of the four drugs were linear over concentration ranges of 50.0-500.0, 0.5-20.0, 0.5-20.0 and 0.5-100.0 µg/mL for paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride, respectively with correlation coefficients higher than 0.999. The method is accurate with mean recoveries between 99.87 and 100.04%, precise, as %RSD for the intraday and interday precision were between 0.61 and 1.64% and very sensitive with limit of detections (LOD)'s between 29 and 147 ng/mL and limit of quantification (LOQ)'s between 95 and 485 ng/mL. The proposed method was successfully applied for the analysis of the four drugs either in raw materials or in prepared tablet with the least amount of chemicals within short time. It is also validated following International Conference on Harmonization Guidelines. The proposed method was found to be green according to the most common greenness assessment tools; NEMI, GAPI, Analytical Eco-Scale and AGREE methods. The advantages of the proposed method qualify it for routine analysis of the studied drugs either in single or co-formulated dosage form in quality control labs.

Children are exposed to various environmental organic and inorganic contaminants with effects on health outcomes still largely unknown. Many matrices (e.g., blood, urine, nail, hair) have been used to characterize exposure to organic and inorganic contaminants. The sampling of feces presents several advantages; it is non-invasive and provides a direct evaluation of the gut microbiome exposure to contaminants. The gut microbiome is a key factor in neurological development through the brain-gut axis. Its composition and disturbances can affect the neurodevelopment of children. Characterization of children exposure to contaminants is often performed on vulnerable populations (e.g., from developing countries, low-income neighborhoods, and large urban centers). Data on the exposure of children from middle-class, semi-urban, and mid-size populations to contaminants is scarce despite representing a significant fraction of the population in North America. In this study, 73 organics compounds from different chemical classes and 22 elements were analyzed in 6 years old (n = 84) and 10 years old (n = 119) children's feces from a middle-class, semi-urban, mid-size population cohort from Eastern Canada. Results show that 67 out of 73 targeted organics compounds and all elements were at least detected in one child's feces. Only caffeine (97% & 80%) and acetaminophen (28% & 48%) were detected in more than 25% of the children's feces, whereas all elements besides titanium were detected in more than 50% of the children.

There is an urgent need for scalable Microphysiological Systems (MPS's)1 that can better predict drug efficacy and toxicity at the preclinical screening stage. Here we present Mera, an automated, modular and scalable system for culturing and assaying microtissues with interconnected fluidics, inbuilt environmental control and automated image capture. The system presented has multiple possible fluidics modes. Of these the primary mode is designed so that cells may be matured into a desired microtissue type and in the secondary mode the fluid flow can be re-orientated to create a recirculating circuit composed of inter-connected channels to allow drugging or staining. We present data demonstrating the prototype system Mera using an Acetaminophen/HepG2 liver microtissue toxicity assay with Calcein AM and Ethidium Homodimer (EtHD1) viability assays. We demonstrate the functionality of the automated image capture system. The prototype microtissue culture plate wells are laid out in a 3 × 3 or 4 × 10 grid format with viability and toxicity assays demonstrated in both formats. In this paper we set the groundwork for the Mera system as a viable option for scalable microtissue culture and assay development.

In the last two decades, extending spin memory in NMR has been used for several purposes. Long-lived states (LLS) or singlet states are one of the first spin memory enhancement techniques used. LLS have the potential to extract structural information and intra- and intermolecular interactions of complex systems other than studying slow phenomenon. The motional regime of β-cyclodextrin (β-CD) drug inclusion complexes generally lies in the intermediate region, where ωτc ≈ 1, and the standard methods of studying these interactions, i.e., NOE and chemical shift monitoring, suffer from insufficient output information. The sensitivity of LLS toward the environmental changes is utilized here to gain insights into the drug assemblies formed by β-CD. One can use change in relaxation of LLS to study the structural changes during complexation. The examples of β-CD with the drugs indomethacin, paracetamol, gliclazide, and CI-933 (a precursor 4-methoxybenzamide) were studied. Indomethacin, paracetamol, and 4-methoxybenzamide show strong interaction through the para-substituted benzene ring, unlike gliclazide. Relaxation of LLS in β-CD-drug complexes is modeled using standard Redfield Relaxation Theory. Computational studies performed support the experimental observations. Docking and molecular dynamics simulation provided the explanation of the relaxation properties of these drug molecules.

