MCT2 Expression and Lactate Influx in Anorexigenic and Orexigenic Neurons of the Arcuate Nucleus

PubMed Central

Cortes-Campos, Christian; Elizondo, Roberto; Carril, Claudio; Martínez, Fernando; Boric, Katica; Nualart, Francisco; Garcia-Robles, Maria Angeles

2013-01-01

Hypothalamic neurons of the arcuate nucleus control food intake, releasing orexigenic and anorexigenic neuropeptides in response to changes in glucose concentration. Several studies have suggested that the glucosensing mechanism is governed by a metabolic interaction between neurons and glial cells via lactate flux through monocarboxylate transporters (MCTs). Hypothalamic glial cells (tanycytes) release lactate through MCT1 and MCT4; however, similar analyses in neuroendocrine neurons have yet to be undertaken. Using primary rat hypothalamic cell cultures and fluorimetric assays, lactate incorporation was detected. Furthermore, the expression and function of MCT2 was demonstrated in the hypothalamic neuronal cell line, GT1-7, using kinetic and inhibition assays. Moreover, MCT2 expression and localization in the Sprague Dawley rat hypothalamus was analyzed using RT-PCR, in situ hybridization and Western blot analyses. Confocal immunohistochemistry analyses revealed MCT2 localization in neuronal but not glial cells. Moreover, MCT2 was localized to ∼90% of orexigenic and ∼60% of anorexigenic neurons as determined by immunolocalization analysis of AgRP and POMC with MCT2-positives neurons. Thus, MCT2 distribution coupled with lactate uptake by hypothalamic neurons suggests that hypothalamic neurons control food intake using lactate to reflect changes in glucose levels. PMID:23638108

Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation

PubMed Central

Sobieski, Courtney; Shu, Hong-Jin

2018-01-01

Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. PMID:29617444

The introduction of umbilical cord lactate measurement and associated neonatal outcomes in a South African tertiary hospital labor ward.

PubMed

Allanson, E R; Pattinson, R C; Nathan, E A; Dickinson, J E

2018-05-01

To investigate the utility of umbilical artery (UA) lactate measurements in a South African hospital for assessing intrapartum care and predicting neonatal outcomes. From 3 March-12 November 2014, we conducted a prospective cohort study of UA lactate levels at Kalafong Hospital, Pretoria, South Africa. Following birth, a UA blood sample (<0.5uL) was taken from a double-clamped segment of cord and the lactate measured. Maternal and neonatal characteristics and outcomes were recorded. During the study, there were 4668 deliveries; including 1091 emergency cesarean and 154 instrumental deliveries. A lactate was recorded for 946 deliveries (20.3%). 190 babies required neonatal resuscitation, with an optimal cutoff for lactate of 5.45 mmol/L (sensitivity 68%, specificity 72%). 124 babies required nursery admission with the optimal cutoff for lactate 4.95 mmol/L (sensitivity 61%, specificity 59%). 55 babies had an Apgar score <7 at 5 min and the optimal lactate for this outcome was 5.65 mmol/L (sensitivity 64%, specificity of 69%). Umbilical lactate can be used in a middle-low resource setting as a measurement of intrapartum hypoxia, with reasonable sensitivity and specificity for the prediction of, or need for, resuscitation, admission to the nursery, and low Apgar scores.

Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain.

PubMed

Martin, Pamela M; Gopal, Elangovan; Ananth, Sudha; Zhuang, Lina; Itagaki, Shiro; Prasad, Balakrishna M; Smith, Sylvia B; Prasad, Puttur D; Ganapathy, Vadivel

2006-07-01

SMCT1 is a sodium-coupled (Na(+)-coupled) transporter for l-lactate and short-chain fatty acids. Here, we show that the ketone bodies, beta-d-hydroxybutyrate and acetoacetate, and the branched-chain ketoacid, alpha-ketoisocaproate, are also substrates for the transporter. The transport of these compounds via human SMCT1 is Na(+)-coupled and electrogenic. The Michaelis constant is 1.4 +/- 0.1 mm for beta-d-hydroxybutyrate, 0.21 +/- 0.04 mm for acetoacetate and 0.21 +/- 0.03 mm for alpha-ketoisocaproate. The Na(+) : substrate stoichiometry is 2 : 1. As l-lactate and ketone bodies constitute primary energy substrates for neurons, we investigated the expression pattern of this transporter in the brain. In situ hybridization studies demonstrate widespread expression of SMCT1 mRNA in mouse brain. Immunofluorescence analysis shows that SMCT1 protein is expressed exclusively in neurons. SMCT1 protein co-localizes with MCT2, a neuron-specific Na(+)-independent monocarboxylate transporter. In contrast, there was no overlap of signals for SMCT1 and MCT1, the latter being expressed only in non-neuronal cells. We also demonstrate the neuron-specific expression of SMCT1 in mixed cultures of rat cortical neurons and astrocytes. This represents the first report of an Na(+)-coupled transport system for a major group of energy substrates in neurons. These findings suggest that SMCT1 may play a critical role in the entry of l-lactate and ketone bodies into neurons by a process driven by an electrochemical Na(+) gradient and hence, contribute to the maintenance of the energy status and function of neurons.

d-Alanine Oxidase from Escherichia coli: Localization and Induction by l-Alanine

PubMed Central

Raunio, R. P.; Jenkins, W. T.

1973-01-01

Dialyzed membranes of Escherichia coli prepared by an ethylenediaminetetraacetic acid-lysozyme method catalyze the oxidation of both l-alanine and d-alanine. The specific activities for the oxidations of both d-alanine and l-alanine are increased fivefold when the cells are grown in the presence of either l-alanine or dl-alanine, but are increased only slightly when grown in the presence of d-alanine. In the dl-alanine-induced system, the specific activities for the oxidations of some other d-amino acids are also raised. dl-alanine also induces two other alanine catabolizing enzymes, alanine dehydrogenase and alanine-glutamate aminotransferase which are found in the “soluble” fraction of lysozyme-treated cells. The oxidations of both l-alanine and d-alanine were associated with the membranes of induced cells. After the membranes were disintegrated by sonic treatment, both l-alanine and d-alanine oxidation catalysts sedimented in a sucrose density gradient together with d-lactate and l-lactate dehydrogenases, apparently as a single multienzyme complex. PMID:4146872

Astrocyte-neuron lactate transport is required for long-term memory formation

PubMed Central

Suzuki, Akinobu; Stern, Sarah A.; Bozdagi, Ozlem; Huntley, George W.; Walker, Ruth H.; Magistretti, Pierre J.; Alberini, Cristina M.

2011-01-01

SUMMARY We report that in the rat hippocampus learning leads to a significant increase in extracellular lactate levels, which derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in-vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. PMID:21376239

Astrocyte-neuron lactate transport is required for long-term memory formation.

PubMed

Suzuki, Akinobu; Stern, Sarah A; Bozdagi, Ozlem; Huntley, George W; Walker, Ruth H; Magistretti, Pierre J; Alberini, Cristina M

2011-03-04

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. Copyright © 2011 Elsevier Inc. All rights reserved.

Lactate transport and signaling in the brain: potential therapeutic targets and roles in body–brain interaction

PubMed Central

Bergersen, Linda Hildegard

2015-01-01

Lactate acts as a ‘buffer' between glycolysis and oxidative metabolism. In addition to being exchanged as a fuel by the monocarboxylate transporters (MCTs) between cells and tissues with different glycolytic and oxidative rates, lactate may be a ‘volume transmitter' of brain signals. According to some, lactate is a preferred fuel for brain metabolism. Immediately after brain activation, the rate of glycolysis exceeds oxidation, leading to net production of lactate. At physical rest, there is a net efflux of lactate from the brain into the blood stream. But when blood lactate levels rise, such as in physical exercise, there is net influx of lactate from blood to brain, where the lactate is used for energy production and myelin formation. Lactate binds to the lactate receptor GPR81 aka hydroxycarboxylic acid receptor (HCAR1) on brain cells and cerebral blood vessels, and regulates the levels of cAMP. The localization and function of HCAR1 and the three MCTs (MCT1, MCT2, and MCT4) expressed in brain constitute the focus of this review. They are possible targets for new therapeutic drugs and interventions. The author proposes that lactate actions in the brain through MCTs and the lactate receptor underlie part of the favorable effects on the brain resulting from physical exercise. PMID:25425080

Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction.

PubMed

Bergersen, Linda Hildegard

2015-02-01

Lactate acts as a 'buffer' between glycolysis and oxidative metabolism. In addition to being exchanged as a fuel by the monocarboxylate transporters (MCTs) between cells and tissues with different glycolytic and oxidative rates, lactate may be a 'volume transmitter' of brain signals. According to some, lactate is a preferred fuel for brain metabolism. Immediately after brain activation, the rate of glycolysis exceeds oxidation, leading to net production of lactate. At physical rest, there is a net efflux of lactate from the brain into the blood stream. But when blood lactate levels rise, such as in physical exercise, there is net influx of lactate from blood to brain, where the lactate is used for energy production and myelin formation. Lactate binds to the lactate receptor GPR81 aka hydroxycarboxylic acid receptor (HCAR1) on brain cells and cerebral blood vessels, and regulates the levels of cAMP. The localization and function of HCAR1 and the three MCTs (MCT1, MCT2, and MCT4) expressed in brain constitute the focus of this review. They are possible targets for new therapeutic drugs and interventions. The author proposes that lactate actions in the brain through MCTs and the lactate receptor underlie part of the favorable effects on the brain resulting from physical exercise.

Immunoglobulin concentration, specific gravity, and nitrogen fractions of colostrum from Jersey cattle.

PubMed

Quigley, J D; Martin, K R; Dowlen, H H; Wallis, L B; Lamar, K

1994-01-01

Colostrum samples from 88 Jersey cows were analyzed for concentrations of IgG, IgM, IgA, total solids, specific gravity, and N fractions. Colostrum (50 ml) was sampled from each cow as soon as possible after parturition, and specific gravity was determined immediately using a hydrometer. Samples then were frozen prior to analysis of Ig, fat, and N fractions. Mean concentrations of IgG, IgM, and IgA were 65.8, 2.4, and 1.7 g/L, respectively. Concentration of IgG was lower, and IgA was higher, in colostrum from second lactation cows than from first lactation cows or from cows in third or later lactations; IgM increased linearly as lactation number increased. Total N, protein N, noncasein N, and fat contents also were lower in second lactation cows. Regression of total Ig (grams per liter) on specific gravity was -1172 + 1180 x specific gravity (r2 = .38). Relationship of total Ig to specific gravity differed from colostrum of Holstein cattle and may have been related to differences in fat and noncasein N concentrations. Use of specific gravity hydrometer to estimate Ig concentration using equations derived from Holstein cattle appears to underestimate Ig concentration in colostrum from Jersey cattle.

Improvement of L(+)-Lactic Acid Production of Rhizopus Oryzae by Low-Energy Ions and Analysis of Its Mechanism

NASA Astrophysics Data System (ADS)

Ge, Chunmei; Yang, Yingge; Fan, Yonghong; Li, Wen; Pan, Renrui; Zheng, Zhiming; Yu, Zengliang

2008-02-01

The wild type strain Rhizopus oryzae PW352 was mutated by means of nitrogen ion implantation (15 keV, 7.8 × 1014 ~ 2.08 × 1015 ions/cm2) to find an industrial strain with a higher L(+)-lactic acid yield, and two mutants RE3303 and RF9052 were isolated. In order to discuss the mechanism primarily, Lactate Dehydrogenase of Rhizopus oryzae was studied. While the two mutants produced L(+)-lactic acid by 75% more than the wild strain did, their specific activity of Lactate Dehydrogenase was found to be higher than that in the wild strain. The optimum temperature of Lactate Dehydrogenase in Rhizopus oryzae RF9052 was higher. Compared to the wild strain, the Michaelis constant (Km) value of Lactate Dehydrogenase in the mutants was changed. All these changes show that L(+)-lactic acid production has a correlation with the specific activity of Lactate Dehydrogenase. The low-energy ions, implanted into the strain, may improve the specific activity of Lactate Dehydrogenase by influencing its gene structure and protein structure.

Interaction of cytoplasmic dehydrogenases: quantitation of pathways of ethanol metabolism.

PubMed

Vind, C; Grunnet, N

1983-01-01

The interaction between xylitol, alcohol and lactate dehydrogenase has been studied in hepatocytes from rats by applying specifically tritiated substrates. A simple model, describing the metabolic fate of tritium from [2-3H] xylitol and (1R) [1-3H]ethanol is presented. The model allows calculation of the specific radioactivity of free, cytosolic NADH, based on transfer of tritium to lactate, glucose and water. From the initial labelling rate of lactate and the specific radioactivity of cytosolic NADH, we have determined the reversible flow through the lactate dehydrogenase catalyzed reaction to 1-5 mumol/min . g wet wt. The results suggest that xylitol, alcohol and lactate dehydrogenase share the same pool of NAD(H) in the cytoplasma. This finding allows estimation of the ethanol oxidation rate by the non-alcohol dehydrogenase pathways from the relative yield of tritium in water and glucose. The calculations are based on a comparison of the fate of the 1-pro-R hydrogen of ethanol and the hydrogen bound to carbon 2 of xylitol or carbon 2 of lactate under identical conditions.

CSF lactate alone is not a reliable indicator of bacterial ventriculitis in patients with ventriculostomies.

PubMed

Hill, Emily; Bleck, Thomas P; Singh, Kamaljit; Ouyang, Bichun; Busl, Katharina M

2017-06-01

In a febrile patient with a ventriculostomy, diagnosing or excluding bacterial or microbial ventriculitis is difficult, as conventional markers in analysis of cerebrospinal fluid (CSF) are not applicable due to presence of blood and inflammation. CSF lactate has been shown to be a useful indicator of bacterial meningitis in CSF obtained via lumbar puncture, but little and heterogenous data exist on patients with ventriculostomies. We reviewed all CSF analyses obtained via ventriculostomy in patients admitted to our tertiary medical center between 2008 and 2013, and constructed receiver operating characteristic (ROC) curves to evaluate the accuracy of CSF lactate concentration in discriminating a positive CSF culture from a negative one in setting of ventriculostomy and prophylactic antibiosis. Among 467 CSF lactate values, there were 22 corresponding CSF cultures with bacterial growth. Sensitivities and specificities for CSF lactate at threshold values 3, 4, 5 and 6mmol/L showed sensitivity and specificity greater than 70% for CSF lactate threshold 4mmol/L. The lowest threshold value of 3mmol/L resulted in higher sensitivity of 81.8%, and the highest chosen threshold value resulted in high specificity of 94.2%, but these values had poor corresponding specificity and sensitivity, respectively. The area under the curve was 0.82 (95% CI 0.72, 0.91). Our data from a large sample of CSF studies in patients with ventriculostomy indicate that no single value of CSF lactate provided both sensitivity and specificity high enough to be regarded as reliable test. Copyright © 2017 Elsevier B.V. All rights reserved.

The metabolism of [3-(13)C]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment.

PubMed

Bouzier, A K; Thiaudiere, E; Biran, M; Rouland, R; Canioni, P; Merle, M

2000-08-01

Lactate metabolism in the adult rat brain was investigated in relation with the concept of lactate trafficking between astrocytes and neurons. Wistar rats were infused intravenously with a solution containing either [3-(13)C]lactate (534 mM) or both glucose (750 mM) and [3-(13)C]lactate (534 mM). The time courses of both the concentration and (13)C enrichment of blood glucose and lactate were determined. The data indicated the occurrence of [3-(13)C]lactate recycling through liver gluconeogenesis. The yield of glucose labeling was, however, reduced when using the glucose-containing infusate. After a 20-min or 1-h infusion, perchloric acid extracts of the brain tissue were prepared and subsequently analyzed by (13)C- and (1)H-observed/(13)C-edited NMR spectroscopy. The (13)C labeling of amino acids indicated that [3-(13)C]lactate was metabolized in the brain. Based on the alanine C3 enrichment, lactate contribution to brain metabolism amounted to 35% under the most favorable conditions used. By contrast with what happens with [1-(13)C]glucose metabolism, no difference in glutamine C2 and C3 labeling was evidenced, indicating that lactate was metabolized in a compartment deprived of pyruvate carboxylase activity. This result confirms, for the first time from an in vivo study, that lactate is more specifically a neuronal substrate.

Identification of a Lactate-Quinone Oxidoreductase in Staphylococcus aureus that is Essential for Virulence

PubMed Central

Fuller, James R.; Vitko, Nicholas P.; Perkowski, Ellen F.; Scott, Eric; Khatri, Dal; Spontak, Jeffrey S.; Thurlow, Lance R.; Richardson, Anthony R.

2011-01-01

Staphylococcus aureus is an important human pathogen commonly infecting nearly every host tissue. The ability of S. aureus to resist innate immunity is critical to its success as a pathogen, including its propensity to grow in the presence of host nitric oxide (NO·). Upon exogenous NO· exposure, S. aureus immediately excretes copious amounts of L-lactate to maintain redox balance. However, after prolonged NO·-exposure, S. aureus reassimilates L-lactate specifically and in this work, we identify the enzyme responsible for this L-lactate-consumption as a L-lactate-quinone oxidoreductase (Lqo, SACOL2623). Originally annotated as Mqo2 and thought to oxidize malate, we show that this enzyme exhibits no affinity for malate but reacts specifically with L-lactate (KM = ∼330 μM). In addition to its requirement for reassimilation of L-lactate during NO·-stress, Lqo is also critical to respiratory growth on L-lactate as a sole carbon source. Moreover, Δlqo mutants exhibit attenuation in a murine model of sepsis, particularly in their ability to cause myocarditis. Interestingly, this cardiac-specific attenuation is completely abrogated in mice unable to synthesize inflammatory NO· (iNOS−/−). We demonstrate that S. aureus NO·-resistance is highly dependent on the availability of a glycolytic carbon sources. However, S. aureus can utilize the combination of peptides and L-lactate as carbon sources during NO·-stress in an Lqo-dependent fashion. Murine cardiac tissue has markedly high levels of L-lactate in comparison to renal or hepatic tissue consistent with the NO·-dependent requirement for Lqo in S. aureus myocarditis. Thus, Lqo provides S. aureus with yet another means of replicating in the presence of host NO·. PMID:22919585

D-Lactate transport and metabolism in rat liver mitochondria.

PubMed

de Bari, Lidia; Atlante, Anna; Guaragnella, Nicoletta; Principato, Giovanni; Passarella, Salvatore

2002-07-15

In the present study we investigated whether isolated rat liver mitochondria can take up and metabolize D-lactate. We found the following: (1) externally added D-lactate causes oxygen uptake by mitochondria [P/O ratio (the ratio of mol of ATP synthesized to mol of oxygen atoms reduced to water during oxidative phosphorylation)=2] and membrane potential (Delta(psi)) generation in processes that are rotenone-insensitive, but inhibited by antimycin A and cyanide, and proton release from coupled mitochondria inhibited by alpha-cyanocinnamate, but not by phenylsuccinate; (2) the activity of the putative flavoprotein (D-lactate dehydrogenase) was detected in inside-out submitochondrial particles, but not in mitochondria and mitoplasts, as it is localized in the matrix phase of the mitochondrial inner membrane; (3) three novel separate translocators exist to mediate D-lactate traffic across the mitochondrial inner membrane: the D-lactate/H(+) symporter, which was investigated by measuring fluorimetrically the rate of endogenous flavin reduction, the D-lactate/oxoacid antiporter (which mediates both the D-lactate/pyruvate and D-lactate/oxaloacetate exchanges) and D-lactate/malate antiporter studied by monitoring photometrically the appearance of the D-lactate counteranions outside mitochondria. The D-lactate translocators, in the light of their different inhibition profiles separate from the monocarboxylate carrier, were found to differ from each other in the V(max) values and in the inhibition and pH profiles and were shown to regulate mitochondrial D-lactate metabolism in vitro. The D-lactate translocators and the D-lactate dehydrogenase could account for the removal of the toxic methylglyoxal from cytosol, as well as for D-lactate-dependent gluconeogenesis.

Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

DTIC Science & Technology

2006-04-01

I analyzed virgin and lactating female mice in which FAK is specifically deleted in the mammary epithelium. No morphological abnormalities were found...in the mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. 15. SUBJECT TERMS... virgin and lactating female mice in which FAK is specifically deleted in the mammary epithelium. No morphological abnormalities were found in the

Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baba, Miyako; Inoue, Masahiro; Itoh, Kazuyuki

2008-09-12

CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited themore » association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells.« less

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children.

PubMed

Nazir, Mudasir; Wani, Wasim Ahmad; Malik, Muzaffar Ahmad; Mir, Mohd Rafiq; Ashraf, Younis; Kawoosa, Khalid; Ali, Syed Wajid

To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. At a cut-off value of 3mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2mmol/L. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Biochemical changes in sweat following prolonged ischemia.

PubMed

Ferguson-Pell, M; Hagisawa, S

1988-01-01

Much emphasis has been placed on the measurement of physical parameters at the body support interface in order to detect and moderate conditions which could result in pressure damage to soft tissues. Major difficulties are encountered both in the design of instrumentation and interpretation of the data collected. Metabolic processes in sweat glands that control sweat secretion have been shown to be sensitive to applied pressure, producing sweating rate suppression and changes in sweat NaCl concentration. In this study, we have demonstrated the feasibility of measuring lactate concentration in sweat collected locally using an electrochemical stimulation technique (iontophoresis of pilocarpine nitrate). Elevated levels of sweat lactate concentration during local tissue indentation were detected in a group of able-bodied subjects. Upon removal of the indentor, however, levels of sweat lactate returned to normal.

Phosphatidylcholine-specific phospholipase C inhibition down- regulates CXCR4 expression and interferes with proliferation, invasion and glycolysis in glioma cells

PubMed Central

Ricci, Alessandro; Pacella, Aurora; Cigliana, Giovanni; Bozzuto, Giuseppina; Podo, Franca; Carpinelli, Giulia

2017-01-01

Background The chemokine receptor CXCR4 plays a crucial role in tumors, including glioblastoma multiforme (GBM), the most aggressive glioma. Phosphatidylcholine-specific phospholipase C (PC-PLC), a catabolic enzyme of PC metabolism, is involved in several aspects of cancer biology and its inhibition down-modulates the expression of growth factor membrane receptors interfering with their signaling pathways. In the present work we investigated the possible interplay between CXCR4 and PC-PLC in GBM cells. Methods Confocal microscopy, immunoprecipitation, western blot analyses, and the evaluation of migration and invasion potential were performed on U87MG cells after PC-PLC inhibition with the xanthate D609. The intracellular metabolome was investigated by magnetic resonance spectroscopy; lactate levels and lactate dehydrogenase (LDH) activity were analyzed by colorimetric assay. Results Our studies demonstrated that CXCR4 and PC-PLC co-localize and are associated on U87MG cell membrane. D609 reduced CXCR4 expression, cell proliferation and invasion, interfering with AKT and EGFR activation and expression. Metabolic analyses showed a decrease in intracellular lactate concentration together with a decrement in LDH activity. Conclusions Our data suggest that inhibition of PC-PLC could represent a new molecular approach in glioma biology not only for its ability in modulating cell metabolism, glioma growth and motility, but also for its inhibitory effect on crucial molecules involved in cancer progression. PMID:28423060

Hyaluronan, CD44, and Emmprin Regulate Lactate Efflux and Membrane Localization of Monocarboxylate Transporters in Human Breast Carcinoma Cells

PubMed Central

Slomiany, Mark G.; Grass, G. Daniel; Robertson, Angela D.; Yang, Xiao Y.; Maria, Bernard L.; Beeson, Craig; Toole, Bryan P.

2013-01-01

Interactions of hyaluronan with CD44 in tumor cells play important cooperative roles in various aspects of malignancy and drug resistance. Emmprin (CD147; basigin)is a cell surface glycoprotein of the immunoglobulin superfamily that is highly up-regulated in malignant cancer cells and stimulates hyaluronan production, as well as several downstream signaling pathways. Emmprin also interacts with various monocarboxylate transporters (MCT). Malignant cancer cells use the glycolytic pathway and require MCTs to efflux lactate that results from glycolysis. Glycolysis and lactate secretion contribute to malignant cell behaviors and drug resistance in tumor cells. In the present study, we find that perturbation of endogenous hyaluronan, using small hyaluronan oligosaccharides, rapidly inhibits lactate efflux from breast carcinoma cells; down-regulation of emmprin, using emmprin small interfering RNA, also results in decreased efflux. In addition, we find that CD44 coimmunoprecipitates with MCT1, MCT4, and emmprin and colocalizes with these proteins at the plasma membrane. Moreover, after treatment of the cells with hyaluronan oligosaccharides, CD44, MCT1, and MCT4 become localized intracellularly whereas emmprin remains at the cell membrane. Together, these data indicate that constitutive interactions among hyaluronan, CD44, and emmprin contribute to regulation of MCT localization and function in the plasma membrane of breast carcinoma cells. PMID:19176383

Impact of the hydrogen partial pressure on lactate degradation in a coculture of Desulfovibrio sp. G11 and Methanobrevibacter arboriphilus DH1.

PubMed

Junicke, H; Feldman, H; van Loosdrecht, M C M; Kleerebezem, R

2015-04-01

In this study, the impact of the hydrogen partial pressure on lactate degradation was investigated in a coculture of Desulfovibrio sp. G11 and Methanobrevibacter arboriphilus DH1. To impose a change of the hydrogen partial pressure, formate was added to the reactor. Hydrogen results from the bioconversion of formate besides lactate in the liquid phase. In the presence of a hydrogen-consuming methanogen, this approach allows for a better estimation of low dissolved hydrogen concentrations than under conditions where hydrogen is supplied externally from the gas phase, resulting in a more accurate determination of kinetic parameters. A change of the hydrogen partial pressure from 1,200 to 250 ppm resulted in a threefold increase of the biomass-specific lactate consumption rate. The 50 % inhibition constant of hydrogen on lactate degradation was determined as 0.692 ± 0.064 μM dissolved hydrogen (831 ± 77 ppm hydrogen in the gas phase). Moreover, for the first time, the maximum biomass-specific lactate consumption rate of Desulfovibrio sp. G11 (0.083 ± 0.006 mol-Lac/mol-XG11/h) and the affinity constant for hydrogen uptake of Methanobrevibacter arboriphilus DH1 (0.601 ± 0.022 μM dissolved hydrogen) were determined. Contrary to the widely established view that the biomass-specific growth rate of a methanogenic coculture is determined by the hydrogen-utilizing partner; here, it was found that the hydrogen-producing bacterium determined the biomass-specific growth rate of the coculture grown on lactate and formate.

An In Vitro Model of the Horse Gut Microbiome Enables Identification of Lactate-Utilizing Bacteria That Differentially Respond to Starch Induction

PubMed Central

Biddle, Amy S.; Black, Samuel J.; Blanchard, Jeffrey L.

2013-01-01

Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaera elsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonella montpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions. PMID:24098591

Determination of lactic acid with special emphasis on biosensing methods: A review.

PubMed

Pundir, Chandra S; Narwal, Vinay; Batra, Bhawna

2016-12-15

Lactic acid (2-Hydroxypropanoic acid) is generated from pyruvic acid under anaerobic condition in skeletal muscles, brain, red blood cells, and kidney. Lactate in normal human subjects get cleared very quickly at a rate of 320mmol/L/hr, mostly by liver metabolism and re-conversion of lactate back to pyruvate. Measurement of lactate level in serum is required for the differential diagnosis and medical management of hyperlactatemia, cardiac arrest and resuscitation, sepsis, reduced renal excretion, hypoxia induced cancer, decreased extra hepatic metabolism, intestinal infarction and lactic acidosis. Determination of lactate is also important in dairy products and beverages to access their quality. Among the various methods available for detection of lactate, most are complicated, nonspecific, less sensitive and require time-consuming sample pretreatment, expensive instrumental set-up and trained persons to operate, specifically for chromatographic methods. Biosensing methods overcome these drawbacks, as these are simple, fast, specific and highly sensitive. Lactate biosensors reported so far, work optimally within 3-180s, between pH, 5.5-8.5 and temperature 22°C to 37°C and lactate concentration ranging from 10 to 2000µM. These biosensors have been employed to measure lactate level in embryonic cell culture, beverages, urine, and serum samples and reused upto 200-times within a period of 7-216 days. This review presents the principles, merits and demerits of various analytical methods for lactate determination with special emphasis on lactate biosensors. The future perspective for improvement of analytic performance of lactate biosensors are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

An in vitro model of the horse gut microbiome enables identification of lactate-utilizing bacteria that differentially respond to starch induction.

PubMed

Biddle, Amy S; Black, Samuel J; Blanchard, Jeffrey L

2013-01-01

Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaeraelsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonellamontpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions.

Lack of utility of arteriojugular venous differences of lactate as a reliable indicator of increased brain anaerobic metabolism in traumatic brain injury.

