Acute exposure to electronic cigarette components alters mRNA expression of pre-osteoblasts.

The use of traditional nicotine delivery products such as tobacco has long been linked to detrimental health effects. However, little work to date has focused on the emerging market of aerosolized nicotine delivery known as electronic nicotine delivery systems (ENDS) or electronic cigarettes, and their potential for new effects on human health. Challenges studying these devices include heterogeneity in the formulation of the common components of most available ENDS, including nicotine and a carrier (commonly composed of propylene glycol and vegetable glycerin, or PG/VG). In the present study, we report on experiments interrogating the effects of major identified components in e-cigarettes. Specifically, the potential concomitant effects of nicotine and common carrier ingredients in commercial "vape" products are explored in vitro to inform the potential health effects on the craniofacial skeleton through novel vectors as compared to traditional tobacco products. MC3T3-E1 murine pre-osteoblast cells were cultured in vitro with clinically relevant liquid concentrations of nicotine, propylene glycol (PG), vegetable glycerin (VG), Nicotine+PG/VG, and the vape liquid of a commercial product (Juul). Cells were treated acutely for 24 h and RNA-Seq was utilized to determine segregating alteration in mRNA signaling. Influential gene targets identified with sparse partial least squares discriminant analysis (sPLS-DA) implemented in mixOmics were assessed using the PANTHER Classification system for molecular functions, biological processes, cellular components, and pathways of effect. Additional endpoint functional analyses were used to confirm cell cycle changes. The initial excitatory concentration (EC50) studied defined a target concentration of carrier PG/VG liquid that altered the cell cycle of the calvarial cells. Initial sPLS-DA analysis demonstrated the segregation of nicotine and non-nicotine exposures utilized in our in vitro modeling. Pathway analysis suggests a strong influence of nicotine exposures on cellular processes including metabolic processes and response to stimuli including autophagic flux. Further interrogation of the individual treatment conditions demonstrated segregation by treatment modality (Control, Nicotine, Carrier (PG+VG), Nicotine+PG/VG) along three dimensions best characterized by: latent variable 1 (PLSDA-1) showing strong segregation based on nicotine influence on cellular processes associated with cellular adhesion to collagen, osteoblast differentiation, and calcium binding and metabolism; latent variable 2 (PLSDA-2) showing strong segregation of influence based on PG+VG and Control influence on cell migration, survival, and cycle regulation; and latent variable 3 (PLSDA-3) showing strong segregation based on Nicotine and Control exposure influence on cell activity and growth and developmental processes. Further, gene co-expression network analysis implicates targets of the major pathway genes associated with bone growth and development, particularly craniofacial (FGF, Notch, TGFß, WNT) and analysis of active subnetwork pathways found these additionally overrepresented in the Juul exposure relative to Nicotine+PG/VG. Finally, experimentation confirmed alterations in cell count, and increased evidence of cell stress (markers of autophagy), but no alteration in apoptosis. These data suggest concomitant treatment with Nicotine+PG/VG drives alterations in pre-osteoblast cell cycle signaling, specifically transcriptomic targets related to cell cycle and potentially cell stress. Although we suspected cell stress and well as cytotoxic effects of Nicotine+PG/VG, no great influence on apoptotic factors was observed. Further RNA-Seq analysis allowed for the direct interrogation of molecular targets of major pathways involved in bone and craniofacial development, each demonstrating segregation (altered signaling) due to e-cigarette-type exposure. These data have implications directed toward ENDS formulation as synergistic effects of Nicotine+PG/VG are evidenced here. Thus, future research will continue to interrogate how varied formulation of Nicotine+PG/VG affects overall cell functions in multiple vital systems.

Electronic Nicotine Delivery Systems and Cardiovascular/Cardiometabolic Health.

The use of electronic nicotine delivery systems, specifically electronic cigarettes (e-cig), has risen dramatically within the last few years; the demographic purchasing these devices is now predominantly adolescents that are not trying to quit the use of traditional combustible cigarettes, but rather are new users. The composition and appearance of these devices has changed since their first entry into the market in the late 2000s, but they remain composed of a battery and aerosol delivery system that is used to deliver breakdown products of propylene glycol/vegetable glycerin, flavorings, and potentially nicotine or other additives. Manufacturers have also adjusted the type of nicotine that is used within the liquid to make the inhalation more palatable for younger users, further affecting the number of youth who use these devices. Although the full spectrum of cardiovascular and cardiometabolic consequences of e-cig use is not fully appreciated, data is beginning to show that e-cigs can cause both short- and long-term issues on cardiac function, vascular integrity and cardiometabolic issues. This review will provide an overview of the cardiovascular, cardiometabolic, and vascular implications of the use of e-cigs, and the potential short- and long-term health effects. A robust understanding of these effects is important in order to inform policy makers on the dangers of e-cigs use.

