Vitamin E Acetate Research Articles

Vaping Aerosols from Vitamin E Acetate and Tetrahydrocannabinol Oil: Chemistry and Composition.

The popularity of vaping cannabis products has increased sharply in recent years. In 2019, a sudden onset of electronic cigarette/vaping-associated lung injury (EVALI) was reported, leading to thousands of cases of lung illness and dozens of deaths due to the vaping of tetrahydrocannabinol (THC)-containing e-liquids that were obtained on the black market. A potential cause of EVALI has been hypothesized due to the illicit use of vitamin E acetate (VEA) in cannabis vape cartridges. However, the chemistry that modifies VEA and THC oil, to potentially produce toxic byproducts, is not well understood under different scenarios of use. In this work, we quantified carbonyls, organic acids, cannabinoids, and terpenes in the vaping aerosol of pure VEA, purified THC oil, and an equal volume mixture of VEA and THC oil at various coil temperatures (100-300 °C). It was found under the conditions of our study that degradation of VEA and cannabinoids, including Δ9-THC and cannabigerol (CBG), occurred via radical oxidation and direct thermal decomposition pathways. Evidence of terpene degradation was also observed. The bond cleavage of aliphatic side chains in both VEA and cannabinoids formed a variety of smaller carbonyls. Oxidation at the ring positions of cannabinoids formed various functionalized products. We show that THC oil has a stronger tendency to aerosolize and degrade compared to VEA at a given temperature. The addition of VEA to the e-liquid nonlinearly suppressed the formation of vape aerosol compared to THC oil. At the same time, toxic carbonyls including formaldehyde, 4-methylpentanal, glyoxal, or diacetyl and its isomers were highly enhanced in VEA e-liquid when normalized to particle mass.

Role of cannabinoids and vitamin E analogues in macrophages foam cells formation

Recently, macrophages foam cells have gained attention in cases of electronic‐cigarette or vaping product use‐associated lung injury (EVALI). An increased number of foam cells was detected in bronchoalveolar lavages and lungs after inhaling e‐cigarette smoke from products containing cannabinoids and the vitamin E analogue, alpha‐tocopherol acetate (αTA), that was present as vape‐cartridge additive. Increased levels of intact αTA are reportedly detected in EVALI indicating that conversion of αTA to αT may less occur in lungs upon inhaling vapors from e‐cigarettes containing αTA.HypothesisWhereas the molecular mechanisms by which macrophages foam cells are formed after vaping are unclear, it appears possible that cannabinoid receptors play a role, as lung‐resident macrophages express cannabinoid receptors. Dysregulation of cannabinoid receptors by αTA and cannabinoids may induce the CD36 scavenger receptor/fatty acids transporter (CD36/FAT) and/or reduce the ATP binding cassette transporters A1 and G1 (ABCA1/G1) expression leading to lipid accumulation. Therefore, we analyzed the regulatory effects on lipid homeostasis of natural alpha‐tocopherol (RRR‐αT), natural RRR‐αTA (αTAn) and synthetic racemic all‐rac‐αTA (αTAr) with and without co‐treatment with cannabinoids (cannabinol (CBD), Δ9‐tetrahydrocannabinol (THC)) in THP‐1 monocytes and macrophages (differentiated for 48 h with 100 ng/ml phorbol‐12‐myristate‐13‐acetate (PMA)).ResultsQuantification of lipids in macrophages indicated that more lipids accumulate with αT, less with αTAn and αTAr, whereas control alpha‐tocopheryl phosphate (αTP) clearly inhibited. Co‐treatment with THC increased lipid accumulation with αT, αTAn as well as with CBD, whereas αTP again clearly inhibited. In THP‐1 monocytes, CD36 scavenger receptor was stimulated with αTAn and THC and with co‐treatment with THC and αTAn or CBD. In THP‐1 macrophages, CD36 was only up‐regulated by CBD and co‐treatment with αTAn or αTAr reduced it. In THP‐1 monocytes, cell cycle progression was only affected by CBD (increased G1, decreased S) and co‐treatment with αTAn and αTAr restored it. In macrophages, no significant toxicity was measured with lactate dehydrogenase (LDH) release assay by these treatments at 24 h, 48 h and 72 h at αTA concentrations below 50 μM.SummaryAlthough the mechanisms by which intact αTA may affect lungs in cases of EVALI are still unclear it may disrupt the pulmonary surfactant, act as linactant, and/or dysregulate lipid homeostasis and contribute to formation of macrophages foam cells and inflammation. Lipid accumulation in monocytes/macrophages and foam cells formation were modulated by cannabinoids and αTA but the involvement of lipid homeostasis genes such as CD36/FAT and ABCA1/G1 remains to be further elucidated. A detailed analysis of the molecular mechanisms by which foam cells are formed will not only be important to understand EVALI but also for atherosclerosis and non‐alcoholic steatohepatitis (NASH).

