Acetoacetic Acid Research Articles

Knockout of acetoacetate degradation pathway gene atoDA enhances the toxicity tolerance of Escherichia coli to isopropanol and acetone.

Isopropanol and acetone are important chemical products and potential high-quality new fuels. Both of them are metabolites of isopropanol synthesis pathway, but they are toxic to most bacteria. In this study, toxicity tolerance of Escherichia coli strains was evaluated by detecting their growth rates under different concentrations of isopropanol and acetone. It was showed that isopropanol was more toxic to E. coli than acetone, and the native strain MG1655 had better tolerance over DH5α to either acetone or isopropanol of 300mM. Key genes of ethanol synthesis pathway, acetic acid metabolism pathway, and acetoacetic acid degradation pathway, including adhE, ackA-pta, and atoDA, were knocked out in MG1655 to form mutants MGΔadhE, MGΔackA-pta, and MGΔatoDA. The tolerance performances of the mutants to isopropanol and acetone were determined under various concentrations including 300mM, 500mM, and 700mM, respectively. The mutant MGΔatoDA exhibited excellent tolerance to both acetone and isopropanol of 500mM, and MGΔackA-pta could tolerate acetone at 500mM rather than isopropanol, while the deletion of adhE in MGΔadhE resulted in a severe cell growth defection. Although isopropanol and acetone at 700mM caused severe growth inhibition on each strain, cell growth could be restored to varying degrees with the prolongation of culture time. This phenomenon was suggested to be related to the volatilization of isopropanol and acetone based on volatilization tests. It was envisioned that MG1655 was a suitable host strain for isopropanol metabolic engineering research, and the acetoacetic acid degradation pathway gene atoDA, was probably the key optimizing point for isopropanol production.

Effect of tofogliflozin on cardiac and vascular endothelial function in patients with type2 diabetes and heart diseases: A pilot study.

Recent studies have shown that sodium–glucose cotransporter 2 inhibitors decrease the risk of heart failure in patients with type 2 diabetes. However, the precise mechanisms of action of these drugs are not well understood. In the present study, we evaluated the effect of treatment with tofogliflozin for 6 months on cardiac and vascular endothelial function in 26 patients with type 2 diabetes and heart diseases. Tofogliflozin treatment significantly decreased left ventricular end‐diastolic dimensions and significantly increased flow‐mediated vasodilation. Although E/e′ did not significantly change after treatment, the decrease observed in the E/e′ ratio was significantly correlated with the increase in acetoacetic acid and 3‐hydroxybutyrate levels. These results suggest that sodium–glucose cotransporter 2 inhibitor might improve left ventricular dilatation and vascular endothelial function in patients with type 2 diabetes. Furthermore, it is suggested that the elevation of ketone bodies induced by sodium–glucose cotransporter 2 inhibitors might contribute to a protective effect in left ventricular diastolic dysfunction.

110th Anniversary: Microkinetic Modeling of the Vapor Phase Upgrading of Biomass-Derived Oxygenates

Bio-oil produced from fast pyrolysis of biomass is a complex mixture of more than 200 compounds, including oxygenates and acids. As these species are highly undesirable in fuels, catalytic upgrading of biomass pyrolysis product vapors, also known as catalytic fast pyrolysis, is performed to upgrade the vapors to valuable fuels and chemicals. This work presents a detailed microkinetic model, composed of elementary steps, of the catalytic upgrading of acetic acid and acetone, two common oxygenates present in bio-oil. An automated network generator was utilized to construct a reaction network composed of 580 unique species and 2160 unique reactions. The kinetic parameters for each reaction in the network were estimated using transition state theory, the Evans–Polanyi relationship, and thermodynamic data. The resulting mechanistic model is able to describe experimental data presented in the literature for the transformation of acetic acid and acetone on HZSM-5 in a fixed-bed reactor, which is modeled as a plug-flow reactor. Additionally, the model solutions reveal vital information regarding the mechanism by which acetic acid and acetone are upgraded to valuable fuels and chemicals. In the first phase of the mechanism, acetic acid is converted to acetone via acylium ion addition to acetic acid; this is followed by decarboxylation of acetoacetic acid. The second phase is dominated by the self-aldol condensation of acetone, which is shown to occur predominantly through the keto form of acetone rather than the enol form, and subsequent deoxygenation reactions leading to olefins and aromatics. Finally, net rate analysis shows that aromatics are primarily formed via a pathway including aldol condensation of mesityl oxide, whereas olefins are produced from the addition of isobutene and subsequent cracking.

