Fluocortolone 0.25% / Fluocortolone hexanoate 0.25% ointment

BackgroundShort chain fatty acids (SCFA) are increasingly recognized for their potential ability to alleviate obesity-associated chronic low-grade inflammation and disturbed energy homeostasis. Evidence suggests that an increase in circulating SCFA might be necessary to induce beneficial alterations in energy metabolism.ObjectiveTo compare the bioaccessibility of two different SCFA-enriched triglycerides: Akovita SCT (butyrate and hexanoate esterified with long chain fatty acids) and tributyrin/caproin (solely butyrate and hexanoate) and investigate whether the SCFA from orally administrated Akovita SCT reach the circulation and affect postprandial metabolism in men with overweight/obesity.MethodsThe site, speed, and amount of SCFA release from Akovita SCT and tributyrin/caproin were assessed in a validated In vitro Model of the stomach and small intestine (TIM-1). Subsequently, a double-blind placebo-controlled randomized crossover study was conducted at Maastricht University with fourteen men with overweight/obesity (BMI 25–35 kg/m2) of which twelve men finished all testdays and were included for analysis. The participants received a liquid high fat mixed meal test containing either a low (650 mg), medium (1,325 mg), or high dose (2,000 mg) of Akovita SCT or a placebo (sunflower oil) in randomized order. Blood was sampled at baseline and after ingestion for 6 h for the primary outcome plasma butyrate and hexanoate concentration. Secondary outcomes included hydrogen breath, appetite, gastrointestinal complaints, circulating glucagon-like peptide 1, free fatty acids, glucose, triglycerides, insulin, and cytokines concentrations.ResultsIn TIM-1, tributyrin/caproin was rapidly cleaved in the gastric compartment whereas the release of SCFA from Akovita SCT occurred predominantly in the small intestine. In vivo, all doses were well-tolerated. The medium dose increased (P < 0.05) and the high dose tended to increase (P < 0.10) postprandial circulating butyrate and both doses increased circulating hexanoate (P < 0.05) compared to placebo. Nevertheless, Akovita SCT supplementation did not affect any secondary outcomes compared to placebo.ConclusionEsterifying SCFA-enriched triglycerides with long chain fatty acids delayed SCFA release from the glycerol backbone. Akovita SCT increased postprandial circulating butyrate and hexanoate without changing metabolic parameters in men with overweight/obesity. Future randomized clinical trials should investigate whether long-term Akovita SCT supplementation can aid in the treatment or prevention of metabolic disorders.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT04662411.

Abstract licence: CC BY 4.0

Abstract Background Chain elongation is emerging as a biotechnological tool to convert waste organics to beneficial fermentation products with wide utility across industrial and agricultural sectors. Glucose, the most abundant sugar on earth, is present in organic feedstocks as both a monomer and as a constituent of complex polymers. In this work, glucose was used as the sole carbon and electron source to enrich a chain elongating microbial community using duplicate bioreactor systems and batch experiments were performed to assess the role of hydrogen supplementation on fermentation. Results Hexanoic acid was the most abundant MCCA produced in both bioreactors with steady-state concentrations of about 4 g COD L− 1 while butyric acid was the most abundant carboxylic acid with concentrations of about 5 g COD L− 1. Metagenomic and metatranscriptomic analyses showed that the microbial communities in the duplicate reactors were very similar, with Caproicibacter sp. 002316805 and Caproicibacterium sp. 002399445 emerging as the most abundant chain elongating bacteria in both bioreactors. The microbiomes also contained a high abundance of lactic acid bacteria, primarily the Coriobacteriaceae Tractidigestivibacter and Olegusella. H2 supplementation with batch experiments resulted in marginal changes in the products compared to controls with N2 supplementation, with butyric acid production being higher than but not hexanoate production. One low-abundance Clostridium_B increased expression of genes for the Wood Ljungdahl pathway during H2 supplementation. Conclusions The duplicate bioreactors behaved similarly, with the same abundant species. Combined, Caproicibacter sp. 002316805, Caproicibacterium sp. 002399445, and Tractidigestivibacter sp902834555 accounted for > 65% of the transcriptome and analysis of transcribed genes suggests butyrate and hexanoate originate from both direct sugar conversion by Caproicibacter sp. 002316805 and Caproicibacterium sp. 002399445 as well as initial conversion to lactate by Tractidigestivibacter sp902834555. Further, it was found that Caproicibacter and Caproicibacterium differ in synteny of chain elongation genes. H2 supplementation during batch experiments did not reliably increase hexanoate production.

Abstract licence: CC BY 4.0

The production of oxygenated bio-additives for traditional fuels represents a key challenge due to the depletion of fossil fuels in the next future and their contribution to environmental pollu-tion. In this context, the present study considers the synthesis of different mixtures of 1-hexanol/hexyl hexanoate produced through the catalytic hydrogenation of hexanoic acid, a car-boxylic acid obtainable from the fermentation of a wide variety of waste biomasses. In particu-lar, crude hexanoic acid deriving from the fermentation of grape pomace, an abundant Italian agrifood waste, has been taken into consideration. The reaction was carried out with the com-mercial 5 wt% Re/γ-Al2O3 catalyst, whose acidity allowed the tuning of the reaction selectivity towards the preferential formation of hexyl hexanoate instead of 1-hexanol. As consequence, the tunable composition of the obtained 1-hexanol/hexyl hexanoate mixtures was leveraged for en-gine applications, thus allowing studying each component influence on the Diesel engine per-formances and verifying their synergistic effects. The engine experimental activity highlighted that both 1-hexanol and hexyl hexanoate, as well as their mixtures, can be used in Diesel engine with a commercial Diesel fuel up to high loadings (20 vol%) without altering engine perfor-mances and significantly lowering soot and CO emissions by more than 40%.

Abstract licence: CC BY 4.0