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ACS Omega Oct 2023Eutectic solvent systems are versatile solvents that have found widespread use in numerous applications. Traditional solvents are homogeneous, having only one component,...
Eutectic solvent systems are versatile solvents that have found widespread use in numerous applications. Traditional solvents are homogeneous, having only one component, and their chemistry is relatively simple, with some exceptions. On the other hand, deep eutectic solvents (DESs) comprise binary components, generally a donor and an acceptor in hydrogen bonding with varying ratios. The interaction chemistry among the donor and acceptor involved in hydrogen bonding in DESs is complicated. Although numerous research is focused on the synthesis and application of DESs, few studies are reported to elucidate the complex structure and dynamic and interaction behavior of DESs. In this study, we employed calorimetry, vibrational spectroscopy techniques including FTIR and Raman, and nuclear magnetic resonance to derive insight into the structural feature and noncovalent contact of choline chloride (ChCl) and citric acid (CA) while they formed DESs. The 1:1 ChCl/CA eutectic system showed phase transitions and melting peaks with the most pronounced peak at 156.22 °C, suggesting the DESs melting at a lower temperature than the melting temperatures of ChCl and CA. In addition to IR and Raman findings, H NMR investigations demonstrate hydrogen bonding intermolecular interactions between ChCl and CA, supporting the formation of 1:1 ChCl/CA DESs based on the deshielded chemical shifts of the proton for Ch. The interaction of the chloride anion with the methyl protons (H4) and methylene protons (H3) of ChCl as well as the strong hydrogen bonding interactions between the hydroxyl hydrogen (H1) of ChCl with one of CA's carbonyl oxygens both supported the formation of conformer E. In addition, molecular dynamics followed by the density functional theory (DFT) was employed to visualize the structure and interaction of DESs using the ωB97XD theory and 6-311++G (d,p) basis set. Both experimental and theoretical IR, Raman, and structural analyses provided evidence of the formation of DESs by possessing hydrogen bonds. These multifaceted experimental and computational investigations provide details of structural and intermolecular interactions of ChCl/CA DESs.
PubMed: 37867676
DOI: 10.1021/acsomega.3c04570 -
International Urogynecology Journal Dec 2023Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION AND HYPOTHESIS
Dysuria is a common symptom present in several urological and gynecological conditions. Management relies on the underlying disease but may require additional symptomatic treatment. This study evaluated the combination of methenamine 250 mg and methylthioninium chloride 20 mg in the treatment of dysuria versus phenazopyridine.
METHODS
This was a multicenter, single-blind, randomized, superiority clinical trial, including individuals over 18 with dysuria and a score ≥ 5 points on the pre-treatment categorical scale for pain. The primary outcome was the proportion of participants presenting excellent clinical response within 24 h after treatment. Improvement up to 72 h, time to reach improvement, sustained healing, investigators' opinion, and safety were also evaluated.
RESULTS
Three hundred and fifteen participants were evaluated. Demographic characteristics and symptoms of dysuria were comparable between groups at baseline. The difference in the excellent response rate between treatments within 24 h was 12.7% (95% CI 6.16, 19.21) for pain, 9.4% (95% CI 3.32, 15.39) for burning, and 12.7% (95% CI 6.37, 18.99) for burning on urination, all in favor of the test drug, which was also superior from 36 to 48 h. Treatments were similar concerning time to reach the absence of symptoms and in the percentage of participants with sustained healing after 72 h.
CONCLUSIONS
The association of methenamine with methylthioninium is superior to phenazopyridine in the treatment of dysuria.
Topics: Humans; Dysuria; Methenamine; Methylene Blue; Pain; Phenazopyridine; Single-Blind Method; Adult
PubMed: 37851092
DOI: 10.1007/s00192-023-05669-0 -
Molecules (Basel, Switzerland) Oct 2023The recent rapid growth of the battery industry has led to a rapid increase in methylene chloride emissions. Methylene chloride causes health and social problems in...
The recent rapid growth of the battery industry has led to a rapid increase in methylene chloride emissions. Methylene chloride causes health and social problems in humans. In this study, cellulose-based activated carbon fibers (CACFs) with improved yield were prepared for the removal of methylene chloride. The concentration of ammonium phosphate in the pretreatment controlled the crosslink density of cellulose fibers and improved the yield. From the results, the specific surface area and total pore volume of cellulose-based activated carbon fibers pretreated with ammonium phosphate (AP-CACFs) were determined to be 1920-2060 m/g and 0.83-1.02 cm/g, respectively, and the total yield improved by 6.78-11.59% compared to that of CACFs (4.97%). In particular, a correlation between the textural properties of CACFs and methylene chloride adsorption/desorption behavior was obtained. This correlation can be used to develop efficient adsorbents for methylene chloride removal.
