lactate acidosis

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation...

This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and hypocalcemia. SARA represents a disorder of ruminal fermentation that is characterized by extended periods of depressed ruminal pH below 5.5-5.6. In the long term, dairy herds experiencing SARA usually exhibit secondary signs of the disease, such as episodes of laminitis, weight loss and poor body condition despite adequate energy intake, and unexplained abscesses usually 3-6 months after an episode of SARA...

Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases...

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (mHS) deficiency is an autosomal recessive disorder of ketone body synthesis caused by biallelic pathogenic variants in HMGCS2 . Clinical symptoms are precipitated by prolonged fasting and/or intercurrent illness with onset before the first year of life. Clinically, patients may present with hypo-/ non-ketotic hypoglycemia, metabolic acidosis, hyperammonemia, lethargy, hepatomegaly, and encephalopathy. During periods of decompensation, elevations of 4-hydroxy-6-methyl-2-pyrone (4-HMP), several hydroxylated hexanoic and hexenoic acid species, and medium-chain dicarboxylic acids in the absence of significant ketonuria may be observed in the urine organic acid profile...

The purpose of this manuscript was to present the evidence for why cells do not produce metabolic acids. In addition, evidence that opposes common viewpoints and arguments used to support the cellular production of lactic acid (HLa) or liver keto-acids have been provided. Organic chemistry reveals that many molecules involved in cellular energy catabolism contain functional groups classified as acids. The two main acidic functional groups of these molecules susceptible to ∼H+ release are the carboxyl and phosphoryl structures, though the biochemistry and organic chemistry of molecules having these structures reveal they are produced in a non-acidic ionic (negatively charged) structure, thereby preventing pH dependent ∼H+ release...

Metformin (N,N-dimethylbiguanide), an inhibitor of gluconeogenesis and insulin sensitizer, is widely used for the treatment of type 2 diabetes. In some patients with renal insufficiency, metformin can accumulate and cause lactic acidosis, known as metformin-associated lactic acidosis (MALA, defined as lactate ≥ 5 mM, pH < 7.35, and metformin concentration > 38.7 µM). Here, we report on the post-translational modification (PTM) of proline (Pro) to 4-hydroxyproline (OH-Pro) in metformin-associated lactic acidosis and in metformin-treated patients with Becker muscular dystrophy (BMD)...

During hypoxia accumulation of lactate may be a key factor in acidosis-induced tissue damage. Binding of hexokinase (HK) to the outer membrane of mitochondria may have a protective effect under these conditions. We have investigated the regulation of lactate metabolism by hexokinases (HKs), using HEK293 cells in which the endogenous hexokinases have been knocked down to enable overexpression of wild type and mutant HKs. To assess the real-time changes in intracellular lactate levels the cells were also transfected with a lactate specific FRET probe...

BACKGROUND/PURPOSE: MEGDHEL syndrome is a rare autosomal recessive metabolic disorder, which is characterized by 3-methylglutaconic aciduria with deafness-dystonia, hepatopathy, encephalopathy and Leigh-like syndrome. It is caused by biallelic pathogenic variants in the SERAC1 gene. Due to the unspecific symptoms and the diverse manifestations of the clinical phenotype, the diagnosis is challenging. Infantile MEGDHEL syndrome often has a severe disease course with acute liver failure...

INTRODUCTION: The link between gut microbiota and host immunity motivated numerous studies of the gut microbiome in tuberculosis (TB) patients. However, these studies did not explore the metabolic capacity of the gut community, which is a key axis of impact on the host's immunity. METHODS: We used deep sequencing of fecal samples from 23 treatment-naive TB patients and 48 healthy donors to reconstruct the gut microbiome's metabolic capacity and strain/species-level content...

A 56-year-old woman was transferred to the intensive care unit (ICU) two days after an allogeneic stem cell transplantation (ASCT) when she presented acute respiratory distress due to the relapse of a SARS-CoV-2 infection. Following that, she received two intravenous doses of 100 mg remdesivir. Subsequently, the patient developed multiple instances of diarrhea, progressing to oliguria and acute kidney injury, necessitating continuous venovenous hemofiltration (CVVH). Despite the absence of signs of hypoxemia or cardiocirculatory failure requiring vasopressor intervention, a progressive lactic acidosis emerged...

