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Contact in Context 2024Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each...
Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide. Chlorothiazide sodium has a molecular weight of 317.71 amu. Since 2020 there have been multiple national shortages of chlorothiazide. Recent studies target chlorothiazide's low bioavailability, aiming to enhance it through nanoparticle production via a supercritical method. The drug's solubility in supercritical carbon dioxide (scCO) is vital, with measurements ranging from 0.417×10 to 1.012×10 mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO boosts solubility, with ethanol proving most effective, enhancing solubility by 2.02-11.75 times. Intra-lot variability was discovered in a sample of a lot of chlorothiazide sodium by the University of Kentucky Drug Quality Task Force. Two vials of six screened in one lot were displaced from the center of the lot by 4.0 and 4.2 SDs, respectively. Inter-lot variability was confirmed in the near-IR spectra of 204 vials obtained from 28 different lots of chlorothiazide sodium. Using full spectrum BEST analysis 13 vials (6.4%) were outliers.
PubMed: 38774605
DOI: 10.6084/m9.figshare.25773429 -
Heliyon May 2024Anti-nucleolin (NCL) aptamer AS1411 is the first anticancer aptamer tested in clinical trials. Gold nanoparticles (AuNP) have been widely exploited for various...
Anti-nucleolin (NCL) aptamer AS1411 is the first anticancer aptamer tested in clinical trials. Gold nanoparticles (AuNP) have been widely exploited for various biomedical applications due to their unique functional properties. In this study, we evaluated the colloidal stability and targeting capacity of AS1411-funtionalized AuNP (AuNP/NCL-Apt) against MCF-7 breast cancer cell line before and after lyophilization. Trehalose, mannitol, and sucrose at various concentrations were evaluated to determine their cryoprotection effects. Our results indicate that sucrose at 10 % (w/v) exhibits the best cryoprotection effect and minimal AuNP/NCL-Apt aggregation as confirmed by UV-Vis spectroscopy and dynamic light scattering (DLS) measurements. Moreover, the lyophilized AuNP/NCL-Apt at optimized formulation maintained its targeting and cytotoxic functionality against MCF-7 cells as proven by the cellular uptake assays utilizing flow cytometry and confocal laser scanning microscopy (CLSM). Quantitative PCR (qPCR) analysis of nucleolin-target gene expression also confirmed the effectiveness of AuNP/NCL-Apt. This study highlights the importance of selecting the proper type and concentration of cryoprotectant in the typical nanoparticle lyophilization process and contributes to our understanding of the physical and biological properties of functionalized nanoparticles upon lyophilization.
PubMed: 38774322
DOI: 10.1016/j.heliyon.2024.e30743 -
Veterinary Research Forum : An... 2024is an important pathogen causing a wide range of diseases in both humans and animals. The aim of this research was to screen the vancomycin resistance-associated genes...
is an important pathogen causing a wide range of diseases in both humans and animals. The aim of this research was to screen the vancomycin resistance-associated genes in methicillin-resistant (MRSA) isolates from animals. A total of 400 nasal swab samples were collected from cattle, goats and sheep between February and August 2022 from both industrial and traditional livestock farms in West Azerbaijan province, Iran. Then, nasal swabs were cultured on mannitol salt agar and molecular analysis was performed after bacteriological examination to confirm the presence of . The gene was used to detect MRSA isolates, and two important vancomycin resistance-associated genes, namely and , were searched in the isolates. Out of 400 nasal swabs, 69 samples had ; of which seven isolates were resistant against methicillin. No vancomycin resistance-associated genes were detected in the MRSA isolates. Based on these findings, vancomycin could be used to treat infections caused by this bacterium
PubMed: 38770377
DOI: 10.30466/vrf.2023.2003964.3902 -
Drug Testing and Analysis May 2024Synthetic opioids have been associated globally with adverse effects in drug users. The nitazene group of drugs is a relatively new addition to the synthetic opioid...
Synthetic opioids have been associated globally with adverse effects in drug users. The nitazene group of drugs is a relatively new addition to the synthetic opioid class emerging in Europe in 2019. Some nitazenes have been shown to be more potent than fentanyl. Overdose clusters in heroin users in Dublin (57 cases) and Cork (20 cases), Ireland, in November and December 2023, respectively, prompted a rapid response from a number of Irish laboratories to identify the substance(s) of concern. Light brown (tan) powders were obtained from cases associated with overdoses, and the results from these analyses by collaboration of four laboratories are reported here. The samples were found to contain N-pyrrolidino protonitazene (protonitazepyne), caffeine, paracetamol, benzoic acid and mannitol.