Changes in the results of the multi reagents strips in a single lot: A comparative study

Topic: Changes in the results of the multi reagents strips in a single lot.AIM: To verify whether the multi reagent strips show changes in results of pH and specific gravity.Introduction: Urine chemical reagent Strips are square measure firm plastic strips onto that many separate reagent areas are affixed. The test is for the detection of one or more lot of the subsequent analytes in urine: Leukocytes, Glucose, organic compound ketone (Acetoacetic acid), Bilirubin, Blood, specific gravity, Protein, Nitrite, Urobilinogen and pH. Urine undergoes several changes throughout states of malady or body pathology before blood composition is altered to a major extent. Urinalysis may be a helpful procedure as an indicator of health or malady as such may be a part of routine health screening.Materials and Methods: Sample size: 100 multi reagent strips were taken from a single lot. The test is for the detection of one or more lot of the subsequent analytes in urine: Leukocytes, Glucose, organic compound ketone (Acetoacetic acid), Bilirubin, Blood, specific gravity, Protein, Nitrite, Urobilinogen and pH.The strips were verified for any changes by dipping it in an artificially prepared single urine sample, analyzed as per the user’s manual and results were analyzed.Result: The average pH value is 7.0, in this slot of 100 strips had variations ranging between 6.19 and 7.82. Whereas specific gravity the average value is 1.01, in this slot of 100 strips had variations ranging between 1.006 and 1.016.Conclusion: When manually analyzed it shows difference and variations in each strip in a single lot for pH and specific gravity of 5.8% and 2.6% respectively. Therefore, it is applicable for manual urine analysis method.

Zn(L-proline)2: An efficient and reusable organocatalyst for the synthesis of polyfunctionally substituted pyrans and 2-amino-4-aryl-8-oxo-4,8-dihydropyrano[3,2-b]pyran derivatives

Efficient synthesis of non-annulated 2-amino-4H-pyrans and 2-amino-8-oxo-4,8-dihydropyrano[3,2-b]pyran derivatives, which are biologically relevant heterocycles is achieved, utilizing a domino three-component reaction of ethyl acetoacetate or kojic acid with aromatic aldehydes and malononitrile catalyzed by Zn(L-proline)2 as reusable organometallic catalyst. The process exhibits high atom economy, short reaction time, simple work up, high yields and environmentally friendly nature. Excellent yields of the targeted molecules have been obtained.

Antimicrobial Activity and Analysis of the Essential Oils of Selected Endemic Edible Apiaceae Plants Root from Caspian Hyrcanian Region (North of Iran)

Background: Different endemic species of Apiaceae that widely grow in Hyrcanian region have long been used as spices and herbal remedies. Chemical compositions and bioactivity of many of these plants have not been studied scientifically. The volatile constituents and antimicrobial activity of four edible Apiaceae plants—Elaeosticta glaucescens Boiss, Malabaila secacul (Mill.) Boiss, Caucalis platycarpos L., and Eryngium caucasicum Trautv—roots were investigated. Methods: Gas chromatography/mass spectrometry (GC–MS) and gas chromatography/flame ionization detection (GC–FID) methods were used for chemical investigation. Antimicrobial potential of the volatile compositions of these roots were investigated using the disc diffusion method on four microorganisms including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis. Results: The best minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of these species were revealed for B. subtilis and S. aureus (500 µg/mL for MIC and MBC) followed by E. caucasicum and C. platycarpus, respectively. The main compounds of E. caucasicum root essential oil were hexyl isovalerate (11.0%) and hexyl valerate (10.1%). E. glaucescens root essential oil was mainly composed of 3(10)-caren-4-ol, acetoacetic acid ester (9.8%), octyl isovalerate (8.9%), and octyl acetate (5.7%). In C. platycarpos root, hexyl isovalerate (9.2%) and n-octyl isobutyrate (8.5%) were constituted the major compositions of the essential oil while n-hexyl isobutyrate (8.5%) and hexyl hexanoate (7.8%) were predominant compounds in M. secacul. Conclusion: The essential oils of E. caucasicum and C. platycarpus roots were contained high amount of short chain fatty acid esters (SCFAE) and trans- pinocarvyl acetate. They exhibited moderate antibacterial activity.