PubMed

Poca, Maria A; Sahuquillo, Juan; Vilalta, Anna; Garnacho, Angel

2007-04-01

Ischemic lesions are highly prevalent in patients with traumatic brain injuries (TBIs) and are the single most important cause of secondary brain damage. The prevention and early treatment of these lesions is the primary aim in the modem treatment of these patients. One of the most widely used monitoring techniques at the bedside is quantification of brain extracellular level of lactate by using arteriojugular venous differences of lactate (AVDL). The purpose of this study was to determine the sensitivity, specificity, and predictive value of AVDL as an indicator of increases in brain lactate production in patients with TBIs. Arteriojugular venous differences of lactate were calculated every 6 hours using samples obtained though a catheter placed in the jugular bulb in 45 patients with diffuse head injuries (57.8%) or evacuated brain lesions (42.2%). Cerebral lactate concentration obtained with a 20-kD microdialysis catheter implanted in undamaged tissue was used as the de facto gold standard. Six hundred seventy-three AVDL determinations and cerebral microdialysis samples were obtained simultaneously; 543 microdialysis samples (81%) showed lactate values greater than 2 mmol/L, but only 21 AVDL determinations (3.1%) showed an increase in brain lactate. No correlation was found between AVDL and cerebral lactate concentration (p = 0.014, p = 0.719). Arteriojugular venous differences of lactate had a sensitivity and specificity of 3.3 and 97.7%, respectively, with a false-negative rate of 96.7% and a false-positive rate of 2.3%. Arteriojugular venous differences of lactate do not reliably reflect increased cerebral lactate production and consequently are not reliable in ruling out brain ischemia in patients with TBIs. The clinical use of this monitoring method in neurocritical care should be reconsidered.

Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

PubMed

Dienel, Gerald A; Cruz, Nancy F

2016-07-01

Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain activation. Aerobic glycolysis, the preferential up-regulation of glucose utilization (CMRglc ) compared with oxygen consumption (CMRO2 ) during brain activation, is blocked by propranolol. Epinephrine release from the adrenal gland stimulates vagus nerve signaling to the locus coeruleus, enhancing norepinephrine release in the brain, and regulation of astrocytic and neuronal metabolism to stimulate CMRglc more than CMRO2 . Propranolol suppresses CMRglc more than CMRO2 . © 2016 International Society for Neurochemistry.

Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice.

PubMed

Porporato, Paolo E; Payen, Valéry L; De Saedeleer, Christophe J; Préat, Véronique; Thissen, Jean-Paul; Feron, Olivier; Sonveaux, Pierre

2012-12-01

Wounds notoriously accumulate lactate as a consequence of both anaerobic and aerobic glycolysis following microcirculation disruption, immune activation, and increased cell proliferation. Several pieces of evidence suggest that lactate actively participates in the healing process through the activation of several molecular pathways that collectively promote angiogenesis. Lactate indeed stimulates endothelial cell migration and tube formation in vitro, as well as the recruitment of circulating vascular progenitor cells and vascular morphogenesis in vivo. In this study, we examined whether the pro-angiogenic potential of lactate may be exploited therapeutically to accelerate wound healing. We show that lactate delivered from a Matrigel matrix improves reperfusion and opposes muscular atrophy in ischemic hindlimb wounds in mice. Both responses involve lactate-induced reparative angiogenesis. Using microdialysis and enzymatic measurements, we found that, contrary to poly-L-lactide (PLA), a subcutaneous implant of poly-D,L-lactide-co-glycolide (PLGA) allows sustained local and systemic lactate release. PLGA promoted angiogenesis and accelerated the closure of excisional skin wounds in different mouse strains. This polymer is FDA-approved for other applications, emphasizing the possibility of exploiting PLGA therapeutically to improve wound healing.

Evaluation of the Lactate-to-N-Acetyl-aspartate Ratio Defined With Magnetic Resonance Spectroscopic Imaging Before Radiation Therapy as a New Predictive Marker of the Site of Relapse in Patients With Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deviers, Alexandra; UMR; INP

Purpose: Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-{sup 1}H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM). Methods and Materials: Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis ofmore » the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence. Results: A LNR of ≥0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm{sup 3}; range: 6-49 cm{sup 3}). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01). Conclusions: Pre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting.« less

Gene regulatory networks in lactation: identification of global principles using bioinformatics.

PubMed

Lemay, Danielle G; Neville, Margaret C; Rudolph, Michael C; Pollard, Katherine S; German, J Bruce

2007-11-27

The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood. Mammary gland microarray data, cellular localization data, protein-protein interactions, and literature-mined genes were integrated and analyzed using statistics, principal component analysis, gene ontology analysis, pathway analysis, and network analysis to identify global biological principles that govern molecular events during pregnancy, lactation, and involution. Several key principles were derived: (1) nearly a third of the transcriptome fluctuates to build, run, and disassemble the lactation apparatus; (2) genes encoding the secretory machinery are transcribed prior to lactation; (3) the diversity of the endogenous portion of the milk proteome is derived from fewer than 100 transcripts; (4) while some genes are differentially transcribed near the onset of lactation, the lactation switch is primarily post-transcriptionally mediated; (5) the secretion of materials during lactation occurs not by up-regulation of novel genomic functions, but by widespread transcriptional suppression of functions such as protein degradation and cell-environment communication; (6) the involution switch is primarily transcriptionally mediated; and (7) during early involution, the transcriptional state is partially reverted to the pre-lactation state. A new hypothesis for secretory diminution is suggested - milk production gradually declines because the secretory machinery is not transcriptionally replenished. A comprehensive network of protein interactions during lactation is assembled and new regulatory gene targets are identified. Less than one fifth of the transcriptionally regulated nodes in this lactation network have been previously explored in the context of lactation. Implications for future research in mammary and cancer biology are discussed.

Isolating the cow-specific part of residual energy intake in lactating dairy cows using random regressions.

PubMed

Fischer, A; Friggens, N C; Berry, D P; Faverdin, P

2018-07-01

The ability to properly assess and accurately phenotype true differences in feed efficiency among dairy cows is key to the development of breeding programs for improving feed efficiency. The variability among individuals in feed efficiency is commonly characterised by the residual intake approach. Residual feed intake is represented by the residuals of a linear regression of intake on the corresponding quantities of the biological functions that consume (or release) energy. However, the residuals include both, model fitting and measurement errors as well as any variability in cow efficiency. The objective of this study was to isolate the individual animal variability in feed efficiency from the residual component. Two separate models were fitted, in one the standard residual energy intake (REI) was calculated as the residual of a multiple linear regression of lactation average net energy intake (NEI) on lactation average milk energy output, average metabolic BW, as well as lactation loss and gain of body condition score. In the other, a linear mixed model was used to simultaneously fit fixed linear regressions and random cow levels on the biological traits and intercept using fortnight repeated measures for the variables. This method split the predicted NEI in two parts: one quantifying the population mean intercept and coefficients, and one quantifying cow-specific deviations in the intercept and coefficients. The cow-specific part of predicted NEI was assumed to isolate true differences in feed efficiency among cows. NEI and associated energy expenditure phenotypes were available for the first 17 fortnights of lactation from 119 Holstein cows; all fed a constant energy-rich diet. Mixed models fitting cow-specific intercept and coefficients to different combinations of the aforementioned energy expenditure traits, calculated on a fortnightly basis, were compared. The variance of REI estimated with the lactation average model represented only 8% of the variance of measured NEI. Among all compared mixed models, the variance of the cow-specific part of predicted NEI represented between 53% and 59% of the variance of REI estimated from the lactation average model or between 4% and 5% of the variance of measured NEI. The remaining 41% to 47% of the variance of REI estimated with the lactation average model may therefore reflect model fitting errors or measurement errors. In conclusion, the use of a mixed model framework with cow-specific random regressions seems to be a promising method to isolate the cow-specific component of REI in dairy cows.

Caudal hindbrain lactate infusion alters glucokinase, SUR1, and neuronal substrate fuel transporter gene expression in the dorsal vagal complex, lateral hypothalamic area, and ventromedial nucleus hypothalamus of hypoglycemic male rats.

PubMed

Vavaiya, Kamlesh V; Briski, Karen P

2007-10-24

While in vitro studies show that the oxidizable energy substrate, lactate, is a preferred fuel for CNS neurons during states of energy crisis, and that lactate may regulate neuronal glucose uptake under those conditions, its role in neuronal function in vivo remains controversial. Glucose-excited neurons in hindbrain dorsal vagal complex (DVC) monitor both glucose and lactate, and express both the glucose sensor, glucokinase (GK), and the SUR1 subunit of the plasma membrane energy transducer, K(ATP). Fourth ventricular lactate infusion exacerbates insulin-induced hypoglycemia (IIH) and IIH-associated patterns of DVC neuronal activation. We investigated the hypothesis that during glucoprivation, lactate regulates neuronal monocarboxylate and glucose transporter gene transcription in the DVC, and adjustments in these gene profiles are correlated with altered GK and SUR1 mRNA expression. We also examined whether caudal hindbrain lactate repletion alters the impact of hypoglycemia on substrate fuel uptake and metabolic sensing functions in other characterized metabolic monitoring sites, e.g., the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA). qPCR was used to measure MCT2, GLUT3, GLUT4, GK, and SUR1 transcripts in the microdissected DVC, VMH, and LHA from groups of male rats treated by continuous infusion of aCSF or lactate into the caudal fourth ventricle (CV4), initiated prior to injection of Humulin R or saline. Blood glucose was decreased in response to insulin, a response that was significantly augmented by CV4 lactate infusion. IIH alone did not alter mean DVC MCT2, GLUT3, GLUT4, GK, or SUR1 mRNA levels, but these transcripts were increased in the lactate plus insulin group, relative to both euglycemic and aCSF-infused hypoglycemic rats. IIH decreased MCT2, GLUT3, and SUR1 gene profiles in the VMH; CV4 lactate infusion during IIH further diminished these transcripts, and suppressed GLUT4 and GK mRNA levels in this site. In LHA, IIH increased GLUT3 and SUR1 gene expression to an equal extent, with or without lactate, while GLUT4, MCT2, and GK mRNA levels were elevated only in response to lactate plus insulin. These studies show that caudal hindbrain-targeted delivery of exogenous lactate during IIH upregulates neuronal monocarboxylate and glucose transporter, GK, and SUR1 gene profiles in the DVC, and results in increased or decreased GLUT4 and GK mRNA in LHA and VMH, respectively. These data suggest that lactate and glucose utilization by DVC neurons may be enhanced in response to local lactate surfeit, alone or relative to glucose deficiency, and that increases in intracellular glucose and net energy yield may be correlated with elevated GK and SUR1 gene transcription, respectively, in local glucose sensing neurons. The results also imply that GLUT4- and GK-mediated glucose uptake and glucose sensing functions in the VMH and LHA may be reactive to DVC signaling of relative lactate abundance within the caudal hindbrain, and/or to physiological sequelae of this fuel augmentation, including amplified hypoglycemia.

Upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts: Morphological characteristics and implications.

PubMed

Ryoko, Okuno; Ito, Yuko; Eid, Nabil; Otsuki, Yoshinori; Kondo, Yoichi; Ueda, Koichi

2018-05-29

Keloid is a fibro-proliferative skin disorder with tumor-like behavior and dependence on anaerobic glycolysis (the Warburg effect), but its exact pathogenesis is unknown. Although autophagy is widely accepted as a lysosomal pathway for cell survival and cellular homeostasis (specifically upon exposure to stressors such as hypoxia), very few studies have investigated the involvement of autophagy and related glycolytic effectors in keloidogenesis. Here the authors examined the expression and cellular localization of autophagy proteins (LC3, pan-cathepsin), glycolytic markers (LDH, MCT1, MCT4) and the transcription factor HIF isoforms in human keloid samples using immunohistochemical analysis and double-labeling immunofluorescence methods. Based on H&E staining and expression of CD31, keloids were compartmentalized into hypoxic central and normoxic marginal zones. Vimentin-expressing fibroblasts in the central zone exhibited greater autophagy than their marginal-zone counterparts, as evidenced by increased LC3 puncta formation and co-localization with lysosomal pan-cathepsin. LDH (a lactate stimulator), MCT4 (a lactate exporter) and HIF-1 α expression levels were also higher in central-zone fibroblasts. Conversely, HIF-2 α expression was upregulated in fibroblasts and endothelial cells of the peripheral zone, while MCT1 was expressed in both zones. Taken together, these observations suggest that upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts may indicate a prosurvival mechanism allowing the extrusion of lactate to marginal-zone fibroblasts via metabolic coupling. The authors believe this is the first report on differential expression of autophagic and glycolytic markers in keloid-zone fibroblasts. The study results indicate that autophagy inhibitors and MCT4 blockers may have therapeutic implications in keloid treatment.

USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF BACTERIAL AND ASEPTIC MENINGITIS.

PubMed

Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

2017-01-01

To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS.

The clinical diagnostic significance of cerebrospinal fluid D-lactate for bacterial meningitis.

PubMed

Chen, Zengqiang; Wang, Yumin; Zeng, Aibing; Chen, Lijiang; Wu, Ruihao; Chen, Bicheng; Chen, Mengquan; Bo, Jinshuang; Zhang, Hu; Peng, Qian; Lu, Jianxin; Meng, Qing H

2012-10-09

To study the clinical and laboratory significance of D‐lactate in the diagnosis of bacterial meningitis (BM). The levels of D‐lactate, L‐lactate, IL-6, IL-8, and other biochemical markers were determined in 83 CSF samples from different types of meningitis and the controls. The CSF values of D‐lactate, L‐lactate, IL-6, IL-8, erythrocytes, leukocytes, and protein were higher in patients with BM than those in the controls and patients with viral meningitis. The levels of D‐lactate, L‐lactate, IL-6, and erythrocytes in the BM group were higher than those in the tuberculous meningitis group. At the cutoff 12.8 μmol/l, D‐lactate showed the diagnostic sensitivity of 94.7%. D‐lactate gave the area under the curve (AUC) 0.905, which was higher than those of other markers. Using multiple marker detection, the AUC reached 0.956, which was the highest among all the parameters. Pearson correlation analysis revealed that D‐lactate was positively correlated to IL-6 and L‐lactate (r=0.727, 0.789 and P=0.000, 0.000, respectively). THE CSF concentrations of D‐lactate are significantly increased in the presence of BM. Measurement of D‐lactate provides a rapid diagnosis and differential diagnosis for BM. Combination of D‐lactate with other biochemical markers improves the specificity. Copyright © 2012 Elsevier B.V. All rights reserved.

Venous glucose, serum lactate and base deficit as biochemical predictors of mortality in patients with polytrauma.

PubMed

Saad, Sameh; Mohamed, Naglaa; Moghazy, Amr; Ellabban, Gouda; El-Kamash, Soliman

2016-01-01

The trauma and injury severity score (TRISS) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) are accurate but complex. This study aimed to compare venous glucose, levels of serum lactate, and base deficit in polytraumatized patients as simple parameters to predict the mortality in these patients versus (TRISS) and (APACHE IV). This was a comparative cross-sectional study of 282 patients with polytrauma presented to the Emergency Department (ED). The best cut off value of TRISS probability of survival score for prediction of mortality among poly-traumatized patients was ≤90. APACHE IV demonstrated 67% sensitivity and 95% specificity at 95% CI at cut off point 99. The best cutoff value of Random Blood Sugar was >140 mg/dl, with 89% sensitivity, 49% specificity; base deficit was less than -5.6 with 64% sensitivity, 93% specificity; lactate was >2.6 mmol/L with 92%, sensitivity, 42% specificity. Venous glucose, serum lactate and base deficit are easy and rapid biochemical predictors of mortality in patients with polytrauma. These predictors could be used as TRISS and APACHE IV in predicting mortality.

Juvenile hormone and insulin suppress lipolysis between periods of lactation during tsetse fly pregnancy.

PubMed

Baumann, Aaron A; Benoit, Joshua B; Michalkova, Veronika; Mireji, Paul; Attardo, Geoffrey M; Moulton, John K; Wilson, Thomas G; Aksoy, Serap

2013-06-15

Tsetse flies are viviparous insects that nurture a single intrauterine progeny per gonotrophic cycle. The developing larva is nourished by the lipid-rich, milk-like secretions from a modified female accessory gland (milk gland). An essential feature of the lactation process involves lipid mobilization for incorporation into the milk. In this study, we examined roles for juvenile hormone (JH) and insulin/IGF-like (IIS) signaling pathways during tsetse pregnancy. In particular, we examined the roles for these pathways in regulating lipid homeostasis during transitions between non-lactating (dry) and lactating periods. The dry period occurs over the course of oogenesis and embryogenesis, while the lactation period spans intrauterine larvigenesis. Genes involved in the JH and IIS pathways were upregulated during dry periods, correlating with lipid accumulation between bouts of lactation. RNAi suppression of Forkhead Box Sub Group O (FOXO) expression impaired lipolysis during tsetse lactation and reduced fecundity. Similar reduction of the JH receptor Methoprene tolerant (Met), but not its paralog germ cell expressed (gce), reduced lipid accumulation during dry periods, indicating functional divergence between Met and gce during tsetse reproduction. Reduced lipid levels following Met knockdown led to impaired fecundity due to inadequate fat reserves at the initiation of milk production. Both the application of the JH analog (JHA) methoprene and injection of insulin into lactating females increased stored lipids by suppressing lipolysis and reduced transcripts of lactation-specific genes, leading to elevated rates of larval abortion. To our knowledge, this study is the first to address the molecular physiology of JH and IIS in a viviparous insect, and specifically to provide a role for JH signaling through Met in the regulation of lipid metabolism during insect lactation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Functional purification of the monocarboxylate transporter of the yeast Candida utilis.

PubMed

Baltazar, Fátima; Cássio, Fernanda; Leão, Cecília

2006-08-01

Plasma membranes of the yeast, Candida utilis, were solubilized with octyl-beta-D-glucopyranoside and a fraction enriched in the lactate carrier was obtained with DEAE-Sepharose anion-exchange chromatography, after elution with 0.4 M NaCl. The uptake of lactic acid into proteoliposomes, containing the purified protein fraction and cytochrome c oxidase, was dependent on a proton-motive force and the transport specificity was consistent with the one of C. utilis intact cells. Overall, we have obtained a plasma membrane fraction enriched in the lactate carrier of C. utilis in which the transport properties were preserved. Given the similarities between the lactate transport of C. utilis and the one of mammalian cells, this purified system could be further explored to screen for specific lactate inhibitors, with potential therapeutic applications.

Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy*

PubMed Central

Zuo, Ru-Juan; Gu, Xiao-Wei; Qi, Qian-Rong; Wang, Tong-Song; Zhao, Xu-Yu; Liu, Ji-Long; Yang, Zeng-Ming

2015-01-01

Decidualization is an essential process of maternal endometrial stromal cells to support pregnancy. Although it is known that enhanced glucose influx is critical for decidualization, the underlying mechanism in regulating glucose metabolism in decidua remains insufficiently understood. Here, we demonstrate that aerobic glycolysis-related genes and factors are all substantially induced during decidualization, indicating the existence of Warburg-like glycolysis in decidua. In vitro, progesterone activates hypoxia-inducible factor 1α (Hif1α) and c-Myc through Pi3k-Akt signaling pathway to maintain aerobic glycolysis in decidualizing cells. Knocking down of pyruvate kinase M2 (Pkm2) attenuates the induction of decidual marker gene. Decidual formation in vivo is also impaired by glycolysis inhibitor 3-bromopyruvate. Besides, lactate exporter monocarboxylate transporter 4 (Mct4) is induced in newly formed decidual cells, whereas lactate importer Mct1 and proliferation marker Ki-67 are complementarily located in the surrounding undifferentiated cells, which are supposed to consume lactate for proliferation. Hif1α activation is required for lactate-dependent proliferation of the undifferentiated cells. Inhibition of lactate flux leads to compromised decidualization and decelerated lactate-dependent proliferation. In summary, we reveal that Warburg-like glycolysis and local lactate shuttle are activated in decidua and play important roles for supporting early pregnancy. PMID:26178372

Lactate clearance as a marker of mortality in pediatric intensive care unit.

PubMed

Munde, A; Kumar, N; Beri, R S; Puliyel, J M

2014-07-01

To correlate lactate clearance with Pediatric Intensive Care Unit (PICU) mortality. 45 (mean age 40.15 mo, 60% males) consecutive admissions in the PICU were enrolled between May 2012 to June 2013. Lactate clearance (Lactate level at admission - level 6 hr later x 100 / lactate level at admission) in first 6 hours of hospitalization was correlated to in-hospital mortality and PRISM score. Twelve out of 45 patients died. 90% died among those with delayed/poor clearance (clearance <30%) compared to 8.5% in those with good clearance (clearance >30%) (P<0.001). Lactate clearance <30% predicted mortality with sensitivity of 75%, specificity of 97%, positive predictive value of 90%, and negative predictive value of 91.42%. Predictability was comparable to PRISM score >30. Lactate clearance at six hours correlates with mortality in the PICU.

Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

PubMed

Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

2016-06-01

In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases.

Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

PubMed

Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki; Cook, Michelle; Law, Mona J; Kaufman, Elaine; Sokoloff, Louis

2003-04-15

Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice.

PubMed

Bornstein, Sheila; Brown, Sue A; Le, Phuong T; Wang, Xunde; DeMambro, Victoria; Horowitz, Mark C; MacDougald, Ormond; Baron, Roland; Lotinun, Sutada; Karsenty, Gerard; Wei, Wei; Ferron, Mathieu; Kovacs, Christopher S; Clemmons, David; Wan, Yihong; Rosen, Clifford J

2014-09-01

Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as receptor activator of nuclear factor κ-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. Fibroblast growth factor 21 (FGF-21) may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In this study, we hypothesized that the metabolic changes during lactation were due in part to increased circulating FGF-21, which in turn could accentuate bone loss. We longitudinally characterized body composition in C57BL/6J (B6) mice during (day 7 and day 21 of lactation) and after normal lactation (day 21 postlactation). At day 7 of lactation, areal bone density declined by 10% (P < .001), bone resorption increased (P < .0001), percent fat decreased by 20%, energy expenditure increased (P < .01), and markers of brown-like adipogenesis were suppressed in the inguinal depot and in preformed brown adipose tissue. At day 7 of lactation there was a 2.4-fold increase in serum FGF-21 vs baseline (P < .0001), a 8-fold increase in hepatic FGF-21 mRNA (P < .03), a 2-fold increase in undercarboxylated osteocalcin (Glu13 OCn) (P < .01), and enhanced insulin sensitivity. Recovery of total areal bone density was noted at day 21 of lactation, whereas the femoral trabecular bone volume fraction was still reduced (P < .01). Because FGF-21 levels rose rapidly at day 7 of lactation in B6 lactating mice, we next examined lactating mice with a deletion in the Fgf21 gene. Trabecular and cortical bone masses were maintained throughout lactation in FGF-21(-/-) mice, and pup growth was normal. Compared with lactating control mice, lactating FGF-21(-/-) mice exhibited an increase in bone formation, but no change in bone resorption. In conclusion, in addition to changes in calciotropic hormones, systemic FGF-21 plays a role in skeletal remodeling and changes in body composition during lactation in B6 mice.

FGF-21 and Skeletal Remodeling During and After Lactation in C57BL/6J Mice

PubMed Central

Bornstein, Sheila; Brown, Sue A.; Le, Phuong T.; Wang, Xunde; DeMambro, Victoria; Horowitz, Mark C.; MacDougald, Ormond; Baron, Roland; Lotinun, Sutada; Karsenty, Gerard; Wei, Wei; Ferron, Mathieu; Kovacs, Christopher S.; Clemmons, David

2014-01-01

Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as receptor activator of nuclear factor κ-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. Fibroblast growth factor 21 (FGF-21) may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In this study, we hypothesized that the metabolic changes during lactation were due in part to increased circulating FGF-21, which in turn could accentuate bone loss. We longitudinally characterized body composition in C57BL/6J (B6) mice during (day 7 and day 21 of lactation) and after normal lactation (day 21 postlactation). At day 7 of lactation, areal bone density declined by 10% (P < .001), bone resorption increased (P < .0001), percent fat decreased by 20%, energy expenditure increased (P < .01), and markers of brown-like adipogenesis were suppressed in the inguinal depot and in preformed brown adipose tissue. At day 7 of lactation there was a 2.4-fold increase in serum FGF-21 vs baseline (P < .0001), a 8-fold increase in hepatic FGF-21 mRNA (P < .03), a 2-fold increase in undercarboxylated osteocalcin (Glu13 OCn) (P < .01), and enhanced insulin sensitivity. Recovery of total areal bone density was noted at day 21 of lactation, whereas the femoral trabecular bone volume fraction was still reduced (P < .01). Because FGF-21 levels rose rapidly at day 7 of lactation in B6 lactating mice, we next examined lactating mice with a deletion in the Fgf21 gene. Trabecular and cortical bone masses were maintained throughout lactation in FGF-21−/− mice, and pup growth was normal. Compared with lactating control mice, lactating FGF-21−/− mice exhibited an increase in bone formation, but no change in bone resorption. In conclusion, in addition to changes in calciotropic hormones, systemic FGF-21 plays a role in skeletal remodeling and changes in body composition during lactation in B6 mice. PMID:24914939

Lactate induces osteoblast differentiation by stabilization of HIF1α.

PubMed

Wu, Yu; Wang, Miaomiao; Feng, Haihua; Peng, Ying; Sun, Jieyun; Qu, Xiuxia; Li, Chunping

2017-09-05

Aerobic glycolysis is involved in osteoblast differentiation induced by Wnt signaling or PTH treatment. However, it is still unclear whether lactate, the end product of aerobic glycolysis, plays any role in osteoblast differentiation. Herein we report that in cultures of osteoblast-lineage cells, lactate promoted alkaline phosphatase-positive cell formation, increased the activity of alkaline phosphatase, and induced the expression of osteocalcin. This osteoblast differentiation-inducing effect of lactate can be inhibited by blocking its entry into cells with MCT1 siRNA or inhibitors, and by interfering with its metabolism by using specific siRNAs for LDHB and PDH. Moreover, lactate stabilized HIF1α expression and inhibited HIF1α activity, with BAY87-2243 lowering the osteoblast differentiation-inducing effect of lactate. Thus, these findings reveal an unrecognized role for aerobic glycolysis in osteoblast differentiation via its end product, lactate. Copyright © 2017 Elsevier B.V. All rights reserved.

The kinetics of lactate production and removal during whole-body exercise

PubMed Central

2012-01-01

Background Based on a literature review, the current study aimed to construct mathematical models of lactate production and removal in both muscles and blood during steady state and at varying intensities during whole-body exercise. In order to experimentally test the models in dynamic situations, a cross-country skier performed laboratory tests while treadmill roller skiing, from where work rate, aerobic power and blood lactate concentration were measured. A two-compartment simulation model for blood lactate production and removal was constructed. Results The simulated and experimental data differed less than 0.5 mmol/L both during steady state and varying sub-maximal intensities. However, the simulation model for lactate removal after high exercise intensities seems to require further examination. Conclusions Overall, the simulation models of lactate production and removal provide useful insight into the parameters that affect blood lactate response, and specifically how blood lactate concentration during practical training and testing in dynamical situations should be interpreted. PMID:22413898

USE OF SCORE AND CEREBROSPINAL FLUID LACTATE DOSAGE IN DIFFERENTIAL DIAGNOSIS OF BACTERIAL AND ASEPTIC MENINGITIS

PubMed Central

Pires, Frederico Ribeiro; Franco, Andréia Christine Bonotto Farias; Gilio, Alfredo Elias; Troster, Eduardo Juan

2017-01-01

ABSTRACT Objective: To evaluate Bacterial Meningitis Score (BMS) on its own and in association with Cerebrospinal Fluid (CSF) lactate dosage in order to distinguish bacterial from aseptic meningitis. Methods: Children diagnosed with meningitis at a tertiary hospital between January/2011 and December/2014 were selected. All data were obtained upon admission. BMS was applied and included: CSF Gram staining (2 points); CSF neutrophil count ≥1,000 cells/mm3 (1 point); CSF protein ≥80 mg/dL (1 point); peripheral blood neutrophil count ≥10,000 cells/mm3 (1 point) and seizures upon/before arrival (1 point). Cutoff value for CSF lactate was ≥30 mg/dL. Sensitivity, specificity and negative predictive value of several BMS cutoffs and BMS associated with high CSF lactate were evaluated for prediction of bacterial meningitis. Results: Among 439 eligible patients, 94 did not have all data available to complete the score, and 345 patients were included: 7 in bacterial meningitis group and 338 in aseptic meningitis group. As predictive factors of bacterial meningitis, BMS ≥1 had 100% sensitivity (95%CI 47.3-100), 64.2% specificity (58.8-100) and 100% negative predictive value (97.5-100); BMS ≥2 or BMS ≥1 associated with high CSF lactate also showed 100% sensitivity (47.3-100); but 98.5% specificity (96.6-99.5) and 100% negative predictive value (98.3-100). Conclusions: 2 point BMS in association with CSF lactate dosage had the same sensitivity and negative predictive value, with increased specificity for diagnosis of bacterial meningitis when compared with 1-point BMS. PMID:29185620

Expression of Lactate Dehydrogenase in Aspergillus niger for L-Lactic Acid Production

PubMed Central

Dave, Khyati K.; Punekar, Narayan S.

