Metformin-associated lactic acidosis:A mini review of pathophysiology,diagnosis and management in critically ill patients

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation,leading to metforminassociated lactic acidosis(MALA).As diabetes mellitus is a common chronic metabolic condition found in critically ill patients,pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit.The aim of this narrative mini review is therefore to update clinicians about MALA,and to provide a practical approach to its diagnosis and treatment.MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis,and confirmed when lactate exceeds 5 mmol/L.Risk factors include those that reduce renal elimination of metformin(renal impairment from any cause,histamine-2 receptor antagonists,ribociclib)and excessive alcohol consumption(as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism).Treatment of MALA involves immediate cessation of metformin,supportive management,treating other concurrent causes of lactic acidosis like sepsis,and treating any coexisting diabetic ketoacidosis.Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy.The optimal time to restart metformin has not been well-studied.It is nonetheless reasonable to first ensure that lactic acidosis has resolved,and then recheck the kidney function post-recovery from critical illness,ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m^(2) or better before restarting metformin.

Application of response surface methodology in medium optimization for pyruvic acid production of Torulopsis glabrata TP19 in batch fermentation

Response surface methodology (RSM) was used to optimize the fermentation medium for enhancing pyruvic acid production by Torulopsis glabrata TP19. In the first step of optimization, with Plackett-Burman design, ammonium sulfate, glucose and nicotinic acid were found to be the important factors affecting pyruvic acid production significantly. In the second step, a 23 full factorial central composite design and RSM were applied to determine the optimal concentration of each significant variable. A second-order polynomial was determined by the multiple regression analysis of the experimental data. The optimum values for the critical components were obtained as follows: ammonium sulfate 0.7498 (10.75 g/L), glucose 0.9383 (109.38 g/L) and nicotinic acid 0.3633 (7.86 mg/L) with a predicted value of maximum pyruvic acid production of 42.2 g/L. Under the optimal conditions, the practical pyruvic acid production was 42.4 g/L. The determination coefficient (R2) was 0.9483, which ensures adequate credibility of the model. By scaling up fermentation from flask to jar fermentor, we obtained promising results.

Sorption of Pyruvic Acid with Weakly Basic Polymer Sorbents

Uptakes of pyruvic acid for two types of commercially available weakly basic polymer sorbents, D301G and D301R, have been measured over a wide pH range and at various salinities of MgSO4. The results show that the overloading adsorption of pyruvic acid occurs on both weakly basic polymer sorbents, and the overloading models can predict the experimental data of uptake very well. The overloading value for D301G is larger than that for D301R. The adsorption isotherm of pyruvic acid for both polymeric sorbents is greatly affected by the solution pH and MgSO4 concentration in the aqueous phase, and a high recovery efficiency of pyruvic acid from aqueous solution can be obtained at the solution pH around 2.

Synthesis and Crystal Structure of a New cis-Dioxovanadium (V) Complex with Pyruvic Acid Isonicotinyl Hydrazone (PAINH)

A new cis-dioxovanadium （V） complex [VO2（C9H8N3O3）]（C5H5N） involving a carboxyl group coordination employing a tridentate Schiff Base derived from pyruvic acid and isonicotinyl hydrazide is reported. This complex crystallizes in triclinic, space group P1^- with a = 7.3522 （12）, b = 7.8376（13）, c = 14.898（2） ,A°, a = 84.010（2）, β = 86.568（2）, γ= 64.586（2）°, V = 771.1（2）A °^3 ,Z = 2, F（000） = 376, Mr = 368.22, D, = 1.586 g/cm^3, g = 0.677 mm ^-1, R = 0.0421 and wR = 0.1253. The vanadium atom of the dioxovanadium （V） is five-coordinated to furnish a distorted trigonal bipyramid geometry.

One-step synthesis of pyruvic acid from glycerol oxidation over Pb promoted Pt/activated carbon catalysts

One‐step production of pyruvic acid through selective oxidation of glycerol was investigated using lead promoted platinum/activated carbon(Pb‐Pt/AC)catalysts under mild conditions.The results of N2physisorption,X‐ray diffraction,X‐ray photoelectron spectroscopy,and high‐resolution transmission electron microscopy revealed that the alloy phases of PtPb and PtxPb were favorable for pyruvic acid production from glycerol oxidation,whereas the Pb3(CO3)2(OH)2and surface Pb0species inhibited the glycerol conversion.The loading of Pb and the catalyst preparation method(including impregnation and deposition precipitation)affected the formation of different metal species.Pyruvic acid was obtained at a yield of18.4%on a5.0wt%Pb‐5.0wt%Pt/AC catalyst prepared by co‐deposition precipitation method and500°C argon treatment.

A reaction density functional theory study of solvent effects on keto-enol tautomerism and isomerization in pyruvic acid

It is important to study the solvent effect on keto-enol tautomerism that has applications in many areas of chemical engineering.In this work,we use a multiscale reaction density functional theory(Rx DFT)to study the keto-enol tautomerism and isomerization of pyruvic acid.The results show that both effects of solvation and water assistance could reduce the reaction barriers.The water molecule participates the reaction as a catalyst to accept/give the protons with forming a hexagonal ring in the transition state.As a result of this temporary and intermediate hexagonal ring,the solute configuration undergoes a small variation during the reaction,giving a diminished contribution to the intrinsic reaction free energy.The solvent distribution shows a local ordering behavior near the solute that also reduces the contribution of solvation effect to the reaction barrier.Water assistance plays a major role in both pre-reaction and postreaction process.In terms of the driving force for the reaction,the effects of both solvation and water assistance are important.