Acetaminophen (N-acetyl-p-aminophenol, APAP) is a common antipyretic agent and analgesic. An overdose of APAP can result in acute liver injury (ALI). Oxidative stress and inflammation are central to liver injury. N-acetylcysteine (NAC), a precursor of glutathione, is used commonly in clinical settings. However, the window of NAC treatment is limited, and more efficacious alternatives must be found. Endogenous cytokines such as fibroblast growth factor (FGF) 21 can improve mitochondrial function while decreasing intracellular oxidative stress and inflammatory responses, thereby exhibiting antioxidant-like effects. In this study, self-assembled nanoparticles comprising chitosan and heparin (CH) were developed to deliver FGF21 (CH-FGF21) to achieve the sustained release of FGF21 and optimize the in vivo distribution of FGF21. CH-FGF21 attenuated the oxidative damage and intracellular inflammation caused by APAP to hepatocytes effectively. In a murine model of APAP-induced hepatotoxicity, CH-FGF21 could alleviate ALI progression and promote the recovery of liver function. These findings demonstrated that a simple assembly of CH nanoparticles carrying FGF21 could be applied for the treatment of liver diseases.

Paracetamol is an optimal non-opioid analgesic and holds considerable advantages over NSAIDs in managing post-operative pain. Literature to date doesn't provide substantial documentation of it's efficacy and safety in major oral and maxillofacial surgeries. The study is designed to compare the effectiveness of intravenous paracetamol with diclofenac sodium for controlling post-operative pain and edema in major oral and maxillofacial surgeries.

1H-14N internuclear distances are readily and accurately measured using the symmetry-based phase-modulated resonance-echo saturation-pulse double-resonance (PM-S-RESPDOR) method in rigid solids. The fraction curve, (S0 - S')/S0, is represented by a single variable of a 1H-14N heteronuclear dipolar coupling, where S0 and S' are the PM-S-RESPDOR signal intensity with and without 14N PM saturation pulse, respectively. Analytical equation of the fraction curve easily provides 1H-14N couplings. This treatment is only applicable when NH proton resonance is well separated from the other proton peaks. With the limited 1H resolution even at fast MAS > 60 kHz, unfortunately, this condition is not necessarily satisfied especially in multi-component systems which often appear in pharmaceutical applications. To overcome this problem, T-HMQC filtering is applied to suppress the 1H signals other than NH proton prior to the PM-S-RESPDOR experiments. The method is well demonstrated on two components acetaminophen-oxalic acid (APAP-OXA) systems. Further analysis of orientation dependence of T-HMQC and PM-S-RESPDOR shows that the analytical equation can be safely applied in the analysis of T-HMQC filtered PM-S-RESPDOR experiments.

The overuse of acetaminophen (APAP) may cause more severe hepatotoxicity in patients with non-alcoholic fatty liver disease (NAFLD). Caveolin-1 (CAV1), is an essential regulator of metabolic function, which can alleviate liver damage by scavenging reactive oxygen species (ROS). Evidence suggests that the NOD-like receptor family pyrin domain-containing 3 (NLRP3) -mediated pyroptosis is involved in the development of NAFLD. Moreover, thioredoxin-interactive protein (TXNIP) activation is a key event linking ROS to NLRP3 inflammasome. However, whether CAV1 alleviates APAP-aggravated hepatotoxicity in NAFLD via the ROS/TXNIP/NLRP3 pathway remains unclear. An in vivo fatty liver model was established by feeding mice a high-fat diet for 56 days. Additionally, using in vitro approach, AML-12 cells were incubated with free fatty acids for 48 h and APAP was added during the last 24 h. We found that the overuse of APAP in NAFLD not only induced oxidative stress, but also increased TXNIP expression, NLRP3-mediated pyroptosis, and lipid deposition. In addition to inhibiting ROS generation and lipid deposition, overexpression of CAV1 reduced the elevated levels of TXNIP expression and NLRP3-mediated pyroptosis. However, the effect of CAV1 on TXNIP expression, NLRP3-mediated pyroptosis, and lipid deposition was reversed by CAV1 small interfering RNA (siRNA) intervention. Finally, N-acetyl cysteine (NAC) treatment reduced CAV1 siRNA-mediated changes in TXNIP expression and NLRP3-mediated pyroptosis levels. These results demonstrate that the inhibitory effect of CAV1 on NLRP3-mediated pyroptosis may be mediated through the ROS/TXNIP axis. Moreover, the current study provides novel mechanistic insights into the protective effects of CAV1 on APAP-aggravated hepatotoxicity in NAFLD.