The effects of vitamin E acetate and its role in vaping: A systematic review

Hypothesis: The inhalation of vitamin E acetate (VEA) results in an e-cigarette or vaping use associated with lung injury (EVALI) and lipoid pneumonia in individuals who vape. Methods: We utilized databases such as PubMed, Google Scholar, Medline, Medscape, and gray literature to search for relevant literature. Results: Our study displayed that after inhalation of vitamin E acetate from vaping, the chemical elicits a strong immune response. Vape liquid has been extensively studied for its composition and toxicity in humans. Many emergency departments have reported cases of EVALI in healthy individuals that have required ventilatory support for survival. Careful history taking of these individuals revealed that they had inhaled vape smoke that contained VEA. In addition, the bronchoalveolar lavage (BAL) fluids of other patients with a positive vaping history showed numerous lipid-laden macrophages, suggesting that exogenous exposure to VEA plays a role in the etiology of lipoid pneumonia. Conclusions: Our study concluded that when heated, vitamin E acetate and its additives are capable of causing significant respiratory harm. However, further research is needed to determine the exact effects of vitamin E acetate in individuals who vape.

E-Cigarette (E-Cig) Liquid Composition and Operational Voltage Define the In Vitro Toxicity of Δ8Tetrahydrocannabinol/Vitamin E Acetate (Δ8THC/VEA) E-Cig Aerosols.

The 2019 United States outbreak of E-cigarette (e-cig), or Vaping, Associated Acute Lung Injury (EVALI) has been linked to presence of vitamin E acetate (VEA) in Δ8tetrahydrocannabinol (Δ8THC)-containing e-liquids, as supported by VEA detection in patient biological samples. However, the pathogenesis of EVALI and the complex physicochemical properties of e-cig emissions remain unclear, raising concerns on health risks of vaping. This study investigates the effect of Δ8THC/VEA e-liquids and e-cig operational voltage on in vitro toxicity of e-cig aerosols. A novel E-cigExposure Generation System platform was used to generate and characterize e-cig aerosols from a panel of Δ8THC/VEA or nicotine-based e-liquids at 3.7 or 5 V. Human lung Calu-3 cells and THP-1 monocytes were exposed to cell culture media conditioned with collected e-cig aerosol condensate at doses of 85 and 257 puffs/m2 lung surface for 24 h, whereafter specific toxicological endpoints were assessed (including cytotoxicity, metabolic activity, reactive oxygen species generation, apoptosis, and inflammatory cytokines). Higher concentrations of gaseous volatile organic compounds were emitted from Δ8THC/VEA compared with nicotine-based e-liquids, especially at 5 V. Emitted PM2.5 concentrations in aerosol were higher for Δ8THC/VEA at 5 V and averagely for nicotine-based e-liquids at 3.7 V. Overall, aerosols from nicotine-based e-liquids showed higher bioactivity than Δ8THC/VEA aerosols in THP-1 cells, with no apparent differences in Calu-3 cells. Importantly, presence of VEA in Δ8THC and menthol flavoring in nicotine-based e-liquids increased cytotoxicity of aerosols across both cell lines, especially at 5 V. This study systematically investigates the physicochemical and toxicological properties of a model of Δ8THC/VEA and nicotine e-cigarette condensate exposure demonstrating that pyrolysis of these mixtures can generate hazardous toxicants whose synergistic actions potentially drive acute lung injury upon inhalation.

Prophylactic efficacy of recombinant interferon alfa-2b in pregnant women during their stay in the family with SARS-CoV-2 infection: prospective study

