-
Frontiers in Neurology 2023One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms...
One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member () 1, , potassium inwardly rectifying channel, subfamily J, member 11 (), and . A protein-protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target , and . Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for . Compared to normal mice, the expression of , , , and was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.
PubMed: 37483435
DOI: 10.3389/fneur.2023.1175007 -
Journal of Chromatography. B,... Aug 2023A multifunctional mixed-mode β-CD polymer adsorbent PNVCD-SIM containing amphoteric ions and multiple functional groups was prepared. Its physicochemical properties...
A multifunctional mixed-mode β-CD polymer adsorbent PNVCD-SIM containing amphoteric ions and multiple functional groups was prepared. Its physicochemical properties were characterized by scanning electron microscope (SEM), H nuclear magnetic resonance (H NMR), C NMR, Fourier transform infrared spectroscopy (FT-IR), nitrogen adsorption-desorption test, elemental analysis (EA), and thermogravimetry and differential scanning calorimetry (TGA-DSC). The acidic indomethacin and alkaline promethazine were selected to evaluate the adsorption properties of PNVCD-SIM at different pH. Under optimal neutral pH conditions, the adsorption performance of PNVCD-SIM on acidic NSAIDs, alkaline phenothiazine, and neutral steroid hormone drugs was investigated. The results showed that PNVCD-SIM exhibited excellent diversified adsorption properties for acidic, alkaline, and neutral mixed drug components through the synergistic effects of β-CD inclusion, electrostatic interaction, hydrogen bond, π-π conjugation, and π-cation effect. The adsorption mechanism was consistent with the pseudo-second-order kinetic model and Langmuir isotherm model. Under the optimized conditions, a dispersive solid phase extraction method combined with high-performance liquid chromatography (dSPE-HPLC) using PNVCD-SIM as the adsorbent was established. The simultaneous extraction and detection of acidic-alkaline multi-component drugs in actual urine and lake water samples were successfully realized. This study provides new insight into the design and preparation of mixed-mode adsorption materials suitable for the rapid analysis and detection of multiple analytes.
Topics: Polymers; Spectroscopy, Fourier Transform Infrared; Acids; Anti-Inflammatory Agents, Non-Steroidal; Solid Phase Extraction; Adsorption
PubMed: 37473535
DOI: 10.1016/j.jchromb.2023.123833 -
Environmental Science and Pollution... Jul 2023This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar...
Competitive adsorptive removal of promazine and promethazine from wastewater using olive tree pruning biochar: operational parameters, kinetics, and equilibrium investigations.
This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar (BC-OTPR). The impact of individual and combinatory effects of operational variables was evaluated for the first time using central composite design (CCD). Simultaneous removal of both drugs was maximized utilizing the composite desirability function. At low concentrations, the uptake of PRO and PMT from their individual solutions was achieved with high efficiency of 98.64%, 47.20 mg/g and 95.87%, 38.16 mg/g, respectively. No major differences in the removal capacity were observed for the binary mixtures. Characterization of BC-OTPR confirmed successful adsorption and showed that the OTPR surface was predominantly mesoporous. Equilibrium investigations revealed that the Langmuir isotherm model best describes the sorption of PRO/PMT from their individual solutions with maximum adsorption capacities of 640.7 and 346.95 mg/g, respectively. The sorption of PRO/PMT conforms to the pseudo-second-order kinetic model. Regeneration of the adsorbent surface was successfully done with desorption efficiencies of 94.06% and 98.54% for PRO and PMT, respectively, for six cycles.
Topics: Wastewater; Promethazine; Olea; Promazine; Kinetics; Adsorption; Charcoal; Water Pollutants, Chemical; Hydrogen-Ion Concentration
PubMed: 37326738
DOI: 10.1007/s11356-023-27688-6 -
Foods (Basel, Switzerland) May 2023This study aimed to determine promethazine (PMZ) and its metabolites, promethazine sulfoxide (PMZSO) and monodesmethyl-promethazine (NorPMZ), in swine muscle, liver,...
Development and Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method to Determine Promethazine and Its Metabolites in Edible Tissues of Swine.