Bipyridine-Confined Silver Single-Atom Catalysts Facilitate In-Plane C-O Coupling for Propylene Electrooxidation.

The electrooxidation of propylene presents a promising route for the production of 1,2-propylene glycol (PG) under ambient conditions. However, the C-O coupling process remains a challenge owing to the high energy barrier. In this work, we developed a highly efficient electrocatalyst of bipyridine-confined Ag single atoms on UiO-bpy substrates (Ag SAs/UiO-bpy), which exposed two in-plane coordination vacancies during reaction for the co-adsorption of key intermediates. Detailed structure and electronic property analyses demonstrate that CH3CHCH2OH* and *OH could stably co-adsorb in a square planar configuration, which then accelerates the charge transfer between them. The combination of stable co-adsorption and efficient charge transfer facilitates the C-O coupling process, thus significantly lowering its energy barrier. At 2.4 V versus a reversible hydrogen electrode, Ag SAs/UiO-bpy achieved a record-high activity of 61.9 gPG m-2 h-1. Our work not only presents a robust electrocatalyst but also advances a new perspective on catalyst design for propylene electrooxidation.

The effect of three additives on properties of mineral trioxide aggregate cements: a systematic review and meta-analysis of in vitro studies.

BACKGROUND: Several efforts have been made to improve mechanical and biological properties of calcium silicate-based cements through changes in chemical composition of the materials. This study aimed to investigate the physical (including setting time and compressive strength) and chemical (including calcium ion release, pH level) properties as well as changes in cytotoxicity of mineral trioxide aggregate (MTA) after the addition of 3 substances including CaCl2, Na2HPO4, and propylene glycol (PG). METHODS: The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic searches were performed on PubMed, Embase, and Scopus databases, spanning from 1993 to October 2023 in addition to manual searches. Relevant laboratory studies were included. The quality of the included studies was assessed using modified ARRIVE criteria. Meta-analyses were performed by RevMan statistical software. RESULTS: From the total of 267 studies, 24 articles were included in this review. The results of the meta-analysis indicated that addition of PG increased final setting time and Ca2+ ion release. Addition of Na2HPO4 did not change pH and cytotoxicity but reduced the final setting time. Incorporation of 5% CaCl2 reduced the setting time but did not alter the cytotoxicity of the cement. However, addition of 10% CaCl2 reduced cell viability, setting time, and compressive strength. CONCLUSION: Inclusion of 2.5% wt. Na2HPO4 and 5% CaCl2 in MTA can be advisable for enhancing the physical, chemical, and cytotoxic characteristics of the admixture. Conversely, caution is advised against incorporating elevated concentrations of PG due to its retarding effect. TRIAL REGISTRATION: PROSPERO registration number: CRD42021253707.

E-cigarette aerosols of propylene glycol impair BK channel activity and parameters of mucociliary function.

Propylene glycol (PG) is a common delivery vehicle for nicotine and flavorings in e-cigarette (e-cig) liquids and is largely considered safe for ingestion. However, little is known about its effects as an e-cig aerosol on the airway. Here, we investigated whether pure PG e-cig aerosols in realistic daily amounts impact parameters of mucociliary function and airway inflammation in a large animal model (sheep) in vivo and primary human bronchial epithelial cells (HBECs) in vitro. Five-day exposure of sheep to e-cig aerosols of 100% PG increased mucus concentrations (% mucus solids) of tracheal secretions. PG e-cig aerosols further increased the activity of matrix metalloproteinase-9 (MMP-9) in tracheal secretions. In vitro exposure of HBECs to e-cig aerosols of 100% PG decreased ciliary beating and increased mucus concentrations. PG e-cig aerosols further reduced the activity of large conductance, Ca2+-activated, and voltage-dependent K+ (BK) channels. We show here for the first time that PG can be metabolized to methylglyoxal (MGO) in airway epithelia. PG e-cig aerosols increased levels of MGO and MGO alone reduced BK activity. Patch-clamp experiments suggest that MGO can disrupt the interaction between the major pore-forming BK subunit human Slo1 (hSlo1) and the gamma regulatory subunit LRRC26. PG exposures also caused a significant increase in mRNA expression levels of MMP9 and interleukin 1 beta (IL1B). Taken together, these data show that PG e-cig aerosols cause mucus hyperconcentration in sheep in vivo and HBECs in vitro, likely by disrupting the function of BK channels important for airway hydration.