Background. The high contagiousness and susceptibility of a pregnant woman's body to a new coronavirus infection requires study not only of etiopathogenesis, but also of developing methods to prevent the development of this disease.
 Aim. To evaluate the preventive effectiveness of the use of a drug containing recombinant interferon alfa-2b (IFN-a2b) and an antioxidant complex in pregnant women during their stay in the family focus of a new coronavirus infection.
 Materials and methods. 75 pregnant women were under observation, in whose family there were patients infected with the virus that causes a new coronavirus infection. Treatment of sick relatives was carried out at home, as the disease in them proceeded in an uncomplicated form. The main group was formed by 37 pregnant women who treated the nasal mucosa with a preparation containing recombinant IFN-a2b in the amount of 5000 IU and an antioxidant complex (alpha-tocopherol acetate, citric and benzoic acids). The comparison group was formed by 38 pregnant women who did not use any drugs for prophylactic purposes. All patients observed generally accepted rules of personal hygiene and behavior. The duration of prophylactic use of the indicated medicinal product depended on obtaining a negative result for the causative agent of a new coronavirus disease, an infected family member. A smear from the nasopharynx and oropharynx was examined to detect SARS-CoV-2 RNA by PCR once every 57 days.
 Results. COVID-19 vaccination did not exclude infection with the SARS-CoV-2. Preventive treatment of the nasal mucosa with an IFN-a2b containing drug reduced the risk of infection with this viral agent in vaccinated patients who were in household contact with a patient with COVID-19 by 6 times. Asymptomatic and mild course of a new coronavirus infection was observed in 3 (25%) and 7 (58.3%) patients of 12 infected women from the main group and in 8 (22.9%) and 18 (51.4%) patients of 35 infected women from the comparison group, respectively. Further local use of the drug containing recombinant IFN-a2b and an antioxidant complex contributed to a decrease in the duration of infection and the course of the disease. Progression of COVID-19 was observed in unvaccinated patients with concomitant somatic pathology (diabetes mellitus, iron deficiency anemia, cardiovascular diseases, etc.): 2 (16.7%) and 9 (25.7%) people in groups, respectively.
 Conclusion. The use of recombinant IFN-a2b with an antioxidant complex in pregnant women with a family focus of new coronavirus infection is clinically appropriate and highly effective.

Temperature dependence of emission product distribution from vaping of vitamin E acetate.

Nearly two years after vitamin E acetate (VEA) was identified as the potential cause of the 2019–2020 outbreak of e-cigarette, or vaping product-associated lung injuries (EVALI), the toxicity mechanisms of VEA vaping are still yet to be fully understood. Studies since the outbreak have found that e-liquids such as VEA undergo thermal degradation during the vaping process to produce various degradation products, which may pose a greater risk of toxicity than exposure to unvaped VEA. Additionally, a wide range of customizable parameters–including the model of e-cigarette used, puffing topography, or the applied power/temperature used to generate aerosols–have been found to influence the physical properties and chemical compositions of vaping emissions. However, the impact of heating coil temperature on the chemical composition of VEA vaping emissions has not been fully assessed. In this study, we investigated the emission product distribution of VEA vaping emissions produced at temperatures ranging from 176 to 356°C, corresponding to a variable voltage vape pen set at 3.3 to 4.8V. VEA degradation was found to be greatly enhanced with increasing temperature, resulting in a shift towards the production of lower molecular weight compounds, such as the redox active duroquinone (DQ) and short-chain alkenes. Low temperature vaping of VEA resulted in the production of long-chain molecules, such as phytol, exposure to which has been suggested to induce lung damage in previous studies. Furthermore, differential product distribution was observed in VEA degradation products generated from vaping and from pyrolysis using a tube furnace in the absence of the heating coil at equivalent temperatures, suggesting the presence of external factors such as metals or oxidation that may enhance VEA degradation during vaping. Overall, our findings indicate that vaping behavior may significantly impact the risk of exposure to toxic vaping products and potential for vaping-related health concerns.

102 Vaping of Vitamin E Acetate Causes Acute Lung Injury in a Dose-dependent Manner in Sheep

IntroductionThe Centers for Disease Control and Prevention and the Food and Drug Administration have reported an increasing number of clinical cases of pulmonary injury following the use of e-cigarette/vaping products. Although the causative factors for the national outbreak of electronic-cigarette, or vaping product use-associated lung injury (EVALI) has not been established, CDC reported that vitamin E acetate (VEA) is strongly linked to the EVALI outbreak. In this study, we tested the hypothesis that VEA vaping causes acute lung injury in a dose-dependent manner in a sheep model.MethodsSheep were surgically prepared under anesthesia and analgesia with multiple vascular catheters (pulmonary arterial, left atrial, and femoral arterial). To assess pulmonary edema, the mediastinal lymph node vessel draining the lung was cannulated. After a 5-day surgical recovery, a tracheostomy tube and urinary catheter were placed. Then, the sheep were placed on a mechanical ventilator and VEA vaping was immediately started in the following groups: (1) vaped with glycerol (n=1); (2) vaped with 0.4mg of VEA (n=2); (3) vaped with 0.6mg of VEA (n=1); (4) vaped with 0.8mg of VEA (n=7); and (5) not injured, not treated (Sham, n=6). Sheep were resuscitated with lactated Ringer’s solution (4mL/kg/hr). Sheep in a conscious state was monitored with 4 hrs intervals for cardiopulmonary variables for 48 hrs.ResultsPulmonary gas exchange, represented by the PaO2/FiO2 ratio, was unchanged in sham, glycerol, and 0.4 mg VEA groups. In the 0.6 VEA group, the PaO2/FiO2 ratio was decreased from 42 to 48 hrs, while in the 0.8 mg VEA group, it was strongly decreased starting at 24 hrs and remained low throughout the remaining period. Lung lymph flow, an index of pulmonary microvascular permeability, was increased more than 2-fold in 0.6 and 0.8 mg VEA groups. Lung compliance also tended to decrease in all VEA groups.ConclusionsVEA vaping causes acute lung injury in a dose-dependent manner in sheep. Further studies should investigate underlying mechanistic aspects that cause increased microvascular permeability.

Aerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages.

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. We used mass spectrometry to evaluate the composition of aerosolized VEA condensate and the VEA deposition in murine or human alveolar macrophages. Extended vaping for 28 days versus 15 days did not worsen lung injury but caused systemic inflammation in the murine EVALI model. Vaping plus influenza increased lung water compared with virus alone. Murine alveolar macrophages exposed to vaped VEA hydrolyzed the VEA to vitamin E with evidence of oxidative stress in the alveolar space and systemic circulation. Aerosolized VEA also induced cell death and chemokine release and reduced efferocytotic function in human alveolar macrophages in vitro. These findings provide new insights into the biological mechanisms of VEA toxicity.

Lipid-liquid crystals for 2 months controlled risperidone release: In-vitro evaluation and pharmacokinetics in rabbits

In this study, a drug delivery system based on lipid liquid crystal (LLC) was developed for the long-term delivery of risperidone to improve psychological treatment. Optimal LLC formulation was achieved based on maximum release after 60 days with different ratios of phosphatidylcholine (PC) to sorbitol monooleate (PC: SMO), tween grade 80 (w/w %), and tocopherol acetate (TA) (w/w %) using the Box-Behnken method. In vitro and ex vivo studies, pharmacokinetics, and histopathological examination in rabbits were conducted to compare the optimal LLC with Risperdal CONSTA®. The optimum formulation containing the PC to SMO ratio of 58.6%, tween 0.82% w/w, and TA 3.6% w/w was selected because it had the highest drug release percentage (100%) during about two months. Polarized optical microscopy (POM) revealed HII mesophase with a 2-dimensional structure. Cell culture also revealed moderate cytotoxicity for LLC-risperidone. Pharmacokinetic data displayed that the optimal LLC created a more consistent drug serum level within 60 days, and histopathology results demonstrated slight to moderate damage in rabbits’ organs. Furthermore, the accelerated stability test confirmed optimum stability for LLC and risperidone. This study confirmed the better pharmacokinetic potentials of SMO-based LLC systems compared with Risperdal CONSTA®, which would promote patient compliance and obviate the difficulties of additional oral therapy.

Analysis of the Aerosol Generated from Tetrahydrocannabinol, Vitamin E Acetate, and Their Mixtures.

E-cigarette, or vaping, product use–associated lung injury (EVALI) outbreak was linked to vitamin E acetate (VEA) used as a solvent for tetrahydrocannabinol (THC). Several studies were conducted to assess the products of VEA (and THC/VEA mixtures) thermal degradation as a result of vaporizing/aerosolizing from a traditional type (coil—cotton wick) and ceramic type coil vape pens. The particle size distribution (PSD) of VEA aerosol and the temperature VEA and THC/VEA mixtures are heated to were also measured for a few types of traditional and ceramic vape pens. The current study assessed the PSD of the aerosol generated from THC, VEA, and a number of THC/VEA mixtures using a dab-type vape pen under two different temperature settings and two puffing flow rates. Thermal degradation of THC, VEA, and THC/VEA mixtures were also assessed, and coil temperature was measured. Results showed the dependence of the PSD upon the chemical content of the aerosolized mixture as well as upon the puffing flow rate. Minimal thermal degradation was observed. Flaws in the vape pen’s design, which most likely affected results, were detected. The suitability of VEA, THC, and THC/VEA mixtures with certain types of vape pens was discussed.

The development of portal hypertension and liver failure on the background of long-term intake of vitamin A in a young woman. Case report

The use of over-the-Counter (OTC) pharmaceuticals is a common phenomenon in today's society. We present a case of liver injury associated with long-term OTC use of vitamin A. The young patient took daily up to 15 capsules of a combined preparation for 2 years containing retinol palmitate 55 mg (100,000 IU) + Alpha-Tocopherol acetate 100 mg, the content of vitamin A in which significantly exceeded the recommended daily dose. Gradually, the patient noted the appearance of arthralgia, skin itching, hyperemia of the palms and feet, exfoliation of the skin on the soles, profuse hair loss, cracks in the corners of the mouth and in the area of the earlobes. Patient's condition worsened with the development of signs of liver cirrhosis in the form of portal hypertension (ascites, splenomegaly) and a decrease in the protein-synthetic function of the organ. Chronic viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis, Wilson's disease, alcoholic liver disease were exclude. Liver biopsy showed characteristic signs of hypervitaminosis A without fibrosis. A complete regression of symptoms was observe within 8 months after discontinuation of the drug. A toxicity can lead to serious liver injury and should be considere in the differential diagnosis of chronic liver disease. Vitamin A should only be prescribe for medical reasons, for a limited period of time, and under close medical supervision.

