Lactic Acidosis Publications (7770)
Lactic Acidosis Publications
Another possible cause is Pearson's syndrome, a rare mitochondrial disease that causes non-regenerative anemia associated with other cytopenias, pancreatic insufficiency, lactic acidosis and great variability in clinical presentation conditioned by heteroplasmy. It is characteristic to find in bone marrow studies variable vacuolization in erythroblastic progenitors and ring sideroblasts. The diagnosis is established by genetic study of mitochondrial deoxyribonucleic acid performed by Southern blot analysis (complete mitochondrial deoxyribonucleic acid amplification by polymerase chain reaction -long), obtaining 70-80% deletion of 4977 bp (NMD 8343-13459). There is no curative therapy and support treatment is the only available nowadays. Death is frequent in early years of life.
6 years old; 72.2 ± 9.0 kg; 179.8 ± 7.5 cm) performed an incremental test (25 W·min(-1)) until exhaustion and several constant load tests of 30 minutes to determine MLSS, on different occasions. Using MLSS determination as the reference method, the agreement with five other parameters (MPVT; first and second ventilatory thresholds: VT1 and VT2; respiratory exchange ratio equal to 1: RER = 1.00; and Maximum) was analysed by the Bland-Altman method. The difference between workload at MLSS and VT1, VT2, RER=1.00 and Maximum was 31.1 ± 20.0, -86.0 ± 18.3, -63.6 ± 26.3 and -192.3 ± 48.6 W, respectively. MLSS was underestimated from VT1 and overestimated from VT2, RER = 1.00 and Maximum. The smallest difference (-27.5 ± 15.1 W) between workload at MLSS and MPVT was in better agreement than other analysed parameters of intensity in cycling. The main finding is that MPVT approached the workload at MLSS in amateur cyclists, and can be used to estimate maximal steady state.
We recently documented that DCA was able to induce a metabolic switch preferentially in glycolytic cancer cells, leading to a more oxidative phenotype and decreasing proliferation, while oxidative cells remained less sensitive to DCA treatment. To evaluate the relevance of this observation in vivo, the aim of the present study was to characterize the effect of DCA in glycolytic MDA-MB-231 tumors and in oxidative SiHa tumors using advanced pharmacodynamic metabolic biomarkers. Oxygen consumption, studied by 17O magnetic resonance spectroscopy, glucose uptake, evaluated by 18F-FDG PET and pyruvate transformation into lactate, measured using hyperpolarized 13C-magnetic resonance spectroscopy, were monitored before and 24 hours after DCA treatment in tumor bearing mice. In both tumor models, no clear metabolic shift was observed. Surprisingly, all these imaging parameters concur to the conclusion that both glycolytic tumors and oxidative tumors presented a similar response to DCA. These results highlight a major discordance in metabolic cancer cell bioenergetics between in vitro and in vivo setups, indicating critical role of the local microenvironment in tumor metabolic behaviors.
Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity.
Renal haemodynamics and microvascular oxygenation (by oxygen-dependent quenching of phosphorescence) were measured as well as concentrations of lactate, gluconate, and acetate in plasma and urine. Kidney wet and dry weight was also assessed.
Partial liver resection resulted in increased liver enzymes compared with control and shock groups (P < 0.01). Haemorrhagic shock decreased systemic and renal perfusion and reduced microvascular kidney oxygenation with lactic acidosis (P < 0.01). Resuscitation with balanced fluids did not fully restore renal oxygenation (P < 0.01). Ringer's acetate and PlasmaLyte increased bicarbonate content and restored pH better than Ringer's lactate or saline after partial liver resection (P < 0.01). Liver resection caused an increase in plasma gluconate after PlasmaLyte resuscitation (P < 0.05).
Acetate-buffered balanced fluids show superior buffering effects compared with Ringer's lactate or saline. Gluconate is partially metabolized by the liver, although it does not contribute to acid-base control because of its excretion in urine. Acetate is metabolized regardless of liver function and may be the most efficient bicarbonate precursor. Lactate infusion tends to overwhelm the metabolism capacity of the residual liver.
Long-term metformin use is associated with decreased vitamin B₁₂ levels, and even with biochemical B₁₂ deficiency; this complication can detected early by annual assessments of serum B₁₂ levels and prevented by annual intramuscular B₁₂ administration.
