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In mice with acute gouty arthritis, this study intends to examine the mechanism of action of Akkermansia muciniphila AKK PROBIO. We developed a mouse model of acute gouty arthritis using sodium urate. The efficiency and mechanism of AKK PROBIO in preventing acute gouty arthritis in mice were then determined by examining the degree of foot swelling, pain threshold, blood biochemical indicators, histological alterations, and messenger RNA (mRNA) expression changes. The results of the animal experiment showed that AKK PROBIO can lessen mouse foot edema severity and increase pain threshold. AKK PROBIO can enhance the enzyme activity of superoxide dismutase (SOD) and the level of glutathione (GSH) in the ankle joint tissues of mice with acute arthritis while decreasing the enzyme activity of myeloperoxidase (MPO) and the level of malondialdehyde (MDA). Interleukin 6 (IL‐6), interleukin 10 (IL‐10), interleukin 1 beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α) levels are all reduced by AKK PROBIO in the blood of mice with acute arthritis. Results from histopathology showed that AKK PROBIO reduced tissue damage in the mouse ankle and foot joints. In the tissues of the ankle joints of mice with acute arthritis, the results of the quantitative polymerase chain reaction (qPCR) and Western blot experiments suggested that AKK PROBIO may inhibit the mRNA and protein expression of extracellular signal‐regulated kinase 1/2 (ERK1/2), cyclooxygenase‐2 (COX‐2), and prostaglandin E2 (PGE2) in the tissues. AKK PROBIO can also regulate gut microbiota, inhibit harmful bacteria, and enhance valeric acid in the intestine, isobutyric acid, and isovaleric acid. Therefore, it is evident that AKK PROBIO prevents acute gouty arthritis better than glucosamine sulfate. It is a strain that has probiotic potential. [ABSTRACT FROM AUTHOR]

As perovskite photovoltaic devices can now compete with silicon technology in terms of efficiency, many strategies are investigated to improve their stability. In particular, degradation reactions can be hindered by appropriate device encapsulation, device architecture, and perovskite formulation. Mesoporous device architectures with a carbon electrode offer a plausible solution for the future commercialization of perovskite solar cells. They represent a low‐cost and stable solution with high potential for large‐scale production. Several studies have already demonstrated the potential of the mixed 2D/3D ammonium valeric acid iodide‐based MAPbI3 formulation to increase the lifetime of pure MAPbI3. They can however not describe the mechanisms responsible for the lifetime improvement. Using a full set of characterization techniques in the initial state and as a function of time during damp‐heat aging, new insights into the performance and degradation mechanisms may be observed. With (5‐AVA)0.05MA0.95PbI3, the solar cells are very stable up to 3500 h and the degradation of performances essentially results from the loss of electrical contacts mainly located at the interfaces. In contrast, for the neat MAPbI3, a poor stability is evidenced (T50 = 500 h) and the loss in performance results from the degradation of the bulk perovskite layer itself. [ABSTRACT FROM AUTHOR]

Understanding how forage can be utilized in the rumen is important for optimizing system efficiency. We aimed to evaluate the ruminal fermentation parameters and methane (CH4) production of Marandu palisadegrass [Brachiaria (syn. Urochloa) brizantha (Hochst. ex A. Rich.) R. D. Webster] growing in monoculture or in integrated systems. The experiment was conducted over 3 years to evaluate four systems [livestock (L), livestock‐forestry (LF), crop‐livestock (CL), and crop‐livestock‐forestry (CLF)] during the dry and rainy seasons. In the dry season, palisadegrass in CLF presented the greater crude protein (CP) and the lesser neutral detergent fibre (NDF) concentrations. The greatest gas volume was produced in L, while LF and CL reduced CH4 production compared to L. The greatest ammoniacal‐nitrogen concentration, propionate and valeric acid proportions, and degradability of NDF were in CLF. In the rainy season, palisadegrass in LF and CLF presented the greater CP concentration and the lesser CH4 production. Integration of crop and forestry components in a forage‐based livestock system affected ruminal fermentation parameters of Marandu palisadegrass, consequently, reducing CH4 production. In addition, the inclusion of a forestry component enhanced forage CP concentration. Integrated systems can improve ruminal fermentation, supporting sustainable livestock production and optimizing forage utilization. [ABSTRACT FROM AUTHOR]

In this article, we address the transition of the Kolbe electrolysis of valeric acid (VA) to n‐octane as an exemplary electrosynthesis process from a batch reaction to a continuous, self‐regulated process. Based on a systematic assessment of chemical boundary conditions and sustainability aspects, we propose a continuous electrosynthesis including a simple product separation and electrolyte recirculation, as well as an online‐pH‐controlled VA feeding. We demonstrate how essential performance parameters such as product selectivity (S) and coulombic efficiency (CE) are significantly improved by the transition from batch to a continuous process. Thus, the continuous and pH‐controlled electrolysis of a 1 M valeric acid, starting pH 6.0, allowed a constantly high selectivity of around 47 % and an average Coulomb efficiency about 52 % throughout the entire experimental duration. Under otherwise identical conditions, the conventional batch operation suffered from lower and strongly decreasing performance values (Sn‐octane, 60min=10.4 %, Sn‐octane, 240min=1.3 %; CEn‐octane, 60min=7.1 %, CEn‐octane, 240min=0.5 %). At the same time, electrolyte recirculation significantly reduces wastes and limits the use of electrolyte components. [ABSTRACT FROM AUTHOR]

Clostridium luticellarii is a recently discovered acetogen that is uniquely capable of producing butyric and isobutyric acid from various substrates (e.g. methanol), but it is unclear which factors influence its (iso)butyric acid production from H2 and CO2. We aimed to investigate the autotrophic metabolism of C. luticellarii by identifying the necessary growth conditions and examining the effects of pH and metabolite levels on product titers and selectivity. Results show that autotrophic growth of C. luticellarii requires the addition of complex nutrient sources and the absence of shaking conditions. Further experiments combined with thermodynamic calculations identified pH as a key parameter governing the direction of metabolic fluxes. At circumneutral pH (~6.5), acetic acid is the sole metabolic end product but C. luticellarii possesses the unique ability to co‐oxidize organic acids such as valeric acid under high H2 partial pressures (>1 bar). Conversely, mildly acidic pH (≤5.5) stimulates the production of butyric and isobutyric acid while partly halting the oxidation of organic acids. Additionally, elevated acetic acid concentrations stimulated butyric and isobutyric acid production up to a combined selectivity of 53 ± 3%. Finally, our results suggest that isobutyric acid is produced by a reversible isomerization of butyric acid, but valeric and caproic acid are not isomerized. These combined insights can inform future efforts to optimize and scale‐up the production of valuable chemicals from CO2 using C. luticellarii. [ABSTRACT FROM AUTHOR]

The surface treatment for solution-processed perovskite films using molecular passivation agents has been reported to be critical for improving the performance of perovskite light-emitting diodes (PeLEDs). Generally, most studies emphasized the binding effect between passivation molecules and perovskite surface, while halide perovskites are dominated by multiple defects and need more comprehensive passivation, which is often neglected. Here, a molecule of 5-ammonium valeric acid trifluoroacetate (5-AVATFA) with multi-functional groups is rationally developed to modify the interface of advanced PeLEDs. Combining experimental and density functional theory analysis, the synergism effects of reduced surface defects and increased steric hindrance of 5-AVATFA, which can greatly suppress the ion migration of PeLEDs, are demonstarated. Because of the passivation effect of multi-functional 5-AVATFA, an optimal device with an external quantum efficiency of22.32%, a radiance of558.46 W sr-1 m-2, and an extended half-lifetime of 103.3 h is obtained. [ABSTRACT FROM AUTHOR]