This study aimed to determine promethazine (PMZ) and its metabolites, promethazine sulfoxide (PMZSO) and monodesmethyl-promethazine (NorPMZ), in swine muscle, liver, kidney, and fat. A sample preparation method and high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were established and validated. The samples were extracted using 0.1% formic acid-acetonitrile and purified with acetonitrile-saturated n-hexane. After concentration by rotary evaporation, the extract was re-dissolved in a mixture of 0.1% formic acid-water and acetonitrile (80:20, /). Analysis was performed using a Waters Symmetry C column (100 mm × 2.1 mm i.d., 3.5 μm) with 0.1% formic acid-water and acetonitrile as the mobile phase. The target compounds were determined using positive ion scan and multiple reaction monitoring. PMZ and NorPMZ were quantified with deuterated promethazine (PMZ-d6) as the internal standard, while PMZSO was quantified using the external standard method. In spiked muscle, liver, and kidney samples, the limits of detection (LOD) and limits of quantification (LOQ) for PMZ and PMZSO were 0.05 μg/kg and 0.1 μg/kg, respectively, while for NorPMZ, these values were 0.1 μg/kg and 0.5 μg/kg, respectively. For spiked fat samples, the LOD and LOQ for all three analytes were found to be 0.05 μg/kg and 0.1 μg/kg, respectively. The sensitivity of this proposed method reaches or exceeds that presented in previous reports. The analytes PMZ and PMZSO exhibited good linearity within the range of 0.1 μg/kg to 50 μg/kg, while NorPMZ showed good linearity within the range of 0.5 μg/kg to 50 μg/kg, with correlation coefficients (r) greater than 0.99. The average recoveries of the target analytes in the samples varied from 77% to 111%, with the precision fluctuating between 1.8% and 11%. This study developed, for the first time, an HPLC-MS/MS method for the determination of PMZ, PMZSO, and NorPMZ in four swine edible tissues, comprehensively covering the target tissues of monitoring object. The method is applicable for monitoring veterinary drug residues in animal-derived foods, ensuring food safety.
PubMed: 37297425
DOI: 10.3390/foods12112180 -
Analytica Chimica Acta Aug 2023Promethazine (PMZ) is an effective antihistamine that is used as a nerve tranquilizer to treat mental disorders. However, drug abuse causes harm to the human body and...
A highly selective and sensitive sensor for promethazine based on molecularly imprinted interface coated Au/Sn bimetal nanoclusters functionalized acupuncture needle microelectrode.
Promethazine (PMZ) is an effective antihistamine that is used as a nerve tranquilizer to treat mental disorders. However, drug abuse causes harm to the human body and also pollutes the environment to a certain extent. Therefore, it is crucial to develop a highly selective and sensitive biosensor for PMZ determination. An acupuncture needle (AN) was used as an electrode in 2015, and further research on the electrode's essence in electrochemistry is needed. In this work, a sensor based on a surface imprinted film coordinated Au/Sn biometal was first fabricated on AN via electrochemistry. The obtained cavities showed complementary and suitable sites for "N atom" electron transfer through the phenyl ring structure in promethazine, which is rigorous for the configuration near the interface. Under the optimal conditions, MIP/Au/Sn/ANE exhibits a good linear relationship in the range of 0.5 μM-500 μM, and the detection limit (LOD) is 0.14 μM (S/N = 3). The sensor exhibits good repeatability, stability, and selectivity and can be successfully used to analyze and detect PMZ in human serum and environmental water. The findings are scientifically significant for AN electrochemistry and the sensors have potential for in vivo medicamentosus monitoring in the future.
Topics: Humans; Microelectrodes; Promethazine; Molecular Imprinting; Electrodes; Needles; Acupuncture Therapy; Limit of Detection; Electrochemical Techniques; Biosensing Techniques
PubMed: 37290856
DOI: 10.1016/j.aca.2023.341395 -
Journal of Chromatographic Science Mar 2024The goal of this study is to provide a single, widely applicable high-performance liquid chromatographic (HPLC) technique for the determination of related substances in...