Evaluation of metabolic status of ewes infected with ketosis

Ketosis in ewes is one of the limiting factors for the development of sheep farming. But the lack of knowledge about this disease is an obstacle in the development of effective treatments and reliable methods of prevention. This article presents the results of studying the peculiarities of the state of metabolism in the body of ewes of the Tsigai breed of the Black Sea type during ketosis. To do this, in the farms of the Crimea the identification of ewes infected with ketosis, which had been subjected to clinical and laboratory research methods, was carried out. It has been established that with this pathology there is an increase in the intensity of ketogenesis against the background of severe energy deficit. This was manifested by a statistically significant increase in the concentration of the total amount of ketone bodies from 0.43±0.01 to 1.57±0.06 mol/l (p <0.001), which occurred mainly due to acetone and acetoacetic acid. Their relative share in the total number of ketone bodies was 28.66%, while in healthy ones - 5.58%. The blood glucose level was reduced by 28.6% compared with clinically healthy sheep. The presence of a negative correlative relationship was revealed between the concentration of glucose and the level of ketone bodies - r = -0.64. Besides, in ewes infected with ketosis, symptoms of hepatocyte damage were noted: an increase in the concentration of total serum protein, hypoalbuminemia, dysproteinaemia, an increase in the level of total bilirubin, total cholesterol, increased activity of AsAT, ALAT and GGTP. It proved the occurrence of the same polymorbid pathology (ketosis and hepatodystrophy) in the same animals. This was confirmed by the revealed positive correlative relationship between the concentration of ketone bodies and the activity of the enzymes under study: AsAT ‒ r = +0.57, ALAT ‒ r = +0.49, GGTP ‒ r = +0.55; and between the level of ketone bodies and total bilirubin ‒ r = +0.44. It has been concluded that the progress of liver dystrophy aggravating the course of the pathological process should be taken into account when developing or improving methods for treating ketosis in pregnant ewes.

The Differences of Salivary and Urine Acetone Levels in Diabetes Mellitus Patients

Ketone objects (acetone, beta-hydroxybutyric, acetoacetic acid) are compounds produced by the body from the breakdown of fatty acids (lipolysis) on the pathway of lipid metabolism. Synthesis of ketones can be caused by insulin hormone disorders such as those experienced by people with diabetes mellitus (DM). Such conditions trigger an increase in lipolysis in adipose tissue which results in the release of free fatty acids as a substrate for the process of ketogenesis in the liver. Acetone as a product of ketogenesis will enter the kidney to be excreted with urine, and if the amount is excessive, then some will accumulate into the saliva. The purpose of this research was to determine differences in salivary and urine acetone levels in DM patients. The type of research is analytic with the cross-sectional approach. Samples were taken using a sequential random sampling technique as many as 18 DM patients, both men and women aged 40-65 years old. The data collection technique was by conducting a direct examination of salivary and urine acetone which measured using spectrophotometric methods. The results showed an average salivary acetone level of 18.9 mg/L, while the mean level of urine acetone was 555.6 mg/L. Mann-Whitney statistical test showed a significance value of 0.000 (P <0.05), so it was concluded that there were significant differences between salivary acetone levels and urine acetone levels. Urine samples with smaller acetone concentrations are able to give positive results, while salivary samples will show positive results when acetone levels in urine are very high.