Limiting molecules' polarized motion effectively reduces the dielectric loss of materials. This article synthesized side chains with different lengths using p‐ethoxyphenol, p‐hydroxybenzoic acid, and long‐chain halohydrins through a two‐step process. These chains' movement was almost unaffected by the main chain of polymers, so they can fill up the free volume of polymers under certain conditions. 1,2‐dihydro‐4‐(4‐hydroxyphenyl)phthalazine‐1‐(2H)‐one(DHPZ), 4,4'‐Difluorophenyl sulfone(DFS), and 4,4‐Bis(4‐hydroxyphenyl) valeric acid(HPV) obtained three polymers with different carboxyl groups (10%, 30%, and 50%) through nucleophilic substitution. They were then grafted and treated with hot‐pressing. The introduction of side chains could reduce the free volume of polymers under hot‐pressing conditions, so further reducing the dielectric loss of materials. Polymer with the shortest and least (10%) side chains showed the most obvious dielectric loss tangent, the reduction rate of the film's dielectric loss tangent was 13.11% (at Tg + 15°C, while the non‐grafted one was only 3.69%) and 20.70% (at Tg + 80°C, while the non‐grafted one was only 8.35%), respectively. In addition, WXRD and DMA tests showed that films' intermolecular chain spacing ("d") and Tg changed after the hot‐pressing process, respectively. The change law of both was consistent with that of dielectric loss tangent. Confirm that grafting high‐motility side chains can significantly reduce polymer's dielectric loss by enhancing the free volume reduction effect after hot‐pressing. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of different dietary fibre sources on growth performance, gastrointestinal tract development, caecal fermentation and bacterial composition in the caecal contents of rabbits. A total of 120 35‐day‐old weaned Minxinan black rabbits were divided into three groups and fed a diet composed of peanut straw powder (Group A), alfalfa powder (Group B) and soybean straw powder (Group C) as the main fibre source. The final body weight and average daily gain in Group B were higher than those in Group C, and the average daily feed intake and feed conversion ratio in Group A were lower than those in Group C (p < 0.05). The relative weights of the stomach, small intestine and caecum of rabbits in Group C were higher than those in Groups of B and A, and the relative weights of the caecal contents in Group C were lower than those in Groups A or B (p < 0.05). The pH value and propionic acid, butyric acid and valeric acid concentrations in the caecum of Group C were lower than those in the caecum of Groups A or B, and the concentration of acetic acid in the caecum was lower (p < 0.05). The dominant microbes in the caecal contents of Minxinan black rabbits were Firmicutes, Bacteroidetes and Proteobacteria at the phylum level, and the number of species, Chao1 index and ACE index measured was different between the B–C and A–C groups (p < 0.05). Different dietary fibre sources could affect the growth performance, gastrointestinal tract development and intestinal microbiota of rabbits, and the nutritional value of alfalfa powder was better than that of peanut straw and soybean straw. [ABSTRACT FROM AUTHOR]

Single‐step conversion of levulinic acid (LA) to valeric biofuel is extremely promising for the development of bio‐refineries. Direct conversion of LA to valeric acid (VA) was investigated over H‐ZSM‐5 supported Ni, Co, and Ni−Co (different Ni/Co wt. % ratios) catalysts under ambient reaction conditions (543 K and atmospheric pressure) in the gas phase. Compared with supported monometallic catalysts, bimetallic Ni−Co catalysts exhibited more activity and selectivity toward VA production. Among Ni−Co/H‐ZSM‐5 catalysts, 15Ni‐5Co/H‐ZSM‐5 catalyst is optimum with 97.5 % conversion of LA and 63 % selectivity to valeric acid even after 6 h time‐on‐stream (TOS). The active metallic sites are responsible for the hydrogenation of LA to γ‐valerolactone (GVL), and acidic sites catalyze the conversion of GVL to VA. All the catalysts were characterized using the XRD, H2‐TPR, N2‐adsorption‐desorption isotherms, NH3‐TPD, Py‐IR, SEM, HR‐TEM and XPS techniques. [ABSTRACT FROM AUTHOR]

In this work, extraction of valeric acid (VA) using tri‐n‐butyl phosphate (TBP) as a reactive extractant was carried out. To reduce the toxic effects of the conventional diluents on microorganisms, non‐toxic and green edible sunflower and soybean oils were tried as the diluents. The high values of the distribution coefficient and extraction efficiency advocated to use them in the bio‐refinery industries. Moreover, it shows intensification of the recovery of VA using reactive extraction process. Sunflower oil appeared to be a better diluent than soybean oil. The complexation reaction stoichiometry (m and n) and equilibrium complexation reaction constant KEm:n were estimated by using the differential evolution technique. In spite of the loading ratio being less than 0.5, the estimated m/n was found to be more than 1.0. The higher values of KEm:n occurred due to the 9higher stability of the VA‐TBP complex in sunflower oil than in soybean oil. The stoichiometry of VA decreased with increasing TBP concentration. The complex concentration, HAmSnorg, was found to be higher for soybean oil. It increased with temperature and initial VA concentration but remained invariant with TBP concentration. Due to the decreasing trend of KEm:n with temperature, the complexation reaction became exothermic. The enthalpy changes due to mass transfer stipulated easier mixing of the phases in sunflower oil than in soybean oil. [ABSTRACT FROM AUTHOR]

An anaerobic granular sludge was enriched to utilize H2/CO2 in a continuous gas‐fed up‐flow anaerobic sludge reactor by applying operating conditions expected to produce acetic acid, butyric acid, and ethanol. Three stages of fermentation were found: Stage I with acetic acid accumulation with the highest concentration of 35 mM along with a pH decrease from initial 6 to 4.5. In Stage II, H2/CO2 was replaced by 100% H2 to induce solventogenesis, whereas butyric acid was produced with the highest concentration of 2.5 mM. At stage III with 10 µM tungsten (W) addition, iso‐valeric acid, valeric acid, and caproic acid were produced at pH 4.5–5.0. In the batch tests inoculated with the enriched sludge taken from the bioreactor (day 70), however, methane production occurred at pH 6. Exogenous 15 mM acetate addition enhanced both the H2 and CO2 consumption rate compared to exogenous 10, 30, and 45 mM acetate by the enriched sludge. Exogenous acetate was failed to be converted to ethanol using H2 as electron donor by the enriched acetogens. [ABSTRACT FROM AUTHOR]