Duckweed as a future food: Evidence from metabolite profile, nutritional and microbial analyses

Duckweed species are nutritionally meaningless plant which grow wildly in unattended areas. Therefore, understanding the metabolites content in duckweed species is essential for designing a future food products. Here, we report an untargeted Gas Chromatography-Mass Spectrometry (GC-MS)-based metabolomics approach for comprehensively discriminating between Lemna minor and Wolffia globosa of duckweeds species using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). Ten differential metabolites levels were tentatively identified between L. minor and W. globosa. Relative to W. globosa, L. minor appeared to enrich with 5-Hydroxyl-L-tryptophan, Tocopheryl acetate, Naringenin, α-linolenic acid and glutamic acid. Furthermore, the nutritional and microbial analyses of ice cream formulated with dried L. minor were investigated. The nutritional analysis results show that relative to control, the ice cream with 2% dried L. minor had significantly increased protein, fiber and ash content. In addition, total plate count (TPC) for microbial analysis of duckweed ice cream was performed. The result suggested that the small amount of bacteria (3.82 cfu/g) was traced in formulated ice cream with 2% dried L. minor. Overall, the metabolites profile, nutritional and microbial analyses of food used L. minor plant indicate that duckweed is a good candidate for future food.

Perianal Application of Glyceryl Trinitrate Ointment Versus Tocopherol Acetate Ointment in the Treatment of Chronic Anal Fissure: A Randomized Clinical Trial.

Medical treatment, including glyceryl trinitrate ointment, represents the first step for the management of chronic anal fissure. However, glyceryl trinitrate ointment is associated with headache and, consequently, a high withdrawal rate of the treatment. The aim of the present study was to evaluate the effect of the topical application of tocopherol acetate ointment on pain relief and chronic anal fissure epithelialization, comparing it with the effect of a standard treatment with glyceryl trinitrate ointment. This is a 2-parallel-group, single-center, randomized controlled, intent-to-treat clinical trial. This study was conducted at the Garcilaso Clinic affiliated with Universidad Alfonso X (Madrid, Spain). Patients with chronic anal fissure were selected. Patients were randomly assigned into 2 groups: patients receiving tocopherol acetate ointment and patients receiving glyceryl trinitrate ointment. The primary end point was quantification of anal pain 8 weeks after beginning the treatment as measured by a Visual Analogue Scale ranging from 0 to 100 mm. The secondary end points were the healing rate (during the treatment period of 8 weeks) and the recurrence rate. One hundred sixty consecutive patients were treated, 80 in each group. By 8 weeks after treatment, mean anal pain score declined by 56.2 mm in the glyceryl trinitrate ointment group compared with a mean anal pain score decline of 67.1 mm in the tocopherol acetate ointment group (mean difference, 10.9 mm (95% CI, 4.3-18.6); p = 0.018). Sixteen weeks after finishing the therapy, the recurrence rate was 13.2% in the glyceryl trinitrate ointment group vs 2.9 in the tocopherol acetate ointment group (p = 0.031). Limitations of the study include the absence of manometric measurements of the internal anal sphincter before and after the treatments and the use of glyceryl trinitrate ointment as an active comparator, whereas calcium channel blockers are actually the standard treatment. Anal pain was significantly lower in the tocopherol acetate ointment group than in the glyceryl trinitrate ointment group at 8 weeks after treatment. Tocopherol acetate ointment achieved a greater healing rate and a lower recurrence rate 16 weeks after finishing the treatment. See Video Abstract at http://links.lww.com/DCR/B751. URL: https://www.clinicaltrials.gov; Identifier: NCT03787030.APLICACIÓN PERIANAL DE POMADA DE TRINITRATO DE GLICERILO FRENTE A LA POMADA DE ACETATO DE TOCOFEROL EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: UN ENSAYO CLÍNICO ALEATORIZADOANTECEDENTES:El tratamiento médico, incluida la pomada de trinitrato de glicerilo, representa el primer paso para el tratamiento de la fisura anal crónica. Sin embargo, la pomada de trinitrato de glicerilo se asocia con cefalea y, en consecuencia, una alta tasa de cancelación del tratamiento.OBJETIVO:El objetivo del presente estudio fue evaluar el efecto de la aplicación tópica de pomada de acetato de tocoferol en el alivio del dolor y la epitelización de la fisura anal crónica, comparándolo con el efecto de un tratamiento estándar con pomada de trinitrato de glicerilo.DISEÑO:Ensayo clínico con intención de tratar controlado, aleatorizado, de un solo centro, con dos grupos paralelos.ESCENARIO:Clínica Garcilaso adscrita a la Universidad Alfonso X (Madrid, España).PACIENTES:Pacientes con fisura anal crónica.INTERVENCIONES:Los pacientes fueron aleatorizados en 2 grupos: pacientes que recibieron pomada de acetato de tocoferol y pacientes que recibieron pomada de trinitrato de glicerilo.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la cuantificación del dolor anal 8 semanas después de comenzar el tratamiento, medido por la escala analógica visual que varía de 0 a 100 mm. Los criterios de valoración secundarios fueron la tasa de curación (durante el período de tratamiento de 8 semanas) y la tasa de recurrencia.RESULTADOS:Se trataron ciento sesenta pacientes consecutivos, 80 en cada grupo. A las ocho semanas después del tratamiento, la puntuación media de dolor anal se redujo en 56.2 mm en el grupo de pomada de trinitrato de glicerilo en comparación con una disminución de la puntuación de dolor anal medio de 67.1 mm en el grupo de pomada de acetato de tocoferol (diferencia media: 10.9 mm (intervalo de confianza del 95%; 4.3 a 18.6; p = 0.018) Dieciséis semanas después de finalizar la terapia, la tasa de recurrencia fue del 13.2% en el grupo de pomada de trinitrato de glicerilo frente a 2.9 en el grupo de pomada de acetato de tocoferol (p = 0.031).LIMITACIONES:Ausencia de medidas manométricas del esfínter anal interno antes y después de los tratamientos. Ungüento de trinitrato de glicerilo como comparador activo, mientras que los bloqueadores de los canales de calcio son en realidad el tratamiento estándar de oro.CONCLUSIONES:El dolor anal fue significativamente menor en el grupo de ungüento de acetato de tocoferol que en el grupo de ungüento de trinitrato de glicerilo a las 8 semanas después del tratamiento. La pomada de acetato de tocoferol logró una mayor tasa de curación y una menor tasa de recurrencia 16 semanas después de finalizar el tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B751. (Traducción-Dr. Jorge Silva Velazco).