Microemulsion Delivery Systems with Low Surfactant Concentrations: Optimization of Structure and Properties by Glycol Cosurfactants.

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.

Permeation of individual cryoprotectants and their different combinations into mouse liver tissue.

Development of successful tissue cryopreservation methods requires specific knowledge regarding tissue permeation of individual cryoprotective agents (CPAs) and their combinations. The present study assessed the permeation of dimethyl sulfoxide, ethylene glycol, and propylene glycol into liver tissue, and addressed whether the diffusion coefficient of individual CPAs changes when combining CPAs. To do this, mouse liver slices were exposed at room temperature to 3.5 mol/L concentrations of CPAs individually or in combination for 15, 30, 45, and 60 min. Subsequently, tissue CPA concentrations were determined using a gas chromatography/mass spectrometry (GC/MS) method. Our results show that (1) the GC/MS method allows measurement of multiple CPA concentrations in a single small tissue sample, (2) dimethyl sulfoxide has a higher diffusion coefficient than ethylene glycol and propylene glycol, and (3) the CPA diffusivity appears to decrease in mixtures with multiple CPAs. These findings may help the development of effective tissue cryopreservation methods.

Development of cryopreservation media for the slow-freezing of cultured primordial germ cells in chicken.

Conservation of chicken germplasm is crucial in supporting commercial breeds for sustainable egg and meat production and preserving the genetic diversity of indigenous breeds for future breeding. Cryopreservation of chicken fertilized eggs or embryos is not feasible, owing to the large yolk-laden structure of the eggs. Primordial germ cells (PGCs), the embryonic precursors of gametes, are the best candidates for the cryobanking of chicken germplasm. Effective cryobanking of chicken PGCs requires an optimal cryopreservation protocol. Cryomedia containing dimethyl sulfoxide (DMSO) or DMSO combined with serum have been widely used for the cryopreservation of chicken PGCs. However, as cryoprotectants are yet to be optimized for chicken PGCs, the efficacy of cryomedia can be further improved. Here, we investigated the cryoprotective effects of propylene glycol (PG), an alternative to DMSO, on chicken PGCs. We found that the addition of non-permeable cryoprotectants, such as trehalose or chicken serum, to DMSO or PG cryomedia improved the recovery and survival rates of post-thawed PGCs. We further investigated the cryoprotective effects of trehalose and chicken serum and found that these additives have different cryoprotective actions. Based on these findings, we designed two different cryomedia: DTS, including 5% DMSO, 0.3 M trehalose, and 1% chicken serum, and PTS, including 7.5% PG, 0.1 M trehalose, and 5% chicken serum. Among the different PGC lines and freshly isolated PGCs, the cryomedia showed similar post-thaw recovery rates. Following transplantation, post-thawed male PGCs can colonize gonads and differentiate into functional sperm. We successfully revived the offspring of Kurokashiwa, a rare chicken breed in Japan, with cryopreserved PGCs. In conclusion, we developed two different cryomedia that achieved > 50% recovery of viable PGCs after thawing while maintaining germline competency.

High risk and low prevalence diseases: Toxic alcohol ingestion.

INTRODUCTION: Toxic alcohol ingestion is a rare but serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of toxic alcohol ingestion, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Toxic alcohols include ethylene glycol, methanol, isopropyl alcohol, propylene glycol, and diethylene glycol. These substances can be found in several settings including hospitals, hardware stores, and the household, and ingestion can be accidental or intentional. Toxic alcohol ingestion presents with various degrees of inebriation, acidemia, and end-organ damage depending on the substance. Timely diagnosis is critical to prevent irreversible organ damage or death and is based primarily on clinical history and consideration of this entity. Laboratory evidence of toxic alcohol ingestion includes worsening osmolar gap or anion-gap acidemia and end organ injury. Treatment depends on the ingestion and severity of illness but includes alcohol dehydrogenase blockade with fomepizole or ethanol and special considerations for the initiation of hemodialysis. CONCLUSIONS: An understanding of toxic alcohol ingestion can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Propylene glycol, skin sensitisation and allergic contact dermatitis: A scientific and regulatory conundrum.