The goal of this study is to provide a single, widely applicable high-performance liquid chromatographic (HPLC) technique for the determination of related substances in multicomponent oral solution of promethazine hydrochloride and dextromethorphan hydrobromide. For the assessment of impurities of promethazine hydrochloride and dextromethorphan hydrobromide in oral solution, a unique, sensitive, quick, stability-indicating gradient HPLC technique has been created. For chromatographic separation, an Agilent Eclipse XDB-C18, 250 mm × 4.6 mm, 5 μm column was used with a buffered mobile phase consisting of a mixture of potassium dihydrogen phosphate pH 3.0:acetonitrile (80:20) v/v as mobile phase A and potassium dihydrogen phosphate pH 3.0:acetonitrile:methanol (10:10:80) v/v/v as mobile phase B. The separation was performed at a flow rate of 1.2 mL/min and a detection wavelength of 224 nm. The temperature of the column oven was regulated at 40°C. With good sensitivity and resolution, all compounds were effectively separated on a reverse-phase HPLC column. Acid, base, photolytic, thermal, oxidative and humidity stress conditions significantly degraded dextromethorphan hydrobromide and promethazine hydrochloride. The developed technique was validated according to the criteria of the International Conference on Harmonization for all validation parameters such as specificity, accuracy, linearity, precision, the limit of detection, the limit of quantitation and robustness.
Topics: Chromatography, High Pressure Liquid; Promethazine; Dextromethorphan; Acetonitriles; Phosphates; Potassium Compounds
PubMed: 37208993
DOI: 10.1093/chromsci/bmad039 -
CJEM Jun 2023The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The objective of this study was to synthesize indication-based evidence for NO for distress and pain in children.
STUDY DESIGN
We included trials of NO in participants 0-21 years, reporting distress or pain for emergency department procedures. The primary outcome was procedural distress. Where meta-analysis was not possible, we used Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," or "unfavorable" (p < 0.05, supporting NO or comparator, respectively). We used the Cochrane Collaboration's Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate risk of bias and quality of evidence, respectively.
RESULTS
We included 30 trials. For pain using the Visual Analog Scale (0-100 mm) during IV insertion, 70% NO (delta:-16.5; 95%CI:-28.6 to -4.4; p = 0.008; three trials; I = 0%) and 50% NO plus eutectic mixture of local anesthetics (EMLA) (delta:-1.2; 95%CI:-2.1 to -0.3; p = 0.007; two trials; I = 43%) were superior to EMLA. 50% NO was not superior to EMLA (delta:-0.4; 95%CI:-1.2 to 0.3; p = 0.26; two trials; I = 15%). For distress and pain during laceration repair, NO was "favorable" versus each of SC lidocaine, oxygen, and oral midazolam but "neutral" versus IV ketamine (five trials). For distress and pain during fracture reduction (three trials), NO was "neutral" versus each of IM meperidine plus promethazine, regional anesthesia, and IV ketamine plus midazolam. For distress and pain during lumbar puncture (one trial), NO was "favorable" versus oxygen. For distress and pain during urethral catheterization (one trial), NO was "neutral" versus oral midazolam. For pain during intramuscular injection (one trial), NO plus EMLA was "favorable" versus NO and EMLA alone. Common adverse effects of NO included nausea (4.4%), agitation (3.7%), and vomiting (3.6%) AEs were less frequent with NO alone (278/1147 (24.2%)) versus NO plus midazolam (48/52 (92.3%)) and NO plus fentanyl (123/201 (61.2%)).
CONCLUSIONS
There is sufficient evidence to recommend NO plus topical anesthetic for IV insertion and laceration repair. Adverse effects are greater when combined with other sedating agents.
Topics: Child; Adolescent; Humans; Nitrous Oxide; Midazolam; Ketamine; Lacerations; Pain; Anesthetics, Local; Lidocaine, Prilocaine Drug Combination; Oxygen
PubMed: 37171705
DOI: 10.1007/s43678-023-00507-0 -
International Journal of Emergency... May 2023Rhabdomyolysis can occur secondary to infections, trauma, or myotoxic substances. Rhabdomyolysis secondary to autoimmune myositis occurs rarely. Distinguishing...
BACKGROUND
Rhabdomyolysis can occur secondary to infections, trauma, or myotoxic substances. Rhabdomyolysis secondary to autoimmune myositis occurs rarely. Distinguishing autoimmune rhabdomyolysis from rhabdomyolysis secondary to other causes is paramount in considering the long-term management of autoimmune rhabdomyolysis. It is further important to continue close follow-up and further testing to completely understand the extent of this disease as diagnoses may be ever-changing.