PubMed: 37836838
DOI: 10.3390/molecules28196997 -
Animals : An Open Access Journal From... Oct 2023Besides living as a free-ranging primate in the horn of Africa and the Arabian Peninsula, the hamadryas baboon has an important place in zoos and can be found in...
Besides living as a free-ranging primate in the horn of Africa and the Arabian Peninsula, the hamadryas baboon has an important place in zoos and can be found in biomedical research centers worldwide. To be valuable as a non-human primate laboratory model for man, its anatomy should be portrayed in detail, allowing for the correct interpretation and translation of obtained research results. Reviewing the literature on the use of the baboon in biomedical research revealed that very limited anatomical works on this species are available. Anatomical atlases are incomplete, use archaic nomenclature and fail to provide high-definition color photographs. Therefore, the skeletons of two male hamadryas baboons were prepared by manually removing as much soft tissues as possible followed by maceration in warm water to which enzyme-containing washing powder was added. The bones were bleached with hydrogen peroxide and degreased by means of methylene chloride. Photographs of the various bones were taken, and the anatomical structures were identified using the latest version of the Nomina Anatomica Veterinaria. As such, the present article shows 31 annotated multipanel figures. The skeleton of the hamadryas baboon generally parallels the human skeleton, but some remarkable differences have been noticed. If these are taken into consideration when evaluating the results of experiments using the hamadryas baboon, justified conclusions can be drawn.
PubMed: 37835730
DOI: 10.3390/ani13193124 -
Biomedicine & Pharmacotherapy =... Nov 2023Clivia miniata (Lindl) is a member of the family Amaryllidaceae known for its chemically diverse alkaloids with a wide range of biological activities. Many reports...
Clivia miniata (Lindl) is a member of the family Amaryllidaceae known for its chemically diverse alkaloids with a wide range of biological activities. Many reports revealed a direct role of oxidative stress in the early stage of Alzheimer's disease (AD). Meanwhile, β-site amyloid precursor protein cleavage enzyme 1 (BACE-1) is a molecular target for the treatment of AD. We aimed to investigate C. miniata root, bulb, and aerial part chemical profiling, antioxidant, BACE-1, and AChE enzyme inhibitory activities. Results showed that the total root had the most potent radical scavenging activity as compared to the total bulb and aerial part, respectively. Ethanol root extract had the most potent BACE-1 inhibitory activity (IC = 0.02 ± 0.001 µg/mL) as compared to the bulb and aerial part (IC = 0.93 ± 0.13, 1.80 ± 0.24 µg/mL), respectively. Moreover, the total root extract mitigated AChE enzyme activity more than total bulb and aerial fractions with IC values of (0.06 ± 0.02, 0.58 ± 0.3, and 1.89 ± 0.42 µg/mL, respectively. Bioassay-guided acid-base fractionation confirmed superior BACE-1 inhibitory activity of the root fractions particularly, methylene chloride and ethyl acetate fractions with (IC values of 0.21 ± 0.60 and 0.01 ± 0.001 µg/mL), respectively. UPLC-MS analysis of ethyl acetate and methylene chloride fractions of C. miniata root led to the identification of eight phenolics and thirteen alkaloids, respectively. Molecular docking studies against BACE-1 protein revealed that lycorine di-hexoside, miniatine, and cliviaaline were the most promising hits. Further investigation of anti-AD potential of the aforementioned small molecules is required.
Topics: Antioxidants; Molecular Docking Simulation; Chromatography, Liquid; Methylene Chloride; Tandem Mass Spectrometry; Alkaloids; Plant Extracts; Alzheimer Disease; Plant Components, Aerial; Amaryllidaceae; Cholinesterase Inhibitors
PubMed: 37778271
DOI: 10.1016/j.biopha.2023.115382 -
International Journal of Molecular... Sep 2023Methylthioninium chloride (MTC) is a standard treatment for methaemoglobinaemia. A preparation of reduced MTC has been reported to increase blood oxygen saturation (SpO)...