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate combination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM “Eighteen Incompatible Medicaments”, are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphinganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of incompatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM “Eighteen Incompatible Medicaments”.

768-P: Efficacy and Safety of Low-Carb Diet of 50g/Day and 120g/Day in Obese Patients

Objective: Nutrition therapy is indispensable in the management of obesity. Low-carb diet is one of the recommended diets. On the other hand, there is little evidence on Low-carb diet in Japan. Besides, we don’t know the optimum amount of carbohydrate. So, we tried to ellucidate the efficacy and safeness of Low-carb diet, and to compare two amounts of Low-carb diet: 50g (LC50g) or 120g carb/day (LC120g). Research Design and Methods: 42 Overweight or obese Japanese adults with one or more metabolic disorders (such as diabetes, hyperlipidemia, hypertension) were randomly assigned to a 3-month Low-Carb diet intervension (50g or 120g carb/day). All food was provided, and patients were assigned to report what they ate every day to the registered dietitian via mail, so that we could check compliance. Total calorie was calculated based on the ideal body weight and physical activity index. Every month, body weight, body composition (measured by multi-frequency BIA) were checked. Blood pressure, HbA1c, FPG, serum ketone body, kidney and liver function and lipid profile, serum C-peptide, urinary albumin, PWV/ABI were checked. We used T test for statistic analysis. Results: No one dropped out. Median age and BMI were 43 and 28.5. Change in BW was -8.5kg in LC50g, -7.2kg in LC120g, there was no significant difference. AST, ALT, γGTP, LDH, Cre decreased after intervention in both groups. LDH, Cre significantly decreased in LC50g. Acetoacetic acid and EPA significantly increased in LC50g. Baseline analysis showed, BW at age 20, early rising, dinner time and exercise habits were related to susceptibility to losing weight. A questionnaires survey revealed patients felt more stressful in LC50g. Conclusion: In this study, both amount of carb restriction was effective and safe, and there was no significant difference in losing weight, diabetes, lipid and hypertension control. LC120g was easy to carry out. Finally, this study is the one and only because it achieved high compliance by food offering and on time follow-up. Disclosure T. Kikuchi: None.

Effects of sildenafil on maximum walking time in patients with arterial claudication: The ARTERIOFIL study

BackgroundPatients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication. MethodsThe ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied. ResultsFourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s–428 s] vs 402 s [95% CI 274 s–529 s] p < 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women. ConclusionsThe ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication. Clinical trial registrationThis clinical trial was registered at clinicaltrials.gov, registration.number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570).

IR Spectroscopic Study of Lanthanide Hydroxo Complexes with Esters of Acetoacetic Acid

The IR spectra of hydroxo complexes of lanthanides (Ln) with the β-ketoesters methyl, ethyl, and allyl acetoacetate with the general formula LnL2OH·H2O (Ln = La, Gd, Lu; L = β-ketoesterate anion) were studied in the range of 400–1700 cm–1. In order to interpret the spectra and assign bands to the vibrations of the β-ketoesterate ligands a normal coordinate analysis of the model complexes LnL(OH)2 (Ln = La, Lu) was performed in the PBE0/ECP46(60) MWB + DZP approximation. The experimental data and the theoretical calculations show that the radius of the Ln(III) ion and the structure of the hydrocarbon radical of the alkoxyl substituent have a negligible effect on the value of π-electron delocalization in the [OCCCO] conjugated system of the chelate fragment, whereas the decrease of the Ln(III) ionic radius leads to increase of conjugation in the ester C(O)O group of the ligands.

An Eco-Friendly Stereoselective Synthesis of Novel Derivatives of Indeno[1,2-b]Pyrrole and Indeno[1,2-c]Pyridazine

A highly efficient and simple synthesis of a number of pharmaceutically interesting functionalized indenopirrole derivatives has been developed via the reaction of ninhydrin and acetoacetic acid amides in ethanol at the absence of catalyst at room temperature. In the case, then N,N-dialkylacetoacetamides were used as the methylene components, novel N,N-dialkyl-3-oxobutanamide derivatives were received. The novel indenopyridazine derivatives were first obtained via the reaction of indenopirroles with hydrazine. Environmental friendliness, mild reaction conditions, simple work-up avoiding chromatographic purification, and excellent yields are the important features of this protocol.

