Undecylenic Acid Research Articles

Transungual Penetration and Antifungal Activity of Prescription and Over-the-Counter Topical Antifungals: Ex Vivo Comparison.

Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosis. Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded. In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1mm; T. mentagrophytes: 63.8mm) were significantly greater than those for tavaborole (63.5mm; 39.1mm), ciclopirox (7.4mm; 3.6mm) and all OTC products (range: 10.5-34.2mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7mm, respectively) and OTC products (range: 31.2-57.8mm and 25.7-47.7mm, respectively). Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail.

Antifungal Effect of Poly(methyl methacrylate) with Farnesol and Undecylenic Acid against Candida albicans Biofilm Formation.

The control of Candida albicans biofilm formation on dentures made of poly(methyl methacrylate) (PMMA) is an important challenge due to the high resistance to antifungal drugs. Interestingly, the natural compounds undecylenic acid (UDA) and farnesol (FAR) both prevent C. albicans biofilm formation and could have a synergetic effect. We therefore modified PMMA with a combination of UDA and FAR (UDA+FAR), aiming to obtain the antifungal PMMA_UDA+FAR composites. Equal concentrations of FAR and UDA were added to PMMA to reach 3%, 6%, and 9% in total of both compounds in composites. The physico-chemical properties of the composites were characterized by Fourier-transform infrared spectroscopy and water contact angle measurement. The antifungal activity of the composites was tested on both biofilm and planktonic cells with an XTT test 0 and 6 days after the composites' preparation. The effect of the UDA+FAR combination on C. albicans filamentation was studied in agar containing 0.0125% and 0.4% UDA+FAR after 24 h and 48 h of incubation. The results showed the presence of UDA and FAR on the composite and decreases in the water contact angle and metabolic activity of both the biofilm and planktonic cells at both time points at non-toxic UDA+FAR concentrations. Thus, the modification of PMMA with a combination of UDA+FAR reduces C. albicans biofilm formation on dentures and could be a promising anti-Candida strategy.

Ultrasound-assisted synthesis of novel undecylenic estolides: Modeling and Tribological characterization

Abstract To overcome the issues related to low-temperature characteristics and thermal degradation of fatty acid based lubricant base stocks, chemical modification is essential. To mitigate these shortcomings, considering unsaturated undecylenic acid, the formation of estolides is one of the best transformations considering application in lubricants. Ultrasonic-assisted sulfuric acid-catalyzed synthesis of estolides of undecylenic was modeled using response surface methodology (RSM) and subsequently validated using artificial neural network (ANN) for known and unknown input variables. At optimal reaction conditions of reaction temperature of 56°C, catalyst loading of 0.63 mole-equivalent, and reaction time of 1.61 hours, estolides with estolide number (EN) of 2.58, extraordinary low pour point (PP) of −52°C and better resistance to thermal degradation was obtained. The thermal degradation was evaluated using thermogravimetric analysis (TGA) to find improved resistance toward degradation due to the formation of estolides. Further, tribological properties like wear characteristics, load carrying capacity, and oxidative stability were studied for 5% blends in SN 70 base oil. The anti-wear ability of the estolides was found to be superior to undecylenic acid, with a lower coefficient of friction, scar diameter, depth, and volume. The blend containing estolide was found to have load carrying capacity as high as 800 kgf. Moreover, owing to the double bond migration during the reaction, the oxidative stability of estolides was found to be inferior to the terminally unsaturated undecylenic acid.

Effect of Fatty Acid Unsaturation on the Intermolecular Weak Interaction at the Low-Rank Coal-Water Interface: Density Functional Theory Calculations and Experimental Study.