Propylene glycol (PG) has widespread use in pharmaceuticals, cosmetics, fragrances and personal care products. PG is not classified as hazardous under the Globally Harmonised System of Classification and Labelling of Chemicals (GHS) but poses an intriguing scientific and regulatory conundrum with respect to allergic contact dermatitis (ACD), the uncertainty being whether and to what extent PG has the potential to induce skin sensitisation. In this article we review the results of predictive tests for skin sensitisation with PG, and clinical evidence for ACD. Patch testing in humans points to PG having the potential to be a weak allergen under certain conditions, and an uncommon cause of ACD in subjects without underlying/pre-disposing skin conditions. In clear contrast PG is negative in predictive toxicology tests for skin sensitisation, including guinea pig and mouse models (e.g. local lymph node assay), validated in vitro test methods that measure various key events in the pathway leading to skin sensitisation, and predictive methods in humans (Human Repeat Insult Patch and Human Maximisation Tests). We here explore the possible scientific basis for this intriguing inconsistency, recognising there are arguably no known contact allergens that are universally negative in, in vitro, animal and human predictive tests methods.

Allergic contact dermatitis from propylene glycol: A case series from Australia.

BACKGROUND: Propylene glycol (PG) is used in a variety of cosmetics, food and pharmaceuticals. PG is a known sensitizer but also irritating when patch tested (PT). OBJECTIVES: The aims were to investigate the frequency of contact sensitization to PG and to identify cases of allergic contact dermatitis (ACD). METHODS: A retrospective study was performed on patients PT at the Skin Health Institute (SHI), Victoria, Australia to PG 5% pet. and PG 10% aq. between 1 January 2005 and 31 December 2020. RESULTS: In all, 6761 patients were PT to PG and 21 (0.31%) reacted. Of those 21 individuals, 9 (42.9%) had a relevant reaction. 75% of relevant positive reactions were in patients PT to PG 10% aq. The most common source of PG exposure was topical medicaments (77.8% of relevant reactions) and moisturizers, with the largest group being topical corticosteroids. CONCLUSION: Contact sensitization to PG in the patch test population remains uncommon, although it is possible that testing with concentrations of 5%-10% PG did not identify all reactions. Topical corticosteroids were the most important cause. Patients with suspected contact dermatitis to topical corticosteroids should be PT to PG.

Difference in Anti-microbial Activity of Propan-1,3-diol and Propylene Glycol.

Propan-1,3-diol (PD) and propan-1,2-diol (propylene glycol, PG) are very similar compounds because their structures, safety data, and anti-microbial activities are almost the same. Actually, both compounds are made up of three carbon atoms and two hydroxyl groups. Regarding their safety, they do not have serious hazard data for animals, and LD50 values (in rats) of both are similar. As for the anti-microbial activity, minimum inhibitory concentration (MIC) values of both PD and PG are approximately 10% (v/v). In this study, we used the preservatives-effectiveness test (PET) to evaluate the anti-microbial activities of PD and PG, because both compounds are used in cosmetics as preservatives. The results indicated that PD was more effective as an anti-microbial agent compared with PG, and the effect of PD was marked against Escherichia coli and Pseudomonas aeruginosa. Scanning electron microscopy (SEM) images showed that the membrane of Escherichia coli was injured by PD and PG, but the damage by PD was more marked. The damage of the cell membrane may be the cause of high anti-microbial activity of PD in PET. These results suggest that PD has greater potential as a preservative, and PD should be recommended as an additive for food and medicine.

Effects of daily propylene glycol drenching during the Ovsynch protocol on fertility and metabolic parameters in lactating dairy cows.