Disordered Metabolic Profiling in Plasma and Tissues of Mice Infected with Artemisinin-Sensitive and -Resistant Plasmodium berghei K173 Determined by 1H NMR Spectroscopy.

Artemisinin resistance has inevitably emerged in several malaria-endemic areas and led to an incremental clinical failure rate for artemisinin-based combination therapy (ACT), which is strongly recommended by the World Health Organization (WHO). Genetically resilient malaria parasites have evolved antimalarial drug-evasion mechanisms; meanwhile, the metabolic cross-talk between the malaria parasites and the host is of significance during the invasion. The intention of this work, therefore, is to propose a feasible method to discover the systematic metabolic phenotypes of mice invaded with artemisinin-sensitive or -resistant Plasmodium berghei K173 when compared with healthy mice. Biological samples, including plasma, liver, spleen, and kidney, of mice collected after euthanasia at day 7 were subjected to 1H nuclear magnetic resonance spectroscopy. Multivariable data analysis was utilized to estimate the metabolic characteristics of these samples from uninfected and infected mice. In contrast with healthy mice, both sensitive and resistant malaria-parasite-infected models displayed distinct metabolic profiles. Parasite invasion significantly changed the glycolysis, Kreb's cycle, and amino acid metabolism in plasma and tissues. Decreased N, N-dimethylglycine and glycine levels in plasma from the artemisinin-sensitive P. berghei-infected group and increased lactate, lipid, and aspartate in the artemisinin-resistant P. berghei-infected group were observed, respectively. In the liver, the artemisinin-sensitive group up-regulated the glutamate level and down-regulated glutamine. Artemisinin-resistant parasite exposure decreased ethanol and allantoin levels. The levels of myo-inositol and valine in the spleen were increased due to artemisinin-sensitive P. berghei infection, together with decreased trimethylamine N-oxide, phosphocholine, β-glucose, and acetoacetic acid. In the artemisinin-resistant group, the spleen showed a remarkably increased phosphocholine content along with decreased dimethylglycine and arginine levels. In the kidney, artemisinin-sensitive P. berghei K173 caused increased lysine, glutamate, creatine, and 2-hydroxybutyrate as well as decreased ethanol. Artemisinin-resistant P. berghei led to low glycerophosphorylcholine and high acetate, betaine, and hypoxanthine. Mutual and specific altered metabolites and, accordingly, metabolic pathways induced by the infection of artemisinin-sensitive or -resistant P. berghei were therefore screened out. This should be considered a preliminary study to establish a direct relationship with the host metabolic background and artemisinin resistance.

Serum metabolic profile involving protective effect of "Neiguan"(PC6)-electroacupuncture preconditioning in rats with myocardial ischemia reperfusion injury