Formation of Redox-Active Duroquinone from Vaping of Vitamin E Acetate Contributes to Oxidative Lung Injury.

In late 2019, the outbreak of e-cigarette or vaping-associated lung injuries (EVALIs) in the United States demonstrated to the public the potential health risks of vaping. While studies since the outbreak have identified vitamin E acetate (VEA), a diluent of tetrahydrocannabinol (THC) in vape cartridges, as a potential contributor to lung injuries, the molecular mechanisms through which VEA may cause damage are still unclear. Recent studies have found that the thermal degradation of e-liquids during vaping can result in the formation of products that are more toxic than the parent compounds. In this study, we assessed the role of duroquinone (DQ) in VEA vaping emissions that may act as a mechanism through which VEA vaping causes lung damage. VEA vaping emissions were collected and analyzed for their potential to generate reactive oxygen species (ROS) and induce oxidative stress-associated gene expression in human bronchial epithelial cells (BEAS-2B). Significant ROS generation by VEA vaping emissions was observed in both acellular and cellular systems. Furthermore, exposure to vaping emissions resulted in significant upregulation of NQO1 and HMOX-1 genes in BEAS-2B cells, indicating a strong potential for vaped VEA to cause oxidative damage and acute lung injury; the effects are more profound than exposure to equivalent concentrations of DQ alone. Our findings suggest that there may be synergistic interactions between thermal decomposition products of VEA, highlighting the multifaceted nature of vaping toxicity.

Chemical Emissions From Heated Vitamin E Acetate-Insights to Respiratory Risks From Electronic Cigarette Liquid Oil Diluents Used in the Aerosolization of Δ9-THC-Containing Products.