PubMed: 38769669
DOI: 10.1002/dta.3707 -
Infection and Drug Resistance 2024Hemorrhagic fever with renal syndrome (HFRS), a naturally occurring epidemic disease, is primarily caused by hantaviruses. It frequently involves the lungs and is...
Hemorrhagic fever with renal syndrome (HFRS), a naturally occurring epidemic disease, is primarily caused by hantaviruses. It frequently involves the lungs and is characterized by symptoms such as fever, hemorrhage, and renal failure. However, the occurrence of acute pancreatitis (AP) in HFRS patients can be neglected, and high intraocular pressure (IOP) is exceedingly uncommon. In this report, we discuss the case of a 30-year-old male who presented with fever, nausea, vomiting, and abdominal pain. Physical examination revealed extremity petechiae rashes and elevated IOP. Laboratory tests indicated coagulopathy and renal failure. A computed tomography scan confirmed AP. Further testing revealed a positive anti-hantavirus IgM antibody. The patient received supportive care, fluid hydration, hemofiltration, mannitol, brinzolamide, and brimonidine to reduce IOP. Three days post-admission, the patient developed shortness of breath and chest pain. Subsequent chest computed tomography revealed pulmonary edema and bilateral pleural effusion. Treatment included oxygen supply, respiratory support, and thoracentesis, with continued hemofiltration. The patient recovered, regaining normal pulmonary and renal functions and normalized IOP. This case underscores the importance of comprehensive evaluations and vigilant monitoring in HFRS patients, particularly measuring IOP in those with visual complaints, to save lives and reduce morbidity.
PubMed: 38766677
DOI: 10.2147/IDR.S454049 -
International Journal of Pharmaceutics Jun 2024Pulmonary delivery is an efficient route of administration to deliver cannabidiol (CBD) due to the high bioavailability and fast onset of action. The major formulation...
Pulmonary delivery is an efficient route of administration to deliver cannabidiol (CBD) due to the high bioavailability and fast onset of action. The major formulation challenge is the poor aqueous solubility of CBD. This study aimed to produce inhalable CBD powders with enhanced solubility and characterise their solid-state properties. CBD was spray freeze dried with mannitol or trehalose dihydrate with and without dipalmitoylphosphatidylcholine (DPPC). All four powders had acceptable yields at > 70 % with porous and spherical particles. The two crystalline mannitol powders contained less residual solvent than both amorphous trehalose ones. The addition of DPPC did not affect the crystallinity and residual solvent level of the powders. Instead, DPPC made the particles more porous, decreased the particle size from 19-23 µm to 11-13 µm, and increased CBD solubility from 0.36 µg/mL to over 2 µg/mL. The two DPPC powders were dispersed from a low resistance RS01 inhaler, showing acceptable aerosol performance with emitted fractions at 91-93 % and fine particle fractions < 5 µm at 34-43 %. These formulations can be used as a platform to deliver CBD and other cannabinoids by inhalation.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Cannabidiol; Administration, Inhalation; Solubility; Freeze Drying; Particle Size; Powders; Aerosols; Mannitol; Trehalose; Excipients; Porosity; Chemistry, Pharmaceutical
PubMed: 38762165
DOI: 10.1016/j.ijpharm.2024.124235 -
Clinical Gastroenterology and... May 2024To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the...
BACKGROUND & AIMS
To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers.
METHODS
We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing.
RESULTS
Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P = .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P = .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR.
CONCLUSION
This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.
PubMed: 38759825
DOI: 10.1016/j.cgh.2024.03.049 -
Journal of Plant Research May 2024Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant...
Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant used to counteract reactive oxygen species. Glutathione is produced by glutamylcysteine synthetase (GCS) and glutathione synthetase (GS). However, evidence for the GCS gene in sweetpotato remains scarce. In this study, the full-length cDNA sequence of IbGCS isolated from sweetpotato cultivar Xu18 was 1566 bp in length, which encodes 521 amino acids. The qRT-PCR analysis revealed a significantly higher expression of the IbGCS in sweetpotato flowers, and the gene was induced by salinity, abscisic acid (ABA), drought, extreme temperature and heavy metal stresses. The seed germination rate, root elongation and fresh weight were promoted in T Arabidopsis IbGCS-overexpressing lines (OEs) in contrast to wild type (WT) plants under mannitol and salt stresses. In addition, the soil drought and salt stress experiment results indicated that IbGCS overexpression in Arabidopsis reduced the malondialdehyde (MDA) content, enhanced the levels of GCS activity, GSH and AsA content, and antioxidant enzyme activity. In summary, overexpressing IbGCS in Arabidopsis showed improved salt and drought tolerance.