Background: Even if breed, parity, dietary and environmental management are same, dairy cows still have notable differences in milk yield that may be underpinned by physiologic differences. Objectives: This study aimed to investigate the physiological dissimilarities of dairy cows with different milk yields. Methods: Thirty cows were sorted into high milk‐yielding cows (group H: 58.93±2.31 kg/day), moderate milk‐yielding cows (group M: 44.99±0.54 kg/day), and low milk‐yielding cows (group L: 24.99±6.83 kg/day) according to milk yield. Blood was collected and serum parameters were assessed. Rumen fluid was collected for the evaluation of rumen fermentation parameters (RFPs) and bacterial community composition (BCC). Results: Serum prolactin, growth hormone, glutathione peroxidase, immunoglobulin A and non‐esterified fatty acid had a significantly positive correlation with milk yield (p < 0.05), whereas serum glucagon and total antioxidant capacity had a significantly negative correlation with milk yield (p < 0.05). The concentration of valeric acid and the ratio of acetic acid to propionic acid in the rumen fluid in group H was significantly lower than that in group L (p < 0.05). The concentration of acetic acid and butyric acid in group H was significantly lower than that in groups M and L (p < 0.05). The relative abundances of Ruminococcaceae_NK4A214_group, Prevotella_1, Rikenellaceae_RC9_gut_group, Christensenellaceae_R‐7_group, Muribaculaceae, and Ruminococcus_2 were negatively correlated with milk yield, whereas the relative abundance of Succinivibrionaceae_UCG‐001, Lachnospiraceae_NK3A20_group, Shuttleworthia and Dialister were positively correlated with milk yield (p < 0.05). Conclusions: This study indicates that dairy cows with different milk yields have clear divergence in serum indicators, RFPs, BCC and rumen microbial metabolism. [ABSTRACT FROM AUTHOR]

The chemical industry is transitioning to more sustainable and biobased processes. One key element of this transition is coupling energy fluxes and feedstock utilization for optimizing processes, routes and efficiencies. Here, we show for the first time the coupling of the Kolbe electrolysis at the anode with a subsequent microbial conversion of the cathodically produced co‐product hydrogen. Kolbe electrolysis of valeric acid yields the liquid drop‐in fuel additive n‐octane. Subsequently, the solvent isopropanol is produced by resting Cupriavidus necator cells using gaseous electrolysis products (esp. CO2 and H2). The resting microbial cells show carbon efficiencies of up to 41 % and Coulombic/Faradaic efficiencies of 60 % and 80 % for anodic and cathodic reactions, respectively. The implementation of a paired electrolyser resulted in superior process performances with overall efficiencies of up to 64.4 %. [ABSTRACT FROM AUTHOR]

The current method used in latex industries to determine the volatile fatty acids contents of Hevea brasiliensis latex is steam distillation. However, the accuracy of the method has been debated for some time. We assessed the accuracy of the method and developed a new, more reliable high‐performance liquid chromatographic method of determining acids in latex. The volatile fatty acids (formic, acetic, propionic, butyric, and valeric acids) and nonvolatile organic acids (oxalic, malic, lactic, citric, and succinic acids) in latex are directly determined simultaneously for the first time with high sensitivity and without losses during sample preparation. To avoid errors from derivatization, an acid‐resistant Prevail HPLC column and a gradient mobile phase of 25 mM potassium dihydrogen phosphate (pH 2.5) and acetonitrile were employed. Under optimum conditions, the calibrations of both types of acids demonstrated satisfactory correlation coefficients of ≥0.990, with limits of detection ranging from 0.02 to 395 mM. The developed method demonstrated the profiles of acids in field and concentrated latex of the same batch. Moreover, the evolution of the profiles of all studied acids in both types of latex during a 3‐month period was also revealed. [ABSTRACT FROM AUTHOR]

Summary: Polyphenols complexes were extracted from Common millet (CM), Long‐grain rice (LGR) and Huaihe wheat (HW), purification method, components and functional characteristics were studied. Higher phenol content (18.7 in CM, 12.9 in LGR and 22.3 mg g−1 in HW) was obtained by the high‐speed shear, with high antioxidants (DPPH 89.2% in HW, ABTS 81.6% in LGR, FRAP 0.83 in HW) after purified. Thirteen typical polyphenol complexes were identified from 21 peaks by UHPLC‐LTQ‐Orbitrap‐MS/MS. Gingerenone A was first detected in CM, HW and LGR; (+/−)‐Gingerol was first detected in CM and HW. Morphology by TEM displayed a rough spherical structure with 200–500 nm. Peculiarly contained hydroxyl polyphenol (5‐(3,4‐Dihydroxyphenyl) valeric acid, Apigenin‐8‐C‐xylosyl‐6‐C‐glucoside), polyphenols with B‐rings (Trans‐cinnamic acid, Gingerenone A) and the highest contents (+/−)‐Gingerol with hydroxyl and Sinapinic acid with B‐rings, CM had a higher α‐amylase inhibition rate (80.5%) than LGR and HW, which providing a foundation for the development of hypoglycaemic drugs. [ABSTRACT FROM AUTHOR]

Electrosynthesis offers an efficient and sustainable strategy for the conversion of biomass‐derived platform molecules. Among this process, developing efficient and cost‐effective electrocatalysts is of vital importance. We report herein the preparation of the nanocrystalline PbO‐In2O3 catalysts for the electrocatalytic reduction of levulinic acid (LA) to valeric acid (VA). A series of non‐noble nanocrystalline PbO‐In2O3 composite materials with different molar compositions were prepared and thoroughly characterized. The prepared nanocrystalline PbO‐In2O3 composite materials were used as working electrode for the electrocatalytic hydrogenation of LA in an H‐type electrolytic cell. A LA conversion of 41.4 % and VA selectivity of 97.8 % was achieved with the VA faradic efficiency of 89.2 % under the high current density of 134 mA cm−2. This is the first report on the electrocatalytic reduction of LA to VA using PbO‐In2O3 composite electrode catalyst. [ABSTRACT FROM AUTHOR]

The changes in polyphenol fractions after in vitro fermentation of apple peel polyphenol (APP) by gut microbiota as well as the effects of APP on the growth, pH value, short‐chain fatty acids (SCFAs) production and intestinal flora composition of gut microbiota fermentation were firstly explored in this study. The relative abundance of Lactobacillus in the APP group was 49.55% with an increment of 49.40% compared with the blank group, while that of Bifidobacterium was 13.32%. Moreover, the flora produced 37.093 ± 0.478 mM of SCFAs including acetic acid, propionic acid, butyric acid and valeric acid during the process of fermentation, thus reduced the environmental pH value. In addition, polyphenol fractions in APP were altered by gut microbiota fermentation to some extent, for example, glycosides were hydrolysed to aglycones. These findings suggested APP as a potential prebiotic agent to alleviate the disorder of intestinal flora. [ABSTRACT FROM AUTHOR]

