-
Mikrochimica Acta Jun 2024The introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput...
The introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput preparation of modified sensor/biosensors, speeding up the development of the analytical method, and automation of the analytical procedure for the determination of paracetamol (PAR) and dopamine (DOP) as target analytes. Within the preparation of gold nanoparticles modified screen-printed carbon electrode (AuNPs-SPCE) by electrodeposition, the deposition potential E, the deposition time t, and the concentration of HAuCl were optimized and their influence was monitored on 1 mM [Ru(NH)] redox probe and 50 μM DOP. The morphology of the AuNPs-SPCE prepared at various modification conditions was observed by SEM. The analytical performance of the AuNPs-SPCE prepared at different modification conditions was evaluated by a construction of the calibration curves of DOP and PAR. SPCE and AuNPs-SPCE at modification condition providing the best sensitivity to PAR and DOP, were successfully used to determine PAR and DOP in tap water by "spike-recovery" approach. The BES yields better reproducibility of the preparation of AuNPs-SPCE (RSD = 3.0%) in comparison with the case when AuNPs-SPCE was prepared manually by highly skilled laboratory operator (RSD = 7.0%).
Topics: Acetaminophen; Dopamine; Gold; Metal Nanoparticles; Electrochemical Techniques; Electrodes; Biosensing Techniques; Limit of Detection; Carbon
PubMed: 38898321
DOI: 10.1007/s00604-024-06454-6 -
Scientific Reports Jun 2024The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight... (Meta-Analysis)
Meta-Analysis
The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).
Topics: Humans; Abortion, Habitual; Heparin, Low-Molecular-Weight; Female; Pregnancy; Aspirin; Anticoagulants; Randomized Controlled Trials as Topic; Live Birth
PubMed: 38898143
DOI: 10.1038/s41598-024-62949-5 -
Mikrochimica Acta Jun 2024Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting...
Binder-free and efficient voltammetric sensor based on Zn-CaCuO nanoparticles for simultaneous determination of amlodipine, acetaminophen, and ascorbic acid in hypertension patients.
Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting molecules acetaminophen (AP) and ascorbic acid (AA) are recommended for hypertension control and prevention. Considering their therapeutic importance and potential side effects due to over dosage, we have fabricated a sensor for individual and simultaneous determination of AA, AP, and AM in pharmaceuticals and human urine using novel Zn-doped CaCuO nanoparticles modified glassy carbon electrode (GCE). Optimally doped CaCuO (2.5 wt% Zn at Cu site) enhanced the detection of target molecules over much wider concentration ranges of 50 to 3130 µM for AA, 0.25 to 417 µM for AP, and 0.8 to 354 µM for AM with the corresponding lowest detection limits of 14 µM, 0.05 µM, and 0.07 µM, respectively. Furthermore, the Zn-CaCuO/GCE exhibited excellent selectivity and high sensitivity even in the presence of several potential interfering agents. The usefulness of the developed electrode was tested using an amlodipine besylate tablet and urine samples of seven hypertension patients under medication. The results confirmed the presence of a significant amount of AP and AM in six patients' urine samples indicating that the personalized medication is essential and the quantum of medication need to be fixed by knowing the excess medicines excreted through urine. Thus, the Zn-CaCuO/GCE with a high recovery percentage and good sensitivity shall be useful in the pharmaceutical and biomedical sectors.
Topics: Amlodipine; Humans; Ascorbic Acid; Copper; Acetaminophen; Zinc; Hypertension; Electrodes; Electrochemical Techniques; Limit of Detection; Metal Nanoparticles; Nanoparticles; Carbon
PubMed: 38898141
DOI: 10.1007/s00604-024-06473-3 -
Drug Delivery and Translational Research Jun 2024Metamizole easily decomposes in the body and has a short action time and low bioavailability. Hence, frequent injection administrations are needed to maintain its plasma...
Metamizole easily decomposes in the body and has a short action time and low bioavailability. Hence, frequent injection administrations are needed to maintain its plasma concentration. This study aimed to design and develop an in-situ gel based on poloxamer 407 and 188 to assess its long-acting antipyretic effects. The in-situ gel-forming systep00m with optimum sol-gel transition temperature of 35.9 °C to 36.3 °C could be formed using a combination of P407 at a ratio of 21-23% (w/v) and P188 at a ratio of 2-4% (w/v). In vitro erosion test showed that the in-situ gel's erosion curve and the metamizole release rate both reached about 90% at 6 h, revealing a good linear relationship between the in-situ gel erosion and the drug release. In vitro release test with dialysis tube showed that the release of metamizole from the in-situ gel was remarkably slower than that from the metamizole solution. Approximately 85% of metamizole was released in the dialysis tube within 7 h, implying a good sustained release effect. Pharmacodynamic study showed that the in-situ gel injection extended the action time of metamizole relative to that when using the metamizole solution. Pharmacokinetic study revealed that the in-situ gel significantly increased the blood serum half-life and area under the curve), contributing to a sustained release and improved bioavailability. This study demonstrated that in-situ gel injection could prolong the action of metamizole in the body to reduce the number of administration times and has good clinical application.