Methylthioninium chloride (MTC) is a standard treatment for methaemoglobinaemia. A preparation of reduced MTC has been reported to increase blood oxygen saturation (SpO) and lower respiratory rates in patients with severe COVID-19. We have developed a stable form of reduced methylthionine (hydromethylthionine-mesylate, HMTM) having a benign safety profile in two Phase 3 trials in Alzheimer's disease. The aim of this prospective study was to determine the effects of oral HMTM on SpO and methaemoglobin (metHb) levels in a cohort of patients with mild hypoxaemia not due to COVID-19. Eighteen participants randomised to a single dose of 4, 75, 100 or 125 mg doses of HMTM had SpO levels below 94% at baseline. Patients were routinely monitored by pulse oximetry after 4 h, and after 2 and 6 weeks of twice daily dosing. Significant ~3% increases in SpO occurred within 4 h and were sustained over 2 and 6 weeks with no dose differences. There were small dose-dependent increases (0.060-0.162%) in metHb levels over 2 to 6 weeks. Minimum-energy computational chemistry revealed that HMT can bind within 2.10 Å of heme iron by donating a pair of electrons from the central nitrogen of HMT to orbitals of heme iron, but with lower affinity than oxygen. In conclusion, HMTM can increase SpO without reducing metHb by acting as a strong displaceable field ligand for heme iron. We hypothesise that this facilitates a transition from the low oxygen affinity T-state of heme to the higher affinity R-state. HMTM has potential as an adjunctive treatment for hypoxaemia.
Topics: Humans; Methylene Blue; Prospective Studies; COVID-19; Oxygen; Heme; Methemoglobin; Hypoxia; Iron
PubMed: 37762050
DOI: 10.3390/ijms241813747 -
ACS Omega Sep 2023Methylene blue (MB) dye or methyl thioninium chloride is one of the hazardous cationic dyes that are discharged into the textile effluent causing a highly negative...
Methylene blue (MB) dye or methyl thioninium chloride is one of the hazardous cationic dyes that are discharged into the textile effluent causing a highly negative environmental impact. The present work targets the investigation of the adsorption performance of some chitosan-modified products toward the MB dye from simulated solutions. The claimed chitosan derivatives were prepared, characterized, and applied for the removal of lead and copper cations from an aqueous medium in a previous work. These include: ,-carboxymethyl chitosan (,-CM/Cs), chitosan grafted with glutaraldehyde (Cs/GA), chitosan cross-linked with GA/epichlorohydrin (Cs/GA/ECH), and chitosan cross-linked with glutaraldehyde/methylene bis(acrylamide) (Cs/GA/MBA). The modified chitosan derivatives in this study displayed outstanding mechanical qualities, exceptional reusability, and a significant amount of adsorption capacity. The ability of prepared Cs derivatives to eradicate MB was as follows: ,-CM/Cs (95.1 mg/g) < Cs/GA (120.1 mg/g) < Cs/GA/ECH (220.1 mg/g) < Cs/GA/MBA (270.0 mg/g). The swelling performance of the prepared sorbents was verified under different experimental conditions, and the data revealed that the maximum swelling was attained at pH = 9, temperature 55 °C, and after 24 h. The produced Cs derivatives showed exceptional reusability by maintaining higher adsorption effectiveness throughout five cycles. The MB dye was adsorbed onto the modified derivatives according to pseudo-second-order kinetics and the Langmuir model. Moreover, the adsorption process was monitored via atomic force microscopy to verify the differences between the dye-free and dye-loaded adsorbents.
PubMed: 37744862
DOI: 10.1021/acsomega.3c03735 -
Se Pu = Chinese Journal of... Sep 2023Khat is a common plant that grows primarily in Eastern Africa and the Arabian Peninsula. Cathinone, norpseudoephedrine, and norephedrine are the main psychoactive...