2015-01-01

Different engineered organisms have been used to produce L-lactate. Poor yields of lactate at low pH and expensive downstream processing remain as bottlenecks. Aspergillus niger is a prolific citrate producer and a remarkably acid tolerant fungus. Neither a functional lactate dehydrogenase (LDH) from nor lactate production by A. niger is reported. Its genome was also investigated for the presence of a functional ldh. The endogenous A. niger citrate synthase promoter relevant to A. niger acidogenic metabolism was employed to drive constitutive expression of mouse lactate dehydrogenase (mldhA). An appraisal of different branches of the A. niger pyruvate node guided the choice of mldhA for heterologous expression. A high copy number transformant C12 strain, displaying highest LDH specific activity, was analyzed under different growth conditions. The C12 strain produced 7.7 g/l of extracellular L-lactate from 60 g/l of glucose, in non-neutralizing minimal media. Significantly, lactate and citrate accumulated under two different growth conditions. Already an established acidogenic platform, A. niger now promises to be a valuable host for lactate production. PMID:26683313

Effect of lactation therapy on Staphylococcus aureus transmission dynamics in two commercial dairy herds

PubMed Central

2013-01-01

Background Treatment of subclinical mastitis during lactation can have both direct (individual animal level) and indirect (population level) effects. With a few exceptions, prior research has focused on evaluating the direct effects of mastitis treatment, and to date no controlled field trials have been conducted to test whether beneficial indirect effects of lactation treatment strategies targeting subclinical mastitis can be demonstrated on commercial dairy farms. Furthermore, there is limited knowledge on the impact of such interventions on the population dynamics of specific bacterial strains. The purpose of this study was to test the hypothesis that lactation therapy targeting S. aureus subclinical intramammary infection reduces transmission of S. aureus strains within dairy herds. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to determine strain specific infection dynamics in treated and control groups in a split herd trial conducted on 2 commercial dairy farms. Results The direct effect of 8 days intramammary lactation therapy with pirlimycin hydrochloride was demonstrated by an increased proportion of cure and a reduction in duration of infection in quarters receiving treatment compared to untreated controls. The indirect effect of lactation therapy was demonstrated by reduction of new S. aureus intramammary infections (IMI) caused by the dominant strain type in both herds. Strain typing of representative isolates taken over the duration of all IMI, including pre- and post-treatment isolates, provided more precise estimates of new infection, cure, and re-infection rates. New S. aureus infections in recovered susceptible quarters and the emergence of a new strain type in one herd influenced incidence measures. Conclusion In addition to demonstrating positive direct effects of lactation therapy, this study provides evidence that treatment of subclinical S. aureus mastitis during lactation can have indirect effects including preventing new IMI and reducing incidence of clinical mastitis within dairy herds. Strain specific transmission parameter estimates for S. aureus MLST clonal complexes 5, 97 and 705 in 2 commercial dairy herds are also reported. PMID:23398676

Effect of lactation therapy on Staphylococcus aureus transmission dynamics in two commercial dairy herds.

PubMed

Barlow, John W; Zadoks, Ruth N; Schukken, Ynte H

2013-02-11

Treatment of subclinical mastitis during lactation can have both direct (individual animal level) and indirect (population level) effects. With a few exceptions, prior research has focused on evaluating the direct effects of mastitis treatment, and to date no controlled field trials have been conducted to test whether beneficial indirect effects of lactation treatment strategies targeting subclinical mastitis can be demonstrated on commercial dairy farms. Furthermore, there is limited knowledge on the impact of such interventions on the population dynamics of specific bacterial strains. The purpose of this study was to test the hypothesis that lactation therapy targeting S. aureus subclinical intramammary infection reduces transmission of S. aureus strains within dairy herds. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to determine strain specific infection dynamics in treated and control groups in a split herd trial conducted on 2 commercial dairy farms. The direct effect of 8 days intramammary lactation therapy with pirlimycin hydrochloride was demonstrated by an increased proportion of cure and a reduction in duration of infection in quarters receiving treatment compared to untreated controls. The indirect effect of lactation therapy was demonstrated by reduction of new S. aureus intramammary infections (IMI) caused by the dominant strain type in both herds. Strain typing of representative isolates taken over the duration of all IMI, including pre- and post-treatment isolates, provided more precise estimates of new infection, cure, and re-infection rates. New S. aureus infections in recovered susceptible quarters and the emergence of a new strain type in one herd influenced incidence measures. In addition to demonstrating positive direct effects of lactation therapy, this study provides evidence that treatment of subclinical S. aureus mastitis during lactation can have indirect effects including preventing new IMI and reducing incidence of clinical mastitis within dairy herds. Strain specific transmission parameter estimates for S. aureus MLST clonal complexes 5, 97 and 705 in 2 commercial dairy herds are also reported.

Prevention of autoimmune diabetes and islet allograft rejection by beta cell expression of XIAP: Insight into possible mechanisms of local immunomodulation.

PubMed

Obach, Mercè; Hosseini-Tabatabaei, Azadeh; Montane, Joel; Wind, Katarina; Soukhatcheva, Galina; Dai, Derek; Priatel, John J; Orban, Paul C; Verchere, C Bruce

2018-06-05

Overexpression of the X-linked inhibitor of apoptosis (XIAP) prevents islet allograft rejection. We constructed an adeno-associated virus expressing XIAP driven by the rat insulin promoter (dsAAV8-RIP-XIAP) for long-term beta-cell gene expression in vivo. Pancreatic delivery of dsAAV8-RIP-XIAP prevented autoimmune diabetes in 70% of non-obese diabetic (NOD) mice, associated with decreased insulitis. Islets from Balb/c mice transduced with dsAAV8-RIP-XIAP were protected following transplantation into streptozotocin (STZ)-diabetic Bl/6 recipients, associated with decreased graft infiltration. Interestingly, dsAAV8-RIP-XIAP transduction induced expression of lactate dehydrogenase (LDHA) and monocarboxylate transporter 1 (MCT1), two genes normally suppressed in beta cells and involved in production and release of lactate, a metabolite known to suppress local immune responses. Transduction of Balb/c islets with AAV8-RIP-LDHA-MCT1 tended to prolong allograft survival following transplant into STZ-diabetic Bl/6 recipients. These findings suggest that XIAP has therapeutic potential in autoimmune diabetes and raise the possibility that local lactate production may play a role in XIAP-mediated immunomodulation. Copyright © 2018. Published by Elsevier B.V.

Juvenile hormone and insulin suppress lipolysis between periods of lactation during tsetse fly pregnancy

PubMed Central

Michalkova, Veronika; Mireji, Paul; Attardo, Geoffrey M.; Moulton, John K.; Wilson, Thomas G.; Aksoy, Serap

2014-01-01

Tsetse flies are viviparous insects that nurture a single intrauterine progeny per gonotrophic cycle. The developing larva is nourished by the lipid-rich, milk-like secretions from a modified female accessory gland (milk gland). An essential feature of the lactation process involves lipid mobilization for incorporation into the milk. In this study, we examined roles for juvenile hormone (JH) and insulin/IGF-like (IIS) signaling pathways during tsetse pregnancy. In particular, we examined the roles for these pathways in regulating lipid homeostasis during transitions between non-lactating (dry) and lactating periods. The dry period occurs over the course of oogenesis and embryogenesis, while the lactation period spans intrauterine larvigenesis. Genes involved in the JH and IIS pathways were upregulated during dry periods, correlating with lipid accumulation between bouts of lactation. RNAi suppression of Forkhead Box Sub Group O (FOXO) expression impaired lipolysis during tsetse lactation and reduced fecundity. Similar reduction of the JH receptor Methoprene tolerant (Met), but not its paralog germ cell expressed (gce), reduced lipid accumulation during dry periods, indicating functional divergence between Met and gce during tsetse reproduction. Reduced lipid levels following Met knockdown led to impaired fecundity due to inadequate fat reserves at the initiation of milk production. Both the application of the JH analog (JHA) methoprene and injection of insulin into lactating females increased stored lipids by suppressing lipolysis and reduced transcripts of lactation-specific genes, leading to elevated rates of larval abortion. To our knowledge, this study is the first to address the molecular physiology of JH and IIS in a viviparous insect, and specifically to provide a role for JH signaling through Met in the regulation of lipid metabolism. PMID:23499946

Real-time measurement of hyperpolarized lactate production and efflux as a biomarker of tumor aggressiveness in an MR compatible 3D cell culture bioreactor.

PubMed

Sriram, Renuka; Van Criekinge, Mark; Hansen, Ailin; Wang, Zhen J; Vigneron, Daniel B; Wilson, David M; Keshari, Kayvan R; Kurhanewicz, John

2015-09-01

We have developed a 3D cell/tissue culture bioreactor compatible with hyperpolarized (HP) (13)C MR and interrogated HP [1-(13)C]lactate production and efflux in human renal cell carcinoma (RCC) cells. This platform is capable of resolving intracellular and extracellular HP lactate pools, allowing the kinetic measurement of lactate production and efflux in the context of cancer aggressiveness and response to therapy. HP (13)C MR studies were performed on three immortalized human renal cell lines: HK2, a normal renal proximal tubule cell line from which a majority of RCCs arise, UMRC6, a cell line derived from a localized RCC, and UOK262, an aggressive and metastatic RCC. The intra- (Lacin ) and extracellular (Lacex ) HP lactate signals were robustly resolved in dynamic (13)C spectra of the cell lines due to a very small but reproducible chemical shift difference (0.031 ± 0.0005 ppm). Following HP [1-(13)C]pyruvate delivery, the ratio of HP Lacin /Lacex was significantly lower for UOK262 cells compared with both UMRC6 and HK2 cells due to a significant (p < 0.05) increase in the Lacex pool size. Lacin /Lacex correlated with the MCT4 mRNA expression of the cell lines, and inhibition of MCT4 transport using DIDS resulted in a significant reduction in the HP Lacex pool size. The extension of these studies to living patient-derived RCC tissue slices using HP [1,2-(13)C2]pyruvate demonstrated a similarly split lactate doublet with a high Lacex pool fraction; in contrast, only a single NMR resonance is noted for HP [5-(13)C]glutamate, consistent with intracellular localization. These studies support the importance of lactate efflux as a biomarker of cancer aggressiveness and metastatic potential, and the utility of the MR compatible 3D cell/tissue culture bioreactor to study not only cellular metabolism but also transport. Additionally, this platform offers a sophisticated way to follow therapeutic interventions and screen novel therapies that target lactate export. Copyright © 2015 John Wiley & Sons, Ltd.

Allogeneic killing by earthworm effector cells.

PubMed

Suzuki, M M; Cooper, E L

1995-01-01

We observed spontaneous allogeneic cytotoxicity by coelomocytes (Lumbricus terrestris) using three assays: trypan blue, lactate dehydrogenase release and chromium-51 release. Cell-cell contact may not be essential to effect cytotoxicity, since killing of allogeneic cells occurred in pooled allogeneic coelomic fluid derived from worms raised in two different geographic locales. We observed no significant spontaneous cytotoxicity against autogeneic target coelomocytes haptenated with 2,4,6-trinitrobenzene sulfonic acid; however, coelomocytes effected significant spontaneous cytotoxicity against haptenated allogeneic targets. These results support the view that earthworm coelomocytes can act as effector cells that can specifically kill nonself target cells.

C-reactive protein is differentially modulated by co-existing infections, vitamin deficiencies and maternal factors in pregnant and lactating indigenous Panamanian women.

PubMed

González-Fernández, Doris; Pons, Emérita Del Carmen; Rueda, Delfina; Sinisterra, Odalis Teresa; Murillo, Enrique; Scott, Marilyn E; Koski, Kristine G

2017-06-02

The usefulness of C-reactive protein (CRP) as a non-specific marker of inflammation during pregnancy and lactation is unclear in impoverished populations where co-existing infections and vitamin deficiencies are common. This cross-sectional study in Panama recruited 120 pregnant and 99 lactating Ngäbe-Buglé women from 14 communities in rural Panama. Obstetric history, indoor wood smoke exposure, fieldwork, BMI, vitamins A, B 12 , D, and folic acid, and inflammation markers (CRP, neutrophil/lymphocyte ratio (NLR), plateletcrit and cytokines) were measured. Multiple regressions explored both associations of CRP with other inflammatory markers and associations of CRP and elevated CRP based on trimester-specific cut-offs with maternal factors, infections and vitamin deficiencies. CRP was higher in pregnancy (51.4 ± 4.7 nmol/L) than lactation (27.8 ± 3.5 nmol/L) and was elevated above trimester specific cut-offs in 21% of pregnant and 30% of lactating women. Vitamin deficiencies were common (vitamin A 29.6%; vitamin D 68.5%; vitamin B 12 68%; folic acid 25.5%) and over 50% of women had two or more concurrent deficiencies as well as multiple infections. Multiple regression models highlighted differences in variables associated with CRP between pregnancy and lactation. In pregnancy, CRP was positively associated with greater indoor wood smoke exposure, caries and hookworm and negatively associated with Ascaris and vaginal Lactobacillus and Bacteroides/Gardnerella scores. Consistent with this, greater wood smoke exposure, caries as well as higher diplococcal infection score increased the odds of trimester-elevated CRP concentrations whereas longer gestational age lowered the likelihood of a trimester-elevated CRP. During lactation, folic acid deficiency was associated with higher CRP whereas parity, number of eosinophils and Mobiluncus score were associated with lower CRP. Also, a higher BMI and Trichomonas vaginalis score increased the likelihood of an elevated CRP whereas higher parity and number of eosinophils were associated with lower likelihood of an elevated CRP. Infections both raise and lower CRP concentrations in pregnant and lactating mothers. Only folic acid deficiency during lactation was associated with higher CRP concentrations. Caution is required when interpreting CRP concentrations in pregnant and lactating women who have co-existing nutrient deficiencies and multiple infections.

Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys.

PubMed

Wang, Bincheng; Wu, Di; Dornbos Iii, David; Shi, Jingfei; Ma, Yanhui; Zhang, Mo; Liu, Yumei; Chen, Jian; Ding, Yuchuan; Luo, Yinghao; Ji, Xunming

2016-06-01

Hypothermia has shown promise as a neuroprotective strategy for stroke. The use of whole body hypothermia has limited clinical utility due to many severe side effects. Selective brain cooling, or local brain hypothermia, has been previously proposed as an alternative treatment strategy. This study investigated the safety, feasibility, and efficacy of selective brain hypothermia induced by local infusion of ice-cold lactated Ringer's solution in rhesus monkeys. Eight male rhesus monkeys were used in this study. Brain temperature in the territory supplied by middle cerebral artery (MCA) was reduced by infusing 100 mL of ice-cold (0 °C) lactated Ringer's solution over 20 min via a micro-catheter placed in the proximal MCA (n = 4). Vital signs and the temperature of the brain and rectum were monitored before and after infusion. Transcranial Doppler, Magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) were used to evaluate cerebral blood flow, cerebrovascular reactivity (CVR), cerebral edema, and vasospasm. Another cohort of rhesus monkeys (n = 4) were used as systemic cooling controls. Oxygen saturation, blood pressure, heart rate, and hematologic analysis of the two groups remained within the normal range after infusion. Mild cerebral hypothermia (<35 °C) was achieved in 10 min (0.3 °C/min) and was maintained for 20 min in local cortex and striatum following local infusion. The average lowest cerebral temperature in the locally cooled animals was 33.9 ± 0.3 °C in the striatum following 20-min infusion. This was not observed in animals cooled by systemic infusion. The decreases in the rectal temperature for local and systemic infusion were 0.5 ± 0.2 °C and 0.5 ± 0.3 °C, respectively. Selective brain cooling did not cause any cerebral edema as determined by MRI or vasospasm in the perfused vessel based on DSA. Selective cerebral hypothermia did not significantly alter CVR. Local infusion of ice-cold lactated Ringer's solution via micro-catheter is a safe and effective method for selective cerebral hypothermia. This cooling method could potentially be developed as a new treatment in acute ischemic stroke.

Nutrient intake and balancing among female Colobus angolensis palliatus inhabiting structurally distinct forest areas: Effects of group, season, and reproductive state.

PubMed

Dunham, Noah T; Rodriguez-Saona, Luis E

2018-06-08

Understanding intraspecific behavioral and dietary variation is critical for assessing primate populations' abilities to persist in habitats characterized by increasing anthropogenic disturbances. While it is evident that some species exhibit considerable dietary flexibility (in terms of species-specific plant parts) in relation to habitat disturbance, it is unclear if primates are characterized by similar variation and flexibility regarding nutrient intake. This study examined the effects of group, season, and reproductive state on nutrient intake and balancing in adult female Colobus angolensis palliatus in the Diani Forest, Kenya. During July 2014 to December 2015, estimates of nutrient intake were recorded for eight females from three groups inhabiting structurally and ecologically distinct forest areas differing in tree species composition and density. There were differences in metabolizable energy (ME) and macronutrient intakes among groups, seasons, and reproductive states. Most notably, females inhabiting one of the more disturbed forest areas consumed less ME and macronutrients compared to females in the more intact forest area. Contrary to prediction, females in early lactation consumed significantly less ME and macronutrients compared to non-lactating and late lactation females. Despite differences in macronutrient intake, the relative contribution of macronutrients to ME were generally more conservative among groups, seasons, and reproductive states. Average daily intake ratios of non-protein energy to available protein ranged from approximately 3.5:1-4.3:1 among groups. These results indicate that female C. a. palliatus demonstrate a consistent nutrient balancing strategy despite significant intergroup differences in consumption of species-specific plant parts. Data from additional colobine species inhabiting different forest types are required to assess the extent to which nutrient balancing is constrained by phylogeny or is more flexible to local ecological conditions. © 2018 Wiley Periodicals, Inc.

Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual

PubMed Central

Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward

2013-01-01

To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944

Early Life Exposure to Undernutrition Induces ER Stress, Apoptosis, and Reduced Vascularization in Ovaries of Adult Rat Offspring1

PubMed Central

Chan, Kaitlyn A.; Bernal, Angelica B.; Vickers, Mark H.; Gohir, Wajiha; Petrik, Jim J.; Sloboda, Deborah M.

2015-01-01

ABSTRACT Maternal nutritional restriction has been shown to induce impairments in a number of organ systems including the ovary. We have previously shown that maternal undernutrition induces fetal growth restriction and low birth weight, and results in an offspring ovarian phenotype characteristic of premature ovarian aging with reduced ovarian reserve. In the present study, we set out to investigate the underlying mechanisms that lead offspring of undernourished mothers to premature ovarian aging. Pregnant dams were randomized to 1) a standard diet throughout pregnancy and lactation (control), 2) a calorie-restricted (50% of control) diet during pregnancy, 3) a calorie-restricted (50% of control) diet during pregnancy and lactation, or 4) a calorie-restricted (50% of control) diet during lactation alone. The present study shows that early life undernutrition-induced reduction of adult ovarian follicles may be mediated by increased ovarian endoplasmic reticulum stress in a manner that increased follicular apoptosis but not autophagy. These changes were associated with a loss of ovarian vessel density and are consistent with an accelerated ovarian aging phenotype. Whether these changes are mediated specifically by a reduction in the local antioxidant environment is unclear, although our data suggest the possibility that ovarian melatonin may play a part in early life nutritional undernutrition and impaired offspring folliculogenesis. PMID:25810471

Aging-associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte-to-neuron lactate shuttle.

PubMed

Drulis-Fajdasz, Dominika; Gizak, Agnieszka; Wójtowicz, Tomasz; Wiśniewski, Jacek R; Rakus, Dariusz

2018-03-01

Lactate derived from astrocytic glycogen has been shown to support memory formation in hippocampi of young animals, inhibiting it in old animals. Here we show, using quantitative mass spectrometry-based proteomics, immunofluorescence, and qPCR that aging is associated with an increase of glycogen metabolism enzymes concentration and shift in their localization from astrocytes to neurons. These changes are accompanied with reorganization of hippocampal energy metabolism which is manifested by elevated capacity of aging neurons to oxidize glucose in glycolysis and mitochondria, and decreased ability for fatty acids utilization. Our observations suggest that astrocyte-to-neuron lactate shuttle may operate in young hippocampi, however, during aging neurons become independent on astrocytic lactate and the metabolic crosstalk between the brain's cells is disrupted. © 2018 The Authors GLIA Published by Wiley Periodicals, Inc.

Diammonium phosphate stimulates transcription of L-lactate dehydrogenase leading to increased L-lactate production in the thermotolerant Bacillus coagulans strain.

PubMed

Sun, Lifan; Li, Yanfeng; Wang, Limin; Wang, Yanping; Yu, Bo

2016-08-01

Exploration of cost-effective fermentation substrates for efficient lactate production is an important economic objective. Although some organic nitrogen sources are also cheaper, inorganic nitrogen salts for lactate fermentation have additional advantages in facilitating downstream procedures and significantly improving the commercial competitiveness of lactate production. In this study, we first established an application of diammonium phosphate to replace yeast extract with a reduced 90 % nitrogen cost for a thermotolerant Bacillus coagulans strain. In vivo enzymatic and transcriptional analyses demonstrated that diammonium phosphate stimulates the gene expression of L-lactate dehydrogenase, thus providing higher specific enzyme activity in vivo and increasing L-lactic acid production. This new information provides a foundation for establishing a cost-effective process for polymer-grade L-lactic acid production in an industrial setting.

Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate.

PubMed

Halestrap, A P; Denton, R M

1974-02-01

alpha-Cyano-4-hydroxycinnamate greatly inhibits the transport of pyruvate but not that of acetate or butyrate in liver mitochondria and erythrocytes. In the latter, lactate uptake is also inhibited. It is concluded that a specific carrier is involved in membrane transport of pyruvate and that the plasma-membrane carrier may also be involved in lactate transport.

Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate.

PubMed

Queirós, Odília; Preto, Ana; Pacheco, António; Pinheiro, Céline; Azevedo-Silva, João; Moreira, Roxana; Pedro, Madalena; Ko, Young H; Pedersen, Peter L; Baltazar, Fátima; Casal, Margarida

2012-02-01

Most malignant tumors exhibit the Warburg effect, which consists in increased glycolysis rates with production of lactate, even in the presence of oxygen. Monocarboxylate transporters (MCTs), maintain these glycolytic rates, by mediating the influx and/or efflux of lactate and are overexpressed in several cancer cell types. The lactate and pyruvate analogue 3-bromopyruvate (3-BP) is an inhibitor of the energy metabolism, which has been proposed as a specific antitumor agent. In the present study, we aimed at determining the effect of 3-BP in breast cancer cells and evaluated the putative role of MCTs on this effect. Our results showed that the three breast cancer cell lines used presented different sensitivities to 3-BP: ZR-75-1 ER (+)>MCF-7 ER (+)>SK-BR-3 ER (-). We also demonstrated that 3-BP reduced lactate production, induced cell morphological alterations and increased apoptosis. The effect of 3-BP appears to be cytotoxic rather than cytostatic, as a continued decrease in cell viability was observed after removal of 3-BP. We showed that pre-incubation with butyrate enhanced significantly 3-BP cytotoxicity, especially in the most resistant breast cancer cell line, SK-BR-3. We observed that butyrate treatment induced localization of MCT1 in the plasma membrane as well as overexpression of MCT4 and its chaperone CD147. Our results thus indicate that butyrate pre-treatment potentiates the effect of 3-BP, most probably by increasing the rates of 3-BP transport through MCT1/4. This study supports the potential use of butyrate as adjuvant of 3-BP in the treatment of breast cancer resistant cells, namely ER (-).

Biochemical identification of the mallard, Anas platyrhynchos, and black duck, A. rubripes

USGS Publications Warehouse

Morgan, R.P.; Noe, L.A.; Henny, C.J.

1976-01-01

1. Eleven tissue systems from mallards and black ducks were examined for soluble proteins, lactate dehydrogenases and non-specific esterases through discontinuous polyacrylamide techniques.2. Biochemical relationships between the black duck and mallard are extremely similar.3. Hemoglobins and lactate dehydrogenase appear to be common in electrophoretic mobility between the two species.4. Approximately 89% of the soluble proteins and 58% of the non-specific esterases are common among the two species, indicating both biochemical similarity at the genus level and species-specificity.

The effect of lactational mastitis on the macronutrient content of breast milk.

PubMed

Say, Birgul; Dizdar, Evrim Alyamaç; Degirmencioglu, Halil; Uras, Nurdan; Sari, Fatma Nur; Oguz, Suna; Canpolat, Fuat Emre

2016-07-01

Mastitis in lactating mothers reduces milk production and alters the cellular composition of milk. Changes occurring in the mammary gland during the inflammatory response are believed to increase the permeability of the blood-milk barrier. This study examined the effect of mastitis during lactation on the macronutrient content of breast milk. The study was conducted at Zekai Tahir Burak Maternity Teaching Hospital. Transitional breast milk samples were obtained from term lactating mothers with or without mastitis. Milk protein, fat, carbohydrate, and energy levels were measured using a mid-infrared human milk analyzer. The study recruited 30 term lactating mothers: 15 mothers diagnosed with mastitis and 15 healthy mothers. The characteristics of the mothers in both groups were similar. Fat, carbohydrate, and energy levels were statistically lower in the milk samples of mothers with mastitis compared with the mothers without mastitis. Lactational mastitis was associated with lower breast milk fat, carbohydrate, and energy levels. The local inflammatory response induced by cytokines and increased blood-milk barrier permeability might account for the changes in the fat, carbohydrate, and energy levels of human milk. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.

PubMed

Otero-Rodiño, Cristina; Librán-Pérez, Marta; Velasco, Cristina; Álvarez-Otero, Rosa; López-Patiño, Marcos A; Míguez, Jesús M; Soengas, José L

2015-12-01

There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.

Plasma lactate concentration as a predictor of gastric necrosis and survival among dogs with gastric dilatation-volvulus: 102 cases (1995-1998).

PubMed

de Papp, E; Drobatz, K J; Hughes, D

1999-07-01

To determine relationships between plasma lactate concentration and gastric necrosis and between plasma lactate concentration and outcome for dogs with gastric dilatation-volvulus. Retrospective study. 102 dogs. Information on signalment, history, plasma lactate concentration, medical and surgical treatment, cost of hospitalization, and outcome was retrieved from medical records. 69 of 70 (99%) dogs with plasma lactate concentration < 6.0 mmol/L survived, compared with 18 of 31 (58%) dogs with plasma lactate concentration > 6.0 mmol/L (1 dog euthanatized for economic reasons was not included). Gastric necrosis was identified in 38 (37%) dogs. Median plasma lactate concentration in dogs with gastric necrosis (6.6 mmol/L) was significantly higher than concentration in dogs without gastric necrosis (3.3 mmol/L). Specificity and sensitivity of using plasma lactate concentration (with a cutoff of 6.0 mmol/L) to predict which dogs had gastric necrosis were 88 and 61%, respectively. Sixty-two of 63 (98%) dogs without gastric necrosis survived, compared with 25 of 38 (66%) dogs with gastric necrosis. Preoperative plasma lactate concentration was a good predictor of gastric necrosis and outcome for dogs with GDV. Preoperative measurement of plasma lactate concentration may assist in determining prognosis of dogs with GDV.

Does Insulin Explain the Relation between Maternal Obesity and Poor Lactation Outcomes? An Overview of the Literature1234

PubMed Central

2016-01-01

It is well established that obese women are at increased risk of delayed lactogenesis and short breastfeeding duration, but the underlying causal contributors remain unclear. This review summarizes the literature examining the role of insulin in lactation outcomes. Maternal obesity is a strong risk factor for insulin resistance and prediabetes, but until recently a direct role for insulin in milk production had not been elucidated. Over the past 6 y, studies in both animal models and humans have shown insulin-sensitive gene expression to be dramatically upregulated specifically during the lactation cycle. Insulin is now considered to play a direct role in lactation, including essential roles in secretory differentiation, secretory activation, and mature milk production. At the same time, emerging clinical research suggests an important association between suboptimal glucose tolerance and lactation difficulty. To develop effective interventions to support lactation success in obese women further research is needed to identify how, when, and for whom maternal insulin secretion and sensitivity affect lactation ability. PMID:26980825

Predicting the Occurrence of Hypotension in Stable Patients With Nonvariceal Upper Gastrointestinal Bleeding: Point-of-Care Lactate Testing.

PubMed

Ko, Byuk Sung; Kim, Won Young; Ryoo, Seung Mok; Ahn, Shin; Sohn, Chang Hwan; Seo, Dong Woo; Lee, Yoon-Seon; Lim, Kyoung Soo; Jung, Hwoon-Yong

2015-11-01

It is difficult to assess risk in normotensive patients with upper gastrointestinal bleeding. The aim of this study was to evaluate whether the initial lactate value can predict the in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. Retrospective, observational, single-center study. Emergency department of a tertiary-care, university-affiliated hospital during a 5-year period. Medical records of 3,489 patients with acute upper gastrointestinal bleeding who were normotensive at presentation to the emergency department. We analyzed the ability of point-of-care testing of lactate at emergency department admission to predict hypotension development (defined as systolic blood pressure <90 mm Hg) within 24 hours after emergency department admission. None. Of the 1,003 patients with acute nonvariceal upper gastrointestinal bleeding, 157 patients experienced hypotension within 24 hours. Lactate was independently associated with hypotension development (odds ratio, 1.6; 95% CI, 1.4-1.7), and the risk of hypotension significantly increased as the lactate increased from 2.5-4.9 mmol/L (odds ratio, 2.2) to 5.0-7.4 mmol/L (odds ratio, 4.0) and to greater than or equal to 7.5 mmol/L (odds ratio, 39.2) (p<0.001). Lactate elevation (≥2.5 mmol/L) was associated with 90% specificity and an 84% negative predictive value for hypotension development. When the lactate levels were greater than 5.0 mmol/L, the specificity and negative predictive value increased to 98% and 87%, respectively. Point-of-care testing of lactate can predict in-hospital occurrence of hypotension in stable patients with acute nonvariceal upper gastrointestinal bleeding. However, subsequently, prospective validate research will be required to clarify this.