PubMed: 38896348
DOI: 10.1007/s13346-024-01651-5 -
Molecules (Basel, Switzerland) May 2024Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. var. (Wolff) Shan et Y. Li belongs to the genus and is distinguished for its high level...
Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. var. (Wolff) Shan et Y. Li belongs to the genus and is distinguished for its high level of saikosaponins and volatile oils; nonetheless, prevailing evidence remains inconclusive regarding its viability as an alternative resource of other official species. This study aims to systematically compare the volatile oil components of both dried and fresh roots of var. and the four legally available species across their chemical, molecular, bionics, and anatomical structures. A total of 962 compounds were determined via GC-MS from the dried roots; var. showed the greatest differences from other species in terms of hydrocarbons, esters, and ketones, which was consistent with the results of fresh roots and the e-nose analysis. A large number of DEGs were identified from the key enzyme family of the monoterpene synthesis pathway in var. via transcriptome analysis. The microscopic observation results, using different staining methods, further showed the distinctive high proportion of phloem in var. , the structure which produces volatile oils. Together, these pieces of evidence hold substantial significance in guiding the judicious development and utilization of genus resources.
Topics: Oils, Volatile; Bupleurum; Plant Roots; Gas Chromatography-Mass Spectrometry; Plants, Medicinal
PubMed: 38893436
DOI: 10.3390/molecules29112561 -
International Journal of Molecular... Jun 2024Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment...
Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment among individuals without prior liver ailments. The primary reasons for liver failure are infection with hepatitis virus or overdose of certain medicines, such as acetaminophen. (PT), a type of microalgae known as a diatom species, has been reported to contain an active ingredient with anti-inflammatory and anti-obesity effects. In this study, we evaluated the preventive and therapeutic activities of PT extract in acute liver failure. To achieve our purpose, we used two different acute liver failure models: acetaminophen- and D-GalN/LPS-induced acute liver failure. PT extract showed protective activity against acetaminophen-induced acute liver failure through attenuation of the inflammatory response. However, we failed to demonstrate the protective effects of PT against acute liver injury in the D-GalN/LPS model. Although the PT extract did not show protective activity against two different acute liver failure animal models, this study clearly demonstrates the importance of considering the differences among animal models when selecting an acute liver failure model for evaluation.
Topics: Animals; Acetaminophen; Mice; Chemical and Drug Induced Liver Injury; Microalgae; Disease Models, Animal; Liver Failure, Acute; Male; Protective Agents; Ethanol; Diatoms; Liver; Lipopolysaccharides
PubMed: 38892435
DOI: 10.3390/ijms25116247 -
International Journal of Molecular... May 2024Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis...
Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUV) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUV compared to controls ( = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.
Topics: Animals; Liver Failure, Acute; Acetaminophen; Male; Mice; Mice, Inbred C57BL; Receptors, GABA; Positron-Emission Tomography; Liver; Positron Emission Tomography Computed Tomography; Fluorine Radioisotopes; Radiopharmaceuticals; Disease Models, Animal; Carbazoles
PubMed: 38892130
DOI: 10.3390/ijms25115942 -
Cell Communication and Signaling : CCS Jun 2024Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the...
A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis.
INTRODUCTION
Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity. In this study, we fabricated the hybrid BDEs fused with liposomes containing silymarin (SM) to enhance the synergistic effect on inhibition of acetaminophen-induced hepatotoxicity (APAP).
OBJECTIVE
Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with SM. Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules.
METHODS
Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated.
RESULTS
BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity.
CONCLUSION
From this study, we know that BDEs are reliable and safe nanovesicles containing natural metabolites derived from balloon flower, and they can facilitate intercellular communication. BDEs are also easily modified to enhance drug loading capacity, targeting effects, and long-term accumulation in vivo. BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death and toxicity. They can be efficiently delivered to the liver and effectively inhibit APAP-induced hepatotoxicity by inhibiting the MAPK signaling pathway and apoptosis, which accelerates liver recovery in the APAP-induced acute liver injury model. These findings highlight that BDEs represent an attractive delivery vehicle for drug delivery.
Topics: Acetaminophen; Apoptosis; Animals; Nanoparticles; Exosomes; Hepatocytes; Silymarin; MAP Kinase Signaling System; Mice; Chemical and Drug Induced Liver Injury; Humans; Liposomes; Male; Plant Roots; Mice, Inbred C57BL
PubMed: 38890646
DOI: 10.1186/s12964-024-01700-z -
AAPS PharmSciTech Jun 2024Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply...
Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.
Topics: Powders; Rheology; Drug Contamination; Excipients; Acetaminophen; Cellulose; Pharmaceutical Preparations; Quality Control; Aspirin; Chemistry, Pharmaceutical; Lactose; Drug Compounding; Lubricants; Bulk Drugs
PubMed: 38890193
DOI: 10.1208/s12249-024-02856-0 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries... (Review)
Review
Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid.
PubMed: 38888755
DOI: 10.1007/s00210-024-03240-2