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SpringerPlus Dec 2013A rapid headspace-gas chromatography (HS-GC) method was developed for the analysis of ethylene glycol and propylene glycol in plasma and serum specimens using...
A rapid headspace-gas chromatography (HS-GC) method was developed for the analysis of ethylene glycol and propylene glycol in plasma and serum specimens using 1,3-propanediol as the internal standard. The method employed a single-step derivitization using phenylboronic acid, was linear to 200 mg/dL and had a lower limit of quantitation of 1 mg/dL suitable for clinical analyses. The analytical method described allows for laboratories with HS-GC instrumentation to analyze ethanol, methanol, isopropanol, ethylene glycol, and propylene glycol on a single instrument with rapid switch-over from alcohols to glycols analysis. In addition to the novel HS-GC method, a retrospective analysis of patient specimens containing ethylene glycol and propylene glycol was also described. A total of 36 patients ingested ethylene glycol, including 3 patients who presented with two separate admissions for ethylene glycol toxicity. Laboratory studies on presentation to hospital for these patients showed both osmolal and anion gap in 13 patients, osmolal but not anion gap in 13 patients, anion but not osmolal gap in 8 patients, and 1 patient with neither an osmolal nor anion gap. Acidosis on arterial blood gas was present in 13 cases. Only one fatality was seen; this was a patient with initial serum ethylene glycol concentration of 1282 mg/dL who died on third day of hospitalization. Propylene glycol was common in patients being managed for toxic ingestions, and was often attributed to iatrogenic administration of propylene glycol-containing medications such as activated charcoal and intravenous lorazepam. In six patients, propylene glycol contributed to an abnormally high osmolal gap. The common presence of propylene glycol in hospitalized patients emphasizes the importance of being able to identify both ethylene glycol and propylene glycol by chromatographic methods.
PubMed: 23741644
DOI: 10.1186/2193-1801-2-203 -
Chemical Research in Toxicology Jan 2018The ever-evolving market of electronic cigarettes (e-cigarettes) presents a challenge for analyzing and characterizing the harmful products they can produce. Earlier we...
The ever-evolving market of electronic cigarettes (e-cigarettes) presents a challenge for analyzing and characterizing the harmful products they can produce. Earlier we reported that e-cigarette aerosols can deliver high levels of reactive free radicals; however, there are few data characterizing the production of these potentially harmful oxidants. Thus, we have performed a detailed analysis of the different parameters affecting the production of free radical by e-cigarettes. Using a temperature-controlled e-cigarette device and a novel mechanism for reliably simulating e-cigarette usage conditions, including coil activation and puff flow, we analyzed the effects of temperature, wattage, and e-liquid solvent composition of propylene glycol (PG) and glycerol (GLY) on radical production. Free radicals in e-cigarette aerosols were spin-trapped and analyzed using electron paramagnetic resonance. Free radical production increased in a temperature-dependent manner, showing a nearly 2-fold increase between 100 and 300 °C under constant-temperature conditions. Free radical production under constant wattage showed an even greater increase when going from 10 to 50 W due, in part, to higher coil temperatures compared to constant-temperature conditions. The e-liquid PG content also heavily influenced free radical production, showing a nearly 3-fold increase upon comparison of ratios of 0:100 (PG:GLY) and 100:0 (PG:GLY). Increases in PG content were also associated with increases in aerosol-induced oxidation of biologically relevant lipids. These results demonstrate that the production of reactive free radicals in e-cigarette aerosols is highly solvent dependent and increases with an increase in temperature. Radical production was somewhat dependent on aerosol production at higher temperatures; however, disproportionately high levels of free radicals were observed at ≥100 °C despite limited aerosol production. Overall, these findings suggest that e-cigarettes can be designed to minimize exposure to these potentially harmful products.
Topics: Aerosols; Electronic Nicotine Delivery Systems; Free Radicals; Glycerol; Propylene Glycol; Solvents; Temperature
PubMed: 29161504
DOI: 10.1021/acs.chemrestox.7b00116 -
Nature Communications May 2022Bacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands of proteins self-assemble to form functional metabolosomes is essential...
Bacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands of proteins self-assemble to form functional metabolosomes is essential for understanding their significance in cellular metabolism and pathogenesis. Here we investigate the de novo biogenesis of propanediol-utilization (Pdu) metabolosomes and characterize the roles of the key constituents in generation and intracellular positioning of functional metabolosomes. Our results demonstrate that the Pdu metabolosome undertakes both "Shell first" and "Cargo first" assembly pathways, unlike the β-carboxysome structural analog which only involves the "Cargo first" strategy. Shell and cargo assemblies occur independently at the cell poles. The internal cargo core is formed through the ordered assembly of multiple enzyme complexes, and exhibits liquid-like properties within the metabolosome architecture. Our findings provide mechanistic insight into the molecular principles driving bacterial metabolosome assembly and expand our understanding of liquid-like organelle biogenesis.