The goal of this paper was to assess the possibilities for one‐stage reactor anaerobic digestion processing of fruit and vegetable biomass within a biorefinery concept for optimum products. Co‐digestion was the simplest strategy to implement to increase product yield among the variables tested (pH, ultrasonification, and co‐digestion). Methane yields from co‐digestion of fruit and vegetable waste (FVW) and pig manure (PM) ranged from 318 to 434 NmL /g VS, with the highest yield (434 NmL /g VS) achieved at a co‐digestion ratio of FVW75:PM25, representing a 20% increase over the methane production from FVW alone. The pH value was determined to be the most effective variable for enhancing methane production, with pH = 8 producing the maximum cumulative methane yield of 497 NmL/g VS. There was no significant change in the composition of volatile fatty acids (VFA) with pH in terms of dominant product type; valeric acid was the predominant VFA synthesized at all starting pH values except pH = 12, where formic acid was the predominant acid formed. As a digestate post‐treatment procedure, hydrothermal carbonization was combined with anaerobic digestion. At 200 °C, the maximum hydrochar yield production was 58.2%, with a higher heating value of 10.75 MJ/kg. © 2022 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Industrial Chemistry and John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Hemorrhagic transformation (HT) is a life‐threatening complication of stroke. Whether changes in gut microbial composition underlie the development of HT remains unknown. This study aimed to investigate whether the gut microbiota is altered in HT rats and examine the association between these changes and inflammatory responses. Methods: HT was successfully established in rats injected with 50% glucose (6 ml/Kg, i.p.) 15 min before middle cerebral artery occlusion (MCAO, 90 min occlusion) with reperfusion. After 5 days, rats were euthanized, and their brains used to estimate infarct volume. The inflammatory factors, the analysis of gut microbiota, and short‐chain fatty acids (SCFA) were assessed. Results: In contrast with non‐HT rats, gut microbiota sequencing showed an elevation in the relative abundance of Proteobacteria and Actinobacteria in HT rats. Total SCFAs, especially butyrate and valeric acid, were significantly lower in the cecal contents of HT rats than in those of non‐HT rats. Hyperglycemia‐induced HT exacerbation was not observed when rats were treated with antibiotics, suggesting that altered microbiota play a critical role in hyperglycemic HT pathogenesis. Furthermore, rats whose gut was colonized with HT rat microbiota showed increased susceptibility to HT. Conclusion: This study provides important information about the gut microbiota profiles and SCFA levels of MCAO rats with HT or non‐HT. The susceptibility to HT in MCAO rats is associated with inflammation and gut microbiota modulation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to evaluate changes in the composition of poly‐3‐hydoxybutyrate‐co‐3‐hydroxyvalerate (PHBV) by the polyhydroxybutyrate (PHB) overproducing mutant OPNA of Azotobacter vinelandii cultured under different conditions. RESULTS: The oxygen transfer rate (OTR) significantly affected PHBV composition in cultures in shaken flasks; the highest content of 3‐hydroxyvalerate (3HV; 28%) was achieved from cultures developed at an OTRmax of 5.87 mmol L−1 h−1. In the bioreactor, cultures were grown under oxygen‐limited conditions and different OTRs, varying the agitation rate. The highest PHBV accumulation (85%) was achieved at a low OTRmax (4.96 mmol L−1 h −1), whereas the maximum content of 3HV (8.5 mol%) was obtained at a higher OTRmax (20.3 mmol L−1 h−1). The OPNA strain produced a copolymer of ultra‐high molecular weight. CONCLUSIONS: Our results reveal that increasing the OTRmax raises the molar fraction of 3HV in the PHBV copolymer. Therefore, the manipulation of OTR could be a feasible strategy to produce PHBV copolymers with different monomeric compositions at industrial level. © 2021 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Background: Short‐chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT. Methods: This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30‐g (superdonor feces), and 60‐g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS‐SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS‐QoL) and Short‐Form Nepean Dyspepsia Index (SF‐NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography. Key Results: The fecal butyric acid level was significantly increased after FMT in both the 30‐g and 60‐g groups (both P ≤ 0.001). In the 60‐g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30‐g and 60‐g FMT groups were significantly inversely correlated with IBS‐SSS and FAS scores (P = 0.001, r = −0.3 and P = 0.0001. r=‐ 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT. Conclusion and Inferences: FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299). [ABSTRACT FROM AUTHOR]

Herein, the production of biohydrogen by dark fermentation was optimized using a novel hybrid approach that combines ANNs (artificial neural networks) with RSM (response surface methodology). Using the limited numbers of data (15 runs) as training data set together with one cross‐out method for validation, the complete 29 runs of well‐established data matrix were created from ANNs for RSM statistical analysis in order to correlated the critical process parameters with hydrogen production performance. This methodology was found to be robust, cost‐effective, reliable, and can be extensively analyzed the critical operational parameters, that is, carbon sources (obtained from potato peel wastes and starchy wastes), metal cofactor Fe0, pH, and dose levels of microbes on the hydrogen production, along with concentrations of other metabolites, such as acetic acid, propionic acid, butyric acid, valeric acid, and ethanol. The established ANNs‐RSM model using Box–Behnken design indicates the significant changes caused by the variations of a few critical operation parameters. The resultant model shows an exceptionally good result in terms of nonlinear noisy processes. Both single and multiple objective optimizations for dark hydrogen fermentation can achieve by using the established hybrid ANN‐RSM system. The optimal operating conditions (starch 6.2 kg/m3, pH 6.7, Fe0 11.7 g/m3, sludge 24.6 g/m3) could lead to the generation of hydrogen with a yield of 106.2 (cm3/g) and metabolites, that is, propionic acid (2.8 kg/m3), butyric acid (2E−2 kg/m3), valeric acid (4E−4 kg/m3) acetic acid (1.9 kg/m3), and ethanol (0.1 kg/m3) simultaneously. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of dietary supplementation with wheat bran fibre, inulin and their combination on growth performance, short‐chain fatty acids (SCFAs) production in caecum and colon and liver lipid metabolism in growing pigs. A total of 48 Duroc × Landrace × Yorkshire cross‐bred growing pigs (73 ± 2 days of age; 24.37 ± 2.86 kg) were allocated to four groups randomly, each group consisting of six pens with two pigs each. The pigs were fed a control diet (CON), a diet containing 2% wheat bran fibre (WB), a diet containing 2% inulin (IN), and a diet containing both of 1% wheat bran fibre and 1% inulin (MIX), respectively. The trial lasted for 28 days. The results showed that MIX fed pigs had a higher percentage of fat in the liver than those fed the CON (p <.05). IN, WB or MIX feeding decreased the concentrations of acetate and total SCFAs in colon compared with CON (p <.01). Feeding WB or IN also decreased the colonic butyrate concentrations compared with CON (p <.01). However, the serum level of valeric acid was elevated in the IN, WB and MIX group (p <.01). MIX fed pigs tended to have lower levels of propionate in serum than the WB fed pigs (p =.098). MIX feeding enhanced the mRNA expression of lipid synthesis‐related genes in liver compared with CON (p <.05). Feeding IN decreased the expression of bile acids synthesis‐related genes in liver and increased mRNA expression of SCFAs transporter SLC16A1 in colon compared with CON (p <.05). In this study, these data indicated that the combined supplementation of wheat bran fibre and inulin decreased the SCFAs concentrations in the colon, enhanced the genes FAS and HNF‐4α mRNA expression in liver and induced liver lipid accumulation in growing pigs. [ABSTRACT FROM AUTHOR]

Gut microbiota and short‐chain fatty acids (SCFAs) are associated with the development of various human diseases. In this study, we examined the role of astragaloside IV in modulating mouse gut microbiota structure and the generation of SCFAs, as well as in slow transit constipation (STC). An STC model was established by treating mice with loperamide, in which the therapeutic effects of astragaloside IV were evaluated. The microbiota community structure and SCFA content were analysed by 16S rRNA gene sequencing and gas chromatography‐mass spectrometry, respectively. The influence of butyrate on STC was assessed using a mouse model and Cajal cells (ICC). Astragaloside IV promoted defecation, improved intestinal mobility, suppressed ICC loss and alleviated colonic lesions in STC mice. Alterations in gut microbiota community structure in STC mice, such as decreased Lactobacillus reuteri diversity, were improved following astragaloside IV treatment. Moreover, astragaloside IV up‐regulated butyric acid and valeric acid, but decreased isovaleric acid, in STC mouse stools. Butyrate promoted defecation, improved intestinal mobility, and enhanced ICC proliferation by regulating the AKT–NF‐κB signalling pathway. Astragaloside IV promoted intestinal transit in STC mice and inhibited ICC loss by regulating the gut microbiota community structure and generating butyric acid. [ABSTRACT FROM AUTHOR]