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

PubMed Central

Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

2016-01-01

Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

"Why Even Bother; They Are Not Going to Do It?" The Structural Roots of Racism and Discrimination in Lactation Care.

PubMed

Thomas, Erin V

2018-03-01

Through semi-structured interviews with 36 International Board Certified Lactation Consultants (IBCLCs) who assist mothers with breastfeeding, this study takes a systematic look at breastfeeding disparities. Specifically, this study documents race-based discrimination against patients in the course of lactation care and links the implicit bias literature to breastfeeding disparities. IBCLCs report instances of race-based discrimination against patients such as unequal care provided to patients of color and overt racist remarks said in front of or behind patient's backs. This study connects patient discrimination in lactation to institutional inequality and offers suggestions to address these inequities.

Bayesian validation of a serum and milk ELISA for antibodies against Mycobacterium avium subspecies paratuberculosis in Greek dairy goats across lactation.

PubMed

Angelidou, E; Kostoulas, P; Leontides, L

2014-02-01

We validated a commercial (Idexx Pourquier, Montpellier, France) serum and milk indirect ELISA that detects antibodies against Mycobacterium avium ssp. paratuberculosis (MAP) in Greek dairy goats. Each goat was sampled 4 times, starting from kidding and covering early, mid, and late lactation. A total of 1,268 paired milk (or colostrum) and serum samples were collected during the 7-mo lactation period. Bayesian latent class models, which allow for the continuous interpretation of test results, were used to derive the distribution of the serum and milk ELISA response for healthy and MAP-infected individuals at each lactation stage. Both serum and milk ELISA, in all lactation stages, had average and similar overall discriminatory ability as measured by the area under the curve (AUC). For each test, the smallest overlap between the distribution of the healthy and MAP-infected does was in late lactation. At this stage, the AUC was 0.89 (95% credible interval: 0.70; 0.98) and 0.92 (0.74; 0.99) for the milk and serum ELISA, respectively. Both tests had comparable sensitivities and specificities at the recommended cutoffs across lactation. Lowering the cutoffs led to an increase in sensitivity without serious loss in specificity. In conclusion, the milk ELISA was as accurate as the serum ELISA. Therefore, it could serve as the diagnostic tool of choice, especially during the implementation of MAP control programs that require frequent testing, because milk sampling is a noninvasive, rapid, and easy process. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Increased titer and reduced lactate accumulation in recombinant retrovirus production through the down-regulation of HIF1 and PDK.

PubMed

Rodrigues, A F; Guerreiro, M R; Formas-Oliveira, A S; Fernandes, P; Blechert, A-K; Genzel, Y; Alves, P M; Hu, W S; Coroadinha, A S

2016-01-01

Many mammalian cell lines used in the manufacturing of biopharmaceuticals exhibit high glycolytic flux predominantly channeled to the production of lactate. The accumulation of lactate in culture reduces cell viability and may also decrease product quality. In this work, we engineered a HEK 293 derived cell line producing a recombinant gene therapy retroviral vector, by down-regulating hypoxia inducible factor 1 (HIF1) and pyruvate dehydrogenase kinase (PDK). Specific productivity of infectious viral titers could be increased more than 20-fold for single gene knock-down (HIF1 or PDK) and more than 30-fold under combined down-regulation. Lactate production was reduced up to 4-fold. However, the reduction in lactate production, alone, was not sufficient to enhance the titer: high-titer clones also showed significant enrollment of metabolic routes not related to lactate production. Transcriptome analysis indicated activation of biological amines metabolism, detoxification routes, including glutathione metabolism, pentose phosphate pathway, glycogen biosynthesis and amino acid catabolism. The latter were validated by enzyme activity assays and metabolite profiling, respectively. High-titer clones also presented substantially increased transcript levels of the viral genes expression cassettes. The results herein presented demonstrate the impact of HIF1 and PDK down-regulation on the production performance of a mammalian cell line, reporting one of the highest fold-increase in specific productivity of infectious virus titers achieved by metabolic engineering. They additionally highlight the contribution of secondary pathways, beyond those related to lactate production, that can be also explored to pursue improved metabolic status favoring a high-producing phenotype. © 2015 Wiley Periodicals, Inc.

Associations of insulin resistance later in lactation on fertility of dairy cows.

PubMed

Baruselli, P S; Vieira, L M; Sá Filho, M F; Mingoti, R D; Ferreira, R M; Chiaratti, M R; Oliveira, L H; Sales, J N; Sartori, R

2016-07-01

The challenge of getting dairy cows pregnant during early lactation is a well-described, worldwide problem. However, specifically in farms with poor reproductive, nutritional, and environmental conditions/management, a low pregnancy rate during early lactation is followed inevitably by an increased number of nonpregnant cows after 150 days in milk, with even more difficulties to achieve pregnancy. Therefore, several studies were designed to understand and develop strategies to mitigate reduced fertility of cows during late lactation. Experiments were performed under tropical regions to determine metabolic status during lactation and association of stage of lactation on oocyte quality and fertility. Lactating cows with extended days not pregnant (e.g.,>150 days in milk) often had systemic metabolic alterations, including development of peripheral insulin resistance and various oocyte alterations, including reduced expression of genes encoding glucose transport proteins, reduced amounts of mtDNA, increased expression of mitochondria-related genes, and increased expression of apoptosis-related genes. Additionally, in vitro embryo production and pregnancy per AI were lower in late- versus early-lactation cows in some but not all studies. Notwithstanding, when a normal embryo was transferred to a cow in late lactation, the pregnancy per transfer was reasonable, reinforcing the assertion that fertility problems in late-lactation cows may be associated with oocyte quality, fertilization, and/or failure of early embryo development. In conclusion, insulin resistance may reduce oocyte competence and consequently fertility in late-lactation dairy cows. Copyright © 2016 Elsevier Inc. All rights reserved.

Temperature- and pH-dependent effect of lactate on in vitro redox stability of red meat myoglobins.

PubMed

Nair, M N; Suman, S P; Li, S; Ramanathan, R; Mancini, R A

2014-01-01

Our objective was to evaluate the influence of lactate on in vitro redox stability and thermostability of beef, horse, pork, and sheep myoglobins. Lactate (200 mM) had no effect (P>0.05) on redox stability at physiological (pH7.4, 37°C) and meat (pH 5.6, 4°C) conditions. However, lactate increased (P<0.05) metmyoglobin formation at a condition simulating stressed live skeletal muscle (pH 6.5, 37°C). The redox stability of myoglobins at stressed live skeletal muscle and meat conditions was species-specific (P<0.05). Myoglobin thermostability at 71°C was lower (P<0.05) in the presence of lactate compared with controls and was influenced (P<0.05) by species. The results of the present study indicate that the effects of lactate on myoglobin are temperature and pH dependent. The observed lack of influence of lactate on myoglobin redox stability at meat condition suggests that the color stability of lactate-enhanced fresh meat is not due to direct interactions between the ingredient and the heme protein. © 2013.

Lactation-Induced Changes in the Volume of Osteocyte Lacunar-Canalicular Space Alter Mechanical Properties in Cortical Bone Tissue.

PubMed

Kaya, Serra; Basta-Pljakic, Jelena; Seref-Ferlengez, Zeynep; Majeska, Robert J; Cardoso, Luis; Bromage, Timothy G; Zhang, Qihong; Flach, Carol R; Mendelsohn, Richard; Yakar, Shoshana; Fritton, Susannah P; Schaffler, Mitchell B

2017-04-01

Osteocytes can remove and remodel small amounts of their surrounding bone matrix through osteocytic osteolysis, which results in increased volume occupied by lacunar and canalicular space (LCS). It is well established that cortical bone stiffness and strength are strongly and inversely correlated with vascular porosity, but whether changes in LCS volume caused by osteocytic osteolysis are large enough to affect bone mechanical properties is not known. In the current studies we tested the hypotheses that (1) lactation and postlactation recovery in mice alter the elastic modulus of bone tissue, and (2) such local changes in mechanical properties are related predominantly to alterations in lacunar and canalicular volume rather than bone matrix composition. Mechanical testing was performed using microindentation to measure modulus in regions containing solely osteocytes and no vascular porosity. Lactation caused a significant (∼13%) reduction in bone tissue-level elastic modulus (p < 0.001). After 1 week postweaning (recovery), bone modulus levels returned to control levels and did not change further after 4 weeks of recovery. LCS porosity tracked inversely with changes in cortical bone modulus. Lacunar and canalicular void space increased 7% and 15% with lactation, respectively (p < 0.05), then returned to control levels at 1 week after weaning. Neither bone mineralization (assessed by high-resolution backscattered scanning electron microscopy) nor mineral/matrix ratio or crystallinity (assessed by Raman microspectroscopy) changed with lactation. Thus, changes in bone mechanical properties induced by lactation and recovery appear to depend predominantly on changes in osteocyte LCS dimensions. Moreover, this study demonstrates that tissue-level cortical bone mechanical properties are rapidly and reversibly modulated by osteocytes in response to physiological challenge. These data point to a hitherto unappreciated role for osteocytes in modulating and maintaining local bone mechanical properties. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Peripheral Serotonin Regulates Maternal Calcium Trafficking in Mammary Epithelial Cells during Lactation in Mice

PubMed Central

Laporta, Jimena; Keil, Kimberly P.; Vezina, Chad M.; Hernandez, Laura L.

2014-01-01

Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation. PMID:25299122

RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis

PubMed Central

Huang, Peng; Chang, Shi; Jiang, Xiaolin; Su, Juan; Dong, Chao; Liu, Xu; Yuan, Zhengtai; Zhang, Zhipeng; Liao, Huijun

2015-01-01

A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma. PMID:25755717

Does Insulin Explain the Relation between Maternal Obesity and Poor Lactation Outcomes? An Overview of the Literature.

PubMed

Nommsen-Rivers, Laurie A

2016-03-01

It is well established that obese women are at increased risk of delayed lactogenesis and short breastfeeding duration, but the underlying causal contributors remain unclear. This review summarizes the literature examining the role of insulin in lactation outcomes. Maternal obesity is a strong risk factor for insulin resistance and prediabetes, but until recently a direct role for insulin in milk production had not been elucidated. Over the past 6 y, studies in both animal models and humans have shown insulin-sensitive gene expression to be dramatically upregulated specifically during the lactation cycle. Insulin is now considered to play a direct role in lactation, including essential roles in secretory differentiation, secretory activation, and mature milk production. At the same time, emerging clinical research suggests an important association between suboptimal glucose tolerance and lactation difficulty. To develop effective interventions to support lactation success in obese women further research is needed to identify how, when, and for whom maternal insulin secretion and sensitivity affect lactation ability. © 2016 American Society for Nutrition.

Fueling and imaging brain activation

PubMed Central

Dienel, Gerald A

2012-01-01

Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

Physiological analysis to quantify training load in badminton.

PubMed Central

Majumdar, P; Khanna, G L; Malik, V; Sachdeva, S; Arif, M; Mandal, M

1997-01-01

OBJECTIVE: To estimate the training load of specific on court training regimens based on the magnitude of variation of heart rate-lactate response during specific training and to determine the magnitude of variation of biochemical parameters (urea, uric acid, and creatine phosphokinase (CPK)) 12 hours after the specific training programme so as to assess training stress. METHODS: The study was conducted on six national male badminton players. Maximum oxygen consumption (VO2), ventilation (VE), heart rate, and respiratory quotient were measured by a protocol of graded treadmill exercise. Twelve training sessions and 35 singles matches were analysed. Heart rate and blood lactate were monitored during technical training routines and match play. Fasting blood samples collected on two occasions--that is, during off season and 12 hours after specific training--were analysed for serum urea, uric acid, and CPK. RESULTS: Analysis of the on court training regimens showed lactate values of 8-10.5 mmol/l in different phases. The percentage of maximum heart rate ranged from 82% to 100%. Urea, uric acid, and CPK activity showed significant changes from (mean (SD)) 4.93 (0.75) mmol/l to 5.49 (0.84) mmol/l, 0.23 (0.04) to 0.33 (0.06) mmol/l, and 312 (211.8) to 363 (216.4) IU/l respectively. CONCLUSION: Maximum lactate reported in the literature ranges from 3-6 mmol/l. Comparatively high lactate values and high percentage of maximum heart rate found in on court training show a considerable stress on muscular and cardiovascular system. The training load needs appropriate monitoring to avoid over-training. Workouts that are too intensive may interfere with coordination, a factor that is important in sports requiring highly technical skill such as badminton. PMID:9429015

Molecular cloning, characterization, and immunolocalization of two lactate dehydrogenase homologous genes from Taenia solium.

PubMed

Du, Wuying; Hu, Fengyu; Yang, Yabo; Hu, Dong; Hu, Xuchu; Yu, Xinbing; Xu, Jin; Dai, Jialin; Liao, Xinjiang; Huang, Jiang

2011-09-01

Two novel genes encoding lactate dehydrogenase A (LDHA) and B (LDHB) homologues, respectively, were identified from the cDNA libraries of adult Taenia solium (T. solium). The two deduced amino acid sequences both show more than 50% identity to the homologues for Danio rerio, Xenopus laevis, Schistosoma japonicum, Sus scrofa, Homo sapiens, et al. The identity of the amino acid sequence between TsLDHA and TsLDHB is 57.4%, and that of the nucleotide sequence is 61.5%. Recombinant TsLDHA homologue (rTsLDHA) and TsLDHB homologue (rTsLDHB) were expressed in Escherichia coli BL21/DE3 and purified. Though there were some differences in the sequence, the two LDH isozyme homologues show similarity in the conserved LDH domain, topological structure, primary immunological traits, localization on the tegument of T. solium adult, and partial physicochemical properties. The linear B-cell epitope analysis of TsLDHA and TsLDHB discovered a TsLDHA specific epitope. The purified rTsLDHA and rTsLDHB could be recognized by rat immuno-sera, serum from swine, or a patient infected with T. solium, respectively, but Western blot analysis showed cross-reactions, not only between these two LDH members but also with other common human tapeworms or helminths. The results suggested that the two LDH homologues are similar in the characteristics of LDH family, and they are not specific antigens for immunodiagnosis.

Polarized lactate transporter activity and expression in the syncytiotrophoblast of the term human placenta.

PubMed

Settle, P; Mynett, K; Speake, P; Champion, E; Doughty, I M; Sibley, C P; D'Souza, S W; Glazier, J

2004-07-01

We investigated the polarization of l-lactate transport in human syncytiotrophoblast by measuring uptake of [(14)C] l-lactate by both microvillous (maternal-facing; MVM) and basal (fetal-facing; BM) plasma membranes. [(14)C] l-lactate uptake by MVM and BM was stimulated in the presence of an inwardly directed H(+)gradient, with a significantly higher uptake in MVM than in BM at initial rate (15.4+/-2.3 vs 5.6+/-0.6 pmol/mg protein/20 sec). Stereospecific inhibition was observed in MVM, with a higher affinity for l-lactate compared with d-lactate. In BM, there was no difference in the inhibition by these two stereoisomers. Inhibition of lactate uptake in both MVM and BM by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of monocarboxylate transporter (MCT) activity, indicated MCT-mediated mechanisms across both membranes. Kinetic modelling supported a two-transporter model as the best fit for both MVM and BM, the K(m)of the major component being 6.21 mm and 25.01 mm in MVM and BM respectively. Western blotting and immunolocalization examining the distribution of MCT1 and MCT4, showed that MCT expression was polarized, MCT1 being predominantly localized to BM and MCT4 showing greater abundance on MVM. CD147, a chaperone protein for MCT1 and MCT4, was equally expressed by both membranes. These studies demonstrate that the opposing plasma membranes of human syncytiotrophoblast are polarized with respect to both MCT activity and expression.

NH4+ triggers the release of astrocytic lactate via mitochondrial pyruvate shunting

PubMed Central

Lerchundi, Rodrigo; Fernández-Moncada, Ignacio; Contreras-Baeza, Yasna; Sotelo-Hitschfeld, Tamara; Mächler, Philipp; Wyss, Matthias T.; Stobart, Jillian; Baeza-Lehnert, Felipe; Alegría, Karin; Weber, Bruno; Barros, L. Felipe

2015-01-01

Neural activity is accompanied by a transient mismatch between local glucose and oxygen metabolism, a phenomenon of physiological and pathophysiological importance termed aerobic glycolysis. Previous studies have proposed glutamate and K+ as the neuronal signals that trigger aerobic glycolysis in astrocytes. Here we used a panel of genetically encoded FRET sensors in vitro and in vivo to investigate the participation of NH4+, a by-product of catabolism that is also released by active neurons. Astrocytes in mixed cortical cultures responded to physiological levels of NH4+ with an acute rise in cytosolic lactate followed by lactate release into the extracellular space, as detected by a lactate-sniffer. An acute increase in astrocytic lactate was also observed in acute hippocampal slices exposed to NH4+ and in the somatosensory cortex of anesthetized mice in response to i.v. NH4+. Unexpectedly, NH4+ had no effect on astrocytic glucose consumption. Parallel measurements showed simultaneous cytosolic pyruvate accumulation and NADH depletion, suggesting the involvement of mitochondria. An inhibitor-stop technique confirmed a strong inhibition of mitochondrial pyruvate uptake that can be explained by mitochondrial matrix acidification. These results show that physiological NH4+ diverts the flux of pyruvate from mitochondria to lactate production and release. Considering that NH4+ is produced stoichiometrically with glutamate during excitatory neurotransmission, we propose that NH4+ behaves as an intercellular signal and that pyruvate shunting contributes to aerobic lactate production by astrocytes. PMID:26286989

Lactate dilates cochlear capillaries via type V fibrocyte-vessel coupling signaled by nNOS.

PubMed

Dai, Min; Yang, Yue; Shi, Xiaorui

2011-10-01

Transduction of sound in the inner ear demands tight control over delivery of oxygen and glucose. However, the mechanisms underlying the control of regional blood flow are not yet fully understood. In this study, we report a novel local control mechanism that regulates cochlear blood flow to the stria vascularis, a high energy-consuming region of the inner ear. We found that extracellular lactate had a vasodilatory effect on the capillaries of the spiral ligament under both in vitro and in vivo conditions. The lactate, acting through monocarboxylate transporter 1 (MCT1), initiated neuronal nitric oxide (NO) synthase (nNOS) and catalyzed production of NO for the vasodilation. Blocking MCT1 with the MCT blocker, α-cyano-4-hydroxycinnamate (CHC), or a suppressing NO production with either the nonspecific inhibitor of NO synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), or either of two selective nNOS inhibitors, 3-bromo-7-nitroindazole or (4S)-N-(4-amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine (TFA), totally abolished the lactate-induced vasodilation. Pretreatment with the selective endothelial NO synthase inhibitor, L-N(5)-(1-iminoethyl)ornithine (L-NIO), eliminated the inhibition of lactate-induced vessel dilation. With immunohistochemical labeling, we found the expression of MCT1 and nNOS in capillary-coupled type V fibrocytes. The data suggest that type V fibrocytes are the source of the lactate-induced NO. Cochlear microvessel tone, regulated by lactate, is mediated by an NO-signaled coupling of fibrocytes and capillaries.

NH4(+) triggers the release of astrocytic lactate via mitochondrial pyruvate shunting.

PubMed

Lerchundi, Rodrigo; Fernández-Moncada, Ignacio; Contreras-Baeza, Yasna; Sotelo-Hitschfeld, Tamara; Mächler, Philipp; Wyss, Matthias T; Stobart, Jillian; Baeza-Lehnert, Felipe; Alegría, Karin; Weber, Bruno; Barros, L Felipe

2015-09-01

Neural activity is accompanied by a transient mismatch between local glucose and oxygen metabolism, a phenomenon of physiological and pathophysiological importance termed aerobic glycolysis. Previous studies have proposed glutamate and K(+) as the neuronal signals that trigger aerobic glycolysis in astrocytes. Here we used a panel of genetically encoded FRET sensors in vitro and in vivo to investigate the participation of NH4(+), a by-product of catabolism that is also released by active neurons. Astrocytes in mixed cortical cultures responded to physiological levels of NH4(+) with an acute rise in cytosolic lactate followed by lactate release into the extracellular space, as detected by a lactate-sniffer. An acute increase in astrocytic lactate was also observed in acute hippocampal slices exposed to NH4(+) and in the somatosensory cortex of anesthetized mice in response to i.v. NH4(+). Unexpectedly, NH4(+) had no effect on astrocytic glucose consumption. Parallel measurements showed simultaneous cytosolic pyruvate accumulation and NADH depletion, suggesting the involvement of mitochondria. An inhibitor-stop technique confirmed a strong inhibition of mitochondrial pyruvate uptake that can be explained by mitochondrial matrix acidification. These results show that physiological NH4(+) diverts the flux of pyruvate from mitochondria to lactate production and release. Considering that NH4(+) is produced stoichiometrically with glutamate during excitatory neurotransmission, we propose that NH4(+) behaves as an intercellular signal and that pyruvate shunting contributes to aerobic lactate production by astrocytes.

The metabolic trinity, glucose-glycogen-lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression.

PubMed

Dienel, Gerald A

2017-01-10

Glucose, glycogen, and lactate are traditionally identified with brain energetics, ATP turnover, and pathophysiology. However, recent studies extend their roles to include involvement in astrocytic signaling, memory consolidation, and gene expression. Emerging roles for these brain fuels and a readily-diffusible by-product are linked to differential fluxes in glycolytic and oxidative pathways, astrocytic glycogen dynamics, redox shifts, neuron-astrocyte interactions, and regulation of astrocytic activities by noradrenaline released from the locus coeruleus. Disproportionate utilization of carbohydrate compared with oxygen during brain activation is influenced by catecholamines, but its physiological basis is not understood and its magnitude may be affected by technical aspects of metabolite assays. Memory consolidation and gene expression are impaired by glycogenolysis blockade, and prevention of these deficits by injection of abnormally-high concentrations of lactate was interpreted as a requirement for astrocyte-to-neuron lactate shuttling in memory and gene expression. However, lactate transport was not measured and evidence for presumed shuttling is not compelling. In fact, high levels of lactate used to preserve memory consolidation and induce gene expression are sufficient to shut down neuronal firing via the HCAR1 receptor. In contrast, low lactate levels activate a receptor in locus coeruleus that stimulates noradrenaline release that may activate astrocytes throughout brain. Physiological relevance of exogenous concentrations of lactate used to mimic and evaluate metabolic, molecular, and behavioral effects of lactate requires close correspondence with the normal lactate levels, the biochemical and cellular sources and sinks, and specificity of lactate delivery to target cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Lactate overrides central nervous but not beta-cell glucose sensing in humans.

PubMed

Schmid, Sebastian M; Jauch-Chara, Kamila; Hallschmid, Manfred; Oltmanns, Kerstin M; Peters, Achim; Born, Jan; Schultes, Bernd

2008-12-01

Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. On the background of marked similarities between central nervous and beta-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose-sensing mechanisms in vivo. The effects of intravenously infused lactate vs placebo (saline) on central nervous and pancreatic glucose sensing were assessed during euglycemic and hypoglycemic clamp experiments in 10 healthy men. The release of neuroendocrine counterregulatory hormones during hypoglycemia was considered to reflect central nervous glucose sensing, whereas endogenous insulin secretion as assessed by serum C-peptide levels served as an indicator of pancreatic beta-cell glucose sensing. Lactate infusion blunted the counterregulatory hormonal responses to hypoglycemia, in particular, the release of epinephrine (P = .007) and growth hormone (P = .004), so that higher glucose infusion rates (P = .012) were required to maintain the target blood glucose levels. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate (P = .60). During euglycemic clamp conditions, lactate infusion did not affect the concentrations of C-peptide and of counterregulatory hormones, with the exception of norepinephrine levels that were lower during lactate than saline infusion (P = .049) independently of the glycemic condition. Data indicate that glucose sensing of beta-cells is specific to glucose, whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's ability to rely on lactate as an alternative major energy source.

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.

PubMed

Soeiro-de-Souza, Márcio Gerhardt; Pastorello, Bruno F; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A; Garcia Otaduy, Maria Concepción

2016-08-01

Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm(3)) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Low sensitivity of anion gap to detect clinically significant lactic acidosis in the emergency department.

PubMed

Xu, Q; HowlettClyne, S; Fuezery, A; Cembrowski, G S

2017-12-01

Lactic acidosis represents the pathologic accumulation of lactate and hydrogen ions. It is important to efficiently diagnose lactic acidosis as delayed treatment will lead to poor patient outcomes. As plasma lactate levels may not be rapidly available, some physicians may use elevated anion gaps to test for the need to measure lactate. All Edmonton metropolitan hospitals have Radiometer blood gas/electrolyte instruments in the ED or close by. As lactate is measured for each set of electrolytes, we were able to determine the effectiveness of a screening anion gap for lactic acidosis. Two years of emergency department lactates and electrolytes from Edmonton's 5 metropolitan hospitals were analyzed. We determined the sensitivity, specificity and positive predictive value of detecting an elevated lactate, defined as ≥2.5mmol/L or ≥4mmol/L. Depending on the elevated anion gap cut-off and the definition of elevated lactate, between 40-80% of elevated lactates are missed. In general, the positive predictive value approaches 40% for AGs ≥12mmol/L and 60% for AGs ≥16mmol/L. Anion gap is an inadequate marker of lactic acidosis. We recommend that lactate be done with each set of electrolytes and/or blood gases. In this way lactic acidosis will not be missed. Copyright © 2017. Published by Elsevier Inc.

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study

PubMed Central

Pastorello, Bruno F.; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A.; Garcia Otaduy, Maria Concepción

2016-01-01

Objective: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Methods: Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm3) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Results: Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. Conclusion: This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. PMID:27207914

[Laboratory diagnostics in transient loss of consciousness : Serum lactate compared to serum creatine kinase as diagnostic indicator for generalized tonic-clonic seizures].

PubMed

Dafotakis, M; Heckelmann, J; Zechbauer, S; Litmathe, J; Brokmann, J; Willmes, K; Surges, R; Matz, O

2018-03-21

Laboratory parameters can help in the differential diagnostics of acute episodes of transient loss of consciousness. Especially serum lactate and serum creatine kinase (CK) levels may provide valuable hints to distinguish generalized tonic-clonic seizures (GTCS) from syncope. Serum lactate levels at admission and CK levels 10-48 h after the episodes that led to admission were compared between patients with GTCS (n = 30) and those with syncope (n = 15). In addition, sensitivity and specificity of lactate and CK as diagnostic markers for syncope and GTCS were determined. The serum lactate and serum CK levels were significantly increased in patients with GTCS as compared to syncope patients (serum lactate: p < 0.001; CK: p < 0.005). The area under the curve (AUC) for serum lactate as an indicator for GTCS was 0.94 (95% confidence interval [CI] 0.88-1.0). For CK the receiver operating characteristics (ROC) analysis produced an AUC of only 0.77 (95% CI: 0.63-0.9). The determination of the lactate value as point-of-care diagnostics appears to be highly relevant in the rapid clarification of unclear episodes with transient loss of consciousness. The CK level at follow-up is also suitable for distinguishing GTCS from syncope but is inferior to the serum lactate value.

Evaluation of plasma lactate concentration and base excess at the time of hospital admission as predictors of gastric necrosis and outcome and correlation between those variables in dogs with gastric dilatation-volvulus: 78 cases (2004-2009).

PubMed

Beer, Kari A Santoro; Syring, Rebecca S; Drobatz, Kenneth J

2013-01-01

To determine the correlation between plasma lactate concentration and base excess at the time of hospital admission and evaluate each variable as a predictor of gastric necrosis or outcome in dogs with gastric dilatation-volvulus (GDV). Retrospective case series. 78 dogs. For each dog, various data, including plasma lactate concentration and base excess at the time of hospital admission, surgical or necropsy findings, and outcome, were collected from medical records. Gastric necrosis was identified in 12 dogs at the time of surgery and in 4 dogs at necropsy. Sixty-five (83%) dogs survived to hospital discharge, whereas 13 (17%) dogs died or were euthanized. Of the 65 survivors and 8 nonsurvivors that underwent surgery, gastric necrosis was detected in 8 and 4 dogs, respectively. Via receiver operating characteristic curve analysis, an initial plasma lactate concentration cutoff of 7.4 mmol/L was 82% accurate for predicting gastric necrosis (sensitivity, 50%; specificity, 88%) and 88% accurate for predicting outcome (sensitivity, 75%; specificity, 89%). Among all dogs, the correlation between initial plasma lactate concentration and base excess was significant, although base excess was a poor discriminator for predicting gastric necrosis or outcome (area under the receiver operating characteristic curve, 0.571 and 0.565, respectively). In dogs with GDV, plasma lactate concentration at the time of hospital admission was a good predictor of gastric necrosis and outcome. However, despite the correlation between initial base excess and plasma lactate concentration, base excess should not be used for prediction of gastric necrosis or outcome in those patients.

Theoretical model of ruminant adipose tissue metabolism in relation to the whole animal.

PubMed

Baldwin, R L; Yang, Y T; Crist, K; Grichting, G

1976-09-01

Based on theoretical considerations and experimental data, estimates of contributions of adipose tissue to energy expenditures in a lactating cow and a growing steer were developed. The estimates indicate that adipose energy expenditures range between 5 and 10% of total animal heat production dependent on productive function and diet. These energy expenditures can be partitioned among maintenance (3%), lipogenesis (1-5%) and lipolysis and triglyceride resynthesis (less thatn 1.0%). Specific sites at which acute and chronic effectors can act to produce changes in adipose function, and changes in adipose function produced by diet and during pregnancy, lactation and aging were discussed with emphasis being placed on the need for additional, definitive studies of specific interactions among pregnancy, diet, age, lactation and growth in producing ruminants.

