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Journal of Neurological Surgery Reports Jul 2024Alpha-gal syndrome (AGS) is an immunoglobulin E-mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate...
Alpha-gal syndrome (AGS) is an immunoglobulin E-mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate mammalian products. Initial exposure to alpha-gal most often occurs through a tick bite, most commonly the lone star tick in the United States. Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis. The allergy restricts dietary intake and may significantly impact perioperative risk, as many medications, anesthetics, and intraoperative surgical products utilize bovine or porcine-derived agents, including those containing magnesium stearate, glycerol, and gelatin. Here, we review the perineurosurgical care of two individuals with AGS and highlight pertinent clinical practices and perioperative management of these patients.
PubMed: 38957306
DOI: 10.1055/a-2341-7365 -
Chemical & Pharmaceutical Bulletin 2024In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry...
In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.
Topics: Tablets; Particle Size; Drug Compounding; Powders; Stearic Acids; Tensile Strength; Excipients; Solubility
PubMed: 38945947
DOI: 10.1248/cpb.c23-00801 -
Frontiers in Bioscience (Elite Edition) Jun 2024Due to the constant and improper use of chemicals, including pesticides, many substances, and their degradation products can accumulate in the soil and negatively affect...
BACKGROUND
Due to the constant and improper use of chemicals, including pesticides, many substances, and their degradation products can accumulate in the soil and negatively affect its organisms.
METHODS
In this study, morphological methods, Gram-staining, and Matrix-Assisted Laser Desorption/Ionzation Time of Flight Mass Spectrometry (MALDI-TOF MS) methods were used to isolate bacteria from agricultural soils, while genetic identification was conducted using 16S rRNA. The density of bacteria was determined using the spectrophotometric method, and the residual amount of cypermethrin was determined and analyzed using Gas chromatograohy-mass spectrometry (GC-MS) methods.
RESULTS
Nine isolates were obtained from various agricultural soils. Isolate No. 3 showed the greatest effectiveness against cypermethrin and was selected for further research. Isolate No. 3 was identified as the strain PDB-3 and was registered in the National Center for Biotechnology Information (NCBI) database (GenBank: OL587509.1). Using this strain, the influence of various external factors on the degradation of cypermethrin was studied. This bacterium demonstrated 100% degradation of cypermethrin in 20 days under optimal conditions (temperature: 30 °C; optical density (OD) = 0.2; cypermethrin concentration: 80 ± 0.02 mg/kg). In addition, PDB-3 changed the original structure of cypermethrin into various intermediate metabolites, such as 2-hydroxy-3-phenoxy benzeneacetonitrile, 3-phenoxybenzaldehyde, 3-phenoxybenzaldehyde, methyl stearate, anethol, citral, and phenol.
CONCLUSIONS
The results obtained using PDB-3 provide the basis for large-scale field trials on the bioremediation of cypermethrin-contaminated soils.
Topics: Pyrethrins; Ochrobactrum; Pesticides; Biodegradation, Environmental; Soil Microbiology; Gas Chromatography-Mass Spectrometry; RNA, Ribosomal, 16S; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 38939915
DOI: 10.31083/j.fbe1602020 -
Bioorganic Chemistry Jun 2024The antifungal bioactivity potential of the organic extract of silk tree (Albizia kalkora) was investigated in the current study. The crude extracts of A. kalkora and...