PubMed: 38758249
DOI: 10.1007/s10265-024-01548-x -
Food Chemistry: X Jun 2024This study investigated the effect of polyols erythritol, d-mannitol, and maltitol on the volatility of aroma compounds γ-butyrolactone, 3-methyl-1-butanol, and...
UNLABELLED
This study investigated the effect of polyols erythritol, d-mannitol, and maltitol on the volatility of aroma compounds γ-butyrolactone, 3-methyl-1-butanol, and 2-phenylethanol in aqueous solution. Headspace solid-phase microextraction/gas chromatography and diffusion-ordered nuclear magnetic resonance techniques were used to obtain information on aroma-food matrix interaction. Results demonstrated that adding polyols at final low concentrations of 5% or 10% (/w) to an aqueous solution of 2-phenylethanol reduced the release of vapor-phase aromas, except in the case of 3-methyl-1-butanol, which was not affected by the presence of polyols in the liquid matrix. Polyols also reduced the diffusion coefficients of all three aroma compounds, probably due to friction between the molecules. At low polyol concentrations, aroma compound volatility and diffusion coefficient values were altered compared to those of aromas released from pure water. This observation is related to the physicochemical properties of the aroma compounds. These insights may help guide the use of the combination of aroma compounds and polyols in the formulation of sugar-free and reduced-sugar beverages.
CHEMICAL COMPOUNDS
γ-butyrolactone (PubChem CID: 7302), 3-methyl-1-butanol (PubChem CID: 31260), 2-phenylethanol (PubChem CID: 6054), erythritol (PubChem CID: 222285), d-mannitol (PubChem CID: 6251), maltitol (PubChem CID: 493591).
PubMed: 38756467
DOI: 10.1016/j.fochx.2024.101440 -
PloS One 2024Bovine mastitis is a widespread and costly disease that affects dairy farming globally, characterized by mammary gland inflammation. Bovine intramammary gland infection...
Alarming multidrug resistance in Staphylococcus aureus isolated from raw milk of cows with subclinical mastitis: Antibiotic resistance patterns and occurrence of selected resistance genes.
Bovine mastitis is a widespread and costly disease that affects dairy farming globally, characterized by mammary gland inflammation. Bovine intramammary gland infection has been associated with more than 135 different pathogens of which Staphylococcus aureus is the main etiology of sub-clinical mastitis (SCM). The current study was designed to investigate the prevalence, antibiotic resistance pattern, and the presence of antibiotic resistance genes (mecA, tetK, aacA-aphD and blaZ) in S. aureus isolated from the raw milk of cows with subclinical mastitis. A total of 543 milk samples were collected from lactating cows such as Holstein Friesian (n = 79), Sahiwal (n = 175), Cholistani (n = 107), and Red Sindhi (n = 182) from different dairy farms in Pakistan. From the milk samples microscopic slides were prepared and the somatic cell count was assessed to find SCM. To isolate and identify S. aureus, milk was streaked on mannitol salt agar (MSA) plates. Further confirmation was done based on biochemical assays, including gram staining (+ coccus), catalase test (+), and coagulase test (+). All the biochemically confirmed S. aureus isolates were molecularly identified using the thermonuclease (nuc) gene. The antibiotic resistance pattern of all the S. aureus isolates was evaluated through the disc diffusion method. Out of 543 milk samples, 310 (57.09%) were positive for SCM. Among the SCM-positive samples, S. aureus was detected in 30.32% (94/310) samples. Out of 94 isolates, 47 (50%) were determined to be multidrug resistant (MDR). Among these MDR isolates, 11 exhibited resistance to Cefoxitin, and hence were classified as methicillin-resistant Staphylococcus aureus (MRSA). The S. aureus isolates showed the highest resistance to Lincomycin (84.04%) followed by Ampicillin (45.74%), while the least resistance was shown to Sulfamethoxazole/Trimethoprim (3.19%) and Gentamycin (6.38%). Polymerase chain reaction (PCR) analysis revealed that 55.31% of the isolates carried blaZ gene, 46.80% carried tetK gene, 17.02% harbored the mecA gene, whereas, aacA-aphD gene was found in 13.82% samples. Our findings revealed a significant level of contamination of milk with S. aureus and half (50%) of the isolates were MDR. The isolated S. aureus harbored various antibiotic resistance genes responsible for the absorbed phenotypic resistance. The alarmingly high prevalence of MDR S. aureus isolates and MRSA strains in these cases possess a serious risk to public health, emphasizes the urgent need to address this issue to protect both human and animal health in Pakistan.
Topics: Animals; Cattle; Mastitis, Bovine; Milk; Female; Staphylococcus aureus; Anti-Bacterial Agents; Staphylococcal Infections; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; Pakistan; Bacterial Proteins
PubMed: 38753608
DOI: 10.1371/journal.pone.0301200