Short Communication: Immunohistochemical localization of the immune cell marker CD68 in bovine adipose tissue: impact of tissue alterations and excessive fat accumulation in dairy cows.

PubMed

Häussler, S; Germeroth, D; Laubenthal, L; Ruda, L F; Rehage, J; Dänicke, S; Sauerwein, H

2017-01-01

With the onset of lactation energy from feed intake is mostly insufficient to meet the requirements of dairy cows. Lipid mobilization from adipose tissue (AT) could lead to a compromised inflammatory response enhancing the incidence for diseases. In addition, tissue alterations can occur, displaying areas of necrosis and inflammation. Furthermore, over-conditioned cows mobilizing more lipids from AT than thin cows are prone to develop metabolic disorders. This might lead to an increased infiltration of phagocytic immune cells into AT. In the present study, CD68 positive cells were localized in AT from 10 early lactating Holstein cows displaying different grades of AT alterations. Biopsies were sampled from visceral and subcutaneous AT and the number of CD68 positive cells was immunohistochemically determined. In addition, AT biopsies from over-conditioned, non-pregnant, non-lactating cows (n=8) were immunohistochemically analyzed for CD68 positive cells. The percentage of CD68 positive cells was less than 2% in AT biopsies with tissue alterations and in AT from over-conditioned cows. Therefore, immune cell infiltration demonstrated via the localization of CD68 positive cells seems to play only a minor role in AT from over-conditioned cows as well as in different bovine AT depots with tissue alterations. Copyright © 2016 Elsevier B.V. All rights reserved.

Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

NASA Astrophysics Data System (ADS)

Sinto, R.; Widodo, D.; Pohan, H. T.

2018-03-01

Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

Secretion of whey acidic protein and cystatin is down regulated at mid-lactation in the red kangaroo (Macropus rufus)

USGS Publications Warehouse

Nicholas, K.R.; Fisher, J.A.; Muths, E.; Trott, J.; Janssens, P.A.; Reich, C.; Shaw, D.C.

2001-01-01

Milk collected from the red kangaroo (Macropus rufus) between day 100 and 260 of lactation showed major changes in milk composition at around day 200 of lactation, the time at which the pouch young begins to temporarily exit the pouch and eat herbage. The carbohydrate content of milk declined abruptly at this time and although there was only a small increase in total protein content, SDS PAGE analysis of milk revealed asynchrony in the secretory pattern of individual proteins. The levels of α-lactalbumin, β-lactoglobulin, serum albumin and transferrin remain unchanged during lactation. In contrast, the protease inhibitor cystatin, and the putative protease inhibitor whey acidic protein (WAP) first appeared in milk at elevated concentrations after approximately 150 days of lactation and then ceased to be secreted at approximately 200 days. In addition, a major whey protein, late lactation protein, was first detected in milk around the time whey acidic protein and cystatin cease to be secreted and was present at least until day 260 of lactation. The co-ordinated, but asynchronous secretion of putative protease inhibitors in milk may have several roles during lactation including tissue remodelling in the mammary gland and protecting specific proteins in milk required for physiological development of the dependent young.

Secretion of whey acidic protein and cystatin is down regulated at mid-lactation in the red kangaroo (Macropus rufus)

USGS Publications Warehouse

Nicholas, K.R.; Fisher, J.A.; Muths, E.; Trott, J.; Janssens, P.A.; Reich, C.; Shaw, D.C.

2001-01-01

Milk collected from the red kangaroo (Macropus rufus) between day 100 and 260 of lactation showed major changes in milk composition at around day 200 of lactation, the time at which the pouch young begins to temporarily exit the pouch and eat herbage. The carbohydrate content of milk declined abruptly at this time and although there was only a small increase in total protein content, SDS PAGE analysis of milk revealed asynchrony in the secretory pattern of individual proteins. The levels of ??-lactalbumin, ??-lactoglobulin, serum albumin and transferrin remain unchanged during lactation. In contrast, the protease inhibitor cystatin, and the putative protease inhibitor whey acidic protein (WAP) first appeared in milk at elevated concentrations after approximately 150 days of lactation and then ceased to be secreted at approximately 200 days. In addition, a major whey protein, late lactation protein, was first detected in milk around the time whey acidic protein and cystatin cease to be secreted and was present at least until day 260 of lactation. The co-ordinated, but asynchronous secretion of putative protease inhibitors in milk may have several roles during lactation including tissue remodelling in the mammary gland and protecting specific proteins in milk required for physiological development of the dependent young. ?? 2001 Elsevier Science Inc.

Establishment of an evaluation model for human milk fat substitutes.

PubMed

Wang, Yong-Hua; Mai, Qing-Yun; Qin, Xiao-Li; Yang, Bo; Wang, Zi-Lian; Chen, Hai-Tian

2010-01-13

Fatty acid composition and distribution of human milk fat (HMF), from mothers over different lactating periods in Guangzhou, China, were analyzed. The universal characteristics were consistent with previously reported results although the fatty acid content was within a different range and dependent on the local population (low saturated fatty acid and high oleic acid for Guangdong mothers' milk fat). Based on the composition of the total and sn-2 fatty acids of mature milk fat, an efficient evaluation model was innovatively established by adopting the "deducting score" principle. The model showed good agreement between the scores and the degree of similarity by assessing 15 samples from different sources including four samples of HMF, eight samples of human milk fat substitutes (HMFSs) and infant formulas, and three samples of fats and oils. This study would allow for the devolvement of individual human milk fat substitutes with different and specific fatty acid compositions for local infants.

[A Listeria breast abscess in a man].

PubMed

Marsaudon, E; Berthy, J; Mamoune, S; Deniel, A; Ksiyer, S; Tiuca, D

2018-03-01

Listeriosis is a food-borne illness leading to bacteriemia or central nervous system infection especially in pregnant women or high-risk patients. It is rarely a localized infection. Breast contamination has rarely been reported in lactating women. We report a breast abscess in man. A 80 year old man, hypertensive and arrhythmic, was explored for weakness and dehydration. Type 2 diabetes and chronic lymphocytic leukemia were diagnosed. Clinical examination disclosed a breast abcess related to L monocytogenes infection. Histopathological study also revealed a breast subcutaneous infiltration by chronic lymphocytic leukemia. Listeriosis sometimes uncover an unknown immunosuppression, especially in the elderly. Breast is a non-sterile tissue containing a stable microbiome partly from digestive origin. It can thereby be contaminated by Listeria. The specific cutaneous infiltrate of chronic lymphocytic leukemia can create the conditions for a local infection. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Isoform-specific function of calpains in cell adhesion disruption: studies in postlactational mammary gland and breast cancer.

PubMed

Rodríguez-Fernández, Lucía; Ferrer-Vicens, Iván; García, Concha; Oltra, Sara S; Zaragozá, Rosa; Viña, Juan R; García-Trevijano, Elena R

2016-09-15

Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca(2+)-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification. In both models, E-cadherin, β-catenin, p-120, and talin-1 were cleaved as assessed by western blot analysis. Both CAPNs were able to cleave adhesion proteins from lactating mammary gland in vitro Nevertheless, CAPN2 was the only isoform found to co-localize with E-cadherin in cell junctions at the peak of lactation. CAPN2/E-cadherin in vivo interaction, analyzed by proximity ligation assay, was dramatically increased during involution. Calpain inhibitor administration prevented the cytosolic accumulation of truncated E-cadherin cleaved by CAPN2. Conversely, in breast cancer cells, CAPN2 was restricted to the nuclear compartment. The isoform-specific expression of CAPNs and CAPN activity was dependent on the breast cancer subtype. However, CAPN1 and CAPN2 knockdown cells showed that cleavage of adhesion proteins and cell migration was mediated by CAPN1, independently of the breast cancer cell line used. Data presented here suggest that the subcellular distribution of CAPN1 and CAPN2 is a major issue in target-substrate recognition; therefore, it determines the isoform-specific role of CAPNs during disruption of cell adhesion in either a physiological or a pathological context. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

[Lactational breast abscesses: Do we still need surgery?].

PubMed

Debord, M-P; Poirier, E; Delgado, H; Charlot, M; Colin, C; Raudrant, D; Golfier, F; Dupuis, O

2016-03-01

To show the effectiveness of ultrasound-guided puncture in the treatment of lactational breast abscess and identify its risk factors. Retrospective descriptive study at the CHU of Lyon-Sud from December 2007 to December 2013, including patients with lactational breast abscess confirmed on ultrasound and treated with antibiotics and analgesics. Realisation of ultrasound-guided needle under local anesthesia by the radiologist and washing the cavity with physiological serum. Forty patients had lactational abscesses at an average of 10 weeks post-partum. Thirty-four patients were treated by needle aspiration, of which 2 had first surgical drainage. The average size of the abscess was 41.2mm. The success rate of needle aspiration was 91.2%. No cases of recurrence were observed, however, there were 5 fistulisations. In all, 91.2% were treated on an outpatient basis. In 87.8% of cases, breastfeeding was continued on the healthy side and in 48.5% of cases on the affected side. The major risk factor for abscess was mastitis in 91.1% of cases. Ultrasound guidance of needle aspiration should be gold standard for the treatment of lactational breast abscesses to continue breastfeeding including the affected side. Copyright © 2015. Published by Elsevier Masson SAS.

Osteoporosis presenting in pregnancy, puerperium, and lactation.

PubMed

Kovacs, Christopher S

2014-12-01

To describe our current state of knowledge about the pathophysiology, incidence, and treatment of osteoporosis that presents during pregnancy, puerperium, and lactation. When vertebral fractures occur in pregnant or lactating women, it is usually unknown whether the skeleton was normal before pregnancy. Maternal adaptations increase bone resorption modestly during pregnancy but markedly during lactation. The net bone loss may occasionally precipitate fractures, especially in women who have underlying low bone mass or skeletal fragility prior to pregnancy. Bone mass and strength are normally restored postweaning. Transient osteoporosis of the hip is a sporadic disorder localized to one or both femoral heads; it is not due to generalized skeletal resorption. Anecdotal reports have used bisphosphonates, strontium ranelate, teriparatide, or vertebroplasty/kyphoplasty to treat postpartum vertebral fractures, but it is unclear whether these therapies had any added benefit over the spontaneous skeletal recovery that normally occurs after weaning. These relatively rare fragility fractures result from multifactorial causes, including skeletal disorders that precede pregnancy, and structural and metabolic stresses that can compromise skeletal strength during pregnancy and lactation. Further study is needed to determine when pharmacological or surgical therapy is warranted instead of conservative or expectant management.

Intake and hedonics of calcium and sodium during pregnancy and lactation in the rat.

PubMed

Leshem, M; Levin, T; Schulkin, J

2002-03-01

These experiments sought to distinguish whether increased calcium intake during pregnancy and lactation in the rat is due to arousal of a specific calcium appetite, with altered taste hedonics, as occurs with sodium depletion, to reduced taste sensitivity, or to the hyperdipsia of reproduction. We find that, during pregnancy and lactation, CaCl(2) intake is not increased more (in fact less) than intakes of control tastants, MgCl(2) and quinine HCl, and multiparous dams do not have a greater calcium intake than primaparous dams. Changes in taste reactivity to CaCl(2) and to NaCl do not correlate with changes in intake of these minerals during pregnancy or lactation, suggesting that alterations in hedonics or sensitivity do not explain the increased intake of these minerals. Taken together with the increased intake of all the tastants, it may be that the increased intakes of calcium and sodium during reproduction are not due to respective specific appetites or to a general mineral appetite but rather to the reproduction-increased ingestion that may meet all the dam's increased mineral and nutrient requirements. Differences in the degree of increased intakes of tastes may be due to specific alterations in their transduction during reproduction.

Factors affecting oxygen consumption in wild-caught yellow-bellied marmots (Marmota flaviventris).

PubMed

Armitage, K B; Salsbury, C M

1992-12-01

1. All age groups gained mass during the active season, but mass-gain of adult females was delayed during lactation. 2. The relationship of body mass to metabolic rate varied widely; when the relationship was significant, R2 varied from 10.3 to 72.6%. Body mass affects VO2 more during lactation than at any other period. 3. Mean VO2 of adult males was higher in June than that of adult, non-lactating females. 4. VO2 of reproductive females was significantly higher during lactation than during gestation or postlactation because specific VO2 varied. Specific VO2 of non-reproductive females declined over the active season. 5. Specific VO2 of all age groups declined between the premolt and postmolt periods. The reduced maintenance costs can contribute 20-46% to daily growth. 6. Observed VO2 was lower than the value predicted from intraspecific or interspecific Bm:M regressions. 7. VO2 of wild-caught marmots was lower than that of marmots maintained in the laboratory, probably because of dietary differences. 8. Because basal metabolism is a stage on a food-deprivation curve, we suggest that basal metabolic rate is not an appropriate measure of the metabolic activity of free-ranging animals.

The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1: Expression and action in brain.

PubMed

Morland, Cecilie; Lauritzen, Knut Husø; Puchades, Maja; Holm-Hansen, Signe; Andersson, Krister; Gjedde, Albert; Attramadal, Håvard; Storm-Mathisen, Jon; Bergersen, Linda Hildegard

2015-07-01

We have proposed that lactate is a "volume transmitter" in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes the cerebral neocortex and the hippocampus, where it can be stimulated by physiological concentrations of lactate and by the HCAR1 agonist 3,5-dihydroxybenzoate to reduce cAMP levels. Cerebral HCAR1 is concentrated on the postsynaptic membranes of excitatory synapses and also is enriched at the blood-brain barrier. In synaptic spines and in adipocytes, HCAR1 immunoreactivity is also located on subplasmalemmal vesicular organelles, suggesting trafficking to and from the plasma membrane. Through activation of HCAR1, lactate can act as a volume transmitter that links neuronal activity, cerebral blood flow, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress, and schizophrenia and in the deposition of phosphorylated tau protein in Alzheimer's disease. HCAR1 could serve to ameliorate these conditions and might also act through downstream mechanisms other than cAMP. Lactate exits cells through monocarboxylate transporters in an equilibrating manner and through astrocyte anion channels activated by depolarization. In addition to locally produced lactate, lactate produced by exercising muscle as well as exogenous HCAR1 agonists, e.g., from fruits and berries, might activate the receptor on cerebral blood vessels and brain cells. © 2015 Wiley Periodicals, Inc.

Evaluation of urinary S100B protein level and lactate/creatinine ratio for early diagnosis and prognostic prediction of neonatal hypoxic-ischemic encephalopathy.

PubMed

Liu, Li; Zheng, Chong-Xun; Peng, Shu-Feng; Zhou, Hong-Yan; Su, Zu-You; He, Li; Ai, Ting

2010-01-01

Early identification and prevention of hypoxic-ischemic encephalopathy (HIE) in newborns may reduce neonatal mortality and neurological dysfunction. To analyze the diagnostic and prognostic values of urinary S100B level and lactate/creatinine ratio in newborns with HIE. Seventy-eight full-term newborns with HIE and 25 normal newborns were enrolled. The Neonatal Behavioral Neurological Assessment (NBNA) and Developmental Screening Test were scored. The concentration of urinary S100B protein was determined using the S100B enzyme-linked immunosorbent assay and the levels of urinary lactate and creatinine were measured with the enzyme colorimetric method. Urinary S100B level on days 1-3 after birth and lactate/creatinine ratio on day 1 were significantly higher in newborns with HIE than those in the control group. Both indexes were positively correlated with the clinical grading of HIE. A cutoff value for the S100B level of 0.47 microg/l on day 3 after birth had a sensitivity of 90% and specificity of 92% for prediction of HIE. A lactate/creatinine ratio of more than 0.55 on day 1 showed the highest sensitivity (92%) and specificity (90%). A combination of both indexes improved the sensitivity and specificity to 99 and 97%, respectively. A negative correlation of both lactate/creatinine ratio on day 1 and S100B level on days 1-3 after birth with the NBNA score was identified on days 3, 7 and 14 after birth. The Developmental Screening Test score of 36 newborns with HIE within 6 months after birth showed that 65% of infants with moderate and high HIE had an abnormal developmental quotient. These data suggest that early measurement of both S100B level and lactate/creatinine ratio in the urine of newborns with HIE is a practical convenient and sensitive way to improve diagnosis on the third day of life and prognostic prediction of HIE. Copyright 2009 S. Karger AG, Basel.

Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children

PubMed Central

2014-01-01

Background Cerebrospinal fluid (CSF) lactate is a potential biomarker for bacterial meningitis in children. To this end, we performed a single-center retrospective cohort study of children from Sao Paulo, Brazil, with CSF pleocytosis to evaluate the ability of CSF lactate to distinguish between children with bacterial and aseptic meningitis. We determined the optimum cutoff point for CSF lactate using receiver-operator curve (ROC) analysis. Findings We identified 451 children of whom 40 (9%) had bacterial meningitis. Children with bacterial meningitis had a higher median CSF lactate level [9.6 mmol/l, interquartile range (IQR) 3.2-38.5 mmol/l bacterial meningitis vs. 2.0 mmol/l, IQR 1.2-2.8 mmol/l aseptic meningitis]. A CSF lactate cutoff point of 3.0 mmol/l had a sensitivity of 95% [95% confidence interval (CI) 83-99%), specificity of 94% (95% CI 90-96%) and negative predictive value of 99.3% (95% CI 97.7-99.9%) for bacterial meningitis. Conclusions In combination with a validated meningitis clinical prediction rule, the CSF lactate level can be used to distinguish between bacterial and aseptic meningitis in children with CSF pleocytosis. PMID:24576334

Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children.

PubMed

Mekitarian Filho, Eduardo; Horita, Sérgio Massaru; Gilio, Alfredo Elias; Nigrovic, Lise E

2014-02-27

Cerebrospinal fluid (CSF) lactate is a potential biomarker for bacterial meningitis in children. To this end, we performed a single-center retrospective cohort study of children from Sao Paulo, Brazil, with CSF pleocytosis to evaluate the ability of CSF lactate to distinguish between children with bacterial and aseptic meningitis. We determined the optimum cutoff point for CSF lactate using receiver-operator curve (ROC) analysis. We identified 451 children of whom 40 (9%) had bacterial meningitis. Children with bacterial meningitis had a higher median CSF lactate level [9.6 mmol/l, interquartile range (IQR) 3.2-38.5 mmol/l bacterial meningitis vs. 2.0 mmol/l, IQR 1.2-2.8 mmol/l aseptic meningitis]. A CSF lactate cutoff point of 3.0 mmol/l had a sensitivity of 95% [95% confidence interval (CI) 83-99%), specificity of 94% (95% CI 90-96%) and negative predictive value of 99.3% (95% CI 97.7-99.9%) for bacterial meningitis. In combination with a validated meningitis clinical prediction rule, the CSF lactate level can be used to distinguish between bacterial and aseptic meningitis in children with CSF pleocytosis.

Acute administration of cefepime lowers L-carnitine concentrations in early lactation stage rat milk.

PubMed

Ling, Binbing; Alcorn, Jane

2008-07-01

Our study investigated the potential for important in vivo drug-nutrient transport interactions at the lactating mammary gland using the L-carnitine transporter substrates, cefepime and L-carnitine, as proof-of-concept. On d 4 (n = 6/treatment) and d 10 (n = 6/treatment) of lactation, rats were administered cefepime (250 mg/h) or saline by continuous i.v. infusion (4 h). Serum and milk L-carnitine and cefepime concentrations were quantified by HPLC-UV. In whole mammary gland, organic cation/carnitine transporter (OCTN)1, OCTN2, OCTN3, amino acid transporter B(0,+) (ATB(0,+)), and L-carnitine transporter 2 expression were determined by quantitative RT-PCR and by western blot and immunohistochemistry when possible. Cefepime caused a 56% decrease in milk L-carnitine concentrations on lactation d 4 (P = 0.0048) but did not affect milk L-carnitine at lactation d 10 or serum L-carnitine concentrations at either time. The mean L-carnitine and cefepime milk:serum ratios (M/S) decreased from 9.1 +/- 0.4 to 4.9 +/- 0.6 (P < 0.0001) and 0.89 +/- 0.3 to 0.12 +/- 0.02 (P = 0.0473), respectively, between d 4 and d 10 of lactation. In both groups, OCTN2 (P < 0.0001), OCTN3 (P = 0.0039), and ATB(0,+) (P = 0.004) mRNA expression and OCTN2 protein (P < 0.0001) were higher in mammary glands at d 4 of lactation compared with d 10. Immunohistochemistry revealed OCTN1 and OCTN2 localization in the mammary alveolar epithelium and OCTN3 expression in the interstitial space and blood vessel endothelium. In conclusion, cefepime significantly decreased milk L-carnitine concentrations only at d 4 of lactation. Relative to d 10, enhanced expression of OCTN2 and ATB(0,+) in mammary glands at d 4 of lactation and higher M/S (L-carnitine and cefepime) suggests cefepime competes with L-carnitine for L-carnitine transporters expressed in the lactating mammary gland to adversely affect L-carnitine milk concentrations and these effects depend upon lactation stage.

Retesting The Validity Of A Specific Field Test For Judo Training

PubMed Central

Santos, Luis; González, Vicente; Iscar, Marta; Brime, Juan I.; Fernández-Río, Javier; Rodríguez, Blanca; Montoliu, Mª Ángeles

2011-01-01

The main goal of this research project was to retest the validity of a specifically designed judo field test (Santos Test) in a different group of judokas. Eight (n=8) national-level male judokas underwent laboratory and field testing. The mean data (mean +/− SD) obtained in the laboratory tests was: HRmax: 200 ± 4.0 beats × min−1, VO2 max: 52.8 ± 7.9 ± ml × kg−1 × min−1, lactate max: 12 ± 2.5 mmol × l−1, HR at the anaerobic threshold: 174.2 ± 9.4 beats × min−1, percentage of maximum heart rate at which the anaerobic threshold appears: 87 ± 3.6 %, lactate threshold: 4.0 ± 0.2 mmol × l−1, and RPE: 17.2 ± 1.0. The mean data obtained in the field test (Santos) was: HRmax: 201.3 ± 4.1 beats × min−1, VO2 max: 55.6 ± 5.8 ml × kg−1 × min−1, lactate max: 15.6 ± 2.8 mmol × l−1, HR at the anaerobic threshold: 173.2 ± 4.3 beats × min−1, percentage of maximum heart rate at which the anaerobic threshold appears: 86 ± 2.5 %, lactate threshold: 4.0 ± 0.2 mmol × l−1, and RPE: 16.7 ± 1.0. There were no significant differences between the data obtained on both tests in any of the parameters, except for maximum lactate concentration. Therefore, the Santos test can be considered a valid tool specific for judo training. PMID:23486994

Immunohistochemical localization of GLUT3, MCT1, and MCT2 in the testes of mice and rats: the use of different energy sources in spermatogenesis.

PubMed

Kishimoto, Ayuko; Ishiguro-Oonuma, Toshina; Takahashi, Ritei; Maekawa, Mamiko; Toshimori, Kiyotaka; Watanabe, Masahiko; Iwanaga, Toshihiko

2015-01-01

Lactate represents a preferential energy substrate of germ cells rather than glucose. Testicular Sertoli cells are believed to produce lactate and pyruvate and to supply these to germ cells, particularly spermatocytes and spermatids. Monocarboxylate transporter (MCT), responsible for the transport of lactate and other monocarboxylates via the cell membrane, is abundant in the testes and sperm (MCT1, MCT2, and MCT4). For the uptake of glucose, germ cells within the seminiferous tubules and sperm have been known to intensely express GLUT3. The present study investigated expression profiles of MCTs and GLUTs and revealed their cellular and subcellular localization in the mouse and rat testis. An in situ hybridization analysis showed significant expressions of MCT1, MCT2, and GLUT3 mRNA in the testis. Immunohistochemically, spermatogonia, spermatocytes, and spermatids expressed MCT1 on their cell surfaces in a stage-dependent manner: in some seminiferous tubules, an intense expression of MCT1 was unique to the spermatogonia. MCT2 was restricted to the tails of elongated spermatids and sperm. An intense immunoreactivity for GLUT3 was shared by spermatocytes, spermatids, and sperm. Sertoli cells were devoid of any immunoreactivities for MCT1, MCT2, and GLUT3. The predominant energy source of germ cells may be lactate and other monocarboxylates--especially for spermatogonia, but glucose and other hexoses may be responsible for an energy supply to spermatocytes and spermatids.

Bisphenol S Alters the Lactating Mammary Gland and Nursing Behaviors in Mice Exposed During Pregnancy and Lactation.

PubMed

LaPlante, Charlotte D; Catanese, Mary C; Bansal, Ruby; Vandenberg, Laura N

2017-10-01

High doses of estrogenic pharmaceuticals were once prescribed to women to halt lactation. Yet, the effects of low-level xenoestrogens on lactation remain poorly studied. We investigated the effects of bisphenol S (BPS), an estrogen receptor (ER) agonist, on the lactating mammary gland; the arcuate nucleus, a region of the hypothalamus important for neuroendocrine control of lactational behaviors; and nursing behavior in CD-1 mice. Female mice were exposed to vehicle, 2 or 200 µg BPS/kg/d from pregnancy day 9 until lactational day (LD) 20, and tissues were collected on LD21. Tissues were also collected from a second group at LD2. BPS exposure significantly reduced the fraction of the mammary gland comprised of lobules, the milk-producing units, on LD21, but not LD2. BPS also altered expression of Esr1 and ERα in the mammary gland at LD21, consistent with early involution. In the arcuate nucleus, no changes were observed in expression of signal transducer and activator of transcription 5, a marker of prolactin signaling, or ERα, suggesting that BPS may act directly on the mammary gland. However, observations of nursing behavior collected during the lactational period revealed stage-specific effects on both pup and maternal nursing behaviors; BPS-treated dams spent significantly more time nursing later in the lactational period, and BPS-treated pups were less likely to initiate nursing. Pup growth and development were also stunted. These data indicate that low doses of BPS can alter lactational behaviors and the maternal mammary gland. Together, they support the hypothesis that pregnancy and lactation are sensitive to low-dose xenoestrogen exposures. Copyright © 2017 Endocrine Society.

Do American Colleges and Universities Support the Lactation Needs of Students?

PubMed

Bostick, Mary Welsh; Albrecht, Susan A; Baghdadi, Nadiah; Haley, Caitlin; Spatz, Diane L

2016-09-01

Despite strong evidence for the health benefits of breastfeeding, many mothers cannot continue breastfeeding their infants upon their return to work or school. Students are especially affected by this transition because they do not have legal protection that requires designated lactation space or time to express milk to be provided by places of education. Furthermore, limited research has been completed that specifically addresses the return to school of mothers who are students. One hundred fifty-seven colleges and universities from across the United States were contacted through telephone and/or e-mail, and their websites were searched to assess the support they offer for lactating students. The presence of a formal policy for lactating students and designated lactation rooms, accessible to students, were the key measures. Information was gathered from 88.53% (n = 139) of the colleges and universities. A mere 3.6% (n = 5) had an official policy for lactating students and/or had the lactation spaces mentioned in the student handbook. However, more than half of the colleges and universities (54.68%; n = 76) had designated lactation spaces accessible to their students. The vast majority of the sample did not have a policy for lactating students, and almost half of the schools did not have designated space for milk expression accessible to students. Lactating students will likely encounter challenges in simultaneously sustaining breastfeeding and meeting their educational goals in these contexts. To meet the recommendation of the American Academy of Pediatrics of 6 months of exclusive breastfeeding and continued breastfeeding for 1 year or more, American colleges and universities must establish not only designated spaces for milk expression but also policies to support lactating students.

Characterization of lactate utilization and its implication on the physiology of Haemophilus influenzae.

PubMed

Lichtenegger, Sabine; Bina, Isabelle; Roier, Sandro; Bauernfeind, Stilla; Keidel, Kristina; Schild, Stefan; Anthony, Mark; Reidl, Joachim

2014-05-01

Haemophilus influenzae is a Gram-negative bacillus and a frequent commensal of the human nasopharynx. Earlier work demonstrated that in H. influenzae type b, l-lactate metabolism is associated with serum resistance and in vivo survival of the organism. To further gain insight into lactate utilization of the non-typeable (NTHi) isolate 2019 and laboratory prototype strain Rd KW20, deletion mutants of the l-lactate dehydrogenase (lctD) and permease (lctP) were generated and characterized. It is shown, that the apparent KM of l-lactate uptake is 20.1μM as determined for strain Rd KW20. Comparison of the COPD isolate NTHi 2019-R with the corresponding lctP knockout strain for survival in human serum revealed no lactate dependent serum resistance. In contrast, we observed a 4-fold attenuation of the mutant strain in a murine model of nasopharyngeal colonization. Characterization of lctP transcriptional control shows that the lactate utilization system in H. influenzae is not an inductor inducible system. Rather negative feedback regulation was observed in the presence of l-lactate and this is dependent on the ArcAB regulatory system. Additionally, for 2019 it was found that lactate may have signaling function leading to increased cell growth in late log phase under conditions where no l-lactate is metabolized. This effect seems to be ArcA independent and was not observed in strain Rd KW20. We conclude that l-lactate is an important carbon-source and may act as host specific signal substrate which fine tunes the globally acting ArcAB regulon and may additionally affect a yet unknown signaling system and thus may contribute to enhanced in vivo survival. Copyright © 2014 Elsevier GmbH. All rights reserved.