In order to prepare new antiepileptic drugs with a broader clinical application and lower toxic side effects, we have employed esterification and condensation reactions (we call it Niche Chemistry) to reduce the use of valproic acid as the target molecule. In combination with the study of a broad‐spectrum of novel anticonvulsants, we have synthesized two valeric acid derivative compounds [(4‐acetamidophenyl 2‐propylvalerate (1), and (E)‐5‐(4‐((2‐propylpentanoyl)oxy)styryl)‐1,3‐phenylene bis(2‐propylvalerate) (2) by an esterification reaction. The maximum shock seizure test for products 1 and 2 has been successfully carried out, and their cytotoxic activity and survival effects have also been carefully investigated. [ABSTRACT FROM AUTHOR]

Perovskite solar cells have attracted a great deal of attention thanks to their high efficiency, ease of manufacturing, and potential low cost. However, the stability of these devices is considered their main drawback and needs to be addressed. Mesoporous carbon perovskite solar cells (m‐CPSC), consisting of three mesoporous layers (TiO2/ZrO2/C) infiltrated with CH3NH3PbI3 (MAPI) perovskite, have presented excellent lifetimes of more than 10 000 h when the additive NH2(CH2)4CO2HI (5‐ aminovaleric acid iodide; 5‐AVAI) is used to modify the perovskite structure. Yet, the role of 5‐AVAI in enhancing the stability has yet to be determined. Here, superoxide‐mediated degradation of MAPI m‐CPSC with and without the 5‐AVAI additive is studied using the fluorescence probe dihydroethidium for superoxide detection. In situ X‐ray diffractometry shows that aminovaleric acid methylammonium lead iodide (AVA‐MAPI) perovskite infiltrated in mesoporous layers presents higher stability in an ambient environment under illumination, evidenced by a slower decrease of the MAPI/PbI2 peak ratio. Superoxide yield measurements demonstrate that AVA‐MAPI generates more superoxide than regular MAPI when deposited on glass but generates significantly less when infiltrated in mesoporous layers. It is believed that superoxide formation in m‐CPSC is dependent on a combination of competitive factors including oxygen diffusion, sample morphology, grain size, and defect concentration. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate the effect of diet Piper sarmentosum extract (PSE) on the growth performance, antioxidant properties, rumen fermentation and microflora in goats. Forty Hainan black goats with similar body weight were divided into four groups with supplementation of PSE in the concentrate at 0, 300, 600 and 1,200 mg/kg, respectively, and fed for 56 days. Results showed that average daily gain (ADG) was higher and feed intake/body gain (F/G) was lower in goats fed with PSE at 300 mg/kg (p <.05). The activities of glutathione peroxidase (GSH‐Px) and total antioxidant capacity (T‐AOC) in the serum of goats differed among treatments and were greatest linearly when PSE was added at 1,200 mg/kg (p <.05). The level of malondialdehyde (MDA) in the serum of goats differed among treatments and was lowest linearly when PSE was added at 1,200 mg/kg (p <.05). The level of protozoal protein in the rumen of goats differed among treatments and was lowest linearly when PSE was added at 1,200 mg/kg (p <.05). The concentrations of ruminal acetic acid and valeric acid and the ratio of acetate to propionate were reduced with PSE supplementation (p <.05). Protozoa, fungi, Ruminococcus flavefaciens and Fibrobacter succinogenes contents differed among treatments and were lowest linearly when PSE was added at 1,200 mg/kg (p <.05). Thus, supplementation of PSE at 300–1,200 mg/kg to goat concentrate is recommended for improving antioxidative ability and rumen efficiency and reducing protozoal content of goat. [ABSTRACT FROM AUTHOR]

Valerate esters (VAEs) commonly derived from levulinic acid (LA), which is deemed as one of the most promising biomass platform molecules, have been hailed as "valeric biofuels" in recent years. The cascade transformation of LA to VAEs consists of a series of acid‐ and metal‐catalyzed processes alternately, in which heterogeneous bifunctional catalysts are required for better catalytic performance. The transformation pathway from LA to VAEs is presented, and bifunctional catalytic systems for the cascade transformation of LA into valeric acid (VA) and its esters, as well as one‐pot conversion processes, are reviewed. Additionally, effects of metal and acid sites on the catalytic performance are discussed in detail. Impacts of and improvements to coke deposition, which is determined to be the primary reason for the reduction in catalytic activity, are also analyzed. Finally, feasible suggestions are proposed for enhanced catalytic performance and a reduction in overall costs. [ABSTRACT FROM AUTHOR]

Anaerobic digestion (AD) is an established method for sustainable energy production. Anaerobic digestion model No.1 (ADM1) was used to simulate methane production (MP) and volatile fatty acid (VFA) concentrations at different ammonium concentrations. In accordance with the incomplete description of several biochemical reactions and the omission of several reaction processes, ADM1 was modified with the consideration of acetic acid inhibition and valeric acid existence. ADM1_ac (ADM1 added acetic acid inhibition) could obtain better simulation accuracy of MP (goodness‐of‐fit value = 0.945), and VFA concentrations (goodness‐of‐fit values > 0.39) were all higher than ADM1_original, but cannot explain the valeric acid production. ADM1_va (ADM1 added valeric acid existence) could achieve better simulation of valeric acid (achieving a breakthrough of zero), nevertheless the accuracy of propionic and butyric acids was poorer than ADM1_ac with differences between experimental and simulation values were 5%–10% lower. With both factors coordinated, MP and VFA concentrations could be simulated accurately by ADM1_ac_va (ADM1 added acetic acid inhibition and valeric acid existence), with the highest goodness‐of‐fit values (>0.85). The results of a verification experiment with ADM1_ac_va simulation further indicated that acetic acid inhibition and valeric acid as new component were both important in ADM1. Practitioner points: ADM1_ac could simulate MP and acetate, propionate and butyrate concentrations better.ADM1_va could explain the valerate production during AD of glucose.ADM1_ac_va could simulate AD process quite accurately, with the highest goodness‐of‐fit values (>0.85).Acetate inhibition and valerate existence were both important and should be considered in ADM1. [ABSTRACT FROM AUTHOR]

The electrochemical production of valeric acid from the renewable bio‐based feedstock levulinic acid has the potential to replace the oxo‐process, which uses fossil‐based feedstock 1‐butylene. The electrochemical reduction of the ketone functionality in levulinic acid using lead or mercury cathodes has already been known for over 100 years. However, large‐scale electrochemical production of valeric acid might be limited, owing to the toxicity of these materials. In this study, we identified three additional cathode materials, cadmium, indium, and zinc, which selectively and efficiently produce valeric acid. Of these materials, indium and zinc are considered more benign. More specifically, at indium there is no formation of the side product γ‐valerolactone, thus resulting in the highest selectivity towards valeric acid. For the electrochemical reduction, a reaction mechanism involving the formation of an organometallic compound is proposed. Furthermore, a possible processing strategy is outlined to enable the continuous electrochemical production of valeric acid on a large scale. [ABSTRACT FROM AUTHOR]