To observe the effect of "Neiguan" (PC6)-electroacupuncture (EA) preconditioning on serum metabolites in myocardial ischemia-reperfusion injury (MIRI) rats, so as to reveal its mechanism underlying improvement of ischemic myocardium from metabonomics. A total of 48 male SD rats were randomly divided into control, model, EA "Neiguan"(PC6) and EA "Hegu"(LI4) groups (n＝12 rats/ group). Rats of the control group were just banded on animal boards for 30 min, once daily for 7 days. The MIRI model was established by occlusion of the left anterior descending branch of the left coronary artery for 40 min, followed by reperfusion for 1 h, and rats of the model group were also banded as those in the control group. Before modeling, EA (10 Hz/50 Hz, 1 mA) was applied to bilateral "Neiguan"(PC6) and "Hegu"(LI4) for 30 min, once daily for 7 successive days. After the treatment, serum samples were collected to be analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. The orthogonal partial least squares discriminate analysis (PLS-DA) was employed to distinguish the serum differential metabolic profile of rats in different groups and identify potential biomarkers. After modeling, the ECG of model group and electroacupuncture groups showed T wave towering, and there was no obvious ST segment between R wave and T wave. The T wave decreased more than 0.2 mV after reperfusion, and there was no obvious ST segment. Compared with the control group, MIRI induced significant changes of metabolites in the serum including increase of acetoacetate acid, lectic acid, creatine, glycerol and glucose, and decrease of alanine, glutamine, glycerophosphoryl choline and phosphorylcholine. In comparison with the model group, PC6-EA preconditioning induced significant changes, including an increase of glucose, and a decrease of leucine，isoleucine, valine，3-hydroxybutyric acid，lactate，acetate，acetone，acetoacetate acid，pyruvic acid，glutamine，creatine and glycerol. There is no significant difference in metabolic patterns between "Hegu" group and model group. Metabolic pathway enrichment analysis indicated that the protective effect of PC6-EA pretreatment was realized mainly by regulating pathways of glycolysis, gluconeogenesis, citric acid metabolism, pyruvate metabolism, ketone body metabolism, etc. PC6-EA pretreatment has a role in regulating gluconeogenesis, pyruvate metabolism, amino metabolism, ketone body metabolism and energy metabolism in rats with MIRI, which maybe contribute to its protective effect on ischemic myocardium, but the specific metabolic pathways and mechanisms need being studied further.

Ketone Bodies Inhibit the Opening of Acid-Sensing Ion Channels (ASICs) in Rat Hippocampal Excitatory Neurons in vitro.

Objectives: Despite the long-term efficacy of antiepileptic drug treatments, frequent attacks of drug-resistant epilepsy necessitate the development of new antiepileptic drug therapy targets. The ketogenic diet is a high-fat, low-carbohydrate diet that has been shown to be effective in treating drug-resistant epilepsy, although the mechanism is yet unclear. In the ketogenic diet, excess fat is metabolized into ketone bodies (including acetoacetic acid, β-hydroxybutyric acid, and acetone). The present study explored the effect of ketone bodies on acid-sensing ion channels and provided a theoretical basis for the study of new targets of antiepileptic drugs based on “ketone body-acid sensing ion channels.”Methods: In this study, rat primary cultured hippocampal neurons were used. The effects of acetoacetic acid, β-hydroxybutyric acid, and acetone on the open state of acid-sensing ion channels of hippocampal neurons were investigated by the patch-clamp technique.Results: At pH 6.0, the addition of acetoacetic acid, β-hydroxybutyric acid, and acetone in the extracellular solution markedly weakened the currents of acid-sensing ion channels. The three ketone bodies significantly inhibited the opening of the acid-sensing ion channels on the surface of the hippocampal neurons, and 92, 47, and 77%, respectively.Conclusions: Ketone bodies significantly inhibit the opening of acid-sensing ion channels. However, a new target for antiepileptic drugs on acid-sensing ion channels is yet to be investigated.

Synthesis of 2-Fluoroacetoacetic Acid and 4-Fluoro-3-hydroxy­butyric Acid

The butyric acid scaffold is the base structure of several human metabolites that serve diverse and prominent biochemical roles including as oxidative sources of cellular energy and as substrates for biosynthesis. Derivatization of metabolites through incorporation of fluorine often alters bioactivity and can facilitate detection and analysis by nuclear magnetic resonance or positron emission tomography depending upon the fluorine isotope employed. We describe the synthesis of two new fluorinated butyric acids (and three related esters) that are derivatives of the metabolites acetoacetic acid and 3-hydroxybutyric acid. 4-Fluoro-3-hydroxybutyric acid is prepared from epoxy ester precursors via ring opening by triethylamine trihydrofluoride. 2-Fluoroacetoacetic acid is prepared by electrophilic fluorination of an acid-labile β-keto ester. The gradual pH-dependent decarboxylation of 2-fluoroacetoacetic acid is investigated by 19F NMR spectroscopy.