CASE PRESENTATION
A previously healthy female presented to the hospital with myalgias and myoglobinuria following a respiratory infection treated with azithromycin and promethazine. Labs demonstrating elevated creatine kinase (CK) prompted treatment for rhabdomyolysis and rheumatology consultation. The patient was given 3 l of intravenous (IV) 0.9% sodium chloride in the Emergency Department. Upon admission, the patient was placed on a continuous IV drip of 0.9% sodium chloride running at 300 cc/hour for all 8 days of her hospital admission. The rheumatology autoantibody panel pointed towards autoimmune myositis as a potential cause of her rhabdomyolysis. The patient was discharged to follow up with rheumatology for further testing.
CONCLUSION
Autoimmune myositis, although less common than other etiologies of rhabdomyolysis, is important to consider as the long-term management of autoimmune myositis includes the use of immunosuppressants, antimalarials, or IV immunoglobulins, which may be inappropriate for other etiologies of rhabdomyolysis.
PubMed: 37170192
DOI: 10.1186/s12245-023-00507-y -
Biofouling Feb 2023This study evaluated the antimicrobial activity of promethazine against , and and its effect on the antimicrobial susceptibility of biofilms grown and on porcine...
This study evaluated the antimicrobial activity of promethazine against , and and its effect on the antimicrobial susceptibility of biofilms grown and on porcine heart valves. Promethazine was evaluated alone and in combination with vancomycin and oxacillin against spp. and vancomycin and ceftriaxone against in planktonic form and biofilms grown and . Promethazine minimum inhibitory concentration range was 24.4-95.31 μg/mL and minimum biofilm eradication concentration range was 781.25-3.125 μg/mL. Promethazine interacted synergistically with vancomycin, oxacillin and ceftriaxone against biofilms . Promethazine alone reduced ( < 0.05) the CFU-counts of biofilms grown on heart valves for spp., but not for , and increased ( < 0.05) the activity of vancomycin, oxacillin and ceftriaxone against biofilms of Gram-positive cocci grown . These findings bring perspectives for repurposing promethazine as adjuvant in the treatment of infective endocarditis.
Topics: Humans; Vancomycin; Anti-Bacterial Agents; Promethazine; Gram-Positive Cocci; Ceftriaxone; Biofilms; Oxacillin; Staphylococcus; Microbial Sensitivity Tests; Endocarditis
PubMed: 37144566
DOI: 10.1080/08927014.2023.2202313 -
Toxicology Jun 2023The current review focuses on the effect of phenothiazine derivatives, tested in vitro, on necrosis and necroptosis, the latter constitutes one of the kinds of... (Review)
Review
The current review focuses on the effect of phenothiazine derivatives, tested in vitro, on necrosis and necroptosis, the latter constitutes one of the kinds of programmed cell death. Necroptosis is a necrotic and inflammatory type of programmed cell death. Phenothiazines are D1 and D2-like family receptor antagonists, which are used in the treatment of schizophrenia. Necroptosis begins from TNF-α, whose synthesis is stimulated by dopamine receptors, thus it can be concluded that phenothiazine derivatives may modulate necroptosis. We identified 19 papers reporting in vitro assays of necroptosis and necrosis in which phenothiazine derivatives, and both normal and cancer cell lines were used. Chlorpromazine, fluphenazine, levomepromazine, perphenazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate necroptosis and necrosis. The type of a drug, concentration and a cell line have an impact on the ultimate effect. Unfortunately, the authors confirmed both processes on the basis of TNF-α and ATP levels as well as the final steps of necrosis/necroptosis related to membrane permeability (PI staining, LDH release, and HMGB1 amount), which makes it impossible to understand the complete mechanism of phenothiazines impact on necroptosis and necrosis. Studies analyzing the effect of phenothiazines on RIPK1, RIPK3, or MLKL has not been performed yet. Only the analysis of the expression of those proteins as well as necrosis and necroptosis inhibitors can help us to comprehend how phenothiazine derivatives act, and how to improve their therapeutic potential.
Topics: Humans; Tumor Necrosis Factor-alpha; Necroptosis; Phenothiazines; Antipsychotic Agents; Necrosis
PubMed: 37127180
DOI: 10.1016/j.tox.2023.153528