Tailoring peptide hydrogelators with tunable mechanical properties and diversified applicabilities is an eternal pursuit today. Here, we report the rational design approach of a short, simple enantiomeric segment, Boc‐δ‐Ava‐L‐Phe‐OH (Hydrogelator I) Boc‐δ‐Ava‐D‐Phe‐OH (Hydrogelator II) that manifests β‐sheet conformation and nanofibrous morphology at supramolecular level. Our hydrogelators have excellent biocompatibility, proteolytic stability, thermoreversibility and self‐healing properties. Remarkably, these Hydrogelators not only demonstrate an unprecedented ability to release the anticancer drugs 5‐Fluoro uracil/curcumin/Doxorubicin at physiological pH and room temperature but also modulates an effective route in successful removal of harmful organic effluents from waste water, with the aptitude to reuse the hydrogelator few times. Interestingly it has been investigated that subtle changes in molecular structure of the gelator, turns the gelator into a nongelator molecule (Boc‐Gaba‐L‐Phe‐OH ;Compound III) and (Boc‐Acp‐L‐Phe‐OH ;Compound IV) supported by MD simulation studies. Overall this study establishes innovative design principles towards the development of advanced functional materials for future drug delivery applications and waste water management. [ABSTRACT FROM AUTHOR]

Abstract: The esterification of valeric acid with n‐butanol was studied with homogeneous and heterogeneous catalysts. The activity and performance of homogeneous p‐toluenesulfonic acid and heterogeneous cation exchange resin catalysts Amberlyst 36, Indion 190, and Amberlite IRC‐50 were evaluated. The pseudo‐homogeneous kinetic model was used to investigate the kinetic parameters of homogeneous‐ and heterogeneous‐catalyzed esterification. The UNIFAC (universal functional activity coefficient) approach was used to study the nonideality of the esterification reaction. The reaction was statistically modeled and optimized by the application of response surface methodology. The effects of independent variables such as reaction temperature, initial molar ratio, and catalyst loading on the conversion of valeric acid were investigated. The optimized conditions for the esterification reaction catalyzed by Amberlyst‐36 were found as temperature 360.4 K, initial molar ratio 3.8, and catalyst loading 6.7 wt%. The predicted conversion (89%) at these optimized conditions is in good agreement with the experimental conversion (87.3 ± 1.6%). [ABSTRACT FROM AUTHOR]

This paper studies liquid‐liquid equilibrium (LLE) of the type 2 systems (water + valeric acid + dibasic ester or monobasic ester or alcohol) at T = (298.2 ± 0.1) K and p = (101.3 ± 0.7) kPa. Equilibrium distribution of valeric acid onto (water + solvent) two‐phase system is better for more structured diethyl sebacate and ethyl caprylate as compared to less structured diethyl succinate, diethyl malonate, ethyl valerate, and isoamyl alcohol. The two‐phase envelope size and the tie line slope on the phase diagrams are varying as follows: ethyl caprylate > diethyl sebacate > ethyl valerate > diethyl succinate ≈ diethyl malonate > isoamyl alcohol. The SERLAS‐integrated (solvation energy relation for liquid associated systems‐integrated) molecular model with nine physical descriptors, originated from LSER (linear solvation energy relation) principles in conjunction with group‐contribution method, is proposed and applied to the prediction of type 2 LLE properties. By combining SERLAS with UNIFAC‐Dortmund, we are able to get along with a simultaneous impact of both methods for satisfactorily simulating type 2 phase behaviour so long as solvent effects are concerned. SERLAS, SERLAS‐modified, SERLAS‐integrated, and UNIFAC‐original models have been stringently tested for consistency in reproducing phase equilibrium properties with average deviations inferior to 28.8 %, 44.3 %, 21.3 %, and 30.4 %, respectively. [ABSTRACT FROM AUTHOR]

Kinetic simulations of polymer chain propagation in an aqueous medium in an initial stage of emulsifier-free, emulsion organotellurium-mediated living radical polymerization (emulsion TERP) of styrene with sodium poly(methacrylic acid)-methyltellanyl (PMAA-TeMe) as a control agent and 4,4′-azobis(4-cyanovaleric acid) as a water-soluble azo-initiator at various polymerization temperatures, which is carried out experimentally at pH > 9 in a previous article, is performed using PREDICI software from CiTGmbH. The approach based on α-chain end-separated kinetic simulation leads us to get important aspects of individual polymer chain growths from both α-end groups, i.e., initiator and PMAA end groups. The larger number percentage of polystyrene (PS) chain having PMAA end group relative to all PS chains is generated at lower polymerization temperature. In addition, the PS chain growth is also pronounced at lower temperature. In other words, the self-assembly nucleation, in which the control agents are contained, predominantly occurs at the lower polymerization temperature than the homogeneous nucleation, in which they are not contained. This indicates that the emulsion TERP effectively proceeds at lower temperature, which is well accorded with the experimental result in the previous article. [ABSTRACT FROM AUTHOR]

Porous molecular nanocontainers of {Mo132}-type Keplerates offer unique opportunities to study a wide variety of relevant phenomena. An impressive example is provided by the highly reactive {Mo132-CO3} capsule, the reaction of which with valeric acid results in the very easy release of carbon dioxide and the uptake of 24 valerate ions/ligands that are integrated as a densely packed aggregate, thus indicating the unique possibility of hydrophobic clustering inside the cavity. Two-dimensional NMR techniques were used to demonstrate the presence of the 24 valerates and the stability of the capsule up to ca. 100 °C. Increasing the number of hydrophobic parts enhances the stability of the whole system. This situation also occurs in biological systems, such as globular proteins or protein pockets. [ABSTRACT FROM AUTHOR]

Producing fuels and chemical intermediates with cell cultures is severely limited by low product concentrations (≤0.2%(v/v)) due to feedback inhibition, cell instability, and lack of economical product recovery processes. We have developed an alternate simplified production scheme based on a cell-free immobilized enzyme system. Two immobilized enzymes (keto-acid decarboxylase (KdcA) and alcohol dehydrogenase (ADH)) and one enzyme in solution (formate dehydrogenase (FDH) for NADH recycle) produced isobutanol titers 8 to 20 times higher than the highest reported titers with S. cerevisiae on a mol/mol basis. These high conversion rates and low protein leaching were achieved by covalent immobilization of enzymes (ADH) and enzyme fusions (fKdcA) on methacrylate resin. The new enzyme system without in situ removal of isobutanol achieved a 55% conversion of ketoisovaleric acid to isobutanol at a concentration of 0.135 (mole isobutanol produced for each mole ketoisovaleric acid consumed). Further increasing titer will require continuous removal of the isobutanol using an in situ recovery system. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:66-73, 2016 [ABSTRACT FROM AUTHOR]