BASIC HYDROLYSIS OF ETHYL OXAL-ACETATE AND SOME CHEMICAL CHARACTERS OF 3-ETHOXY CAEBONYL PYRUVIC ACID

The products of basic hydrolysis of ethyl oxal-acetate and the preparation of 3-ethoxy carbonyl pyruvic acid 1 are reported.Esterification reaction of 1 with unhindered alcohols could be carried out smoothly, but it was unsuccessful with hindered alcohols.

Theory Study on Structures and Vibrational Frequencies of Pyruvic acid

Density functional theory BLYP (using Becke's and Lee-Yang-Pars's correlation functionals), ab initio Hartree-Fock (HF) and hybrid DFT/HF B3LYP calculations were carried out to study the structure and vibrational spectra of pyruvic acid. The scaled B3LYP/6-31G* frequencies correspond well with available experimental assignment of the functional vibrational modes and the mean absolut devation is only 12.3cm^(-1).

Characterization of Streptococcus oligofermentans sucrose metabolism demonstrates reduced pyruvic and lactic acid production

Background Streptococcus （S.） oligofermentans is a newly identified bacteria with a yet to be defined mechanism of sucrose metabolism that results in acid production. This study aimed to investigate the biochemical mechanisms of S. oligoferm-entans glucose metaolism. Methods The S. oligofermentans LMG21532, Lactobacillus （L.） fermentum 38 and the S. mutans UA140 were used to characterize sucrose metabolism by measuring lactate dehydrogenase （LDH） activity and lactic acid production. Continuous dynamics and high performance capillary electrophoresis were used to determine LDH activity and lactic acid production, respectively, from bacteria collected at 0, 10 and 30 minutes after cultured in 10% sucrose. Results These analyses demonstrated that LDH activity of the three bacterial strains examined remained stable but significantly different throughout the sucrose fermentation process. The S. oligofermentans LDH activity （（0.61±0.05） U/mg） was significantly lower than that of L. fermentum （（52.91±8.97） U/mg）. In addition, the S. oligofermentans total lactate production （（0.048±0.021） mmol/L） was also significantly lower than that of L. fermentum （（0.958±0.201） mmol/L）. Although the S. oligofermentans LDH production was almost double of that produced by S. mutans （（0.32±0.07） U/mg）, lactic acid production was approximately one sixth that of S. mutans （（0.296±0.058） mmol/L）. Additional tests examining pyruvic acid production （the LDH substrate） demonstrated that lactic acid concentrations correlated with pyruvic acid production. That is, pyruvic acid production by S. oligofermentans was undetectable following sucrose incubation, however, （0.074±0.024） and （0.175±0.098） mmol/L pyruvic acid were produced by S. mutans and L. fermentum, respectively. Conclusion S. oligofermentans is incapable of fermenting carbohydrates to produce enough pyruvic acid, which results in reduced lactic acid production.

Synthesis, Characterization, Thermal Decomposition Mechanism and Non-Isothermal Kinetics of the Pyruvic Acid-Salicylhydrazone and Its Complex of Praseodymium(III)

The pyruvic acid salicylhydrazone and its new complex of Pr(III) were synthesized. The formulae C 10 H 10 N 2O 4 (mark as H 3L) and [Pr 2(L) 2(H 2O) 2]·3H 2O (L=the triad form of the pyruvic acid salicylhydrazone [C 10 H 7N 2O 4] 3- ) were determined by elemental and EDTA volumetric analysis. Molar conductance, IR, UV, X ray and 1H NMR were carried out for the characterizations of the complex and the ligand. The thermal decompositions of the ligand and the complex with the kinetic study were carried out by non isothermal thermogravimetry. The Kissinger's method and Ozawa's method are used to calculate the activation energy value of the main step decomposition. The stages of the decompositions were identified by TG DTG DSC curve. The non isothermal kinetic data were analyzed by means of integral and differential methods. The possible reaction mechanism and the kinetic equation were investigated by comparing the kinetic parameters.

A bacterial effector protein uncovers a plant metabolic pathway involved in tolerance to bacterial wilt disease

Bacterial wilt caused by the soil-borne plant pathogen Ralstonia solanacearum is a devastating disease worldwide.Upon plant colonization,R.solanacearum replicates massively,causing plant wilting and death;collapsed infected tissues then serve as a source of inoculum.In this work,we show that the plant metabolic pathway mediated by pyruvate decarboxylases(PDCs)contributes to plant tolerance to bacterial wilt disease.Arabidopsis and tomato plants resp ond to R.solanacearum infection by in creasing PDC activity,and plants with deficient PDC activity are more susceptible to bacterial wilt.Treatment with either pyruvic acid or acetic acid(substrate and product of the PDC pathway,respectively)enhances plant tolerance to bacterial wilt disease.An effector protein secreted by R.solanacearum,RipAK,interacts with PDCs and inhibits their oligomerization and enzymatic activity.Collectively,our work reveals a metabolic pathway involved in plant resistance to biotic and abiotic stresses,and a bacterial virulence strategy to promote disease and the completion of the pathogenic life cycle.