Microbiota Is Involved in Post-resection Adaptation in Humans with Short Bowel Syndrome.

PubMed

Gillard, Laura; Mayeur, Camille; Robert, Véronique; Pingenot, Isabelle; Le Beyec, Johanne; Bado, André; Lepage, Patricia; Thomas, Muriel; Joly, Francisca

2017-01-01

Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrictive surgery. The objective of this study was to determine the functional contribution of SBS-microbiota after resection. It is well-known that SBS-microbiota displayed specific features with a prevalence of Lactobacillus, a low amount of some anaerobic microbes ( Clostridium leptum ) and an accumulation of fecal lactate in some patients. Patients with jejuno-colonic anastomosis were stratified according to the presence of lactate in their feces and, we observe that the lactate-producing bacteria were predominant in the sub-group of patients accumulating fecal lactate. One case of D-encephalopathy crisis occurred when the D-lactate isoform accumulated in the feces and plasma bicarbonate levels decreased. The fecal sample at the time of the encephalopathy was transferred to germ free rats (SBS-H rats). The SBS-H microbiota conserved some characteristics of the SBS donnor, predominated by lactate-producing bacteria (mainly Lactobacillus ), a low level of lactate-consuming bacteria and undetectable C. leptum . However, lactate did not accumulate in feces of recipient rats and the D-encephalopathy was not reproduced in SBS-H rats. This suggests that the intact small bowel of the recipient rats protected them from lactate accumulation and that D-lactate encephalopathy can occur only in the absence of small intestine. After fecal transfer, we also show that gnotobiotic rats exhibited high levels of circulating GLP-1 and ghrelin, two hormones that are known to be induced in SBS patients. Therefore, the microbiota of SBS is a reservoir of biological signals involved in post-resection adaptation.

Microbiota Is Involved in Post-resection Adaptation in Humans with Short Bowel Syndrome

PubMed Central

Gillard, Laura; Mayeur, Camille; Robert, Véronique; Pingenot, Isabelle; Le Beyec, Johanne; Bado, André; Lepage, Patricia; Thomas, Muriel; Joly, Francisca

2017-01-01

Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrictive surgery. The objective of this study was to determine the functional contribution of SBS-microbiota after resection. It is well-known that SBS-microbiota displayed specific features with a prevalence of Lactobacillus, a low amount of some anaerobic microbes (Clostridium leptum) and an accumulation of fecal lactate in some patients. Patients with jejuno-colonic anastomosis were stratified according to the presence of lactate in their feces and, we observe that the lactate-producing bacteria were predominant in the sub-group of patients accumulating fecal lactate. One case of D-encephalopathy crisis occurred when the D-lactate isoform accumulated in the feces and plasma bicarbonate levels decreased. The fecal sample at the time of the encephalopathy was transferred to germ free rats (SBS-H rats). The SBS-H microbiota conserved some characteristics of the SBS donnor, predominated by lactate-producing bacteria (mainly Lactobacillus), a low level of lactate-consuming bacteria and undetectable C. leptum. However, lactate did not accumulate in feces of recipient rats and the D-encephalopathy was not reproduced in SBS-H rats. This suggests that the intact small bowel of the recipient rats protected them from lactate accumulation and that D-lactate encephalopathy can occur only in the absence of small intestine. After fecal transfer, we also show that gnotobiotic rats exhibited high levels of circulating GLP-1 and ghrelin, two hormones that are known to be induced in SBS patients. Therefore, the microbiota of SBS is a reservoir of biological signals involved in post-resection adaptation. PMID:28469580

Validation of a hand-held point of care device for lactate in adult and pediatric patients using traditional and locally-smoothed median and maximum absolute difference curves.

PubMed

Colon-Franco, Jessica Marie; Lo, Stanley F; Tarima, Sergey S; Gourlay, David; Drendel, Amy L; Brook Lerner, E

2017-05-01

Lactate is commonly used in septic patients and is a viable biomarker for trauma patients. Its pre-hospital use could assist triaging and managing patients with these conditions. We evaluated the analytical performance of the point-of-care (POC) StatStrip Xpress Lactate Meter (Nova Biomedical) and compared it to the ABL 800 (Radiometer). We measured lactate in 250 adult and 250 pediatric whole blood samples in 2 laboratories. The performance of the POC meter was assessed by traditional linear regression and Bland-Altman plots, and locally-smoothed (LS) median absolute difference and maximum absolute difference (MAD and MaxAD) curves. The StatStrip was linear with acceptable reproducibility at clinically relevant concentrations. Correlation with the ABL800 showed a negative bias for both populations with slope, bias ±SD (% bias) of 0.78, -0.4±0.7 (-14.5%) in children and 0.80-0.3±0.6 (-13.3%) in adults. The proportional bias appeared more significant at concentrations >4mmol/l (36.0mg/dl). The StatStrip misclassified 7.6 and 8.8% pediatric and adult samples, respectively, to lower risk categories defined using guidelines driven cut-offs. The LS MAD curves identified one breakout, concentration where the LS MAD exceeds the total allowable error limit of 0.3mmol/l (2.7mg/dl), at lactate concentrations of 3.8 and 3.2mmol/l (34.2 and 28.8mg/dl) in the pediatric and adult curves, respectively. Breakthroughs, points at which the LS MaxAD curve exceeds the 95th percentile of MaxADs, occur at concentrations above 7.5mmol/l (67.6mg/dl) for both populations where the performance of the POC meter became erratic. We concluded that if serial lactate measurements are performed, the same method should be used for baseline and follow up measurements. The LS MAD and LS MaxAD curves allowed visual and quantitative mapping of the performance of the lactate POC meter over the range of concentrations measured. This approach seems useful for the identification of points at which the performance of a POC meter differs significantly from a comparison method and thresholds of poor analytical performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Factors associated with colostral specific gravity in dairy cows.

PubMed

Morin, D E; Constable, P D; Maunsell, F P; McCoy, G C

2001-04-01

The objectives of this study were to identify factors associated with colostral specific gravity in dairy cows, as measured by a commercially available hydrometer (Colostrometer). Colostral specific gravity was measured in 1085 first-milking colostrum samples from 608 dairy cows of four breeds on a single farm during a 5-yr period. Effects of breed, lactation number, and month and year of calving on colostral specific gravity were determined, as were correlations between colostral specific gravity, nonlactating period length, and 305-d yields of milk, protein, and fat. For 75 multiparous Holstein cows, relationships between colostral specific gravity, colostral IgG1, protein, and fat concentrations, and season of calving were determined. Colostral specific gravity values were lower for Brown Swiss and Ayrshire cows than for Jersey and Holstein cows, and lower for cows entering first or second lactation than third or later lactations. Month of calving markedly affected colostral specific gravity values, with highest values occurring in autumn and lowest values in summer. In multiparous Holstein cows, colostral specific gravity was more strongly correlated with colostral protein concentration (r = 0.76) than IgG1 concentration (r = 0.53), and colostral protein concentration varied seasonally (higher in autumn than summer). Our results demonstrate that colostral specific gravity more closely reflects colostral protein concentration than IgG1 concentration and is markedly influenced by month of calving. These results highlight potential limitations of using colostral specific gravity as an indicator of IgG1 concentration.

In Vivo{sup 1}H Magnetic Resonance Spectroscopy of Lactate in Patients With Stage IV Head and Neck Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le, Quynh-Thu; Koong, Albert; Lieskovsky, Yee Yie

2008-07-15

Purpose: To investigate in vivo{sup 1}H magnetic resonance spectroscopy imaging of lactate for assessing tumor hypoxia in head and neck cancers and to determine its utility in predicting the response and outcomes. Methods and Materials: Volume-localized lactate-edited {sup 1}H magnetic resonance spectroscopy at 1.5 T was performed in vivo on involved neck nodes and control subcutaneous tissues in 36 patients with Stage IV head and neck cancer. The signal intensities (SIs) of lactate, choline, and creatine and the choline/creatine ratio were measured. The tumor partial pressure of oxygen (pO{sub 2}) was obtained in the same lymph node before MRS. Patientsmore » were treated with either two cycles of induction chemotherapy (tirapazamine, cisplatin, 5-fluorouracil) followed by simultaneous chemoradiotherapy or the same regimen without tirapazamine. The lactate SI and the choline/creatine ratio correlated with the tumor pO{sub 2}, nodal response, and locoregional control. Results: The lactate SI was greater for the involved nodes (median, 0.25) than for the subcutaneous tissue (median, 0.04; p = 0.07). No significant correlation was found between the lactate SI and tumor pO{sub 2} (mean, 0.46 {+-} 0.10 for hypoxic nodes [pO{sub 2} {<=}10 mm Hg, n = 15] vs. 0.36 {+-} 0.07 for nonhypoxic nodes [pO{sub 2} >10 mm Hg, n = 21], p = 0.44). A significant correlation was found between the choline/creatine ratios and tumor pO{sub 2} (mean, 2.74 {+-} 0.34 for hypoxic nodes vs. 1.78 {+-} 0.31 for nonhypoxic nodes, p = 0.02). No correlation was found between the lactate SI and the complete nodal response (p = 0.52) or locoregional control rates. Conclusions: The lactate SI did not correlate with tumor pO{sub 2}, treatment response, or locoregional control. Additional research is needed to refine this technique.« less

Ruminal Bacterial Community Composition in Dairy Cows Is Dynamic over the Course of Two Lactations and Correlates with Feed Efficiency

PubMed Central

Jewell, Kelsea A.; McCormick, Caroline A.; Odt, Christine L.; Weimer, Paul J.

2015-01-01

Fourteen Holstein cows of similar ages were monitored through their first two lactation cycles, during which ruminal solids and liquids, milk samples, production data, and feed consumption data were collected for each cow during early (76 to 82 days in milk [DIM]), middle (151 to 157 DIM), and late (251 to 257 DIM) lactation periods. The bacterial community of each ruminal sample was determined by sequencing the region from V6 to V8 of the 16S rRNA gene using 454 pyrosequencing. Gross feed efficiency (GFE) for each cow was calculated by dividing her energy-corrected milk by dry matter intake (ECM/DMI) for each period of both lactation cycles. Four pairs of cows were identified that differed in milk production efficiency, as defined by residual feed intake (RFI), at the same level of ECM production. The most abundant phyla detected for all cows were Bacteroidetes (49.42%), Firmicutes (39.32%), Proteobacteria (5.67%), and Tenericutes (2.17%), and the most abundant genera included Prevotella (40.15%), Butyrivibrio (2.38%), Ruminococcus (2.35%), Coprococcus (2.29%), and Succiniclasticum (2.28%). The bacterial microbiota between the first and second lactation cycles were highly similar, but with a significant correlation between total community composition by ruminal phase and specific bacteria whose relative sequence abundances displayed significant positive or negative correlation with GFE or RFI. These data suggest that the ruminal bacterial community is dynamic in terms of membership and diversity and that specific members are associated with high and low milk production efficiency over two lactation cycles. PMID:25934629

Reproductive effects on fecal nitrogen as an index of diet quality: an experimental assessment

USGS Publications Warehouse

Monteith, Kyle B.; Monteith, Kevin L.; Bowyer, R. Terry; Leslie,, David M.; Jenks, Jonathan A.

2014-01-01

Concentration of fecal nitrogen has been used widely as an indicator of dietary quality for free-ranging ruminants. Differences in digestive function between species of dimorphic ungulates render interspecific comparisons of fecal nitrogen unreliable; however, whether intraspecific sexual differences in digestive function also bias this nutritional index is unknown. Our objective was to compare sex-specific variation in concentration of fecal nitrogen using male, nonlactating female, and lactating female white-tailed deer (Odocoileus virginianus) on high- and low-quality diets. During weekly trials over spring and summer (2008-2009), we monitored intake rates, collected feces twice daily, and used micro-Kjeldahl procedures to determine percent fecal nitrogen. We also determined nitrogen content of feces following a neutral detergent fiber (NDF) rinse during pre-, peak, and postlactation. Fecal nitrogen reflected general differences in dietary quality between diets; however, fecal nitrogen of lactating females in both dietary groups was lower than for males or nonlactating females throughout lactation. Nitrogen concentration following an NDF rinse also was lower for lactating females during peak lactation. We hypothesize that the remodeling of the digestive tract and increased rumination by lactating females may enhance their ability to extract nitrogen from their forage. These adjustments may expand the foraging options of lactating females by increasing their ability to process low-quality foods, but also affects the interpretation of fecal nitrogen during the season of lactation.

MCT Expression and Lactate Influx/Efflux in Tanycytes Involved in Glia-Neuron Metabolic Interaction

PubMed Central

Cortés-Campos, Christian; Elizondo, Roberto; Llanos, Paula; Uranga, Romina María; Nualart, Francisco; García, María Angeles

2011-01-01

Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes. PMID:21297988

Osmotic agents and buffers in peritoneal dialysis solution: monocyte cytokine release and in vitro cytotoxicity.

PubMed

Plum, J; Schoenicke, G; Grabensee, B

1997-09-01

Peritonitis remains a major problem in peritoneal dialysis. The incidence of peritonitis may be reduced by the use of more "biocompatible" peritoneal dialysis solutions that do not impair local host defense mechanisms, such as occurs with conventional lactate-buffered glucose solutions. In the present study, we investigated the use of bicarbonate and lactate as buffer systems and glucose, amino acids, and glucose polymer as osmotic agents on specific cellular functions of isolated fresh blood monocytes in vitro. The bicarbonate-buffered solutions had a physiologic pH (7.0 to 7.6). Lactate-buffered solutions were tested with a pH between 5.5 and 7.3. RPMI 1640 (Roswell Park Memorial Institute, supplied by Biochrom, Berlin, Germany) and phosphate-buffered saline were used as control mediums. The test solutions were incubated with 200,000 monocytes/mL for 45 minutes followed by a 1:1 mix with RPMI 1640 (with supplements) during a 24- or 4-hour tetrazolium bromide test (MTT test) recovery period. Constitutive and lipopolysaccharide (LPS)-stimulated release of interleukin-1beta (IL-1beta) and IL-6 in the supernatants as parameters of cellular host defense and lactate dehydrogenase concentrations and MTT-formazan production as parameters for cell cytotoxicity were measured. Significantly higher IL-6 and IL-1beta release was found in the bicarbonate-buffered solutions, both under basal conditions and after LPS stimulation, compared with the lactate-buffered solutions (LPS stimulation: 1% amino acids/34 mmol/L bicarbonate, IL-1beta: 1,166 +/- 192 pg/mL; 1.5% glucose/34 mmol/L bicarbonate, IL-1beta: 752 +/- 107 pg/mL; 1.5% glucose/35 mmol/L lactate/pH 5.5, IL-1beta: 174 +/- 51 pg/mL). Some of these differences could even be detected in spent dialysate after a 6-hour dwell in continuous ambulatory peritoneal dialysis patients (n = 10). A lower degree of cellular cytotoxicity (lactate dehydrogenase activity) and better-preserved metabolic activity (MTT test) also were found for the bicarbonate-buffered solutions. Amino acids (1%) proved to be comparable to glucose (1.5%) as an osmotic agent at a neutral pH with regard to LPS-stimulated cytokine release and cytotoxicity. The incubation with a glucose polymer solution (7.5% glucose polymer in phosphate-buffered saline, pH 7.3) resulted in a significantly lowered cytokine release (LPS stimulation: IL-1beta, 69 +/- 19 pg/mL) compared with the other solutions with neutral pH (P < 0.01). These results suggest that bicarbonate as a buffer provided better biocompatibility with regard to mononuclear cytokine release and viability compared with lactate. Amino acids and glucose were equivalent to these parameters at a physiologic pH. The glucose polymer solution, however, was associated with a marked depression of cytokine release.

Recovery from Short Term Intense Exercise: Its Relation to Capillary Supply and Lactate Release,

DTIC Science & Technology

1982-01-01

accumulate at a higher rate in fast twitch (FT or Type II) than in slow twitch (ST or Type I) fibers of exercised muscles . Lactate form- ed and accumulated...is made up by a high percentage of FT fibers than can be expected in a " slow twitch " muscle . Moreover, the over-all metabolic profile of the ST fiber...local muscular fatigue. Eur. J. Appl. Physiol. 38, 9-15 (1978b) Baldwin, K.M., Tipton, C.M.: Work and metabolic patterns of fast and slow twitch

Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation.

PubMed Central

Jhappan, C; Geiser, A G; Kordon, E C; Bagheri, D; Hennighausen, L; Roberts, A B; Smith, G H; Merlino, G

1993-01-01

Transforming growth factor-beta 1 (TGF-beta 1) possesses highly potent, diverse and often opposing cell-specific activities, and has been implicated in the regulation of a variety of physiologic and developmental processes. To determine the effects of in vivo overexpression of TGF-beta 1 on mammary gland function, transgenic mice were generated harboring a fusion gene consisting of the porcine TGF-beta 1 cDNA placed under the control of regulatory elements of the pregnancy-responsive mouse whey-acidic protein (WAP) gene. Females from two of four transgenic lines were unable to lactate due to inhibition of the formation of lobuloalveolar structures and suppression of production of endogenous milk protein. In contrast, ductal development of the mammary glands was not overtly impaired. There was a complete concordance in transgenic mice between manifestation of the lactation-deficient phenotype and expression of RNA from the WAP/TGF-beta 1 transgene, which was present at low levels in the virgin gland, but was greatly induced at mid-pregnancy. TGF-beta 1 was localized to numerous alveoli and to the periductal extracellular matrix in the mammary gland of transgenic females late in pregnancy by immunohistochemical analysis. Glands reconstituted from cultured transgenic mammary epithelial cells duplicated the inhibition of lobuloalveolar development observed in situ in the mammary glands of pregnant transgenic mice. Results from this transgenic model strongly support the hypothesis that TGF-beta 1 plays an important in vivo role in regulating the development and function of the mammary gland. Images PMID:8491177

Single nucleotide polymorphisms in specific candidate genes are associated with phenotypic differences in days open for first lactation in Holstein cows

USDA-ARS?s Scientific Manuscript database

Previously, a candidate gene approach identified 51 single nucleotide polymorphisms (SNP) associated with genetic merit for reproductive traits and 26 associated with genetic merit for production in dairy bulls. We evaluated association of the 77 SNPs with days open (DO) for first lactation in a pop...

Faecal D/L Lactate Ratio Is a Metabolic Signature of Microbiota Imbalance in Patients with Short Bowel Syndrome

PubMed Central

Mayeur, Camille; Gratadoux, Jean-Jacques; Bridonneau, Chantal; Chegdani, Fatima; Larroque, Béatrice; Kapel, Nathalie; Corcos, Olivier; Thomas, Muriel; Joly, Francisca

2013-01-01

Our objective was to understand the functional link between the composition of faecal microbiota and the clinical characteristics of adults with short bowel syndrome (SBS). Sixteen patients suffering from type II SBS were included in the study. They displayed a total oral intake of 2661±1005 Kcal/day with superior sugar absorption (83±12%) than protein (42±13%) or fat (39±26%). These patients displayed a marked dysbiosis in faecal microbiota, with a predominance of Lactobacillus/Leuconostoc group, while Clostridium and Bacteroides were under-represented. Each patient exhibited a diverse lactic acid bacteria composition (L. delbrueckii subsp. bulgaricus, L. crispatus, L. gasseri, L. johnsonii, L. reuteri, L. mucosae), displaying specific D and L-lactate production profiles in vitro. Of 16 patients, 9/16 (56%) accumulated lactates in their faecal samples, from 2 to 110 mM of D-lactate and from 2 to 80 mM of L-lactate. The presence of lactates in faeces (56% patients) was used to define the Lactate-accumulator group (LA), while absence of faecal lactates (44% patients) defines the Non lactate-accumulator group (NLA). The LA group had a lower plasma HCO3− concentration (17.1±2.8 mM) than the NLA group (22.8±4.6 mM), indicating that LA and NLA groups are clinically relevant sub–types. Two patients, belonging to the LA group and who particularly accumulated faecal D-lactate, were at risk of D-encephalopathic reactions. Furthermore, all patients of the NLA group and those accumulating preferentially L isoform in the LA group had never developed D-acidosis. The D/L faecal lactate ratio seems to be the most relevant index for a higher D- encephalopathy risk, rather than D- and L-lactate faecal concentrations per se. Testing criteria that take into account HCO3− value, total faecal lactate and the faecal D/L lactate ratio may become useful tools for identifying SBS patients at risk for D-encephalopathy. PMID:23372709

The effects of lactate and acid on articular chondrocytes function: Implications for polymeric cartilage scaffold design.

PubMed

Zhang, Xiaolei; Wu, Yan; Pan, Zongyou; Sun, Heng; Wang, Junjuan; Yu, Dongsheng; Zhu, Shouan; Dai, Jun; Chen, Yishan; Tian, Naifeng; Heng, Boon Chin; Coen, Noelle D; Xu, Huazi; Ouyang, Hongwei

2016-09-15

Poly (lactic-co-glycolic acid) (PLGA) and poly-l-lactate acid (PLLA) are biodegradable polymers widely utilized as scaffold materials for cartilage tissue engineering. Their acid degradation products have been widely recognized as being detrimental to cell function. However, the biological effects of lactate, rather than lactic acid, on chondrocytes have never been investigated. This is the major focus of this study. The amounts of lactate and the pH value (acid) of the PLGA and PLLA degradation medium were measured. The effects of PLGA and PLLA degradation medium, as well as different lactate concentrations and timing of exposure on chondrocytes proliferation and cartilage-specific matrix synthesis were investigated by various techniques including global gene expression profiling and gene knockdown experiments. It was shown that PLGA and PLLA degradation medium differentially regulated chondrocyte proliferation and matrix synthesis. Acidic pH caused by lactate inhibited chondrocyte proliferation and matrix synthesis. The effect of lactate on chondrocyte matrix synthesis was both time and dose dependent. A lactate concentration of 100mM and exposure duration of 8h significantly enhanced matrix synthesis. Lactate could also inhibit expression of cartilage matrix degradation genes in osteoarthritic chondrocytes, such as the major aggrecanase ADAMTS5, whilst promoting matrix synthesis simultaneously. Pulsed addition of lactate was shown to be more efficient in promoting COL2A1 expression. Global gene expression data and gene knock down experiments demonstrated that lactate promote matrix synthesis through up-regulation of HIF1A. These observed differential biological effects of lactate on chondrocytes would have implications for the future design of polymeric cartilage scaffolds. Lactic acid is a widely used substrate for polymers synthesis, PLGA and PLLA in particular. Although physical and biological modifications have been made on these polymers to make them be better cartilage scaffolds, little concern has been given on the biological effect of lactic acid, the main degradation product of these polymers, on chondrocytes. Our finding illustrates the differential biological function of lactate and acid on chondrocytes matrix synthesis. These results can facilitate future design of lactate polymers-based cartilage scaffolds. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Lactate clearance as the predictor of outcome in pediatric septic shock.

PubMed

Choudhary, Richa; Sitaraman, Sadasivan; Choudhary, Anita

2017-01-01

Septic shock can rapidly evolve into multiple system organ failure and death. In the recent years, hyperlactatemia has been found to be a risk factor for mortality in critically ill adults. To evaluate the predictive value of lactate clearance and to determine the optimal cut-off value for predicting outcome in children with septic shock. A prospective observational study was performed on children with septic shock admitted to pediatric Intensive Care Unit (PICU). Serial lactate levels were measured at PICU admission, 24 and 48 h later. Lactate clearance, percent decrease in lactate level in 24 h, was calculated. The primary outcome measure was survival or nonsurvival at the end of hospital stay. We performed receiver operating characteristic analyses to calculate optimal cut-off values. The mean lactate levels at admission were significantly higher in the nonsurvivors than survivors, 5.12 ± 3.51 versus 3.13 ± 1.71 mmol/L ( P = 0.0001). The cut-off for lactate level at admission for the best prediction of mortality was determined as ≥4 mmol/L (odds ratio 5.4; 95% confidence interval [CI] =2.45-12.09). Mean lactate clearance was significantly higher in survivors than nonsurvivors (17.9 ± 39.9 vs. -23.2 ± 62.7; P < 0.0001). A lactate clearance rate of <10% at 24 h had a sensitivity and specificity of 78.7% and 72.2%, respectively and a positive predictive value of 83.1% for death. Failure to achieve a lactate clearance of more than 10% was associated with greater risk of mortality (likelihood ratio + 2.83; 95% CI = 1.82-4.41). Serial lactate levels can be used to predict outcome in pediatric septic shock. A 24 h lactate clearance cut-off of <10% is a predictor of in-hospital mortality in such patients.

Effects of maternal dietary egg intake during early lactation on human milk ovalbumin concentration: a randomized controlled trial.

PubMed

Metcalfe, J R; Marsh, J A; D'Vaz, N; Geddes, D T; Lai, C T; Prescott, S L; Palmer, D J

2016-12-01

There is limited understanding of how maternal diet affects breastmilk food allergen concentrations, and whether exposure to allergens through this route influences the development of infant oral tolerance or sensitization. To investigate how maternal dietary egg ingestion during early lactation influences egg protein (ovalbumin) levels detected in human breastmilk. In a randomized controlled trial, women were allocated to a dietary group for the first six weeks of lactation: high-egg diet (> 4 eggs per week), low-egg diet (one-three eggs per week) or an egg-free diet. Breastmilk samples were collected at 2, 4 and 6 weeks of lactation for the measurement of ovalbumin. The permeability of the mammary epithelium was assessed by measuring the breastmilk sodium : potassium ratio. Egg-specific IgE and IgG4 were measured in infant plasma at 6 weeks, and prior to the introduction of egg in solids at 16 weeks. Average maternal egg ingestion was associated with breastmilk ovalbumin concentration. Specifically, for each additional egg ingested per week, there was an average 25% increase in ovalbumin concentration (95% CI: 5-48%, P = 0.01). Breastmilk ovalbumin concentrations were significantly higher in the 'high-egg' group (> 4 eggs per week) compared with the 'egg-free' group (P = 0.04). However, one-third of women had no breastmilk ovalbumin detected. No detectable associations were found between mammary epithelium permeability and breastmilk ovalbumin concentrations. Infant plasma egg-specific IgG4 levels were also positively associated with maternal egg ingestion, with an average 22% (95% CI: 3-45%) increase in infant egg-specific IgG4 levels per additional egg consumed per week (P = 0.02). Increased maternal egg ingestion is associated with increased breastmilk ovalbumin, and markers of immune tolerance in infants. These results highlight the potential for maternal diet to benefit infant oral tolerance development during lactation. © 2016 John Wiley & Sons Ltd.

Lactate as a Metabolite and a Regulator in the Central Nervous System

PubMed Central

Proia, Patrizia; Di Liegro, Carlo Maria; Schiera, Gabriella; Fricano, Anna; Di Liegro, Italia

2016-01-01

More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time. PMID:27598136

CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.

PubMed

Giulieri, S; Chapuis-Taillard, C; Jaton, K; Cometta, A; Chuard, C; Hugli, O; Du Pasquier, R; Bille, J; Meylan, P; Manuel, O; Marchetti, O

2015-10-01

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.

The Predominant Proteins that React to the MC-20 Estrogen Receptor Alpha Antibody Differ in Molecular Weight between the Mammary Gland and Uterus in the Mouse and Rat.

PubMed

Bollig-Fischer, Aliccia; Thakur, Archana; Sun, Yuan; Wu, Jiusheng; Liao, D Joshua

2012-03-01

There are many estrogen receptor α (ERα) antibodies available but few of them target a rodent ERα. Using the MC-20 antibody raised against the C-terminus of mouse ERα, we show in this communication that in the mammary gland of female mice and rats, the wild type (wt) ERα was detected on immunoblots as a dominant protein only during lactation, and the protein was lactating specific as it migrated slightly faster than the 67-kD wt ERα in the uterus, likely due to a different phosphorylation status. In contrast, in the nulliparous, pregnant, involuting and involuted mammary glands, the dominant protein recognized by MC-20 was about 61-kD, which is dubbed herein as "MC-20 reactive protein" or MC20RP in abbreviation as its identity is unknown. Our results showed that it was not derived from proteolysis or de-phosphorylation of the 67-kD ERα and was unlikely to be translated from an ERα mRNA variant. Ovariectomy decreased the lactating specific wt ERα but increased the 61-kD MC20RP in the mammary tumors from MMTV-c-myc transgenic mice but these two proteins in the uterus were unaffected. The 61-kD MC20RP was decreased in the mammary tumors, compared with proliferating mammary glands, in estrogen-treated ACI rats. These results suggest that while the lactating specific wt ERα alone or together with the MC20RP may sustain lactation, the MC20RP may support proliferation of the mammary gland and some mammary tumors.

Stringency of substrate specificity of Escherichia coli malate dehydrogenase.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boernke, W. E.; Millard, C. S.; Stevens, P. W.