Two new sesquiterpenes, cyperusol A3 ( 1) and 3 β-hydroxycyperenoic acid ( 2), along with three known sesquiterpenes, britanlin E ( 3), 1 β,4 α-dihydroxyeudesm-11-ene ( 4), and 11,12-dihydroxyeudesm-4-en-3-one ( 5), were isolated from the AcOEt-soluble fraction of rhizomes of Cyperus rotundus L. The structures of 1 and 2 were elucidated by physical and spectroscopic methods (1H- and 13C-NMR, 2D-NMR, and MS). All of the isolates, 1- 5, were evaluated for their cytotoxic activities against human ovarian cancer cells (A2780) and endometrial adenocarcinoma cells ( Ishikawa) using MTT assays. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether functional changes of the gut flora over time were related to sensitization and allergic symptoms at four years of age. Methods: The levels of short chain fatty acids (SCFAs) in faecal samples at one (n = 139) and four (n = 53) years of age were related to the development of positive skin prick tests (SPT) and allergic symptoms during the first four years of life. Results: Faecal acetic (p < 0.01) and propionic (p < 0.01) acids decreased from one to four years of age, while valeric acid (p < 0.001) increased. Low levels of i-butyric (p = 0.01), i-valeric (p = 0.03) and valeric acids (p = 0.02) at one year were associated with questionnaire-reported symptoms of food allergy at four years. Positive SPTs and allergic symptoms at four years were associated with low faecal levels of i-butyric, i-valeric and valeric acids. At one year of age, infants with, as compared to without older siblings had higher median levels of valeric acid. Conclusion: A slow functional maturation of the gut microflora, as measured by faecal levels of SCFAs is associated with allergy both at one and four years. The findings lend further support to an association between allergy and the development of microbial diversity. [ABSTRACT FROM AUTHOR]

The interaction between intestinal epithelial cells and microbes is partly mediated by Toll-like receptors (TLRs). Sensing of Gram-positive and Gram-negative bacteria by TLR2 and TLR4, respectively, can result in immune system activation and in an exclusion of bacteria from the intestine. To test the impact of these TLRs on bacterial composition, germ-free TLR2/TLR4 double-knock out mice and the corresponding C57BL/10ScSn wild-type mice where associated with fecal bacteria from one single donor mouse. In addition, C3H/HeOuJ and BALB/c mice were used in this study. Fecal bacteria were monitored over 13 weeks with denaturing-gradient gel electrophoresis (DGGE). Colonic bacteria were enumerated by fluorescent in situ hybridization (FISH) and short-chain fatty acids (SCFA) were measured in caecal samples. No effect of the TLRs on intestinal microbiota composition and SCFA concentrations was observed. However, the microbiota composition as reflected by DGGE band patterns differed between C3H and BALB/c mice on the one hand and C57BL/10 mice on the other hand. Corresponding differences between the mouse strains were also observed in cecal propionic, valeric and i-valeric acid concentrations. No differences between the animals were observed in the numbers of bacteria detected by FISH. We conclude that genetic traits but not TLR2 and TLR4 have an impact on the intestinal microbiota composition. [ABSTRACT FROM AUTHOR]

The molecules of the title compound, C11H13N3O3, are linked by O—H⋯N and N—H⋯O interactions into a linear hydrogen-bonded chain. [ABSTRACT FROM AUTHOR]

Objective – Status epilepticus (SE) and serial attacks (SA) represent neurological emergencies, and mortality rate for SE/SA is high, ranging from 3% to 25%, depending on cause and co-morbidity. As SE/SA become more refractory to treatment over time, rapid, appropriate treatment is extremely important. Here, we report a prospective registration of the effect of intravenous (IV) valproate (VPA) on SE/SA in a group of Norwegian patients. Patients and methods – Forty-one adult patients (18 males, 23 females) were included in the study. All had previously been unsuccessfully treated with diazepam. For 19, the main SE/SA seizure type was generalized tonic-clonic, while 16 had complex-partial seizures. Six had seizures that were difficult to classify. The treatment protocol recommended 25 mg/kg of VPA loading dose over 30 min, followed by continuous infusion of 100 mg/h for at least 24 h, then per oral administration. If seizures persisted after the loading dose, general anaesthesia (barbiturates/propofol/midazolam) was administered. Results – No serious side effects were reported. In 76% of the cases (31 of 41), SE/SA stopped and anaesthesia was not required. Of the patients treated within 3 h, only 5% needed anaesthesia, whereas of those treated after 3–24 h, 38% needed anaesthesia. Of those who waited for more than 24 h before treatment, 60% required anaesthesia. Furthermore, 60% of the patients who needed anaesthesia were given loading doses below 2100 mg. Conclusions – VPA seems to be a safe, effective treatment of SE/SA, but efficacy is dependent on time lapse between symptoms and VPA treatment, and administration of a sufficiently high loading dose. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is a potent anti-epileptic and effective mood stabilizer. It is known that VPA enhances central GABAergic activity and activates the mitogen-activated protein kinase–extracellular signal-regulated kinase (MAPK–ERK) pathway. It can also inhibit various isoforms of the enzyme, histone deacetylase (HDAC), which is associated with modulation of gene transcription. Recent in vivo studies indicate a neuroprotective role for VPA, which has been found to up-regulate the expression of brain-derived neurotrophic factor (BDNF) in the rat brain. Given the interaction between the pineal hormone, melatonin, and GABAergic systems in the central nervous system, the effects of VPA on the expression of the mammalian melatonin receptor subtypes, MT1 and MT2, were examined in rat C6 glioma cells. The effects of VPA on the expression of glial cell line-derived neurotrophic factor (GDNF) and BDNF were also examined. RT-PCR studies revealed a significant induction of melatonin MT1 receptor mRNA in C6 cells following treatment with 3 or 5 m m VPA for 24 h or 5 m m VPA for 48 h. Western analysis and immunocytochemical detection confirmed that the VPA-induced increase in MT1 mRNA results in up-regulation of MT1 protein expression. Blockade of the MAPK–ERK pathway by PD98059 enhanced the effect of VPA on MT1 expression, suggesting a negative role for this pathway in MT1 receptor regulation. In addition, significant increases in BDNF, GDNF and HDAC mRNA expression were observed after treatment with VPA for 24 or 48 h. Taken together, the present findings suggest that the neuroprotective properties of VPA involve modulation of neurotrophic factors and receptors for melatonin, which is also thought to play a role in neuroprotection. Moreover, the foregoing suggests that combinations of VPA and melatonin could provide novel therapeutic strategies in neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

The α-ketoglutarate dehydrogenase complex (KGDHC) is a mitochondrial enzyme in the TCA cycle. Inhibition of KGDHC activity by α-keto-β-methyl-n-valeric acid (KMV) is associated with neuron death. However, the effect of KMV in microglia is unclear. Therefore, we investigated the effect of KMV on BV-2 microglial cells exposed to hypoxia or oxidative stress. The results showed that KMV (1-20 mM) enhanced the cell viability under hypoxia. KMV dose-dependently reduced ROS and LDH releases from hypoxic BV-2 cells. KMV also reduced ROS production and enhanced the cell viability under H2O2 but failed to reduce the SIN-1 and sodium nitroprusside (SNP) toxicity. KMV also reduced caspase-3 and -9 activation under stress. These results suggest that KMV protects BV-2 cells from stress and acts by reducing ROS production through inhibition of KDGHC. [ABSTRACT FROM AUTHOR]