As of February 18, 2020, the e-cigarette, or vaping, product use associated lung injury (EVALI) outbreak caused the hospitalization of a total of 2,807 patients and claimed 68 lives in the United States. Though investigations have reported a strong association with vitamin E acetate (VEA), evidence from reported EVALI cases is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC or non-THC products. This study characterized chemicals evolved when diluent oils were heated to temperatures that mimic e-cigarette, or vaping, products (EVPs) to investigate production of potentially toxic chemicals that might have caused lung injury. VEA, vitamin E, coconut, and medium chain triglyceride (MCT) oil were each diluted with ethanol and then tested for constituents and impurities using a gas chromatograph mass spectrometer (GC/MS). Undiluted oils were heated at 25°C (control), 150°C, and 250°C in an inert chamber to mimic a range of temperatures indicative of aerosolization from EVPs. Volatilized chemicals were collected using thermal desorption tubes, analyzed using a GC/MS, and identified. Presence of identified chemicals was confirmed using retention time and ion spectra matching with analytic standards. Direct analysis of oils, as received, revealed that VEA and vitamin E were the main constituents of their oils, and coconut and MCT oils were nearly identical having two main constituents: glycerol tricaprylate and 2-(decanoyloxy) propane-1,3-diyl dioctanoate. More chemicals were measured and with greater intensities when diluent oils were heated at 250°C compared to 150°C and 25°C. Vitamin E and coconut/MCT oils produced different chemical emissions. The presence of some identified chemicals is of potential health consequence because many are known respiratory irritants and acute respiratory toxins. Exposure to a mixture of hazardous chemicals may be relevant to the development or exacerbation of EVALI, especially when in concert with physical damage caused by lung deposition of aerosols produced by aerosolizing diluent oils.

In Silico Evaluation of Enzymatic Tunnels in the Biotransformation of α-Tocopherol Esters.

Motivation: α-Tocopherol is a molecule obtained primarily from plant sources that are important for the pharmaceutical and cosmetics industry. However, this component has some limitations such as sensitivity to oxygen, presence of light, and high temperatures. For this molecule to become more widely used, it is important to carry out a structural modification so that there is better stability and thus it can carry out its activities. To carry out this structural modification, some modifications are carried out, including the application of biotransformation using enzymes as biocatalysts. Thus, the application of a computational tool that helps in understanding the transport mechanisms of molecules in the tunnels present in the enzymatic structures is of fundamental importance because it promotes a computational screening facilitating bench applications. Objective: The aim of this work was to perform a computational analysis of the biotransformation of α-tocopherol into tocopherol esters, observing the tunnels present in the enzymatic structures as well as the energies which correspond to the transport of molecules. Method: To carry out this work, 9 lipases from different organisms were selected; their structures were analyzed by identifying the tunnels (quantity, conformation, and possibility of transport) and later the calculations of substrate transport for the biotransformation reaction in the identified tunnels were carried out. Additionally, the transport of the product obtained in the reaction through the tunnels was also carried out. Results: In this work, the quantity of existing tunnels in the morphological conformational characteristics in the lipases was verified. Thus, the enzymes with fewer tunnels were RML (3 tunnels), LBC and RNL (4 tunnels), PBLL (5 tunnels), CALB (6 tunnels), HLG (7 tunnels), and LCR and LTL (8 tunnels) and followed by the enzyme LPP with the largest number of tunnels (39 tunnels). However, the enzyme that was most likely to transport substrates in terms of α-tocopherol biotransformation (in relation to the Emax and Ea energies of ligands and products) was CALB, as it obtains conformational and transport characteristics of molecules with a particularity. The most conditions of transport analysis were α-tocopherol tunnel 3 (Emax: −4.6 kcal/mol; Ea: 1.1 kcal/mol), vinyl acetate tunnel 1 (Emax: −2.4 kcal/mol; Ea: 0.1 kcal/mol), and tocopherol acetate tunnel 2 (Emax: −3.7 kcal/mol; Ea: 2 kcal/mol).

Effect of α-dl tocopherol acetate (antioxidant) enriched edible coating on the physicochemical, functional properties and shelf life of minimally processed carrots (Daucus carota subsp. sativus)

The present study was carried out to investigate the effect of varying sodium alginate-based edible coating (1, 2, and 3 %, w/v) supplemented with α- tocopherol acetate (antioxidant) at different concentrations (0.5 and 1 % w/v) on minimally processed carrot slices during 15 d storage at 10 °C and 65 % relative humidity. Seven different formulations (T1- T7) comprising different alginate and antioxidant combination were tested for selecting the best formulation maintaining the physicochemical attributes, antioxidant potential, carotenoid content, and overall acceptability (microbial counts) of carrot slices. Treatment T4 (2% sodium alginate + 1% α-tocopherol acetate) served as the best formulation in maintaining the quality, acceptability, nutritive value of minimally processed carrots. The T4 treated carrot samples showed minimum variation in weight loss, TSS, pH, whiteness index, reducing sugar, ascorbic acid content, TPC, antioxidant activity, total carotenoids, total aerobic bacterial count and yeast and mold counts, respectively in comparison to other treatments during storage. The statistical analysis also confirmed the significant (p<0.05) variation in physicochemical properties, antioxidant potential, carotenoid content and microbial count in control samples than edible coating formulations during storage.