The study on the effect of fatty acid saturation on low-rank coal (LRC) flotation is still limited. In this investigation, density functional theory (DFT) combined with Zeta potential and Fourier transform infrared spectroscopy (FTIR) was used to study the mechanism of intermolecular weak interaction at the LRC-water interface of fatty acids (decanoic acid (DA), undecylenic acid (UA), and phenyl propionic acid (PA)) with different saturations and different dodecane (D) composition hydrocarbon oil-fatty acid mixed collectors (D-DA, D-UA, D-PA). The findings demonstrated that the hydrogen bond interaction and electrostatic interaction between the UA/PA with unsaturated bonded carbon chains and the LRC molecular fragments/water molecules were stronger than DA without a saturated bond carbon chain, and UA/PA strengthened its interaction with water molecules on the whole, even PA molecules would preferentially interact with water molecules. The unsaturated bond had a minimal impact on the adsorption of the LRC hydrophobic site, and the strength of the hydrogen bond between the mixed collector and LRC is D-DA > D-UA > D-PA. In the actual flotation process, the strong hydrogen bonding and electrostatic interaction between UA/PA and water molecules weaken the collection performance of the mixed collector D-UA/D-PA for LRC, which also confirmed the research results of DFT, FTIR, and Zeta.

Transungual Penetration and Antifungal Activity of Seven Prescription and Over-the-Counter Topical Antifungals: In Vitro Comparison

Background: Onychomycosis is typically caused by dermatophytes of the species Trichophyton. Topical antifungals must penetrate the nail to reach the infection, though this can be inhibited by keratin binding within the nail. These in vitro experiments compared penetration of commercially available topical antifungals through keratin-free cellulose disks versus human nails to inhibit Trichophyton growth.&#x0D; Methods: Seven topical antifungals were tested: 3 FDA-approved products indicated for the treatment of onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and 4 over-the-counter (OTC) products for fungal infections (tolnaftate 1% solutions [Formula 3, Formula 7, Tolcylen] and undecylenic acid 25% solution [Terpenicol]). Antifungal efficacy was assessed via cellulose disk diffusion assay. Each product was applied to a 6-mm cellulose disk and placed in the center of an agar plate (85 mm radius) seeded with a clinical isolate of T. rubrum or T. mentagrophytes (2 strains each; 3 replicates/strain for each product). After 4-7 days incubation, the zone of inhibition (ZI)—defined as the radius of the area of no fungal growth—was recorded. To assess the impact of nail penetration on antifungal efficacy, products were applied to the tops of human cadaverous great toenails and allowed to dry. Five 4-mm disks were punched from the middle of each nail and placed treated side up on seeded plates prior to measurement of ZI (5 replicates/strain for each product). In both experiments, results were averaged across the 2 strains of each fungal species and untreated nails served as negative controls.&#x0D; Results: Among FDA-approved topicals in the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal inhibition (ZI=85 mm) against both T. rubrum and T. mentagrophytes; for ciclopirox, average ZIs were lower (59.0 mm; 55.7 mm, respectively). For OTC products, ZIs were 31.2-57.8 mm against T. rubrum and 25.7-47.7 mm against T. mentagrophytes. In the nail penetration assay, average ZI for FDA-approved topicals against both species was greatest for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm), followed by tavaborole (63.5 mm; 39.1 mm) and ciclopirox (7.4 mm; 3.6 mm). Average ZI of OTC products ranged from 10.5-34.2 mm against both species. ZIs were generally not affected by nail thickness.&#x0D; Conclusions: Our data show that FDA-approved and OTC topical antifungals penetrate cellulose disks more efficiently than cadaver nails, suggesting that keratin in the nails hampers nail penetration. Among all antifungals tested, ability to penetrate human toenails and inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, perhaps due to lower keratin binding in the nail.&#x0D; Funding: Ortho Dermatologics

A fully bio‐based monomer derived from undecylenic acid, glycerol, and CO2 useful for the synthesis of polyhydroxyurethanes