1995-09-10

Malate dehydrogenase and lactate dehydrogenase are members of the structurally and functionally homologous family of 2-ketoacid dehydrogenases. Both enzymes display high specificity for their respective keto substrates, oxaloacetate and pyruvate. Closer analysis of their specificity, however, reveals that the specificity of malate dehydrogenase is much stricter and less malleable than that of lactate dehydrogenase. Site-specific mutagenesis of the two enzymes in an attempt to reverse their specificity has met with contrary results. Conversion of a specific active-site glutamine to arginine in lactate dehydrogenase from Bacillus stearothermophilus generated an enzyme that displayed activity toward oxaloacetate equal to that of the nativemore » enzyme toward pyruvate (H. M. Wilks et al. (1988) Science 242, 1541-1544). We have constructed a series of mutants in the mobile, active site loop of the Escherichia coli malate dehydrogenase that incorporate the complementary change, conversion of arginine 81 to glutamine, to evaluate the role of charge distribution and conformational flexibility within this loop in defining the substrate specificity of these enzymes. Mutants incorporating the change R81Q all had reversed specificity, displaying much higher activity toward pyruvate than to the natural substrate, oxaloacetate. In contrast to the mutated lactate dehydrogenase, these reversed-specificity mutants were much less active than the native enzyme. Secondary mutations within the loop of the E. coli enzyme (A80N, A80P, A80P/M85E/D86T) had either no or only moderately beneficial effects on the activity of the mutant enzyme toward pyruvate. The mutation A80P, which can be expected to reduce the overall flexibility of the loop, modestly improved activity toward pyruvate. The possible physiological relevance of the stringent specificity of malate dehydrogenase was investigated. In normal strains of E. coli, fermentative metabolism was not affected by expression of the mutant malate dehydrogenase. However, when expressed in a strain of E. coli unable to ferment glucose, the mutant enzyme restored growth and produced lactic acid as the sole fermentation product.« less

The α-Arrestin Bul1p Mediates Lactate Transporter Endocytosis in Response to Alkalinization and Distinct Physiological Signals.

PubMed

Talaia, Gabriel; Gournas, Christos; Saliba, Elie; Barata-Antunes, Cláudia; Casal, Margarida; André, Bruno; Diallinas, George; Paiva, Sandra

2017-11-24

Eukaryotic α-arrestins connect environmental or stress signaling pathways to the endocytosis of plasma membrane transporters or receptors. The Saccharomyces cerevisiae lactate transporter Jen1p has been used as a model cargo for elucidating the mechanisms underlying endocytic turnover in response to carbon sources. Here, we discover a novel pathway of Jen1p endocytosis mediated by the α-arrestin Bul1p in response to the presence of cycloheximide or rapamycin, or prolonged growth in lactate. While cycloheximide or rapamycin modify cells pleiotropically, the major effect of prolonged growth in lactate was shown to be external pH alkalinization. Importantly, employment of specific inactive Jen1p versions showed that Bul1p-dependent endocytosis requires lactate transport, according to the signal imposed. Our results support a model where conformational changes of Jen1p, associated with substrate/H + symport, are critical for the efficiency of Bul1p-dependent Jen1p turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

Base excess is an accurate predictor of elevated lactate in ED septic patients.

PubMed

Montassier, Emmanuel; Batard, Eric; Segard, Julien; Hardouin, Jean-Benoît; Martinage, Arnaud; Le Conte, Philippe; Potel, Gille

2012-01-01

Prior studies showed that lactate is a useful marker in sepsis. However, lactate is often not routinely drawn or rapidly available in the emergency department (ED). The study aimed to determine if base excess (BE), widely and rapidly available in the ED, could be used as a surrogate marker for elevated lactate in ED septic patients. This was a prospective and observational cohort study. From March 2009 to March 2010, consecutive patients 18 years or older who presented to the ED with a suspected severe sepsis were enrolled in the study. Lactate and BE measurements were performed. We defined, a priori, a clinically significant lactate to be greater than 3 mmol/L and BE less than -4 mmol/L. A total of 224 patients were enrolled in the study. The average BE was -4.5 mmol/L (SD, 4.9) and the average lactate was 3.5 mmol/L (SD, 2.9). The sensitivity of a BE less than -4 mmol/L in predicting elevated lactate greater than 3 mmol/L was 91.1% (95% confidence interval, 85.5%-96.6%) and the specificity was 88.6% (95% confidence interval, 83.0%-94.2%). The area under the curve was 0.95. Base excess is an accurate marker for the prediction of elevated lactate in the ED. The measurement of BE, obtained in a few minutes in the ED, provides a secure and quick method, similar to the electrocardiogram at triage for patients with chest pain, to determine the patients with sepsis who need an early aggressive resuscitation. Copyright © 2012 Elsevier Inc. All rights reserved.

[The role of lactate acidosis in the development and treatment of various neurologic syndromes in children and adolescents].

PubMed

Arveladze, G A; Geladze, N M; Sanikidze, T B; Khachapuridze, N S; Bakhtadze, S Z

2015-02-01

The aim of the study was to detect the role of lactate acidosis, also to find the share of mitochondrial insufficiency in development of various neurologic syndromes in children and adolescents. The detection of cellular energetic metabolism and acid based imbalance is also important for finding the specific method of management. We have studied 200 patients with various degree of neurodevelopment delay with epilepsy and epileptic syndromes, headache, vertigo, early strokes, floppy infant syndrome, atrophy of ophthalmic nerve, cataracta, neurosensory deafness, systemic myopathy, cerebral palsy. In 27% of cases with various ages we have detected lactate acidosis and increase level of pyruvate. Mitochondrial insufficiency was seen in 8% of cases which gives us opportunity to find the specific method of treatment in this group of patients. Each patient with neurological symptoms requires correction of parameters of energetic and oxidative metabolism.

Accumulation of lactate by supercooled hatchlings of the painted turtle (Chrysemys picta): implications for overwinter survival.

PubMed

Hartley, L M; Packard, M J; Packard, G C

2000-02-01

Hatchlings of the North American painted turtle (Chrysemys picta) typically spend their first winter of life inside the shallow, subterranean nest where they completed embryogenesis the preceding summer. Neonates at northern localities consequently may be exposed during winter to subzero temperatures and frozen soil. Hatchlings apparently survive exposure to such conditions by supercooling, but the physiological consequences of this adaptive strategy have not been examined. We measured lactate in hatchling painted turtles after exposure to each of three temperatures (0 degree C, -4 degrees C, and -8 degrees C) for three time periods (5 days, 15 days, and 25 days) to determine the extent to which overwintering hatchlings might rely on anaerobic metabolism to regenerate ATP. Whole-body lactate increased with increasing duration of exposure and decreasing temperature, and the highest levels were associated with the group that experienced the highest mortality. These results indicate that animals may develop a considerable lactic acidosis during a winter in which temperatures fall below 0 degree C for weeks or months and that accumulation of lactate may contribute to mortality of overwintering animals.

Layered Double Hydroxide Nanotransporter for Molecule Delivery to Intact Plant Cells

PubMed Central

Bao, Wenlong; Wang, Junya; Wang, Qiang; O’Hare, Dermot; Wan, Yinglang

2016-01-01

Here we report a powerful method that facilitates the transport of biologically active materials across the cell wall barrier in plant cells. Positively charged delaminated layered double hydroxide lactate nanosheets (LDH-lactate-NS) with a 0.5‒2 nm thickness and 30‒60 nm diameter exhibit a high adsorptive capacity for negatively charged biomolecules, including fluorescent dyes such as tetramethyl rhodamine isothiocyanate (TRITC), fluorescein isothiocyanate isomer I(FITC) and DNA molecules, forming neutral LDH-nanosheet conjugates. These neutral conjugates can shuttle the bound fluorescent dye into the cytosol of intact plant cell very efficiently. Furthermore, typical inhibitors of endocytosis and low temperature incubation did not prevent LDH-lactate-NS internalization, suggesting that LDH-lactate-NS penetrated the plasma membrane via non-endocytic pathways, which will widen the applicability to a variety of plant cells. Moreover, the absence of unwanted side effects in our cytological studies, and the nuclear localization of ssDNA-FITC suggest that nano-LDHs have potential application as a novel gene carrier to plants. PMID:27221055

Monocarboxylate Transporters MCT1 and MCT4 Regulate Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells.

PubMed

Kong, Su Chii; Nøhr-Nielsen, Asbjørn; Zeeberg, Katrine; Reshkin, Stephan Joel; Hoffmann, Else Kay; Novak, Ivana; Pedersen, Stine Falsig

2016-08-01

Novel treatments for pancreatic ductal adenocarcinoma (PDAC) are severely needed. The aim of this work was to explore the roles of H-lactate monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in PDAC cell migration and invasiveness. Monocarboxylate transporter expression, localization, activity, and function were explored in human PDAC cells (MIAPaCa-2, Panc-1, BxPC-3, AsPC-1) and normal human pancreatic ductal epithelial (HPDE) cells, by quantitative polymerase chain reaction, immunoblotting, immunocytochemistry, lactate flux, migration, and invasion assays. MCT1 and MCT4 (messenger RNA, protein) were robustly expressed in all PDAC lines, localizing to the plasma membrane. Lactate influx capacity was highest in AsPC-1 cells and lowest in HPDE cells and was inhibited by the MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), MCT1/MCT2 inhibitor AR-C155858, or knockdown of MCT1 or MCT4. PDAC cell migration was largely unaffected by MCT1/MCT2 inhibition or MCT1 knockdown but was reduced by 4-CIN and by MCT4 knockdown (BxPC-3). Invasion measured in Boyden chamber (BxPC-3, Panc-1) and spheroid outgrowth (BxPC-3) assays was attenuated by 4-CIN and AR-C155858 and by MCT1 or MCT4 knockdown. Human PDAC cells exhibit robust MCT1 and MCT4 expression and partially MCT1- and MCT4-dependent lactate flux. PDAC cell migration is partially dependent on MCT4; and invasion, on MCT1 and MCT4. Inhibition of MCT1 and MCT4 may have clinical relevance in PDAC.

Clinical utility of serum lactate levels for differential diagnosis of generalized tonic-clonic seizures from psychogenic nonepileptic seizures and syncope.

PubMed

Doğan, Ebru Apaydın; Ünal, Ali; Ünal, Aslıhan; Erdoğan, Çağla

2017-10-01

The differential diagnosis of generalized tonic-clonic seizures (GTCS), psychogenic nonepileptic seizures (PNES), and syncope constitutes a major challenge. Misdiagnosis rates up to 20 to 30% are reported in the literature. To assess the clinical utility of serum lactate levels for differentiation of GTCS, PNES, and syncope based on gender differences. Data from 270 patients were evaluated retrospectively. Only patients ≥18 years old with the final diagnosis of GTCS, PNES, or syncope in their chart were recruited. Serum lactate levels were measured in the first 2h of the index event. Serum lactate levels in patients with GTCS (n=157) were significantly higher than in the patients with PNES (n=25) (p<0.001) and syncope (n=88) (p<0.001). When compared with the females, serum lactate levels in patients with GTCS were significantly higher in the male subgroup (p=0.004). In male patients the ROC analysis yielded a serum lactate value of 2.43mmol/l with a sensitivity of 0.85 and a specificity of 0.88 as the optimal cut-off value to distinguish GTCS from other events. The ROC analysis for the AUC yielded a high estimate of 0.94 (95% confidence interval: 0.91-0.98). When a cut-off value of 2.43mmol/l was chosen for the females, which was an optimal value for male patients, the specificity was 0.85, however, the sensitivity was 0.64. We propose that serum lactate level when measured in the first 2h after the index event has a high clinical utility in the differential diagnosis of GTCS, PNES, and syncope. With concomitant clinical signs and physical examination findings besides neuroimaging and EEG, elevated levels of lactate should be taken into account when evaluating a patient with impaired consciousness. On the other hand, the suggested cut-off value 2.43mmol/l might not have a discriminative effect between GTCS, PNES, and syncope in female patients. This finding should be verified in a prospectively designed study with a larger patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic evaluation of lactation persistency for five breeds of dairy cattle.

PubMed

Cole, J B; Null, D J

2009-05-01

Cows with high lactation persistency tend to produce less milk than expected at the beginning of lactation and more than expected at the end. Best prediction of lactation persistency is calculated as a function of trait-specific standard lactation curves and linear regressions of test-day deviations on days in milk. Because regression coefficients are deviations from a tipping point selected to make yield and lactation persistency phenotypically uncorrelated it should be possible to use 305-d actual yield and lactation persistency to predict yield for lactations with later endpoints. The objectives of this study were to calculate (co)variance components and breeding values for best predictions of lactation persistency of milk (PM), fat (PF), protein (PP), and somatic cell score (PSCS) in breeds other than Holstein, and to demonstrate the calculation of prediction equations for 400-d actual milk yield. Data included lactations from Ayrshire, Brown Swiss, Guernsey (GU), Jersey (JE), and Milking Shorthorn (MS) cows calving since 1997. The number of sires evaluated ranged from 86 (MS) to 3,192 (JE), and mean sire estimated breeding value for PM ranged from 0.001 (Ayrshire) to 0.10 (Brown Swiss); mean estimated breeding value for PSCS ranged from -0.01 (MS) to -0.043 (JE). Heritabilities were generally highest for PM (0.09 to 0.15) and lowest for PSCS (0.03 to 0.06), with PF and PP having intermediate values (0.07 to 0.13). Repeatabilities varied considerably between breeds, ranging from 0.08 (PSCS in GU, JE, and MS) to 0.28 (PM in GU). Genetic correlations of PM, PF, and PP with PSCS were moderate and favorable (negative), indicating that increasing lactation persistency of yield traits is associated with decreases in lactation persistency of SCS, as expected. Genetic correlations among yield and lactation persistency were low to moderate and ranged from -0.55 (PP in GU) to 0.40 (PP in MS). Prediction equations for 400-d milk yield were calculated for each breed by regression of both 305-d yield and 305-d yield and lactation persistency on 400-d yield. Goodness-of-fit was very good for both models, but the addition of lactation persistency to the model significantly improved fit in all cases. Routine genetic evaluations for lactation persistency, as well as the development of prediction equations for several lactation end-points, may provide producers with tools to better manage their herds.

Failure to Clear Elevated Lactate Predicts 24-Hour Mortality in Trauma Patients

PubMed Central

Dezman, Zachary D.W.; Comer, Angela C.; Smith, Gordon S.; Narayan, Mayur; Scalea, Thomas M.; Hirshon, Jon Mark

2015-01-01

Background Lactate clearance is a standard resuscitation goal in patients in non-traumatic shock but has not been investigated adequately as a tool to identify trauma patients at risk of dying. Our objective was to determine if trauma patients with impaired lactate clearance have a higher 24-hour mortality rate than patients whose lactate concentration normalizes. Methods A retrospective chart review identified patients who were admitted directly from the scene of injury to an urban trauma center between 2010 and 2013 and who had at least one lactate concentration measurement within 24 hours. Transfers, patients without lactate measurement, and those who were dead on arrival were excluded. Of the 26,545 screened patients, 18,304 constituted the initial lactate measurement population and 3,887 were the lactate clearance cohorts. Results Initial lactate had an area-under-the-receiver operating curve of 0.86 and 0.73 for mortality at 24 hours and in-hospital, respectively. An initial concentration ≥3 mmol/L had sensitivity of 0.86 and specificity of 0.73 for mortality at 24 hours. The mortality rate among patients with elevated lactate concentrations (n=2381, 5.6±2.8 mmol/L) that did not decline to <2.0 mmol/L in response to resuscitative efforts (mean second measurement, 3.7±1.9 mmol/L) was nearly seven times higher (4.1% vs 0.6% [p<0.001]) than among those with an elevated concentration (n=1506, 5.3±2.7 mmol/L) that normalized (1.4±0.4 mmol/L). Logistic regression analysis showed that failure to clear lactate was associated with death more than any other feature (OR=7.4; CI, 1.5–35.5), except having an Injury Severity Score >25 (OR=8.2; CI, 2.7–25.2). Conclusions Failure to clear lactate is a strong negative prognostic marker after injury. An initial lactate measurement combined with a second measurement for high-risk individuals might constitute a useful method of risk-stratifying injured patients. PMID:26402531

Prolactin-induced Subcellular Targeting of GLUT1 Glucose Transporter in Living Mammary Epithelial Cells

PubMed Central

Riskin, Arieh; Mond, Yehudit

2015-01-01

Background Studying the biological pathways involved in mammalian milk production during lactation could have many clinical implications. The mammary gland is unique in its requirement for transport of free glucose into the cell for the synthesis of lactose, the primary carbohydrate in milk. Objective To study GLUT1 trafficking and subcellular targeting in living mammary epithelial cells (MEC) in culture. Methods Immunocytochemistry was used to study GLUT1 hormonally regulated subcellular targeting in human MEC (HMEC). To study GLUT1 targeting and recycling in living mouse MEC (MMEC) in culture, we constructed fusion proteins of GLUT1 and green fluorescent protein (GFP) and expressed them in CIT3 MMEC. Cells were maintained in growth medium (GM), or exposed to secretion medium (SM), containing prolactin. Results GLUT1 in HMEC localized primarily to the plasma membrane in GM. After exposure to prolactin for 4 days, GLUT1 was targeted intracellularly and demonstrated a perinuclear distribution, co-localizing with lactose synthetase. The dynamic trafficking of GFP-GLUT1 fusion proteins in CIT3 MMEC suggested a basal constitutive GLUT1 recycling pathway between an intracellular pool and the cell surface that targets most GLUT1 to the plasma membrane in GM. Upon exposure to prolactin in SM, GLUT1 was specifically targeted intracellularly within 90–110 minutes. Conclusions Our studies suggest intracellular targeting of GLUT1 to the central vesicular transport system upon exposure to prolactin. The existence of a dynamic prolactin-induced sorting machinery for GLUT1 could be important for transport of free glucose into the Golgi for lactose synthesis during lactation. PMID:26886772

Evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients.

PubMed

Karon, Brad S; Tolan, Nicole V; Wockenfus, Amy M; Block, Darci R; Baumann, Nikola A; Bryant, Sandra C; Clements, Casey M

2017-11-01

Lactate, white blood cell (WBC) and neutrophil count, procalcitonin and immature granulocyte (IG) count were compared for the prediction of sepsis, and severe sepsis or septic shock, in patients presenting to the emergency department (ED). We prospectively enrolled 501 ED patients with a sepsis panel ordered for suspicion of sepsis. WBC, neutrophil, and IG counts were measured on a Sysmex XT-2000i analyzer. Lactate was measured by i-STAT, and procalcitonin by Brahms Kryptor. We classified patients as having sepsis using a simplification of the 1992 consensus conference sepsis definitions. Patients with sepsis were further classified as having severe sepsis or septic shock using established criteria. Univariate receiver operating characteristic (ROC) analysis was performed to determine odds ratio (OR), area under the ROC curve (AUC), and sensitivity/specificity at optimal cut-off for prediction of sepsis (vs. no sepsis), and prediction of severe sepsis or septic shock (vs. no sepsis). There were 267 patients without sepsis; and 234 with sepsis, including 35 patients with severe sepsis or septic shock. Lactate had the highest OR (1.44, 95th% CI 1.20-1.73) for the prediction of sepsis; while WBC, neutrophil count and percent (neutrophil/WBC) had OR>1.00 (p<0.05). All biomarkers had AUC<0.70 and sensitivity and specificity <70% at the optimal cut-off. Initial lactate was the best biomarker for predicting severe sepsis or septic shock, with an odds ratio (95th% CI) of 2.70 (2.02-3.61) and AUC 0.89 (0.82-0.96). Traditional biomarkers (lactate, WBC, neutrophil count, procalcitonin, IG) have limited utility in the prediction of sepsis. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Lactation curves of dairy camels in an intensive system.

PubMed

Musaad, Abdelgadir; Faye, Bernard; Nikhela, Abdelmoneim Abu

2013-04-01

Weekly milk records of 47 she-camels in a multibreed dairy camel herd were collected for over a period of 5 years. A total of 72 lactation curves were defined, and relationships with parity, calving season, lactation length, milk production level, following lactations, and dam weight were analyzed. Overall mean values were milk yield up to 12 months, 1,970 ± 790 l; lactation length, 12.5 months; persistency, 94.7 %; weekly peak yield, 50.7 l; monthly peak yield, 220 ± 90 l; and the number of weeks to reach peak yield, 28. The highest productivity was recorded in summer with a weekly mean of 48.2 ± 19.4 l, compared with 34.1 ± 16.3 l in winter. The highest average yield recorded was for camels at sixth parity, whereas the highest weekly peak was at eighth parity, and highest persistency at fifth parity. Camels that calved during the cold months (November to February) were most productives, with the highest persistency, peak yield, and longest lactation length. Four types of curves were identified corresponding to different parities and milk yield levels. Based on these data, specific models for camels are proposed.

Management of hyperthyroidism during pregnancy and lactation.

PubMed

Azizi, Fereidoun; Amouzegar, Atieh

2011-06-01

Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome. Fetal and neonatal hypo- or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods. To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation. A literature review was performed using MEDLINE with the terms 'hyperthyroidism and pregnancy', 'antithyroid drugs and pregnancy', 'radioiodine and pregnancy', 'hyperthyroidism and lactation', and 'antithyroid drugs and lactation', both separately and in conjunction with the terms 'fetus' and 'maternal.' Antithyroid drugs are the main therapy for maternal hyperthyroidism. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester. Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern. Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy. MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation. Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate.

Lactate production as representative of the fermentation potential of Corynebacterium glutamicum 2262 in a one-step process.

PubMed

Khuat, Hoang Bao Truc; Kaboré, Abdoul Karim; Olmos, Eric; Fick, Michel; Boudrant, Joseph; Goergen, Jean-Louis; Delaunay, Stéphane; Guedon, Emmanuel

2014-01-01

The fermentative properties of thermo-sensitive strain Corynebacterium glutamicum 2262 were investigated in processes coupling aerobic cell growth and the anaerobic fermentation phase. In particular, the influence of two modes of fermentation on the production of lactate, the fermentation product model, was studied. In both processes, lactate was produced in significant amount, 27 g/L in batch culture, and up to 55.8 g/L in fed-batch culture, but the specific production rate in the fed-batch culture was four times lower than that in the batch culture. Compared to other investigated fermentation processes, our strategy resulted in the highest yield of lactic acid from biomass. Lactate production by C. glutamicum 2262 thus revealed the capability of the strain to produce various fermentation products from pyruvate.

Sequencing the transcriptome of milk production: milk trumps mammary tissue.

PubMed

Lemay, Danielle G; Hovey, Russell C; Hartono, Stella R; Hinde, Katie; Smilowitz, Jennifer T; Ventimiglia, Frank; Schmidt, Kimberli A; Lee, Joyce W S; Islas-Trejo, Alma; Silva, Pedro Ivo; Korf, Ian; Medrano, Juan F; Barry, Peter A; German, J Bruce

2013-12-12

Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation.

Lactation induction as a predictor of post-parturition transgene expression in bovine milk.

PubMed

Powell, Ann; Kerr, David; Guthrie, David; Wall, Robert

2007-05-01

The bovine's long generation interval results in a delay of several years when evaluating mammary specific transgenes in genetically engineered animals. This experiment was conducted to evaluate the feasibility of reducing that waiting period. Lactation was induced in prepubertal bull and heifer calves as a means of predicting transgene behaviour during subsequent post-parturient lactations in the heifers themselves, and in daughters sired by the bulls. The animals carry a lactation-specific transgene encoding lysostaphin, an antimicrobial protein that kills Staphlococcus aureus, a mastitis-causing pathogen. Oestrogen, progesterone and dexamethasone were administered as previously described (Ball et al. 2000) to nine heifers (five transgenics) ranging in weight from 80 to 145 kg. Eight bull calves (seven transgenics) weighing 81-178 kg received additional oestrogen and progesterone injection prior to dexamethasone treatment. All nine heifers responded to the milk induction scheme yielding between 19 ml and 4.5 l over 5 d. Milk volume from the four responding males (30 microl to 2.5 ml) was significantly less than that harvested from females (P=0.025). Only bull calves >117 kg had a positive response. Lysostaphin was detected in all transgenic prepubertal heifers and in two transgenic prepubertal bull calves induced. A positive relationship was observed between lysostaphin's stapholytic activity in the two types of lactations (r2=0.907, P<0.001) thus providing a useful means of predicting subsequent lysostaphin production in post-partum milk.

Actin isoform specificity is required for the maintenance of lactation

PubMed Central

Weymouth, Nate; Shi, Zengdun; Rockey, Don C.

2014-01-01

Smooth muscle α-actin (Acta2) is one of six highly conserved mammalian actin isoforms that appear to exhibit functional redundancy. Nonetheless, we have postulated a specific functional role for the smooth muscle specific isoform. Here, we show that Acta2 deficient mice have a remarkable mammary phenotype such that dams lacking Acta2 are unable to nurse their offspring effectively. The phenotype was rescued in cross fostering experiments with wild type mice, excluding a developmental defect in Acta2 null pups. The mechanism for the underlying phenotype is due to myoepithelial dysfunction postpartum resulting in precocious involution. Further, we demonstrate a specific defect in myoepithelial cell contractility in Acta2 null mammary glands, despite normal expression of cytoplasmic actins. We conclude that Acta2 specifically mediates myoepithelial cell contraction during lactation and that this actin isoform therefore exhibits functional specificity. PMID:22123032

Some Lactobacillus l-Lactate Dehydrogenases Exhibit Comparable Catalytic Activities for Pyruvate and Oxaloacetate

PubMed Central

Arai, Kazuhito; Kamata, Takeo; Uchikoba, Hiroyuki; Fushinobu, Shinya; Matsuzawa, Hiroshi; Taguchi, Hayao

2001-01-01

The nonallosteric and allosteric l-lactate dehydrogenases of Lactobacillus pentosus and L. casei, respectively, exhibited broad substrate specificities, giving virtually the same maximal reaction velocity and substrate Km values for pyruvate and oxaloacetate. Replacement of Pro101 with Asn reduced the activity of the L. pentosus enzyme toward these alternative substrates to a greater extent than the activity toward pyruvate. PMID:11114942

Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

PubMed

Shrestha, P K; Tamrakar, P; Ibrahim, B A; Briski, K P

2014-10-10

Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Females of the communally breeding rodent, Octodon degus, transfer antibodies to their offspring during pregnancy and lactation.

PubMed

Becker, María Inés; De Ioannes, Alfredo E; León, Cecilia; Ebensperger, Luis A

2007-06-01

Females in numerous rodent species engage in communal nesting and breeding, meaning that they share a nest to rear their young together. One potential benefit to communally nesting mothers is that infants improve their immunocompetence. Thus, suckling from two or more females might provide newborns with a more diverse array of antibodies and defensive cells. As a first step toward testing the immunocompetence hypothesis, we assessed whether female degus (Octodon degus), a communally nesting and breeding caviomorph rodent, transfer immunoglobulins to their young through the yolk sac or placenta while in the uterus and, during lactation, through milk. With this aim, adult degu females were immunized with four antigens, including two mollusk hemocyanins from Concholepas and Megathura (CCH and KLH, respectively), porcine thyroglobulin and tetanus toxoid. Specific antibodies against the experimental antigens were used to track the origin of antibodies in the young. To establish the presence of specific antibodies of IgG and IgA isotypes in sera and milk of animals, an indirect enzyme-linked immunosorbent assay (ELISA) was developed. Degu females produced specific antibodies against antigens not found in their natural environment, and mothers were able to transfer the induced antibodies to their litters during pregnancy (IgG) and during lactation (IgA). However, we recorded only limited evidence of degu offspring acquiring antibodies from lactating mothers other than their own, giving little support to the increased immunocompetence hypothesis.

Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load.

PubMed

Iredahl, Fredrik; Högstedt, Alexandra; Henricson, Joakim; Sjöberg, Folke; Tesselaar, Erik; Farnebo, Simon

2016-10-01

Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load. Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI). Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load. Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load. © 2016 John Wiley & Sons Ltd.

Silicon/SU8 multi-electrode micro-needle for in vivo neurochemical monitoring.

PubMed

Vasylieva, Natalia; Marinesco, Stéphane; Barbier, Daniel; Sabac, Andrei

2015-10-15

Simultaneous monitoring of glucose and lactate is an important challenge for understanding brain energetics in physiological or pathological states. We demonstrate here a versatile method based on a minimally invasive single implantation in the rat brain. A silicon/SU8-polymer multi-sensing needle-shaped biosensor, was fabricated and tested. The multi-electrode array design comprises three platinum planar microelectrodes with a surface area of 40 × 200 µm(2) and a spacing of 200 µm, which were micromachined on a single 3mm long micro-needle having a 100 × 50 µm(2) cross-section for reduced tissue damage during implantation. Platinum micro-electrodes were aligned at the bottom of micro-wells obtained by photolithography on a SU8 photoresist layer. After clean room processing, each micro-electrode was functionalized inside the micro-wells by means of a micro-dispensing device, either with glucose oxidase or with lactate oxidase, which were cross-linked on the platinum electrodes. The third electrode covered with Bovine Serum Albumin (BSA) was used for the control of non-specific currents. The thick SU8 photoresist layer has revealed excellent electrical insulation of the micro-electrodes and between interconnection lines, and ensured a precise localization and packaging of the sensing enzymes on platinum micro-electrodes. During in vitro calibration with concentrations of analytes in the mM range, the micro-wells patterned in the SU8 photoresist proved to be highly effective in eliminating cross-talk signals, caused by H2O2 diffusion from closely spaced micro-electrodes. Moreover, our biosensor was successfully assayed in the rat cortex for simultaneous monitoring of both glucose and lactate during insulin and glucose administration. Copyright © 2015 Elsevier B.V. All rights reserved.

Reduction of ammonia and lactate through the coupling of glutamine synthetase selection and downregulation of lactate dehydrogenase-A in CHO cells.