BACKGROUND: Metformin is a biguanide hyperglycemic agent used to manage non-insulin-dependent diabetes mellitus. Adverse reactions include mainly mild gastrointestinal adverse effects, but severe complications, such as metformin-associated lactic acidosis (MALA) can occur. Metformin is excreted renally and, therefore, not recommended in patients with renal impairment. The reported incidence of MALA is 3 cases per 100,000 patient-years. CASE REPORT: A 79-year-old woman with a complex medical history, including end-stage renal disease on dialysis and type 2 diabetes, presented to the emergency department (ED) for altered mental status...

OBJECTIVES: Brain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. METHODS: Term newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included...

AIM: This study aims to compare the outcome of neonatal left congenital diaphragmatic hernia (CDH, Bochdalek type) repair through laparotomy with and without abdominal muscle closure. MATERIALS AND METHODS: This retrospective study was conducted between January 2012 and May 2021 at a neonatal surgical unit of a Tertiary Care Center. Demographic details, preoperative management, Two-dimensional-echo, intra-operative findings, postoperative course, and follow-up data were collected and analyzed...

Transmembrane prolyl 4-hydroxylase (P4H-TM) is an enigmatic enzyme whose cellular function and primary substrate remain to be identified. Its loss-of-function mutations cause a severe neurological HIDEA syndrome with hypotonia, intellectual disability, dysautonomia and hypoventilation. Previously, P4H-TM deficiency in mice was associated with reduced atherogenesis and lower serum triglyceride levels. Here, we characterized the glucose and lipid metabolism of P4h-tm-/- mice in physiological and tissue analyses...

Solid tumors frequently present a heterogeneous tumor microenvironment. Because tumors have the potential to proliferate quickly, the consequence is a reduction in the nutrients, a reduction in the pH (<6.8), and a hypoxic environment. Although it is often assumed that tumor clones show a similar growth rate with little variations in nutrient consumption, the present study shows how growth-specific rate (µ), the specific rates of glucose, lactate, and glutamine consumption (qS), and the specific rates of lactate and glutamate production (qP) of 2D-cultured lung tumor cells are affected by changes in their environment...

INTRODUCTION: Excessive intake of lactate caused by improper use of silage in animal husbandry has adverse effects on rumen fermentation, such as rumen acidosis. The speed of absorption and metabolism of D -lactate in rumen epithelial cells was slower than that of L -lactate, making D -lactate more prone to accumulate and induce rumen acidosis. Therefore, this study was conducted to explore the effects of dietary D -lactate levels on rumen fermentation of beef cattle and its mechanism in an in vitro system...

BACKGROUND: D-lactic acidosis (DLA) is a serious complication of short bowel syndrome (SBS) in children with intestinal failure (IF). Malabsorbed carbohydrates are metabolized by bacteria in the intestine to D-lactate which can lead to metabolic acidosis and neurologic symptoms. METHODS: A retrospective chart review was performed in children ≤18 years old with SBS who had one of the following criteria: unexplained metabolic acidosis, neurologic signs or symptoms, history of antibiotic therapy for small bowel bacterial overgrowth, or high clinical suspicion of DLA...

d-lactate dehydrogenases are known to be expressed by prokaryotes and by eukaryotic invertebrates, and over the years the functional and structural features of some bacterial representatives of this enzyme ensemble have been investigated quite in detail. Remarkably, a human gene coding for a putative d-lactate dehydrogenase (DLDH) was identified and characterized, disclosing the occurrence of alternative splicing of its primary transcript. This translates into the expression of two human DLDH (hDLDH) isoforms, the molecular mass of which is expected to differ by 2...

First-lactation cows are particularly prone to subacute ruminal acidosis (SARA) during transition. Besides common risk factors of SARA, such as feeding of starch-rich diets, an individual severity of SARA in cows has been recently evidenced. Yet, the factors that play a role in SARA severity have not been elucidated. The main goal of this research was to evaluate the factors of SARA severity in first-lactation cows during transition and early lactation, which go beyond high-grain feeding, and to explore their impact on behavior, health, and fermentation in the rumen and hindgut...

BACKGROUND: Hyperlactatemia (HL) is a common phenomenon after cardiac surgery which is related to tissue hypoperfusion and hypoxia and associated with poor outcomes. It is also often seen in the postoperative period after orthotopic heart transplantation (OHTx), but the association between HL and outcomes after OHTx is not well known. We evaluated the incidence and outcome of HL after OHTx. METHODS: This was a retrospective study of 209 patients who underwent OHTx between January 2011 and December 2020...