AbstractUndecylenic acid, glycerol, and CO2 were used as building blocks for obtaining a fully bio‐based carbonated monomer, useful for polyurethanes. The functionality of the monomer was close to 3 cyclic carbonates/mol, located in terminal positions. In a first stage, a synthetic triglyceride was obtained with 99% selectivity by esterification of glycerol and undecylenic acid at 160°C. The triglyceride was then epoxidized using H2O2 and Amberlyst 15 or Amberlite IR‐120 acidic exchange resins at 57°C. The selectivity to epoxide was kept constant at 98% using Amberlite IR‐120. Terminal cyclic carbonates were then inserted through epoxide moieties under mild conditions by the chemical fixation of CO2 at 80°C and 6 MPa in 6 h. A complete conversion was obtained in 6 h reaction while the selectivity to carbonate groups was near to 99% during all the reaction time. An elastomeric polyhydroxyurethane was obtained by aminolysis of the carbonated monomer with ethylenediamine at 70°C, affording a Young's modulus of 22.6 MPa and Tg of −15.2°C. The material showed a good thermal stability below 240°C.

Undecylenic acid and N,N-dibutylundecenamide as effective antibacterials against antibiotic-resistant strains

Evaluation of undecylenic acid (UA) and its tertiary amide N,N-dibutylundecenamide (DBUA) activity­ in vitro against the standard and antibiotic-resistant Escherichia coli and Staphylococcus aureus strains was carried out. The antibacterial potential of the acid and its amide at 2.5 and 5.0 μM concentration both against gram-positive bacteria (S. aureus) and gram-negative (E. coli) cultures was confirmed by monitoring the diameter of the bacterial growth inhibition zones. The docking study identified methionine aminopeptidase (MAP) as the most energy-favorable potential biotarget associated with the drug resistance of E. coli and S. aureus with a binding energy in the range from -8.0 to -8.5 kcal/mol. The ligands complexation was due to the formation of hydrogen bonds with ASP108, HIS171, HIS178, GLU204, GLU235, HIS76, ASP104, GLU233, ASP93 and metal-acceptor interactions with Co2+. Overall, the results indicated that UA and DBUA activity against antibiotic-resistant strains creates prospects for the development of new antibacterial formulations. Keywords: Escherichia coli, methionine aminopeptidase, molecular docking, Staphylococcus aureus, tertiary amide, undecylenic acid

Epstein Barr virus infection in tree shrews alters the composition of gut microbiota and metabolome profile

BackgroundEpstein-Barr virus (EBV) infection is a major global threat; its manifestations range from the absence of symptoms to multiorgan malignancies and various gastrointestinal diseases. Analyzing the composition and metabolomic profile of gut microbiota during acute EBV infection might be instrumental in understanding and controlling EBV.MethodsSix tree shrews were inoculated with EBV by intravenous injection. Blood was collected at regular intervals thereafter from the femoral vein to detect EBV and inflammatory biomarker. At the same time, tree shrew faeces were collected for 16 S rRNA gene sequencing and Non-targeted metabolomics analysis.Results16 S rRNA gene characterization along with β diversity analysis exhibited remarkable alterations in gut microflora structure with a peak at 7 days post-infection(dpi). Some alterations in the relative richness of bacterial taxon were linked to infectious indicators. Of note, Butyricicoccus relative richness was positively linked to EBV presence in the blood and plasma, the opposite correlation was seen with Variovorax and Paramuribaculum. Non-targeted metabolomics indicated the fecal metabolome profile altered during EBV infection, particularly 7 dpi. The relative abundance of geranic acid and undecylenic acid in stool samples was positively linked to systemic inflammatory biomarkers, and an inverse relationship was reported with the estrone glucuronide, linoleic acid, protoporphyrin IX and tyramine.ConclusionCollectively, EBV infection in this model correlated with changes in the composition and metabolome profile of the gut microbiota.