This survey of pediatric ophthalmic surgeons on analgesia for postoperative adult strabismus patients indicates that 65% prescribed acetaminophen and/or nonsteroidal anti-inflammatory drugs (NSAIDs), and 12% to 16% prescribed opioids. Most surgeons reported reasonable control of pain regardless of analgesia. Acetaminophen and/or NSAIDs may adequately control pain, although certain circumstances may warrant opioid prescriptions. [J Pediatr Ophthalmol Strabismus. 2023;60(1):e5-e7.].

Information on the pattern of acute poisonings in hospitals of Birjand city, Iran, is limited. This study aimed to address this knowledge gap by examining the admissions in a major poisoning center in eastern Iran. This cross-sectional study included patients admitted to the Imam Reza Hospital in Birjand over 12 months. Medical records of the poisoned patients were reviewed, and the study variables were used for data analysis. During the study period, 534 cases of acute poisonings were evaluated. The patient's ages ranged from 12 to 84 years, with a high rate of poisonings between 15 and 35 years. The female predominance in poisoning cases was 52.1%. Most cases of poisonings occurred in spring, and the common route of exposure was oral (93.1%). The incidence of poisoning in married couples, uneducated patients, and residents of urban areas was 56.5%, 90.1%, and 74.6%, respectively. Patients with a previous medical history experienced addiction and psychiatric disorders. Intentional poisoning accounted for 23.4% of acute poisoning cases referred to the hospital in the current study. The main groups of toxicants were pharmaceutical products (48.1%), narcotics (25.8%), chemical products (10.1%), envenomation (7.1%), and alcohol (1.7%). The mean hospital stay was 2.5 ± 3.0 days, and the final treatment outcome was complete recovery, except for one patient intoxicated by warfarin and alprazolam. Our results indicate that the high toxicity cases were related to pharmaceutical product and opioids abuse, especially methadone (8.4%), alprazolam (7.9%), clonazepam (7.5%), and acetaminophen (9.9%) taken orally and more commonly happened at home. Due to the high rate of deliberate poisonings, especially among young adults and students, monitoring drug distribution and exceptional attention to mental health should be seriously considered by national health authorities to prevent suicide attempts.

Analytical techniques must be sensitive, specific, and accurate in order to assess the active pharmaceutical ingredients in pharmaceutical dosage forms. The Quality by Design (QbD) application has proven to be a practical method for magnifying HPLC operations. This article discusses the successfully developed QbD-based stability-indicative LC method for evaluating acetaminophen, caffeine, and aspirin in tablet dosage form. To achieve the necessary chromatographic separation, milli-Q water, methanol, and glacial acetic acid were employed in the following ratios: 63:35:2 (v/v/v) for mobile phase-A and 18:80:2 (v/v/v) for mobile phase-B, respectively. The flow rate, column temperature, and detecting wavelength were 1.0 mL min-1 , 40° C, and 275 nm, respectively, with Inert sustain C18, (150 × 4.6mm), 3 μm analytical column. Linearity between 10.0 and 150.0 μgmL-1 of aspirin and acetaminophen and 2.6 to 39.0 μg mL-1 of caffeine. The accuracy findings were more than 97%, and the correlation coefficient for all three components was found to be greater than 0.999. The validated HPLC methodology yielded reliable and accurate results. Aspirin was shown to be very vulnerable to both acid and alkaline hydrolysis in the forced degradation study. The described method is capable of separating the degradants produced during stress testing and is regarded as stability-indicating. The proposed method can be used for a wider range of other formulations with an appropriate diluent selection and sample preparation procedure optimization.

Binding of therapeutics to proteins in blood plasma is important in influencing their distribution as it is their free (unbound) form that is able to cross cellular membranes to enter tissues and exert their actions. The concentration and composition of plasma proteins vary during pregnancy and development, resulting in potential changes to drug protein binding. Here, we describe an ultrafiltration method to investigate the extent of protein binding of six drugs (digoxin, paracetamol, olanzapine, ivacaftor, valproate and lamotrigine) and two water soluble inert markers (sucrose and glycerol) to plasma proteins from pregnant and developing rats. Results showed that the free fraction of most drugs was lower in the non-pregnant adult plasma where protein concentration is the highest. However, plasma of equivalent protein concentration to younger pups obtained by diluting adult plasma did not always exhibit the same extent of drug binding, reinforcing the likelihood that both concentration and composition of proteins in plasma influence drug binding. Comparison between protein binding and brain drug accumulation in vivo revealed a correlation for some drugs, but not others. Results suggests that plasma protein concentration should be considered when using medications in pregnant and paediatric patients to minimise potential for fetal and neonatal drug exposure.