Normalized glucose variability by Low Carbohydrate Diet (LCD) in CGM study

In diabetic practice, continuous glucose monitoring (CGM) has been more used for glucose variability. Authors have reported and developed the clinical study of Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) through Japan LCD Promotion Association (JLCDPA). A diabetic case is presented with normalizing glucose variability by LCD meal checked by CGM. Case is 51 years female with type 2 diabetes mellitus (T2DM). At first visit, HbA1c was 10.0%, glucose was 288mg/dL, BMI 39.1, GOT 16IU/mL, HDL-C 33mg/dL, Triglyceride 152mg/dL. CR meal was provided on day-1 to day-5 and LCD meal with 12% carbohydrate on day-6 to day-13. Average glucose value from CGM was 292mg/dL, 235mg/dL, 160mg/dL, 140mg/dL, 124mg/dL in day 3,5,7,9,11 respectively. On day-13, total Ketone bodies (T-KB) 540μmol/L (-131), Acetoacetic acid (AcAc) 86μmol/L (-55) and 3-hydroxybutyric acid (3-OHBA) 454μmol/L (-85). Weight reduction was 5kg on day-14 and 11.2kg on day-70 with BMI 34.6. Thus, LCD showed a remarkable glucose-lowering effect in short term. FreeStyle Libre (Abbott, USA) seems to be a useful apparatus for monitoring the detailed fluctuation of blood glucose. These results would become fundamental and reference data and contribute to the LCD research development in the future.

Synthesis of Substituted 1,2-Dihydropyridines by the Reaction of (Ethoxymethylidene)cyanoacetic Ester and Arylamides of Acetoacetic Acid

The reaction of (ethoxymethylidene)cyanoacetic ester with arylamides of acetoacetic acid proceeds under heating in the presence of triethylamine or at room temperature in the presence of sodium ethoxide. According to the NMR and IR data, the intermediate adduct undergoes no other transformations but azacyclization which predominantly involves the cyano group and forms ethyl 5-acetyl-1-aryl-6-hydroxy-2-imino-1,2-dihydropyridine-3-carboxylates in yields of 30–78%. In some cases, 5-acetyl-1-aryl-2-hydroxy-6-oxo-1,6-dihydropyridine-3-carbonitriles resulting from cyclization involving the ethoxycarbonyl group were isolated as minor products (3–12%).

Growth and morphological responses of Chlorella vulgaris at different initial algal densities to treatment with Ceratophyllum demersum methanol extracts

The allelopathically inhibitory effects of submerged macrophytes on phytoplankton have been extensively studied and are utilised as an effective strategy for water restoration. However, this technique has been minimally implemented in natural in situ water bodies because of the unclear and complex interactions involved. Our study considered the uneven density distribution of algae in natural aquatic ecosystems and the biomass-dependent effects of submerged macrophytes on target algae. Ceratophyllum demersum methanol extracts of gradient concentration on Chlorella vulgaris with different initial algal density were conducted in the present laboratory study. Results indicated that methanol extracts of C. demersum could not only inhibit the growth of but also promote colony formation of C. vulgaris. C. vulgaris of a low density exerted increased inhibition and colony proportion responses to C. demersum extracts. By 0.42 g/mL C. demersum treatment, the inhibition rate on C. vulgaris under 0.02 IAD (Initial Alagal Density) and 0.05 IAD (p &lt; 0.05) was 88.7%, 70.9%, respectively. We also suggested that the effects of C. demersum were biomass dependent, such that extracts with high concentration could produce increased inhibitory effects on C. vulgaris. According to GC-MS analysis, the study revealed five potential compounds (i.e. hexanoic, acetoacetic, azelaic, palmitic and stearic acid) in the C. demersum methanol extracts. However, the individual or combined effects of those compounds require further exploration. This study proposed certain theoretical basis for future water restoration by submerged macrophytes, that the biomass of the macrophytes and the density of the algae should both be taken into account.