Circulating metabolites modulated by diet are associated with depression

Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression. In a conservative model adjusting for life style factors and cardiovascular and antidepressant medication use we identified 8 metabolites, including 6 novel, significantly associated with depression. In individuals with depression, increased levels of retinol (vitamin A), 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) (lecithin) and mannitol/sorbitol and lower levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate (alpha-aminocaprylic acid), 10-undecenoate (11:1n1) (undecylenic acid), 1-linoleoyl-GPA (18:2) (lysophosphatidic acid; LPA 18:2) are observed. These metabolites are either directly food derived or are products of host and gut microbial metabolism of food-derived products. Our Mendelian randomization analysis suggests that low hippurate levels may be in the causal pathway leading towards depression. Our findings highlight putative actionable targets for depression prevention that are easily modifiable through diet interventions.

Preparation and Characterization of fluorinated copolymer emulsion for concrete protection

Emulsifier-free copolymerizations of 2,2,2-trifluoroethyl 2-methylpropanoate (TFMPA) and methyl acrylate in the presence of surface-active commoner, undecylenic acid (UA), were carried out using potassium persulfate (KPS) as initiator. The prepared copolymer emulsions were characterized and analyzed by FT-IR, 1H and 19F NMR spectra, TEM, dynamic light scattering (DLS), and contact angle testing. The results showed that the average particle size of copolymer latex particles was 200-300 nm with a relatively uniform particle size distribution. The glass transition temperature was controlled with the monomer feed ratios. After copolymer emulsions coating on the concrete surface, the contact angle was significantly increased, and the water absorption of the concrete was significantly reduced.

Dielectric Relaxation in Nanocrystals: A Scale Effect

The study explores a scale effect inherent to the dielectric relaxation in nanocrystals: the dependence of dielectric relaxation parameters on the size of a nanocrystal. We offer a model of the scale effect for the dielectric relaxation caused by thermally activated motion. In this model, a nanocrystal is considered as a physical infinitesimal volume: a region where a local equilibrium exists. We conclude that the thermally activated motion causes the energy fluctuations in a nanocrystal as a whole. A relation between the intensity of these fluctuations and the size of nanocrystals is derived. According to this relation, the intensity of the fluctuations decreases with the decrease of the nanocrystal sizes. Using the relation, a characteristic of a thermally activated motion–the size of the activation zone–can be determined experimentally. We verify the model using experimental data for the complex dielectric permittivity of the composites (silica gel matrix with undecylenic acid nanocrystalline inclusions of various sizes) in the temperature range from −190 to 50 °C at frequencies 5, 10, 20, and 50 kHz. The results of the experiment agree with the predictions of the model.

Heptaldehyde and undecylenic acid production from thermal and thermo-catalytic cracking of castor oil

With the breakdown of ricinoleic acid through the cracking technique, either in the thermal or thermo-catalytic form, compounds of interest for green chemistry, such as heptaldehyde and undecylenic acid, can be obtained. These supplies are envisioned since they are building block chemicals. Therefore, the influence of operational conditions on the cracking process was evaluated using a 2 ³ experimental design, including temperature, water, and catalyst, with the aim of improving the yield of heptaldehyde and undecylenic acid supplies from castor oil, inedible oil. The operating conditions used in the cracking process were: temperature of 500, 525, and 550 °C, water fractions of zero, 12.5%, and 25%, and catalyst fractions of benzoyl peroxide of zero, 0.55%, and 1.1%. The analysis suggests that the central point utilizing thermo-catalytic cracking demonstrates superior operational conditions as they generate an average of 78.5% bio-oil, 21.97% heptaldehyde, and 17.25% undecylenic acid, with 12.5% water and 0.55% catalyst at a temperature of 525 °C.

Two-step single-reactor synthesis of oleic acid- or undecylenic acid-stabilized magnetic nanoparticles by thermal decomposition.