Expression Profiling of Selected Immune Genes and Trabecular Microarchitecture in Breast Cancer Skeletal Metastases Model: Effect of α-Tocopherol Acetate Supplementation.

Breast cancer bone metastases (BCBM) result in serious skeletal morbidity. Although there have been important advances in cancer treatment methods such as surgery and chemotherapy, the complementary treatments, such as α-tocopherol acetate (ATA), still remain of key role via complementary and/or synergistic effects. The aim of this work was to study immune response in a rat model of BCBM due to Walker 256/B cells inoculation and the effect of ATA alone. Compared to the control group (CTRL), rat injected with Walker 256/B cells (5 × 104) in the medullar cavity (W256 group) showed osteolytic damages with marked tumor osteolysis of both cancellous and trabecular bone as assessed by X-ray radiology, micro-computed tomography, and histology. Rats inoculated with Walker 256/B cells and treated with ATA (45mg/kg BW, W256ATA group) presented marked less tumor osteolysis, less disturbance of Tb.Th and Tb.Sp associated with conversion of rods into plates, and increased structure model index and trabecular pattern factor (Tb.Pf). Elsewhere, 3D frequency distributions of Tb.Th and Tb.Sp were highly disturbed in metastatic W256 rats. Overexpression of some genes commonly associated with cancer and metastatic proliferation: COX-2, TNF-α, and pro-inflammatory interleukins 1 and 6 was outlined. ATA alleviated most of the Walker 256/B cells-induced microarchitectural changes in the target parameters without turning back to normal levels. Likewise, it alleviates the BCSM-induced overexpression of COX-2, TNF-α, IL-1, and IL-6. In silico approach showed that ATA bound these proteins with high affinities, which satisfactory explain its beneficial effects. In conclusion,BCBM is associated with bone microarchitectural disorders and an immune response characterized by an overexpression of some key role genes in cancer proliferation and invasion. ATA exerted favorable effects on trabecular bone distribution and morphology, which may involve the COX-2, TNF-α, and ILs pathways.

EFFECT OF IONIC STRENGTH AND ACTIVE ACIDITY OF THE MEDIUM ON THE STABILITY OF VITAMIN E NANOEMULSIONS (ALPHA-TOCOPHEROL ACETATE)

In this work, the influence of the ionic strength and active acidity of the medium on the stability of vitamin E (alpha-tocopherol acetate) nanoemulsions was studied. Vitamin E nanoemulsions were obtained by mixing an aqueous solubilizer solution with vitamin E. Nonionic surfactants Tween 80 and Kolliphor HS 15 were used as solubilizers. The obtained samples were studied by dynamic light scattering on a Photocor-Complex device. It has been established that samples of vitamin E nanoemulsions have a monomodal size distribution. The hydrodynamic radius of vitamin E micelles obtained with Kolliphor HS 15 is 12 ± 4 nm, and with Tween 80 it is 160 ± 21 nm. The study of the influence of ionic strength on the stability of vitamin E nanoemulsions showed that in the range of ionic strength from 0.1 to 3.0 mol/dm3, there are no significant changes in the hydrodynamic radius of vitamin E micelles, and with an increase in ionic strength up to 5.0 mol/dm3 “jumping” change in the hydrodynamic radius of vitamin E micelles when using both nonionic surfactants. It has been shown that at pH &gt; 9, the hydrodynamic radius of micelles of vitamin E nanoemulsion obtained using Kolliphor HS 15 increases from 12 to 255 nm, which is associated with alkaline hydrolysis of ether groups of Kolliphor HS 15. Nanoemulsions of vitamin E solubilized in Tween 80 micelles are stable over the entire pH range from 1.65 to 12.43.

Влияние метаболического синдрома на изменение показателей микроэлементного статуса и системы перекисного окисления липидов у пациентов с вульгарным псориазом

Aim. To study the effect of metabolic syndrome on changes in the indicators of trace element status and lipid peroxidation system in patients with psoriasis vulgaris. Materials and methods. In the framework of this work, 80 patients were examined with a diagnosis of vulgar psoriasis (group I without metabolic syndrome, group II with metabolic syndrome). The study of the trace element status, the serum content of 25-OH hydroxycalciferol, alpha– tocopherol acetate, as well as the state of the lipid peroxidation system were carried out. Results. in patients with metabolic syndrome, were discovered: a decrease in the indicators of trace element status and vitamins, an increase in the overall oxidative capacity of the blood, an increase in the level of oxidative low-density lipoproteins, as well as a decrease in the overall antioxidant activity of the blood. Conclusion. The obtained data allows to develop recommendations for the management and treatment of patients with vulgar psoriasis by correcting the microelement status and vitamins, which will reduce the influence of metabolic syndrome on the course of the psoriatic process at an early stage.