Khat is a common plant that grows primarily in Eastern Africa and the Arabian Peninsula. Cathinone, norpseudoephedrine, and norephedrine are the main psychoactive components of khat. Experimental studies have shown that red and green khat have similar cathinone contents, but green khat contains more norpseudoephedrine and norephedrine than red khat. Research indicates that Ethiopians believe that red khat has stronger psychoactive effects than green khat. Therefore, we speculated that other substances in red khat may enhance its psychoactive effects. Using the sampling method, we identified two other psychoactive components in khat: methcathinone and ethcathinone. At present, only a few studies on the extraction and detection of alkaloids from khat have been published in China, and no reports on the extraction and detection of methcathinone and ethcathinone from khat are available. In this study, we established an extraction and detection method for five alkaloids in dried khat using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS). To establish the extraction method, we optimized the extraction solvent and process. The amounts of dichloromethane and sodium hydroxide added during the purification step were also optimized. To establish the detection method, we optimized the chromatographic and MS conditions. The final extraction and detection method was as follows: Dried khat powder (0.1 g) was loaded into a polypropylene centrifuge tube, added with 1 mL of 0.05 mol/L hydrochloride aqueous solution, and vortex-oscillated for 3 min for extraction. The sample was centrifuged at 10000 r/min for 3 min. Next, 600 μL of the supernatant was placed in a centrifuge tube, added with 1 mL of dichloromethane, shaken for 1 min, and centrifuged at 10000 r/min for 3 min. Subsequently, 300 μL of the supernatant was placed in a centrifuge tube, added with 80 μL of 1 mol/L sodium hydroxide aqueous solution, shaken for 1 min, and added with 1 mL of acetonitrile. Vortex oscillation was performed for 2 min to extract the sample, after which solid sodium chloride (0.4 g) was added to the mixture, followed by shaking for 1 min to separate the acetonitrile and aqueous phases. The mixture was then centrifuged at 10000 r/min for 3 min. Finally, the supernatant was collected and diluted for further testing. The five target analytes were separated on a ZORBAX Eclipse Plus Phenyl-Hexyl column (100 mm×3.0 mm, 1.8 μm) via gradient elution using 0.1% acetic acid aqueous solution and acetonitrile as mobile phases with a flow rate of 0.3 mL/min and column temperature of 30 ℃. The analytes were identified using the targeted MS/MS method under positive electrospray ionization mode and quantified using the external standard method. The five alkaloids showed good correlations (all correlation coefficients ()≥0.9976) with their respective linear ranges. The limits of detection were between 0.08 and 0.75 μg/L, and the limits of quantification were between 0.25 and 2.50 μg/L. The average recoveries of the five alkaloids from two plants with different alkaloid contents were between 90.7% and 105.2%. The intra-sample precision ranged from 0.5% to 2.3%, the intra-day precision was between 1.0% and 2.5%, and the inter-day precision was between 1.3% and 3.3%. Using the developed method, we extracted and analyzed 15 khat samples, and detected five alkaloids. This method enables rapid sample pretreatment and has high sensitivity, good stability, and suitable accuracy. Based on the above results, we conclude that the proposed method meets the inspection and identification requirements for khat. Thus, it can provide a valuable reference for the physical and chemical identification of khat and support for further studies on its psychoactive components.
Topics: Humans; Tandem Mass Spectrometry; Catha; Chromatography, High Pressure Liquid; Methylene Chloride; Sodium Hydroxide; Alkaloids; Acetonitriles
PubMed: 37712541
DOI: 10.3724/SP.J.1123.2023.03009 -
Acta Pharmaceutica (Zagreb, Croatia) Sep 2023Riolozatrione (RZ) is a diterpenoid compound isolated from a dichloromethane extract of the root. This compound has been shown to possess moderate antiherpetic activity...
Riolozatrione (RZ) is a diterpenoid compound isolated from a dichloromethane extract of the root. This compound has been shown to possess moderate antiherpetic activity . However, because of the poor solubility of this compound in aqueous vehicles, generating a stable formulation for potential use in the treatment of infection is challenging. The aim of this work was to optimize and physio-chemically characterize Eudragit L100-55-based polymeric nanoparticles (NPs) loaded with RZ (NPR) for antiherpetic application. The NPs formulation was initially optimized using the dichloromethane extract of , the major component of which was RZ. The optimized NPR formulation was stable, with a size of 263 nm, polydispersity index < 0.2, the zeta potential of -37 mV, and RZ encapsulation efficiency of 89 %. The NPR showed sustained release of RZ for 48 h with release percentages of 95 and 97 % at neutral and slightly acidic pH, respectively. Regarding antiherpetic activity, the optimized NPR showed a selectivity index for HSV-1 of ≈16 and for HSV-2 of 13.
Topics: Methylene Chloride; Diterpenes; Excipients; Nanoparticles; Polymers
PubMed: 37708959
DOI: 10.2478/acph-2023-0028 -
Cureus Aug 2023Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified... (Review)
Review
Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.
PubMed: 37664357
DOI: 10.7759/cureus.42854