Different iron oxides (i.e., magnetite, maghemite, goethite, wüstite), particularly nanosized particles, show distinct effects on living organisms. Thus, it is of primary importance for their biomedical applications that the morphology and phase-structural state of these materials are investigated. The aim of this work was to obtain magnetic nanoparticles in a single reactor using Fe(III) acetylacetonate as the initial precursor for the synthesis of Fe(III) oleate or Fe(III) undecylate followed by their thermolysis in situ. We proposed a new approach, according to which the essential magnetite precursor (a complex salt of higher acids - Fe(III) alkanoates) is obtained in a solvent with a high boiling point via displacement reaction of acetylacetone with a higher acid from Fe(III) acetylacetonate during its elimination from the reaction mixture under vacuum conditions. Magnetic nanoparticles (NPM) were characterized in terms of morphology, hydrodynamic diameter, and composition via several techniques, such as transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, Fourier-transform infrared spectroscopy/attenuated total reflectance, 57Fe Mössbauer spectroscopy, and X-ray diffraction. The effect of unsaturated oleic (OA) and undecylenic (UA) acids, which are both used as a reagent and as a nanoparticle stabilizer, as well as the influence of their ratio to Fe(III) acetylacetonate on the properties of particles were investigated. Stable dispersions of NPM were obtained in 1-octadecene within the OA or UA ratio from 3.3 mol to 1 mol of acetylacetonate and up to 5.5 mol/mol. Below the mentioned limit, NPM dispersions were colloidally unstable, and at higher ratios no NPM were formed which could be precipitated by an applied magnetic field. Monodisperse nanoparticles of iron oxides were synthesized with a diameter of 8-13 nm and 11-16 nm using OA and UA, respectively. The organic shell that enables the particle to be dispersed in organic media, in the case of oleic acid, covers their inorganic core only with a layer similar to the monomolecular layer, whereas the undecylenic acid forms a thicker layer, which is 65% of the particle mass. The result is a significantly different resistance to oxidation of the nanoparticle inorganic cores. The core of the particles synthesized using oleic acid is composed of more than 90% of maghemite. When undecylenic acid is used for the synthesis, the core is composed of 75% of magnetite.

Green chemical production based on thermal cracking of inedible vegetable oil

This work evaluated the process for heptaldehyde, undecylenic acid, and methyl undecenoate production from castor oil, methyl ester of castor oil, and ricinoleic acid. Experiments were performed in a continuous pilot-plant scale pyrolysis reactor. Those are very important green chemical products that the thermal cracking of castor oil might produce. Transesterification of castor oil produces methyl ricinoleate, and its thermal cracking generates methyl undecenoate and heptaldehyde. The pyrolysis temperatures tested were 530?C, 545?C, 560?C, and 575?C, with residence time from 17 s to 32 s and mass flow at 400 g/h of the mixture of materials with 25% distilled water. It was observed that the temperature influenced the bio-oil yield in different degree for each material. The bio-oil was characterized by iodine index, acid number, and mass, and the contents of its compounds were obtained by GC-FID chromatography. The best result for the undecylenic acid mass yield of the desired compounds occurred at 530?C, achieving 17.8% from ricinoleic acid and 16.5% from castor oil. For the heptaldehyde, the highest production was also obtained at 530?C, with a value of 20.7% from methyl ester and 15.2% from ricinoleic acid.

Novel Formulation of Undecylenic Acid induces Tumor Cell Apoptosis.

Undecylenic acid, a monounsaturated fatty acid, is currently in clinical use as a topical antifungal agent, however the potential for therapeutic application in other disease settings has not been investigated. In this study, we describe a novel platform for the solubilization of fatty acids using amino acids and utilize this approach to define a tumoricidal activity and underlying mechanism for undecylenic acid. We examined a novel formulation of undecylenic acid compounded with L-Arginine, called GS-1, that induced concentration-dependent tumor cell death, with undecylenic acid being the cytotoxic component. Further investigation revealed that GS-1-mediated cell death was caspase-dependent with a reduction in mitochondrial membrane potential, suggesting a pro-apoptotic mechanism of action. Additionally, GS-1 was found to localize intracellularly to lipid droplets. In contrast to previous studies where lipid droplets have been shown to be protective against fatty acid-induced cell death, we showed that lipid droplets could not protect against GS-1-induced cytotoxicity. We also found a role for Fatty Acid Transport Protein 2 (FATP2) in the uptake of this compound. Collectively, this study demonstrates that GS-1 has effective pro-apoptotic antitumor activity in vitro and, together with the novel platform of fatty acid solubilization, contributes to the re-emerging field of fatty acids as potential anti-cancer therapeutics.