The antifungal bioactivity potential of the organic extract of silk tree (Albizia kalkora) was investigated in the current study. The crude extracts of A. kalkora and methanol, n-hexane, chloroform, and ethyl acetate fractions were prepared. The antifungal activity of obtained fractions of A. kalkora was studied at different concentrations ranging from 0.39-50 µg/mL. Dimethyl sulfoxide (DMSO) was taken as a toxicity control, whereas thiophanate methyl (TM) as a positive control. All the fractions significantly reduced the FOL growth (methanolic: 9.49-94.93 %, n-hexane: 11.12-100 %, chloroform: 20.96-91.41 %, and ethyl acetate: 18.75-96.70 %). The n-hexane fraction showed 6.25 µg/mL MIC as compared to TM with 64 µg/mL MIC. The non-polar (n-hexane) fraction showed maximum antifungal bioactivity against FOL in comparison with chloroform, methanol, and ethyl acetate fractions. GC/MS analysis exhibited that the n-hexane fraction contained hexadecanoic acid, 9,12,15-octadecatrienoic acid, 9,12-octadecadienoic acid, bis(2-ethylhexyl) phthalate, methyl stearate, and [1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic acid. The results of in vitro antifungal inhibition were further reinforced by molecular docking analysis. Five virulence proteins of FOL i.e., pH-responsive PacC transcription factor (PACC), MeaB, TOR; target of rapamycin (FMK1), Signal transducing MAP kinase kinase (STE-STE7), and High Osmolarity Glycerol 1(HOG1) were docked with identified phytocompounds in the n-hexane fraction by GC/MS analysis. MEAB showed maximum binding affinities with zinnimide (-12.03 kcal/mol), HOG1 and FMK1with α-Tocospiro-B (-11.51 kcal/mol) and (-10.55 kcal/mol) respectively, STE-STE7 with docosanoic acid (-11.31 kcal/mol), and PACC with heptadecanoic acid (-9.88 kcal/mol) respectively with strong hydrophobic or hydrophilic interactions with active pocket residues. In conclusion, the n-hexane fraction of the A. kalkora can be used to manage FOL.
PubMed: 38936050
DOI: 10.1016/j.bioorg.2024.107561 -
Chemistry & Biodiversity Jun 2024Monoacylglycerols are eco-friendly and inexpensive emulsifiers with a range of applications. The traditional synthetic route is not eco-friendly, while enzymatic...
Monoacylglycerols are eco-friendly and inexpensive emulsifiers with a range of applications. The traditional synthetic route is not eco-friendly, while enzymatic catalysis offers milder reaction conditions and higher selectivity. However, its application still is limited due to the costs. In this context, endophytic fungi can be source to new biocatalysts with enhanced catalytic activity. Based on this perspective, the aim of this study was perform the synthesis of MAG's through transesterification reactions of solketal and different vinyl esters, using crude and immobilized lipolytic extracts from the endophytic fungi Stemphylium lycopersici, isolated from Humiria balsamifera. The reactions were conducted using 100 mg of biocatalyst, 1 mmol of substrates, 9 : 1 n-heptane/acetone, at 40 °C, 200 rpm for 96 h. In the reactions using the ILE and stearate, laureate and decanoate vinyl esters it was possible to obtain the correspondent products with conversion rates of 52-75 %. Also, according to the structure drivers used in MCM-48 synthesis, different morphologies and conversions rates were observed. Employing [C16MI] Cl, [C14MI] Cl and [C4MI] Cl, the 1-lauroyl- glycerol conversion was 36 %, 79 % and 44 %, respectively. This is the first work involving the immobilization of an endophytic fungi and its utilization as a biocatalyst in the production of MAG's.
PubMed: 38935347
DOI: 10.1002/cbdv.202400667 -
International Journal of Molecular... Jun 2024Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying...
Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying the IL-6 exacerbation in the adipose tissue remains unclear. There is general agreement that TNF-α and stearate concentrations are mildly elevated in adipose tissue in the state of obesity. We hypothesize that TNF-α and stearate co-treatment induce the increased expression of IL-6 in mouse adipocytes. We therefore aimed to determine IL-6 gene expression and protein production by TNF-α/stearate treated adipocytes and investigated the mechanism involved. To test our hypothesis, 3T3-L1 mouse preadipocytes were treated with TNF-α, stearate, or TNF-α/stearate. IL-6 gene expression was assessed by quantitative real-time qPCR. IL-6 protein production secreted in the cell culture media was determined by ELISA. Acetylation of histone was analyzed by Western blotting. Il6 region-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac) was determined by ChIP-qPCR. 3T3-L1 mouse preadipocytes were co-challenged with TNF-α and stearate for 24 h, which led to significantly increased IL-6 gene expression (81 ± 2.1 Fold) compared to controls stimulated with either TNF-α (38 ± 0.5 Fold; = 0.002) or stearate (56 ± 2.0 Fold; = 0.013). As expected, co-treatment of adipocytes with TNF-α and stearate significantly increased protein production (338 ± 11 pg/mL) compared to controls stimulated with either TNF-α (28 ± 0.60 pg/mL; = 0.001) or stearate (53 ± 0.20 pg/mL, = 0.0015). Inhibition of histone acetyltransferases (HATs) with anacardic acid or curcumin significantly reduced the IL-6 gene expression and protein production by adipocytes. Conversely, TSA-induced acetylation substituted the stimulatory effect of TNF-α or stearate in their synergistic interaction for driving IL-6 gene expression and protein production. Mechanistically, TNF-α/stearate co-stimulation increased the promoter-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac), rendering a transcriptionally permissive state that favored IL-6 expression at the transcriptional and translational levels. Our data represent a TNF-α/stearate cooperativity model driving IL-6 expression in 3T3-L1 cells via the H3K9/18Ac-dependent mechanism, with implications for adipose IL-6 exacerbations in obesity.