Purpose:Women with epilepsy apparently have a higher incidence of polycystic ovary syndrome (PCOS) than do women without epilepsy. Whether the underlying disease or the antiepileptic drug (AED) treatment is responsible for this increased risk is unknown, although clinical reports implicate valproic acid (VPA) as a potential cause. The steroidogenic enzymes 3βHSDII (3β-hydroxysteroid dehydrogenase) and P450c17 (17α-hydroxylase/17,20 lyase) are essential for C19 steroid biosynthesis, which is enhanced during adrenarche and in PCOS.Methods:To determine whether the AEDs VPA, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LYG) directly affect the activities of human 3βHSDII and P450c17, we added them to yeast expressing human P450c17 or 3βHSDII and assayed enzymatic activities in the microsomal fraction.Results:Concentrations of VPA≤10 mMhad no effect on activities of P450c17; however, VPA inhibited 3βHSDII activity starting at 0.3 mM(reference serum unbound concentration, 0.035–0.1 mM) with an IC50 of 10.1 mM. CBZ, TPM, and LTG did not influence 3βHSDII or P450c17 activities at typical reference serum unbound concentrations, but did inhibit 3βHSDII and P450c17 at concentrations>10-fold higher.Conclusions:None of the tested AEDs influenced 3βHSDII or P450c17 activities at concentrations normally used in AED therapy. However, VPA started to inhibit 3βHSDII activity at concentrations 3 times above the typical reference serum unbound concentration. Because inhibition of 3βHSDII activity will shift steroidogenesis toward C19 steroid production when P450c17 activities are unchanged, very high doses of VPA may promote C19 steroid biosynthesis, thus resembling PCOS. CBZ, TPM, and LTG influenced 3βHSDII and P450c17 only at toxic concentrations. [ABSTRACT FROM AUTHOR]

Purpose:To determine whether valproic acid[divalproex (DVP)] extended-release, administered at a higher proportionate once-daily dosage, can be safely substituted for delayed-release or sprinkle in pediatric patients with epilepsy.Methods:Patients between ages 6 and 17 years with stable epilepsy taking DVP were randomized to 7 days of either DVP delayed-release/sprinkle (at the usual daily dose taken before study entry) or extended-release DVP (daily dose, 8% to 25% higher than their usual dose), and then (crossed over to) 7 days of the comparator formulation. Patient's clinical status was evaluated at a screening visit and on days 8 and 15, and with telephone follow-up 1 month after study completion.Results:No statistically significant difference in mean plasma VPA levels measured at the end of treatment was observed: 99, 92, and 103μg/ml with the delayed-release tablets (n= 4), the sprinkle formulation (n= 11), and the extended-release tablets (n= 16), respectively. Seizure-control rates were stable during patients' use of the extended-release formulation. None of the study patients experienced a treatment-related adverse event.Conclusions:The total daily dose for patients taking the delayed-formulation may need to be increased by≤20% when they are switched to the extended-release formulation. When switching from sprinkles to the extended-release formulation, individual variability must be considered. In patients who have VPA levels near the very high end of the therapeutic range (>100μg/ml), it may be more prudent to make only minor modifications to the total daily dose during conversion and then to individualize the DVP extended-release dose based on plasma levels. [ABSTRACT FROM AUTHOR]

Purpose:Valproate (VPA) induces postural tremor in 6–45% of patients. The characteristics of VPA-induced tremor have not yet been quantitatively assessed, and it is not known whether tremor prevalence or severity is affected by VPA formulation (controlled-release CR-VPA vs. conventional VPA). The aim of this study was quantitatively to assess tremor in epilepsy patients receiving VPA and to compare the effects of two VPA formulations (CR-VPA vs. VPA) on tremor severity.Methods:In a prospective study, 18 consecutive patients with newly diagnosed focal or generalized epilepsy were assigned to receive alternately either VPA (n= 10) or CR-VPA (n= 8) monotherapy. Computerized tremor analysis was performed at baseline 1 day before initiating VPA treatment and repeated after a seizure-free period of≥8 weeks, during which VPA doses had remained stable. Rest and postural tremor were recorded by accelerometry, and surface electromyograms (EMGs) were recorded from the wrist flexors and extensors.Results:At baseline, the two groups had similar postural tremor amplitudes. At follow-up, the CR-VPA group had remained at the same level, whereas VPA subjects exhibited a significant increase in tremor amplitudes (p<0.05) despite comparable VPA doses and comparable plasma VPA concentrations at the time of tremor testing.Conclusions:This is the first study to assess quantitatively VPA-induced tremor by standardized tremor analysis. These results suggest that CR-VPA may cause less tremorigenic activity as compared with standard VPA. The mechanisms underlying this difference are unclear but may include greater peak–trough variation with VPA than with CR-VPA. [ABSTRACT FROM AUTHOR]

The incidence of intentional or accidental valproic acid (VPA) overdose is increasing. Severe VPA toxicity may lead to coma and death. Traditionally the treatment of patients with VPA toxicity has been limited to supportive measures. VPA is highly protein bound and therefore it is considered not to be removable by extracorporeal means. However, studies of VPA toxicokinetics indicate that at blood levels that exceed therapeutic concentrations, VPA protein binding sites become saturated, leading to increased concentration of the free unbound drug. The free unbound drug has a small molecular weight and therefore it is theoretically amenable to removal by extracorporeal means. We present a patient with VPA toxicity who was successfully treated with“in-series” hemodialysis and hemoperfusion followed by continuous venovenous hemodiafiltration (CVVHDF) and review the literature on the management of VPA toxicity using extracorporeal therapies. [ABSTRACT FROM AUTHOR]

The possible interaction of glutamatergic metabotropic agonists and N-methyl-D-aspartate (NMDA) receptors was investigated in the nucleus tractus solitarii (NTS) of awake rats. The cardiovascular responses to unilateral microinjection of trans-1-amino-1,3cyclopentanediocarboxylic acid (trans-ACPD; 250pmol/50nL) into the NTS (n=8) produced hypotension (-64 ± 4mmHg) and bradycardic (-206 ± 11 bpm) responses, which were blocked by previous microinjection of 2-amino-5-phosphonovaleric acid (AP5; 10 nmol/50 nL), a selective antagonist of NMDA ionotropic receptors, into the same site. Intravenous injection of methyl-atropine blocked both the bradycardic and hypotensive responses to microinjection of trans-ACPD into the NTS, indicating that the hypotension was secondary to the intense bradycardic response. The data also showed that the bradycardic and hypotensive responses to microinjection of an NMDA agonist (10 pmol/50 nL) into the NTS were not affected by previous microinjection of α-methyl-4-carboxyphenylglycine (MCPG; 5 nmol/50 nL), a non-selective antagonist of metabotropic receptors. The results showing that the cardiovascular responses to microinjection of trans-ACPD into the NTS were blocked by AP-5 indicate that the responses to metabotropic agonists in the NTS involves NMDA receptors. [ABSTRACT FROM AUTHOR]

Propionic acid and valeric acid at 1 mM reduced the mitotic index of root meristem cells of Pisum sativum to M reduced the uptake of [14C]-leucine but conversion rates to protein were constant regardless of whether any acid was present. Another longer fatty acid, caprylic acid, at 1 mM did not significantly reduce the mitotic index nor did 1 mM benzoic acid, another organic acid. This information suggests that only the short-chain fatly acids, propionic acid and valeric acid, limit progression through the cell cycle by inhibiting DNA synthesis and arresting cells in G1 and G2 in a manner similar to butyric acid, a known cell arresting agent. [ABSTRACT FROM AUTHOR]

Butyrate kinase (BK) was extracted from Escherichia coli DH5 pJc7*, purified, immobilized on porous glass beads and packed in a glass tube as a biosensor coupled with a flow-injection analysis system (FIA). The limits of detection were: FIA (25ppm) and batch method (BM, 5ppm). BK is highly specific for butyric, propionic and valeric acids. Regression coefficient values were: FIA r=0.992 and free enzvme r=0.987. The FIA and BM were tested on butter samples with high correlation (r = 1.000) between the methods. Correlation coefficients were: r=0.994 and r=0.988 between acid degree value and FIA/BM. [ABSTRACT FROM AUTHOR]