A comprehensive review of castor oil‐derived renewable and sustainable industrial products

AbstractCastor oil is one important raw material that could serve as a renewable feedstock for industries in the age of exhausting fossil fuels. The chemical composition of oil and the structure of hydroxyl fatty acid are responsible for its unique physicochemical properties. The oil has diverse applications from pharmaceuticals to polyamides, from the manufacturing of ski boots to durable frames, and from lubricants to laxatives. The present review gives an insight into the physicochemical properties of castor oil and its application. The oil is used for the production of a great variety of its derivatives. Out of many derivatives of castor oil, four are produced and utilized at a larger scale. The names of the four derivates are ricinoleic acid, sebacic acid, undecylenic acid, and γ‐decalactone. The review will aim toward an insight into the evolved techniques for the manufacturing of these derivatives of castor oil, the biotechnological route of production, and metabolic engineering approaches. Though the industrial significance of castor oil and its derivatives had been known for ages, methods for their production are continuously changing.

Catalytic cracking of castor oil via microwave assisted method

Castor oil extracted from seeds of Ricinus Communis plant has an immense potential being used to yield valuable hydrocarbons with shorter chain length. Castor oil contains chemical structures of heavy hydrocarbons and long chains may undergo a cracking process which are similar to that as in petrochemical industries. However, cracking process requires extremely high temperature and energy input. This research came by with an attempt to reduce waste of energy using both microwave assisted method and modified metal catalyst, Zn/ZSM-5 to provide sufficient energy for cracking process to occur at comparatively low temperature. Wet impregnation method was used for Zn/ZSM-5 catalyst preparation and the experiments were carried out via microwave-assisted method. The microwave effect on the temperature and mass of condensate formed was investigated at three different output powers; 650, 700 and 750 W, under different Zn/ZSM-5 concentrations; 5, 8 and 10 wt% for 1 h. Results showed that cracking of castor oil is feasible at low temperature (<250 °C) using modified Zn/ZSM-5 via microwave assisted method. The highest yield of total mass of condensate (5.61%) was obtained from 750 W output power and 10 wt% Zn/ZSM-5 catalyst concentration. In addition, the highest cracking percentage (97.7%) was obtained from 750 W output power and 5 wt% Zn/ZSM-5 catalyst concentration. Valuable cracked compounds such as octane for fuel products and undecylenic acid for pharmaceutical uses were obtained.

S3412 Functional Medicine Approach to Care Improves Quality of Life and Blood Alcohol Levels in a Patient With Autobrewery Syndrome