Negative energy balance (NEB) caused by restricted feed intake leads to body condition loss (BCS), increased metabolic stress and reduced fertility in dairy cows. Propylene glycol (PG) is a precursor of ruminal propionate for gluconeogenesis used to increase metabolic adaptation to the early postpartum period. The aim of this study was to determine the effects of daily drenching of PG during the fixed-time artificial insemination (FTAI) protocol on beta-hydroxybutyric acid (BHBA), glucose, adiponectin, insulin-like growth factor-1 (IGF1) concentrations, follicle size and pregnancy rate in dairy cows. Cows (n = 148) were randomly divided into two groups and received either 300 mL of PG (PG-OVS, n = 76) or 300 mL of water (CON-OVS, n = 72) each day of the Ovsynch protocol (GnRH-7 days-PGF2α -56 hours-GnRH-16-18-hour FTAI) between days 57 ± 3 to 67 ± 3 postpartum for the first service. Body condition scores (14 days before expected calving, at calving, on days 21 and 42 postpartum) were recorded. Blood samples were collected days 7 ± 3, 21 ± 3 postpartum, at the beginning of the Ovsynch (days 57 ± 3) and at the time of FTAI (days 67 ± 3) for measurements of BHBA, glucose, adiponectin and IGF1 concentrations. Ultrasonographic examinations were done to measure follicle size at the beginning of Ovsynch and FTAI and to determine pregnancy on days 30 and 60 following FTAI. There were no differences (p > .05) in glucose, adiponectin and IGF1 concentrations between the groups during the study. Although there was no difference (p > .05) in BHBA concentrations on postpartum day 7 ± 3, 21 ± 3 and 57 ± 3 between the groups, BHBA concentrations at the time of insemination was lower (p < .05) in the PG-OVS group (0.72 ± 0.03 mmol/L) than in the CON-OVS group (0.81 ± 0.03 mmol/L). Follicle sizes at the beginning of Ovsynch (PG-OVS, 14.5 ± 0.48 mm; CON-OVS, 14.3 ± 0.59 mm) and FTAI (PG-OVS, 17.8 ± 0.52 mm; CON-OVS, 17.7 ± 0.42 mm) were not different (p < .05). Pregnancy rate of the cows in the PG-OVS group (46.1%, 35/76) was higher (p = .05) than in the CON-OVS group (30.6%, 22/72) on day 30 following FTAI. In conclusion, decreasing serum BHBA concentrations at the time of FTAI by means of daily drenching of PG during the Ovsynch protocol, increased the pregnancy rate at first service in lactating dairy cows. On the other hand, blood glucose was not related with pregnancy rates in our study, probably as a result of our sampling time and more rapid fluctuations of blood glucose concentrations when compared to BHBA.

Designed Fabrication of Phloretin-Loaded Propylene Glycol Binary Ethosomes: Stability, Skin Permeability and Antioxidant Activity.

Binary ethosome vesicles have been developed as flexible lipid vesicles for the enhanced physicochemical stability and skin delivery of drugs. This work aimed to prepare phloretin-loaded propylene glycol ethosomes (PHL-PGEs) to improve their stability, skin permeability and antioxidant activity. PHL-PGEs were prepared via the ethanol injection method and optimized using different weight ratios of ethanol to propylene glycol (PG). When the ethanol/PG mass ratio changed from 10:0 to 0:10, the encapsulation efficiency and stability of ethosomes increased. At a PHL concentration of 1mg/mL, the EE% was 89.42 ± 2.42 and the DL% was 4.21 ± 0.04, which exhibited their highest values. The encapsulation of the PHL in the PHL-PGEs was strengthened via XRD analysis and FTIR analysis. The results of the in vitro percutaneous permeability test demonstrated that the combined use of ethanol and PG exhibited a notable enhancement in skin permeability, and the skin retention of PHL-PGEs was 1.06 times that of PHL-ethosomes (PHL-Es) and 2.24 times that of the PHL solution. An in vitro antioxidant activity study indicated that solubility and antioxidant activity was potentiated via the nanoencapsulation of phloretin. Therefore, these results confirm the potential of this nanocarrier to enhance physicochemical stability, skin permeability and antioxidant activity.

Two Fast GC-MS Methods for the Measurement of Nicotine, Propylene Glycol, Vegetable Glycol, Ethylmaltol, Diacetyl, and Acetylpropionyl in Refill Liquids for E-Cigarettes.

The use of e-cigarettes (ECs) has become increasingly popular worldwide, even though scientific results have not established their safety. Diacetyl (DA) and acetylpropionyl (AP), which can be present in ECs, are linked with lung diseases. Ethyl maltol (EM)-the most commonly used flavoring agent-can be present in toxic concentrations. Until now, there is no methodology for the determination of nicotine, propylene glycol (PG), vegetable glycerin (VG), EM, DA, and acetylpropionyl in e-liquids that can be used as a quality control procedure. Herein, gas chromatography coupled with mass spectrometry (GC-MS) was applied for the development of analytical methodologies for these substances. Two GC-MS methodologies were developed and fully validated, fulfilling the standards for the integration in a routine quality control procedure by manufacturers. As proof of applicability, the methodology was applied for the analysis of several e-liquids. Differences were observed between the labeled and the experimental levels of PG, VG, and nicotine. Three samples contained EM at higher concentrations compared to the other samples, while only one contained DA. These validated methodologies can be used for the quality control analysis of EC liquid samples regarding nicotine, PG, and VG amounts, as well as for the measurement of the EM.