Absence of tafazzin activity results in cardiolipin molecular species heterogeneity, increased levels of monolysocardiolipin and lower cardiolipin abundance. In skeletal muscle and cardiac tissue mitochondria these alterations in cardiolipin perturb the inner membrane, compromising electron transport chain function and aerobic respiration. Decreased electron flow from fuel metabolism via NADH ubiquinone oxidoreductase activity leads to a buildup of NADH in the matrix space and product inhibition of key TCA cycle enzymes. As TCA cycle activity slows pyruvate generated by glycolysis is diverted to lactic acid. In turn, Cori cycle activity increases to supply muscle with glucose for continued ATP production. Acetyl CoA that is unable to enter the TCA cycle is diverted to organic acid waste products that are excreted in urine. Overall, reduced ATP production efficiency in BTHS is exacerbated under conditions of increased energy demand. Prolonged deficiency in ATP production capacity underlies cell and tissue pathology that ultimately is manifest as dilated cardiomyopathy.
ACAD9, specifically, is implicated in the processing of palmitoyl-CoA and long-chain unsaturated substrates, but unlike other acyl-CoA dehydrogenases (ACADs), it has a significant role in mitochondrial complex I assembly (Nouws et al. 2010 & 2014). Mutations in this enzyme typically cause mitochondrial complex I deficiency, as well as a mild defect in long chain fatty acid metabolism (Haack et al. 2010, Kirby et al. 2004, Mcfarland et al. 2003, Nouws et al. 2010 & 2014). The clinical phenotype of ACAD9 deficiency and the associated mitochondrial complex I deficiency reflect this unique duality, and symptoms are variable in severity and onset. Patients classically present with cardiac dysfunction due to hypertrophic cardiomyopathy. Other common features include Leigh syndrome, macrocephaly, and liver disease (Robinson et al. 1998). We report the case of an 11-month old girl presenting with microcephaly, dystonia, and lactic acidosis, concerning for a mitochondrial disorder, but atypical for ACAD9 deficiency. Muscle biopsy showed mitochondrial proliferation, but normal mitochondrial complex I activity. The diagnosis of ACAD9 deficiency was not initially considered, due both to these findings and to her atypical presentation. Biochemical assay for ACAD9 deficiency is not clinically available. Family trio-based whole exome sequencing (WES) identified 2 compound heterozygous mutations in the ACAD9 gene. This discovery led to optimized treatment of her mitochondrial dysfunction, and supplementation with riboflavin, resulting in clinical improvement. There have been fewer than 25 reported cases of ACAD9 deficiency in the literature to date. We review these and compare them to the unique features of our patient. ACAD9 deficiency should be considered in the differential diagnosis of patients with lactic acidosis, seizures, and other symptoms of mitochondrial disease, including those with normal mitochondrial enzyme activities. This case demonstrates the utility of WES, in conjunction with biochemical testing, for the appropriate diagnosis and treatment of disorders of energy metabolism.
Such diseases include Friedreich ataxia, combined oxidative phosphorylation deficiency 19, infantile complex II/III deficiency defect, hereditary myopathy with lactic acidosis and mitochondrial muscle myopathy, lipoic acid biosynthesis defects, multiple mitochondrial dysfunctions syndromes and non ketotic hyperglycinemia due to glutaredoxin 5 gene defect. Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. With advances in next generation sequencing technologies, more disorders related to ISC biogenesis defects are expected to be elucidated. In this article, we aim to shed the light on mitochondrial ISC biogenesis, related proteins and their function, pathophysiology, clinical phenotypes of related disorders, diagnostic approach, and future implications.
contortisiliquum pods developed ruminal acidosis and were treated with sodium bicarbonate to try to control this metabolic disturbance, thus providing additional evidence of the involvement of ruminal acidosis in the pathogenesis of toxicosis. Two of the sheep died, and one recovered after treatment. In the two sheep that developed severe signs of ruminal acidosis, the values of blood lactate were 18 mg/dL and 196.88 mg/dL, indicating metabolic acidosis as the cause of death. Additionally, four sheep developed elevated serum levels of aspartate aminotransferase and gamma glutamyl transferase, indicating that the pods had hepatotoxic effects. Necropsy findings included the accentuation of the hepatic lobular pattern and multiple focally extensive red areas in the rumen mucosa and on the surface of the liver. Repeated ingestion of small doses induced tolerance but did not induce cumulative effects. Histopathologically, the epithelial mucosa of the rumen and reticulum exhibited swollen and vacuolated epithelia with intraepithelial pustules. Focal ulceration of the mucosa was also observed. Multifocal vacuolar degeneration of hepatocytes and scattered individual hepatocellular necrosis were evident in the liver. We concluded that the main clinical manifestation of intoxication by E. contortisiliquum pods in sheep was acute ruminal lactic acidosis and metabolic acidosis. Ingestion of repeated sublethal doses could stimulate proliferation of the ruminal fauna that degrades the sugar present in the pods, and thereby prevent the occurrence of ruminal acidosis. The plant is also hepatotoxic, and no abortions were observed.