Topics: Animals; Mice; Histones; Interleukin-6; 3T3-L1 Cells; Tumor Necrosis Factor-alpha; Acetylation; Adipocytes; Stearic Acids; Gene Expression Regulation
PubMed: 38928498
DOI: 10.3390/ijms25126776 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Jun 2024The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising...
The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.
Topics: Tablets; Enalapril; Administration, Buccal; Mouth Mucosa; Drug Compounding; Chemistry, Pharmaceutical
PubMed: 38925868
DOI: 10.62958/j.cjap.2024.003 -
Journal of Colloid and Interface Science Jun 2024Aqueous solutions of long-chain water-soluble sucrose ester surfactants exhibit non-trivial response to temperature variations, revealing a peak in viscosity around...
HYPOTHESIS
Aqueous solutions of long-chain water-soluble sucrose ester surfactants exhibit non-trivial response to temperature variations, revealing a peak in viscosity around 40-50 °C. While previous investigations have explored the structures within sucrose stearate systems at various constant temperatures, a comprehensive understanding of the entire temperature dependence and the underlying molecular factors, contributing to this phenomenon is currently missing.
EXPERIMENTS
Temperature dependent properties and supramolecular structures formed in aqueous solutions of commercial sucrose palmitate were examined using SAXS/WAXS, DSC, optical microscopy, rheological measurements, NMR, and cryo-TEM.
FINDINGS
The underlying mechanism governing this unusual behavior is revealed and is shown to relate to the mono- to di-esters ratio in the solutions. Solutions primarily containing sucrose monoesters (monoesters molecules ≳ 98% of all surfactant molecules) exhibit behavior typical of nonionic surfactants, with minimal changes with temperature. In contrast, the coexistence of mono- and di-esters results in the formation of discrete monodisperse diester particles and a network of partially fused diester particles at low temperature. As the temperature approaches the diesters' melting point, wormlike mixed micelles form, causing a viscosity peak. The height of this peak increases significantly with the diester concentration. Further temperature increase leads to fluidization of surfactant tails and formation of branched micelles, while excess diester molecules phase separate into distinct droplets.
PubMed: 38925066
DOI: 10.1016/j.jcis.2024.06.061 -
International Journal of Pharmaceutics Jun 2024Limited attempts have been made previously to develop high-loading CBD inhalable powders, which are essential for high dose delivery. Therefore, this study aimed to...
Limited attempts have been made previously to develop high-loading CBD inhalable powders, which are essential for high dose delivery. Therefore, this study aimed to develop and characterise inhalable powders with ≥ 95 % w/w CBD by wet ball milling. The effects of magnesium stearate (2 % and 5 %) and inhaler resistance (low-resistance and high-resistance RS01 inhalers) on aerosol performance were also compared. Wet ball milling produced CBD powders with > 50 % production yield. The milled particles showed irregular shapes. The powders were crystalline with minimal amorphous content, low residual solvent level (<1%), and low moisture sorption (<4%). Magnesium stearate improved both the emitted and fine particle fractions. The aerodynamic particle size distribution of the formulations differed between the low-resistance and high-resistance RS01 inhalers. The latter decreased throat deposition but increased inhaler retention. The dissolution profiles showed that all three formulations released CBD steadily and plateaued at 30 min. The best scenario was CBD with 5 % magnesium stearate dispersed from the high resistance RS01 inhaler, showing the highest FPF with the lowest throat deposition. This combination may be tested in vivo in the future to investigate its pharmacokinetic profile.
PubMed: 38906498
DOI: 10.1016/j.ijpharm.2024.124370 -
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