Topics: Bacteria; Bacterial Proteins; Organelles; Propylene Glycol
PubMed: 35614058
DOI: 10.1038/s41467-022-30608-w -
Scientific Reports Jul 2018Electronic cigarette has the potential to serve as a tobacco cessation aid if the prerequisites which are safety and efficacy in term of nicotine delivery are achieved....
Electronic cigarette has the potential to serve as a tobacco cessation aid if the prerequisites which are safety and efficacy in term of nicotine delivery are achieved. The nicotine-based liquids are mainly composed by propylene glycol and glycerol playing the important role of airborne carriers. 1,3 propanediol is proposed as a propylene glycol substitute to potentially improve the thermal stability, nicotine delivery and to decrease inhaled flavors concentrations. We have implemented various thermal, physicochemical and computational methods to evaluate the use of 1,3 propanediol as a substitute (or additional ingredient) to propylene glycol in e-liquids compositions. Our results indicate that 1,3 propanediol is stable upon heating when electronic cigarette are used in recommended conditions. We demonstrate that 1,3 propanediol gave better thermic profile compared to propylene glycol and glycerol, showing less thermal decomposition by-products. In addition, 1,3 propanediol gives to nicotine a more basic environment ensuring a high level of free base nicotine form. We have also established a quantum mechanical based computational method to validate e-liquids as flavor enhancer. Our findings showed that globally 1,3 propanediol seems to have better flavoring properties than glycerol and propylene glycol. Finally, 1,3 propanediol seems to induce quite similar aerodynamic properties compared to propylene glycol and glycerol.
Topics: Computer Simulation; Electronic Nicotine Delivery Systems; Flavoring Agents; Glycerol; Hot Temperature; Models, Chemical; Nicotine; Propylene Glycol; Propylene Glycols; Proton Magnetic Resonance Spectroscopy; Tobacco Use Cessation Devices
PubMed: 30013226
DOI: 10.1038/s41598-018-29066-6 -
Molecular Pharmaceutics Jan 2023Extensive use of microemulsions as delivery systems raises interest in the safe ingredients that can form such systems. Here, we assessed the use of two glycols, i.e.,...
Extensive use of microemulsions as delivery systems raises interest in the safe ingredients that can form such systems. Here, we assessed the use of two glycols, i.e., propylene glycol and pentylene glycol, and their mixtures to manipulate the properties and structure of microemulsions. Obtained systems with glycols were extensively characterized in terms of capacity to incorporate water phase, droplet size, polydispersity, structure type, and rheological and thermal properties. The results of these studies indicate that the composition, structure, and viscosity of the microemulsions can be changed by appropriate quantification of glycols. It has been shown that the type of glycol used and its amount may favor or worsen the formation of microemulsions with the selected oils. In addition, a properly selected composition of oils and glycols resulted in the formation of microemulsions with a reduced content of surfactants and consequently improved the safety of using microemulsions as delivery systems.
Topics: Surface-Active Agents; Oils; Propylene Glycol; Emulsions
PubMed: 36354760
DOI: 10.1021/acs.molpharmaceut.2c00599 -
Drug Delivery and Translational Research Apr 2022Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical...
Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical properties of the molecule, amitriptyline is also a promising candidate for delivery as a topical analgesic. Here we report the dermal delivery of amitriptyline from a range of simple formulations. The first stage of the work required the conversion of amitriptyline hydrochloride to the free base form as confirmed by nuclear magnetic resonance (NMR). Distribution coefficient values were measured at pH 6, 6.5, 7, and 7.4. Solubility and stability of amitriptyline were assessed prior to conducting in vitro permeation and mass balance studies. The compound demonstrated instability in phosphate-buffered saline (PBS) dependent on pH. Volatile formulations comprising of isopropyl alcohol (IPA) and isopropyl myristate (IPM) or propylene glycol (PG) were evaluated in porcine skin under finite dose conditions. Compared with neat IPM, the IPM:IPA vehicles promoted 8-fold and 5-fold increases in the amount of amitriptyline that permeated at 24 h. Formulations containing PG also appear to be promising vehicles for dermal delivery of amitriptyline, typically delivering higher amounts of amitriptyline than the IPM:IPA vehicles. The results reported here suggest that further optimization of topical amitriptyline formulations should be pursued towards development of a product for clinical investigational studies.