[This retracts the article DOI: 10.1155/2022/1794258.].

Acetaminophen (APAP) overdose is a leading cause of acute liver injury in the USA. The chitinase 3-like-1 (Chi3l1) protein contributes to APAP-induced liver injury (AILI) by promoting hepatic platelet recruitment. Here, we report the development of a Chi3l1-targeting antibody as a potential therapy for AILI. By immunizing a rabbit successively with the human and mouse Chi3l1 proteins, we isolated cross-reactive monoclonal antibodies (mAbs) from single memory B cells. One of the human and mouse Chi3l1 cross-reactive mAbs was humanized and characterized in both in vitro and in vivo biophysical and biological assays. X-ray crystallographic analysis of the lead antibody C59 in complex with the human Chi3l1 protein revealed that the kappa light contributes to majority of the antibody-antigen interaction; and that C59 binds to the 4α-5β loop and 4α-helix of Chi3l1, which is a functional epitope and hotspot for the development of Chi3l1 blocking antibodies. We humanized the C59 antibody by complementarity-determining region grafting and kappa chain framework region reverse mutations. The humanized C59 antibody exhibited similar efficacy as the parental rabbit antibody C59 in attenuating AILI in vivo. Our findings validate Chi3l1 as a potential drug target for AILI and provide proof of concept of developing Chi3l1 blocking antibody as a therapy for the treatment of AILI.

Wood-rotting fungi and their enzymatic systems represent promising biocatalysts for the removal of pharmaceuticals and personal care products (PPCPs) from wastewater. We designed a fungal wheel reactor (FWR) based on solid-state fermentation (SSF) of Trametes versicolor and a lignocellulosic substrate, which was used as an immobilization carrier for fungal biomass and the sole initial nutrient source for producing fungal oxidative enzymes. Three pharmaceutical and personal care products, acetaminophen, bisphenol A and carbamazepine, were spiked into the synthetic wastewater and the treatment was carried out under non-sterile conditions. Acetaminophen was completely removed from the FWR until laccase was observed. The acetaminophen removal efficiency was retrieved by replacing the fungal wheel with fresh SSF products. Bisphenol A and carbamazepine were removed via enzymatic activity and adsorption. When the fungal wheel was replaced, acetaminophen began to be completely removed, even after laccase depletion. The microbial community analysis indicated that the continuous removal of acetaminophen was mainly due to the high proportion of T. versicolor. The relative abundance of the co-occurring microbial community might be responsible for the divergence in acetaminophen removal between two of fungal wheel-replaced reactors. Overall, FWRs are promising tools for the removal of PPCPs by highly reactive enzymatic mechanisms as well as adsorption on the carrier surface. By replacing SSF and settled microbial communities, FWRs may continuously contribute to bioremediation over a long-term period.

Escherichia coli is one of the main indicators in the quality control of water, pharmaceuticals, and other samples. Compared with the time-consuming and high prices of the classical methods, with their high risks in the case of insensitive, contamination and offline detections, biosensors have long been a fast and accurate approach for identifying different bacteria. The present study reports the development of a newly electrochemical biosensor using a glassy carbon electrode (GCE) modified by multi-walled carbon nanotubes/AuNPs/E. coli polyclonal antibody/Bovine Serum Albumin in 0.1 M phosphate-buffered saline (pH 7) in the presence of acetaminophen, for the detection of E. coli in pharmaceuticals and some real samples. Acetaminophen was added as an indicator for the detection of E. coli by changes in conductivity and current. To identify E. coli, square-wave voltammetry (SWV), differential pulse voltammetry (DPV), and cyclic voltammetry (CV) techniques were used. According to the obtained results of square-wave voltammetry, a limit of 3.02 CFU/ml E. coli detection in 3 min with desirable sensitivity, repeatability, and reproducibility was found with the designed biosensor. This biosensor could be a powerful tool for the detection of indicator bacteria in the food industry, drug safety, quality control, clinical diagnostics, and environmental monitoring.