Propylene glycol, a component of electronic cigarette liquid, damages epithelial cells in human small airways.

BACKGROUND: Electronic cigarettes (e-cigarettes) are used worldwide as a substitute for conventional cigarettes. Although they are primarily intended to support smoking cessation, e-cigarettes have been identified as a gateway to smoking habits for young people. Multiple recent reports have described the health effects of inhaling e-cigarettes. E-cigarette liquid (e-liquid) is mainly composed of propylene glycol (PG) and glycerol (Gly), and the aerosol generated by these devices primarily contains these two components. Thus, this study aimed to evaluate the effects of PG and Gly on human small airway epithelial cells (SAECs). METHODS: SAECs were exposed to PG or Gly, and cell proliferation, cell viability, lactate dehydrogenase (LDH) release, DNA damage, cell cycle, and apoptosis were evaluated. Additionally, SAECs derived from chronic obstructive pulmonary disease (COPD) patients (COPD-SAECs) were investigated. RESULTS: Exposure of SAECs to PG significantly inhibited proliferation (1%, PG, p = 0.021; 2-4% PG, p < 0.0001) and decreased cell viability (1-4% PG, p < 0.0001) in a concentration-dependent manner. Gly elicited similar effects but to a reduced degree as compared to the same concentration of PG. PG also increased LDH release in a concentration-dependent manner (3% PG, p = 0.0055; 4% PG, p < 0.0001), whereas Gly did not show a significant effect on LDH release. SAECs exposed to 4% PG contained more cells that were positive for phosphorylated histone H2AX (p < 0.0001), a marker of DNA damage, and an increased proportion of cells in the G1 phase (p < 0.0001) and increased p21 expression (p = 0.0005). Moreover, caspase 3/7-activated cells and cleaved poly (ADP-ribose) polymerase 1 expression were increased in SAECs exposed to 4% PG (p = 0.0054). Furthermore, comparing COPD-SAECs to SAECs without COPD in PG exposure, cell proliferation, cell viability, DNA damage and apoptosis were significantly greater in COPD-SAECs. CONCLUSION: PG damaged SAECs more than Gly. In addition, COPD-SAECs were more susceptible to PG than SAECs without COPD. Usage of e-cigarettes may be harmful to the respiratory system, especially in patients with COPD.

Propylene glycol toxicity from compulsive corn starch ingestion.

INTRODUCTION: Propylene glycol (PG) is usually considered safe, however, toxicity can develop with high doses or when used for prolonged periods of time. PG can be found in some medications as well as some food products. We report a case of likely PG toxicity that occurred after compulsive daily ingestion of large amounts of corn starch. CASE REPORT: Our patient initially presented to an outside hospital (OSH) via ambulance for altered mental status. Her mental status improved after her blood sugar of 25 was corrected. On admission to OSH Emergency Department her initial vital signs included a heart rate of 115 bpm, blood pressure 113/59 mm/hg, temperature 35.8C. Pertinent labs included: sodium 119 mEq/L, bicarbonate 9 mEq/L, anion gap 29 mEq/L, creatinine 2.5 mg/dL and lactic acid 20 mEq/L. On transfer to our hospital her repeat lactic acid was 20 mEq/L, osmolar gap was 20. Her PG level, which was drawn several hours after her initial presentation, was 11 mg/dL. Our patient noted that she ingested a 16 oz. package of corn starch mixed with baking soda approximately every 2 days. Given the concerns for PG she was underwent intermittent hemodialysis. PG and lactic acid levels improved, however, she ultimately died due to complications from her hospitalization. DISCUSSION: PG causes toxicity through metabolism to lactic acid. While there are small amounts in food products and medications, under the right circumstances, PG can accumulate and lead to significant toxicity.

Evaluating the incidence of engraftment syndrome with different melphalan formulations in adult multiple myeloma and immunoglobulin light chain amyloidosis patients undergoing autologous hematopoietic cell transplantation.