Introduction: Autobrewery syndrome, or gut fermentation syndrome (GFS), is a rare condition characterized by elevated blood alcohol concentration (BAC) in the absence of alcohol consumption. Treatment involves antifungals and a low carb diet, which are often ineffective. In this case, we describe a patient with GFS who failed traditional therapy, was unable to complete activities of daily living due to high BAC, and responded well to a functional medicine approach to care with sustained improvement in BAC. Case Description/Methods: In 7/2020, a 58-year-old man with T2D, obesity, HTN and gout developed recurrent episodes of dysarthria, behavioral changes, and somnolence. On multiple occasions in the ER, his BAC level was found to be elevated. The patient and family denied alcohol use. He was ultimately diagnosed with GFS. He self-initiated a strict low-carb diet with initial success in controlling his BAC from 11/2020 to 12/2020. From 10/2020 to 10/2021, he underwent multiple courses of antifungal medications (nystatin, fluconazole, micafungin, and oral amphotericin). The longest period of remission (BAC 0) was 41 days while on micafungin. After 41 days on micafungin and a restricted diet, his BAC increased. Over this time, he lost 80 lbs. In 11/2021, he established with a functional medicine GI and dietitian. Stool metabolomics showed no obvious abnormalities. The 5 R protocol (remove, replace, repair, reinoculate, rebalance) was introduced. He started with an aggressive bowel regimen with prucalopride and lactulose. He completed 15 days of high-potency Bacillus subtilis probiotic, followed by a transition to a more diverse probiotic. He added daily intake of a medical food to his restricted diet. New foods were then introduced, one at a time, in the evening, with subsequent monitoring of BAC. In 2/2022, he started Undecylenic acid (10-Undecenoic Acid) as fatty acid support. Lifestyle modifications were added to emphasize more exercise, daily outdoor walks, optimal sleep, and decreasing stress. He did well until BAC levels spiked in 3/2022 due to consumption of alcohol, triggered by cravings that developed when the gut production of alcohol decreased. After alcohol cessation, BAC levels have remained undetectable for 60+ days with continued diet modifications and supplements (Figure). Discussion: GFS is difficult to treat with minimal traditional treatment options. This case is a patient with GFS that failed all medical options and is now thriving after a functional medicine approach to care.Figure 1.: BAC levels continued to spike with medical therapies and have sustained improvement with functional medicine care.

SiO2‐Supported Ni(II) and Fe(II) Catalysts Bearing Sodium‐Sulfonate Group for Olefin Polymerization†

Comprehensive SummaryHeterogeneous catalysts have been dominant for industrial polyolefin production, offering many distinct advantages, such as controlling the morphology of the polymer and preventing reactor fouling. In this contribution, we designed several types of imine ligands bearing sodium‐sulfonate ionic groups and the corresponding nickel/iron catalysts. These catalysts could be immobilized on SiO2 with strong affinity and high catalyst loadings. The SiO2‐supported catalysts behaved better than their homogeneous counterparts during ethylene polymerization with extremely high activity (2.6 × 104 kg·mol−1·h−1) and high thermal stability. In addition, the supported nickel catalysts generated free‐flowing polyethylene with high molecular weight (Mn up to 2.65 × 103 kg·mol–1) and excellent morphology control, indicating no reactor fouling due to the leaching of catalyst. Moreover, for copolymerization, immobilized nickel catalysts showed a higher tolerance of polar monomers, and the efficient copolymerization of ethylene with undecylenic acid was achieved with high activity (450 kg·mol−1·h−1) and a high incorporation ratio (up to 12.3%).

Integrated multiproduct biorefinery from Ricinus communis in Mexico: Conceptual design, evaluation, and optimization, based on environmental and economic aspects

Currently, biorefineries require production of multiple value-added bioproducts to compete with oil-derived products. Castor oil, extracted from the Ricinus communis plant, is a valuable biorefinery feedstock for producing a wide range of biochemical products, besides biofuels. However, the castor oil biorefinery requires further investigation to determine its feasibility. The aims were to make the conceptual design and the environmental and economic evaluation of an integrated multiproduct biorefinery based on castor oil plant in the Mexican context. Four different scenarios were analyzed. Azelaic, sebacic, and undecylenic acids, biodiesel, heat, and power were the major marketable products. An optimization approach allowed upgrading both economic and environmental performances, resulting in a more sustainable process design. The optimal results indicated that 42 % of castor oil is used for biodiesel, 38 % for azelaic acid, 7 % for undecylenic acid, and 13 % for sebacic acid. The main novelty of this work is the optimal design of a biorefinery for the multi-production of biopharmaceutical products in a sustainable way, using Ricinus communis, an abundant biomass in Mexico, replacing the consumption of fossil resources.