Topics: Administration, Cutaneous; Amitriptyline; Analgesia; Analgesics; Animals; Excipients; Propylene Glycol; Skin; Skin Absorption; Swine
PubMed: 33886076
DOI: 10.1007/s13346-021-00982-x -
Scientific Reports Jul 2021Cryopreservation is the only reliable method for long-term storage of biological material that guarantees genetic stability. This technique can be extremely useful for...
Cryopreservation is the only reliable method for long-term storage of biological material that guarantees genetic stability. This technique can be extremely useful for the conservation of endangered species and restock natural populations for declining species. Many factors have negatively affected the populations of high economical value shellfish in Spain and, as a result, many are declining or threatened nowadays. This study was focused on early-life stages of Venerupis corrugata, Ruditapes decussatus and Ruditapes philippinarum to develop successful protocols to enhance the conservation effort and sustainable shellfishery resources. Firstly, common cryoprotecting agents (CPAs) were tested to select the suitable permeable CPA attending to toxicity. Cryopreservation success using different combinations of CPA solutions, increasing equilibrium times and larval stages was evaluated attending to survival and shell growth at 2 days post-thawing. Older clam development stages were more tolerant to CPA toxicity, being ethylene-glycol (EG) and Propylene-glycol (PG) the least toxic CPAs. CPA solution containing EG yielded the highest post-thawing survival rate and the increase of equilibration time was not beneficial for clam larvae. Cryopreservation of trochophores yielded around 50% survivorship, whereas over 80% of cryopreserved D-larvae were able to recover after thawing.
Topics: Animals; Bivalvia; Conservation of Natural Resources; Cryopreservation; Cryoprotective Agents; Dimethyl Sulfoxide; Endangered Species; Ethylene Glycol; Fisheries; Glycerol; Larva; Propylene Glycol; Shellfish; Spain
PubMed: 34326357
DOI: 10.1038/s41598-021-94197-2 -
American Journal of Physiology. Heart... Apr 2021After more than a decade of electronic cigarette (E-cig) use in the United States, uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk....
After more than a decade of electronic cigarette (E-cig) use in the United States, uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk. As all E-cigs use propylene glycol and vegetable glycerin (PG-VG) and generate abundant saturated aldehydes, mice were exposed by inhalation to PG-VG-derived aerosol, formaldehyde (FA), acetaldehyde (AA), or filtered air. Biomarkers of exposure and cardiopulmonary injury were monitored by mass spectrometry (urine metabolites), radiotelemetry (respiratory reflexes), isometric myography (aorta), and flow cytometry (blood markers). Acute PG-VG exposure significantly affected multiple biomarkers including pulmonary reflex (decreased respiratory rate, -50%), endothelium-dependent relaxation (-61.8 ± 4.2%), decreased WBC (-47 ± 7%), and, increased RBC (+6 ± 1%) and hemoglobin (+4 ± 1%) versus air control group. Notably, FA exposure recapitulated the prominent effects of PG-VG aerosol on pulmonary irritant reflex and endothelial dysfunction, whereas AA exposure did not. To attempt to link PG-VG exposure with FA or AA exposure, urinary formate and acetate levels were measured by GC-MS. Although neither FA nor AA exposure altered excretion of their primary metabolite, formate or acetate, respectively, compared with air-exposed controls, PG-VG aerosol exposure significantly increased post-exposure urinary acetate but not formate. These data suggest that E-cig use may increase cardiopulmonary disease risk independent of the presence of nicotine and/or flavorings. This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA. Use of electronic cigarettes (E-cig) induces endothelial dysfunction (ED) in healthy humans, yet the specific constituents in E-cig aerosols that contribute to ED are unknown. Our study implicates formaldehyde that is formed in heating of E-cig solvents (propylene glycol, PG; vegetable glycerin, VG). Exposure to formaldehyde or PG-VG-derived aerosol alone stimulated ED in female mice. As ED was independent of nicotine and flavorants, these data reflect a "universal flaw" of E-cigs that use PG-VG.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/e-cigarettes-aldehydes-and-endothelial-dysfunction/.