BACKGROUND: Engraftment syndrome (ES) is a common complication of autologous hematopoietic cell transplantation (HCT). The difference in incidence of ES between melphalan formulations has not been widely reported throughout the literature and would allow for a more comprehensive understanding of the advantages and disadvantages of both melphalan formulations. PATIENTS AND METHODS: This retrospective, single-center, observational study evaluated 83 adult multiple myeloma and immunoglobulin light chain amyloidosis patients who received either propylene glycol-containing (PG) or propylene glycol-free (PG-free) melphalan 140 mg/m2 as single-agent conditioning chemotherapy for autologous HCT from May 31, 2015 to May 31, 2019. The primary outcome was to assess the incidence of ES, as defined using the Maiolino criteria, with both melphalan formulations. Secondary outcomes included an analysis of potential risk factors for the development of ES, as well as an evaluation of overall length of stay (LOS). RESULTS: The incidence of ES for PG and PG-free melphalan did not differ significantly, 14/39 (35.9%) and 12/44 (27.3%) (P = 0.4), respectively. No potential risk factors for ES were identified on multivariate logistic regression analysis. A statistically significant difference in number of days to engraftment was identified for PG and PG-free melphalan, 15.56 vs. 13.82 days (P = 0.01), respectively; although, this did not translate to a decrease in LOS, 19.9 vs. 18.59 days (P = 0.14). CONCLUSIONS: The incidence of ES did not differ significantly between melphalan formulations. Future research is needed to determine whether the faster time to engraftment seen with PG-free melphalan may translate to a decrease in LOS.

Design and evaluation of molecular organogel based on folic acid as a potential green drug carrier for oral route.

OBJECTIVE: The low molecular weight organogels are interesting carriers for pharmaceutical compounds. However, their uses are limited due to the toxicity burden of the organic solvent used. Hence, this study aimed to prepare organogel using folic acid (FA) in different concentrations as a gelator for propylene glycol (PG) biocompatible solvent. METHODS: The simple mixing method followed by incubation in a water bath at 90 °C was used to prepare organogels. Then, formulations were assessed using different methods including differential scanning calorimetry (DSC), dropping method, attenuated total reflectance - Fourier transform infrared spectroscopy (ATR-FTIR), oscillatory rheology studies, scanning electron microscopy (SEM), and in vitro dissolution study. RESULTS: Gel formation and its consistency were highly depending on FA concentration. The results showed that increasing the concentration of FA in the organogel led to accelerating the gelation process, and the least amount of FA that could gel the PG was 0.25% w/w. However, higher concentrations were needed to create an organogel with excellent properties. The DSC and dropping studies revealed stable organogels formulations at body temperature. The ATR-FTIR showed interactions between the pteridine ring of FA and PG. The strain amplitude and frequency sweep tests demonstrated an increase in storage modulus values as the concentration of FA increased at 37 °C, which were frequency independent at high frequencies. In addition, the SEM exposed the fabrics like the structure of these organogels. Furthermore, the in vitro dissolution of organogel was pH-dependent, with a high possibility of taking place in the large intestine. CONCLUSION: FA/PG organogel formulation is a promising carrier for drug and nutraceuticals compound for the oral delivery system.

In Situ-Generated, Dispersed Cu Catalysts for the Catalytic Hydrogenolysis of Glycerol.

The present study is dedicated to the experimental verification of a concept for the hydrogenolysis of glycerol over in situ-generated Cu dispersed particles (Cu-DP). The Cu-DP were generated by in situ reduction of a precursor salt (Cu(OAc)2, CuSO4, CuCl2) in the presence of KOH and were active in glycerol conversion under hydrogen (T = 200-220 °C, p(H2) = 1-4 MPa), where 1,2-propylene glycol (PG) and lactic acid (LA) were detected to be the main products. The influence of the reaction conditions (temperature, hydrogen pressure, reaction time, catalyst-to-feed ratio and the KOH/Cu ratio) on the yields of the products is described. It was shown that the selectivity between the PG and LA could be tuned by changing p(H2) or by the KOH amount, i.e., higher yields of LA corresponded to lower p(H2) and higher alkalinity of the reaction media. The activity of the in situ-generated Cu-DP was found to be comparable to that of an industrial Cu-Cr2O3 catalyst. The Cu-DP catalysts were characterized by XRD, XPS, HRTEM and SEM. During the reaction, the catalyst evolved by the sintering and recrystallization of the separate Cu-DP; the crystallite sizes after 1 and 15 h reaction times amounted to 35 and 49 nm, respectively.