Topics: Acetaldehyde; Aerosols; Animals; Aorta, Thoracic; Biomarkers; E-Cigarette Vapor; Endothelium, Vascular; Female; Formaldehyde; Glycerol; Inhalation Exposure; Lung; Male; Mice, Inbred C57BL; Propylene Glycol; Respiration; Risk Assessment; Solvents; Vasoconstriction; Vasodilation; Mice
PubMed: 33543686
DOI: 10.1152/ajpheart.00878.2020 -
Basic & Clinical Pharmacology &... May 2018Polymedicated neonates and young infants may be at risk of harmful cumulative exposure to toxic excipients like ethanol, propylene glycol and benzyl alcohol during... (Observational Study)
Observational Study
Polymedicated neonates and young infants may be at risk of harmful cumulative exposure to toxic excipients like ethanol, propylene glycol and benzyl alcohol during routine clinical care. The aim of this study was to calculate the cumulative daily alcohol exposure (mg/kg/day) in polymedicated neonates and infants and compare these levels to the tolerance limits found in guidelines published by European Medicines Agency (EMA). As part of the SEEN study, all medicinal products administered to neonates and infants were recorded. All included neonates received ≥2 medicinal products/day and infants ≥3 medicinal products/day. Daily excipient levels were calculated based on quantities obtained from manufacturers or databases. Excipient levels were compared to tolerance limits proposed by the EMA. Altogether, 470 neonates and 160 infants were included, recording 4207 prescriptions and 316 products. In total, 45% (n = 288) of patients were exposed to an alcohol of interest; 2% (n = 14) were exposed to benzyl alcohol (BA), 38% (n = 237) to ethanol and 23% (n = 146) to propylene glycol (PG). Of the total number of prescriptions involving ethanol-containing medicinal products (n = 334), 51% would alone exceed tolerance limit of 6 mg/kg/day. Of the total number of prescriptions involving PG-containing medicinal products (n = 174), 70% would alone exceed a maximum tolerance limit of 50 mg/kg/day. Maximal daily exposure to ethanol (1563 mg/kg/day) or PG (954 mg/kg/day) exceeded the tolerance limits recommended by EMA 260.5 and 19.1 times, respectively. Tolerance limits for ethanol and PG as proposed by the EMA are frequently exceeded in polymedicated neonates and infants due to the cumulative effect of these alcohols. Alternative formulations may minimize excipient exposure.
Topics: Age Factors; Dose-Response Relationship, Drug; Drug Compounding; Ethanol; Excipients; Female; Humans; Infant; Infant, Newborn; Male; Maximum Tolerated Dose; No-Observed-Adverse-Effect Level; Polypharmacy; Propylene Glycol; Retrospective Studies; Risk Assessment
PubMed: 29281181
DOI: 10.1111/bcpt.12950 -
Journal of Dairy Science Jul 2004The effect of peripartal supplementation with concentrate enriched at 10% propylene glycol (PG) on metabolism, animal health, fertility, and milk production was studied... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The effect of peripartal supplementation with concentrate enriched at 10% propylene glycol (PG) on metabolism, animal health, fertility, and milk production was studied using 234 cows from 8 dairy farms with production averages of 8019 to 10,656 kg/yr. The feeding schedule for the PG group (n=117) was as follows: 13 d antepartum: 1.5 kg/d (= 150 mL PG); 12 d antepartum until parturition: 3 kg/d (= 300 mL PG); 1 to 12 d postpartum: 1 kg/d (= 100 mL PG). Control cows (n=117) received the same concentrate without PG. From a subset of cows (PG: n = 43; control: n = 40), blood samples were collected at 6, 3, and 1 wk antepartum, 3 d antepartum, on the day of parturition, and 1, 3, 5, 7, 9, and 11 wk postpartum for the determination of nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), insulin-like growth factor (IGF)-I, and activities of aspartate-aminotransferase (AST) and glutamate-dehydrogenase (GLDH). From another subset of cows (PG: n=11; control: n=10), blood samples were collected 1 wk antepartum, on the day of parturition, and 1 wk postpartum to determine immunophenotypical and functional parameters of blood neutrophils. From 1 wk antepartum to 1 d postpartum, concentrations of NEFA were significantly lower in cows receiving PG compared with controls. Also, concentrations of BHBA in cows receiving PG were significantly lower from 1 wk antepartum until 7 wk postpartum. Concentrations of IGF-I were significantly higher in the PG group, from 1 wk antepartum until 1 wk postpartum than in the control group. Activities of AST and GLDH did not differ between groups. Immunophenotypical and functional characteristics of blood neutrophils were not influenced by treatment nor were animal health, reproduction, or milk production. Although indicators of metabolic status were improved by peripartal use of PG-enriched concentrate, economic benefits are questionable for dairy farms with good nutritional programs, as economically important factors such as milk production, animal health, and fertility were not influenced.
Topics: 3-Hydroxybutyric Acid; Animals; Aspartate Aminotransferases; Cattle; Dietary Supplements; Fatty Acids, Nonesterified; Female; Fertility; Glutamate Dehydrogenase; Health Status; Immunophenotyping; Insulin-Like Growth Factor I; Lactation; Neutrophils; Parturition; Progesterone; Propylene Glycol
PubMed: 15328227
DOI: 10.3168/jds.S0022-0302(04)70033-8