PubMed

Noh, Soo Min; Park, Jin Hyoung; Lim, Myung Sin; Kim, Jong Won; Lee, Gyun Min

2017-02-01

Chinese hamster ovary (CHO) cell cultivation for production of therapeutic proteins is accompanied by production of metabolic wastes, mostly ammonia and lactate. To reduce ammonia production, the glutamine synthetase (GS) system was used to develop therapeutic monoclonal antibody (mAb)-producing CHO cells (SM-0.025). Additionally, the lactate dehydrogenase-A (LDH-A) was downregulated with shRNA to reduce lactate production in SM-0.025. The resulting mAb-producing cell lines (#2, #46, and #52) produced less ammonia than the host cell line during the exponential phase due to GS protein overexpression. LDH-A downregulation in SM-0.025 not only reduced lactate production but also further reduced ammonia production. Among the three LDH-A-downregulated clones, clone #2 had the highest mAb production along with significantly reduced specific lactate and ammonia production rates compared to those in SM-0.025. Waste reduction increased the galactosylation level of N-glycosylation, which improved mAb quality. LDH-A downregulation was also successfully applied to the host cell lines (CHO K1 and GS knockout CHO-K1). However, LDH-A downregulated host cells could not survive the pool-selection process wherein glutamine was excluded and methionine sulfoximine was added to the media. Taken together, LDH-A downregulation in the mAb-producing cell line generated with the GS system successfully reduced both ammonia and lactate levels, improving mAb galactosylation. However, LDH-A downregulation could not be applied to host cell lines because it hampered the selection process of the GS system.

Medium-chain fatty acid synthesis in lactating-rabbit mammary gland. Intracellular concentration and specificity of medium-chain acyl thioester hydrolase.

PubMed Central

Knudsen, J

1979-01-01

The concentration of medium-chain acyl thioester hydrolase and of fatty acid synthetase was determined by rocket immunoelectrophoresis in nine different particle-free supernatant fractions from lactating-rabbit mammary gland. The molar ratio of the hydrolase to fatty acid synthetase was 1.99 +/- 0.66 (mean +/- S.D.). A rate-limiting concentration of malonyl-CoA was required to ensure the predominant synthesis of medium-chain fatty acids when 2 mol of the hydrolase was added per mol of fatty acid synthetase. The interaction of the hydrolase with fatty acid synthetase was concentration-dependent, though an optimum concentration of hydrolase to synthetase could not be obtained. The lactating-rabbit mammary gland hydrolase altered the pattern of fatty acids synthesized by fatty acid synthetases prepared from cow, goat, sheep and rabbit lactating mammary glands, rabbit liver and cow adipose tissue. PMID:574008

Fragment growing and linking lead to novel nanomolar lactate dehydrogenase inhibitors.

PubMed

Kohlmann, Anna; Zech, Stephan G; Li, Feng; Zhou, Tianjun; Squillace, Rachel M; Commodore, Lois; Greenfield, Matthew T; Lu, Xiaohui; Miller, David P; Huang, Wei-Sheng; Qi, Jiwei; Thomas, R Mathew; Wang, Yihan; Zhang, Sen; Dodd, Rory; Liu, Shuangying; Xu, Rongsong; Xu, Yongjin; Miret, Juan J; Rivera, Victor; Clackson, Tim; Shakespeare, William C; Zhu, Xiaotian; Dalgarno, David C

2013-02-14

Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small molecules is therefore of interest for potential cancer treatments. We describe the identification and optimization of LDH-A inhibitors by fragment-based drug discovery. We applied ligand based NMR screening to identify low affinity fragments binding to LDH-A. The dissociation constants (K(d)) and enzyme inhibition (IC(50)) of fragment hits were measured by surface plasmon resonance (SPR) and enzyme assays, respectively. The binding modes of selected fragments were investigated by X-ray crystallography. Fragment growing and linking, followed by chemical optimization, resulted in nanomolar LDH-A inhibitors that demonstrated stoichiometric binding to LDH-A. Selected molecules inhibited lactate production in cells, suggesting target-specific inhibition in cancer cell lines.

Maternal Zinc Intakes and Homeostatic Adjustments during Pregnancy and Lactation

PubMed Central

Donangelo, Carmen Marino; King, Janet C.

2012-01-01

Zinc plays critical roles during embryogenesis, fetal growth, and milk secretion, which increase the zinc need for pregnancy and lactation. Increased needs can be met by increasing the dietary zinc intake, along with making homeostatic adjustments in zinc utilization. Potential homeostatic adjustments include changes in circulating zinc, increased zinc absorption, decreased zinc losses, and changes in whole body zinc kinetics. Although severe zinc deficiency during pregnancy has devastating effects, systematic reviews and meta-analysis of the effect of maternal zinc supplementation on pregnancy outcomes have consistently shown a limited benefit. We hypothesize, therefore, that zinc homeostatic adjustments during pregnancy and lactation improve zinc utilization sufficiently to provide the increased zinc needs in these stages and, therefore, mitigate immediate detrimental effects due to a low zinc intake. The specific questions addressed are the following: How is zinc utilization altered during pregnancy and lactation? Are those homeostatic adjustments influenced by maternal zinc status, dietary zinc, or zinc supplementation? These questions are addressed by critically reviewing results from published human studies on zinc homeostasis during pregnancy and lactation carried out in different populations worldwide. PMID:22852063

Divergent lactate dehydrogenase isoenzyme profile in cellular compartments of primate forebrain structures.

PubMed

Duka, Tetyana; Collins, Zachary; Anderson, Sarah M; Raghanti, Mary Ann; Ely, John J; Hof, Patrick R; Wildman, Derek E; Goodman, Morris; Grossman, Lawrence I; Sherwood, Chet C

2017-07-01

The compartmentalization and association of lactate dehydrogenase (LDH) with specific cellular structures (e.g., synaptosomal, sarcoplasmic or mitochondrial) may play an important role in brain energy metabolism. Our previous research revealed that LDH in the synaptosomal fraction shifts toward the aerobic isoforms (LDH-B) among the large-brained haplorhine primates compared to strepsirrhines. Here, we further analyzed the subcellular localization of LDH in primate forebrain structures using quantitative Western blotting and ELISA. We show that, in cytosolic and mitochondrial subfractions, LDH-B expression level was relatively elevated and LDH-A declined in haplorhines compared to strepsirrhines. LDH-B expression in mitochondrial fractions of the neocortex was preferentially increased, showing a particularly significant rise in the ratio of LDH-B to LDH-A in chimpanzees and humans. We also found a significant correlation between the protein levels of LDH-B in mitochondrial fractions from haplorhine neocortex and the synaptosomal LDH-B that suggests LDH isoforms shift from a predominance of A-subunits toward B-subunits as part of a system that spatially buffers dynamic energy requirements of brain cells. Our results indicate that there is differential subcellular compartmentalization of LDH isoenzymes that evolved among different primate lineages to meet the energy requirements in neocortical and striatal cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Toll-like receptor 4 regulates lipopolysaccharide-induced inflammation and lactation insufficiency in a mouse model of mastitis.

PubMed

Glynn, Danielle J; Hutchinson, Mark R; Ingman, Wendy V

2014-05-01

Lactation mastitis is a debilitating inflammatory breast disease in postpartum women. Disease severity is associated with markers of inflammation rather than bacterial load, suggesting that immune-signaling pathways activated in the host are important in the disease pathology. The role of the innate pattern recognition receptor toll-like receptor 4 (TLR4) in progression and resolution of mastitislike disease was investigated in a mouse model. Lipopolysaccharide in Matrigel (10 μg/10 μl) was administered into the teat canal of lactating Tlr4 null mutant and wild-type mice to induce a localized area of inflammation. Mastitis induction resulted in a marked influx of RB6-positive neutrophils and F4/80-positive macrophages, which was higher in Tlr4(-/-) mice compared to wild-type mice. Tlr4 null mutation resulted in an altered immune-signaling fingerprint following induction of mastitis, with attenuated serum cytokines, including CXCL1, CCL2, interleukin 1 beta, and tumor necrosis factor alpha compared to wild-type mice. In both genotypes, the localized area of inflammation had resolved after 7 days, and milk protein was evident. However, the mammary glands of wild-type mice exhibited reduced capacity for milk production, with decreased percent area populated with glandular epithelium and decreased abundance of nuclear phosphorylated signal transducer and activator of transcription 5 compared to Tlr4 null mice. This study demonstrates that inflammatory pathways activated in the host are critically important in mastitis disease progression and suggests that lactation insufficiency associated with mastitis may be a consequence of TLR4-mediated inflammation, rather than the bacterial infection itself.

Metabolomic and proteomic analysis of D-lactate-producing Lactobacillus delbrueckii under various fermentation conditions.

PubMed

Liang, Shaoxiong; Gao, Dacheng; Liu, Huanhuan; Wang, Cheng; Wen, Jianping

2018-05-28

As an important feedstock monomer for the production of biodegradable stereo-complex poly-lactic acid polymer, D-lactate has attracted much attention. To improve D-lactate production by microorganisms such as Lactobacillus delbrueckii, various fermentation conditions were performed, such as the employment of anaerobic fermentation, the utilization of more suitable neutralizing agents, and exploitation of alternative nitrogen sources. The highest D-lactate titer could reach 133 g/L under the optimally combined fermentation condition, increased by 70.5% compared with the control. To decipher the potential mechanisms of D-lactate overproduction, the time-series response of intracellular metabolism to different fermentation conditions was investigated by GC-MS and LC-MS/MS-based metabolomic analysis. Then the metabolomic datasets were subjected to weighted correlation network analysis (WGCNA), and nine distinct metabolic modules and eight hub metabolites were identified to be specifically associated with D-lactate production. Moreover, a quantitative iTRAQ-LC-MS/MS proteomic approach was employed to further analyze the change of intracellular metabolism under the combined fermentation condition, identifying 97 up-regulated and 42 down-regulated proteins compared with the control. The in-depth analysis elucidated how the key factors exerted influence on D-lactate biosynthesis. The results revealed that glycolysis and pentose phosphate pathways, transport of glucose, amino acids and peptides, amino acid metabolism, peptide hydrolysis, synthesis of nucleotides and proteins, and cell division were all strengthened, while ATP consumption for exporting proton, cell damage, metabolic burden caused by stress response, and bypass of pyruvate were decreased under the combined condition. These might be the main reasons for significantly improved D-lactate production. These findings provide the first omics view of cell growth and D-lactate overproduction in L. delbrueckii, which can be a theoretical basis for further improving the production of D-lactate.

A novel amperometric biosensor based on gold nanoparticles anchored on reduced graphene oxide for sensitive detection of l-lactate tumor biomarker.

PubMed

Azzouzi, Sawsen; Rotariu, Lucian; Benito, Ana M; Maser, Wolfgang K; Ben Ali, Mounir; Bala, Camelia

2015-07-15

In this work, a novel amperometric biosensor based on gold nanoparticles anchored on reduced graphene oxide (RGO-AuNPs) and l-lactate dehydrogenase (LDH) was developed for the sensing of l-lactate. Firstly, the RGO-AuNPs modified screen printed electrodes were tested for NADH detection showing a wide dynamic range and a low detection limit. Next, the biosensor was constructed by incorporating both enzyme and RGO-AuNPs in a sol gel matrix derived from tetrametoxysilane and methyltrimetoxysilane. The enzyme loading, working pH, and coenzyme concentration were optimized. The biosensor linearly responded to l-lactate in the range of 10µM-5mM and showed a good specific sensitivity of 154µA/mMcm(2) with a detection limit of 0.13µM. This was accompanied by good reproducibility and operational stability. Tests on artificial serum proved that l-lactate can be determined practically without interferences from commonly interfering compounds such as urate, paracetamol and l-ascorbate. Our LDH/RGO-AuNPs/SPCE based biosensor thus performs as electrochemical device for the detection of l-lactate as a viable early cancer bio-marker. Copyright © 2015 Elsevier B.V. All rights reserved.

Pathogen-specific effects on milk yield in repeated clinical mastitis episodes in Holstein dairy cows.

PubMed

Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

2014-03-01

The objective of this study was to estimate the effects of clinical mastitis (CM) cases due to different pathogens on milk yield in Holstein cows. The first 3 CM cases in a cow's lactation were modeled. Eight categories of pathogens were included: Streptococcus spp.; Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level detectable by our microbiological procedures) observed in the culture sample, and cases with contamination (≥ 3 pathogens in the sample); other pathogens that may be treated with antibiotics (included Citrobacter, Corynebacterium bovis, Enterobacter, Enterococcus, Pasteurella, Pseudomonas; "other treatable"); and other pathogens not successfully treated with antibiotics (Trueperella pyogenes, Mycoplasma, Prototheca, yeasts; "other not treatable"). Data from 38,276 lactations in cows from 5 New York State dairy herds, collected from 2003-2004 until 2011, were analyzed. Mixed models with an autoregressive correlation structure (to account for correlation among the repeated measures of milk yield within a lactation) were estimated. Primiparous (lactation 1) and multiparous (lactations 2 and 3) cows were analyzed separately, as the shapes of their lactation curves differed. Primiparas were followed for up to 48 wk of lactation and multiparas for up to 44 wk. Fixed effects included parity, calving season, week of lactation, CM (type, case number, and timing of CM in relation to milk production cycle), and other diseases (milk fever, retained placenta, metritis, ketosis, displaced abomasum). Herd was modeled as a random effect. Clinical mastitis was more common in multiparas than in primiparas. In primiparas, Streptococcus spp. occurred most frequently as the first case. In multiparas, E. coli was most common as the first case. In subsequent cases, CM cases with no specific growth or contamination were most common in both parity groups. The hazard of CM increased with case number. Mastitic cows were generally higher producers before the CM episode than their nonmastitic herdmates. Milk loss varied with pathogen and case number. In primiparas, the greatest losses were associated with E. coli and "other not treatable" organisms. In multiparas, the greatest losses were associated with Klebsiella spp. and "other not treatable" organisms. Milk loss was not associated with occurrence of CNS. The findings may help farmers to make optimal management decisions for their cows. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Sequencing the transcriptome of milk production: milk trumps mammary tissue

PubMed Central

2013-01-01

Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

Cerebrospinal Fluid Glucose and Lactate: Age-Specific Reference Values and Implications for Clinical Practice

PubMed Central

Leen, Wilhelmina G.; Willemsen, Michèl A.; Wevers, Ron A.; Verbeek, Marcel M.

2012-01-01

Cerebrospinal fluid (CSF) analysis is an important tool in the diagnostic work-up of many neurological disorders, but reference ranges for CSF glucose, CSF/plasma glucose ratio and CSF lactate based on studies with large numbers of CSF samples are not available. Our aim was to define age-specific reference values. In 1993 The Nijmegen Observational CSF Study was started. Results of all CSF samples that were analyzed between 1993 and 2008 at our laboratory were systematically collected and stored in our computerized database. After exclusion of CSF samples with an unknown or elevated erythrocyte count, an elevated leucocyte count, elevated concentrations of bilirubin, free hemoglobin, or total protein 9,036 CSF samples were further studied for CSF glucose (n = 8,871), CSF/plasma glucose ratio (n = 4,516) and CSF lactate values (n = 7,614). CSF glucose, CSF/plasma glucose ratio and CSF lactate were age-, but not sex dependent. Age-specific reference ranges were defined as 5–95th percentile ranges. CSF glucose 5th percentile values ranged from 1.8 to 2.9 mmol/L and 95th percentile values from 3.8 to 5.6 mmol/L. CSF/plasma glucose ratio 5th percentile values ranged from 0.41 to 0.53 and 95th percentile values from 0.82 to 1.19. CSF lactate 5th percentile values ranged from 0.88 to 1.41 mmol/L and 95th percentile values from 2.00 to 2.71 mmol/L. Reference ranges for all three parameters were widest in neonates and narrowest in toddlers, with lower and upper limits increasing with age. These reference values allow a reliable interpretation of CSF results in everyday clinical practice. Furthermore, hypoglycemia was associated with an increased CSF/plasma glucose ratio, whereas hyperglycemia did not affect the CSF/plasma glucose ratio. PMID:22880096

Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Millan, J.L.; Driscoll, C.E.; LeVan, K.M.

The sequence and structure of human testis-specific L-lactate dehydrogenase (LDHC/sub 4/, LDHX; (L)-lactate:NAD/sup +/ oxidoreductase, EC 1.1.1.27) has been derived from analysis of a complementary DNA (cDNA) clone comprising the complete protein coding region of the enzyme. From the deduced amino acid sequence, human LDHC/sub 4/ is as different from rodent LDHC/sub 4/ (73% homology) as it is from human LDHA/sub 4/ (76% homology) and porcine LDHB/sub 4/ (68% homology). Subunit homologies are consistent with the conclusion that the LDHC gene arose by at least two independent duplication events. Furthermore, the lower degree of homology between mouse and human LDHC/submore » 4/ and the appearance of this isozyme late in evolution suggests a higher rate of mutation in the mammalian LDHC genes than in the LDHA and -B genes. Comparison of exposed amino acid residues of discrete anti-genic determinants of mouse and human LDHC/sub 4/ reveals significant differences. Knowledge of the human LDHC/sub 4/ sequence will help design human-specific peptides useful in the development of a contraceptive vaccine.« less

Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia.

PubMed

Sawada, Yusuke; Konno, Ayumu; Nagaoka, Jun; Hirai, Hirokazu

2016-06-13

Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkinje cells (PCs) and interneurons, but not Bergmann glia (BG). However, we found BG-predominant transduction without PC transduction along a traumatic needle tract for viral injection. The enhancement of neuroinflammation by the co-application of lipopolysaccharide (LPS) with AAV9 significantly expanded the BG-predominant area concurrently with the potentiated microglial activation. The BG-predominant transduction was gradually replaced by the PC-predominant transduction as the neuroinflammation dissipated. Experiments using glioma cell cultures revealed significant activation of the NSE promoter due to glucose deprivation, suggesting that intracellularly stored glycogen is metabolized through the glycolytic pathway for energy. Activation of the glycolytic enzyme promoter in BG concurrently with inactivation in PC may have pathophysiological significance for the production of lactate in activated BG and the utilization of lactate, which is provided by the BG-PC lactate shuttle, as a primary energy resource in injured PCs.

Raised serum lactate: a marker of necrotizing fasciitis?

PubMed

Murphy, George; Markeson, Daniel; Choa, Robert; Armstrong, Anthony

2013-12-01

Distinguishing necrotizing fasciitis from non-necrotizing soft-tissue infections remains a difficult clinical judgement call, with a paucity of diagnostic aids to the clinician. The aim of this study was to assess raised serum lactate as a point-of-care test to aid in differentiating necrotizing from non-necrotizing soft tissue infections. The authors performed a post-hoc analysis of a prospectively compiled database. All patients referred to a single surgeon (A.P.A.) as suspected cases of necrotizing fasciitis at one hospital between September 2000 and September 2010 were included. Serum lactate at presentation was recorded, along with demographic and outcome data. Using histological evidence of tissue necrosis as the 'gold standard', patients were divided into those with or without necrotizing fasciitis, and their serum lactate at presentation compared. Fifty three patients met the inclusion criteria. Twenty eight had histologically proven necrosis, 25 did not. Serum lactate (mean±SD) was 4.1±1.62 mmol/l in the necrotizing fasciitis group and 1.8±0.46 mmol/l in the non-necrotizing fasciitis group (p≤0.0001). A serum lactate level above 2.0 mmol/l had a sensitivity of 1.00 and a specificity of 0.76 for necrotizing fasciitis in this series. In this series of patients with suspected necrotizing soft tissue infection, serum lactate levels above 2.0 mmol/l at presentation were strongly associated with the presence of tissue necrosis. Although no test can be relied upon in isolation, our results suggest that serum lactate is a promising adjunct to the diagnosis of necrotizing infection, which could help to expedite appropriate management. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

DTIC Science & Technology

2007-04-01

analysis of virgin and lactating female mice in which FAK was specifically deleted in the mammary epithelium. No morphological abnormalities were found in...the mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. After completing the analysis...were collected to prepare protein extracts. Organs were first snap-frozen in liquid nitrogen and then were ground using a mortar and a pestle

The kinetics of transport of lactate and pyruvate into rat hepatocytes. Evidence for the presence of a specific carrier similar to that in erythrocytes.

PubMed Central

Edlund, G L; Halestrap, A P

1988-01-01

Time courses of L-lactate and pyruvate uptake into isolated rat hepatocytes were measured in a citrate-based medium to generate a pH gradient (alkaline inside), by using the silicone-oil-filtration technique at 0 degrees C to minimize metabolism. At low concentrations of lactate and pyruvate (0.5 mM), transport was inhibited by over 95% by 5 mM-alpha-cyano-4-hydroxycinnamate, whereas at higher concentrations (greater than 10 mM) a significant proportion of transport could not be inhibited. The rate of this non-inhibitable transport was linearly related to the substrate concentration, was less with pyruvate than with L-lactate, and appeared to be due to diffusion of undissociated acid. Uptake of D-lactate was not inhibited by alpha-cyano-4-hydroxycinnamate and occurred only by diffusion. Kinetic parameters for the carrier-mediated transport process were obtained after correction of the initial rates of uptake of lactate and pyruvate in the absence of 5 mM-alpha-cyano-4-hydroxycinnamate by that in the presence of inhibitor. Under the conditions used, the Km values for L-lactate and pyruvate were 2.4 and 0.6 mM respectively and the Ki for alpha-cyano-4-hydroxycinnamate as a competitive inhibitor was 0.11 mM. Km values for the transport of L-lactate and pyruvate into rat erythrocytes under similar conditions were 3.0 and 0.96 mM. The Vmax. of lactate and pyruvate transport into hepatocytes at 0 degrees C was 3 nmol/min per mg of protein. Carrier-mediated transport of 0.5 mM-L-lactate was inhibited by 0.2 mM-p-chloromercuribenzenesulphonate (greater than 90%), 0.5 mM-quercetin (80%), 0.6 mM-isobutylcarbonyl-lactyl anhydride (70%) and 0.5 mM-4,4'-di-isothiocyanostilbene-2,2'-disulphonate (50%). A similar pattern of inhibition of lactate transport is seen in erythrocytes. It is suggested that the same or a similar carrier protein exists in both tissues. The results also show that L-lactate transport into rat hepatocytes is very rapid at physiological temperatures and is unlikely to restrict the rate of its metabolism. Differences between our results and those of Fafournoux, Demigne & Remesy [(1985) J. Biol. Chem. 260, 292-299] are discussed. PMID:3342001

Social anthropology in INCAP.

PubMed

Adams, Richard N

2010-03-01

Social anthropology at INCAP evolved through a series of stages. The initial work in the 1950s was concerned with finding ways to make INCAP nutritional research more effective. In a second phase, emerging in the 1960s, anthropology examined the nutrition process in the population, especially as it was manifested in child care and feeding, lactation, and population growth and in the relation of economic process to nutritional progress. In the 1970s, anthropology once more became an adjunct of nutritional research. Anthropological awareness was introduced into project planning, and field studies were undertaken by way of shaping the research process to work in accord with local realities. In the 1980s and 1990s, there was a shift away from more descriptive research to research directed to supporting and facilitating specific nutrition and health behavior change.

Presentation and management of osteoporosis presenting in association with pregnancy or lactation.

PubMed

Kovacs, C S; Ralston, S H

2015-09-01

In this review, we summarize our current understanding of the pathophysiology of fragility fractures that occur for the first time during pregnancy and lactation, and provide guidance on appropriate investigations and treatment strategies. Most affected women will have had no prior bone density reading, and so the extent of bone loss that may have occurred during pregnancy or lactation is uncertain. During pregnancy, intestinal calcium absorption doubles in order to meet the fetal demand for calcium, but if maternal intake of calcium is insufficient to meet the combined needs of the mother and baby, the maternal skeleton will undergo resorption during the third trimester. During lactation, several hormonal changes, independent of maternal calcium intake, program a 5-10 % loss of trabecular mineral content in order to provide calcium to milk. After weaning the baby, the maternal skeleton is normally restored to its prior mineral content and strength. This physiological bone resorption during reproduction does not normally cause fractures; instead, women who do fracture are more likely to have additional secondary causes of bone loss and fragility. Transient osteoporosis of the hip may affect one or both femoral heads during pregnancy but it involves localized edema and not skeletal resorption. Case reports have described the use of calcitonin, bisphosphonates, strontium ranelate, teriparatide, vertebroplasty, and kyphoplasty to treat post-partum vertebral fractures. However, the need for such treatments is uncertain given that a progressive increase in bone mass subsequently occurs in most women who present with a fracture during pregnancy or lactation.

RNA Sequencing of the Human Milk Fat Layer Transcriptome Reveals Distinct Gene Expression Profiles at Three Stages of Lactation

PubMed Central

Lemay, Danielle G.; Ballard, Olivia A.; Hughes, Maria A.; Morrow, Ardythe L.; Horseman, Nelson D.; Nommsen-Rivers, Laurie A.

2013-01-01

Aware of the important benefits of human milk, most U.S. women initiate breastfeeding but difficulties with milk supply lead some to quit earlier than intended. Yet, the contribution of maternal physiology to lactation difficulties remains poorly understood. Human milk fat globules, by enveloping cell contents during their secretion into milk, are a rich source of mammary cell RNA. Here, we pair this non-invasive mRNA source with RNA-sequencing to probe the milk fat layer transcriptome during three stages of lactation: colostral, transitional, and mature milk production. The resulting transcriptomes paint an exquisite portrait of human lactation. The resulting transcriptional profiles cluster not by postpartum day, but by milk Na:K ratio, indicating that women sampled during similar postpartum time frames could be at markedly different stages of gene expression. Each stage of lactation is characterized by a dynamic range (105-fold) in transcript abundances not previously observed with microarray technology. We discovered that transcripts for isoferritins and cathepsins are strikingly abundant during colostrum production, highlighting the potential importance of these proteins for neonatal health. Two transcripts, encoding β-casein (CSN2) and α-lactalbumin (LALBA), make up 45% of the total pool of mRNA in mature lactation. Genes significantly expressed across all stages of lactation are associated with making, modifying, transporting, and packaging milk proteins. Stage-specific transcripts are associated with immune defense during the colostral stage, up-regulation of the machinery needed for milk protein synthesis during the transitional stage, and the production of lipids during mature lactation. We observed strong modulation of key genes involved in lactose synthesis and insulin signaling. In particular, protein tyrosine phosphatase, receptor type, F (PTPRF) may serve as a biomarker linking insulin resistance with insufficient milk supply. This study provides the methodology and reference data set to enable future targeted research on the physiological contributors of sub-optimal lactation in humans. PMID:23861770

ADSA Foundation Scholar Award: A role for serotonin in lactation physiology-Where do we go from here?

PubMed

Hernandez, L L

2018-04-25

Lactation is a physiological event that is exclusive to mammals. Lactation evolved as a strategy to improve the survival of the young by providing them with the complete nutrition that is required for survival upon birth as well as maternal-offspring bonding. Typically, milk production by the dam matches the demand of the young. The dairy cow is a unique exception in which the discoveries and genetic selection related to lactation physiology have been applied and resulted in a dramatic increase in milk yield of dairy cows. Studies on the role of mammary-derived serotonin and the coordination of various aspects of milk production and maternal metabolism have revealed novel mechanisms by which milk production and maternal metabolism can be improved. Furthermore, the investigation into molecular and cellular mechanisms regulating mammary gland function has revealed the importance of epigenetics on mammary gland function. Understanding mammary gland function at the cellular and physiological levels will be important for improving mammary gland control of maternal metabolism during early lactation. The early lactation period is a critical time for a dairy cow as that is when she is most susceptible to disease and metabolic disorders that can lead to negative effects on her productive capacity and overall health. Our research in the area of serotonin physiology has illustrated the importance of serotonin on the regulation of lactation and maternal homeostasis. Future research in the area of lactation physiology should be targeted at improving maternal health and longevity in the herd through manipulation of the signals the mammary gland sends to coordinate maternal metabolism and synthesize milk. Specifically, we believe that serotonin will play a central role in understanding the communication between the mammary gland and the maternal physiology during lactation. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Escherichia coli strains engineered for homofermentative production of D-lactic acid from glycerol.

PubMed

Mazumdar, Suman; Clomburg, James M; Gonzalez, Ramon

2010-07-01

Given its availability and low price, glycerol has become an ideal feedstock for the production of fuels and chemicals. We recently reported the pathways mediating the metabolism of glycerol in Escherichia coli under anaerobic and microaerobic conditions. In this work, we engineer E. coli for the efficient conversion of glycerol to d-lactic acid (d-lactate), a negligible product of glycerol metabolism in wild-type strains. A homofermentative route for d-lactate production was engineered by overexpressing pathways involved in the conversion of glycerol to this product and blocking those leading to the synthesis of competing by-products. The former included the overexpression of the enzymes involved in the conversion of glycerol to glycolytic intermediates (GlpK-GlpD and GldA-DHAK pathways) and the synthesis of d-lactate from pyruvate (d-lactate dehydrogenase). On the other hand, the synthesis of succinate, acetate, and ethanol was minimized through two strategies: (i) inactivation of pyruvate-formate lyase (DeltapflB) and fumarate reductase (DeltafrdA) (strain LA01) and (ii) inactivation of fumarate reductase (DeltafrdA), phosphate acetyltransferase (Deltapta), and alcohol/acetaldehyde dehydrogenase (DeltaadhE) (strain LA02). A mutation that blocked the aerobic d-lactate dehydrogenase (Deltadld) also was introduced in both LA01 and LA02 to prevent the utilization of d-lactate. The most efficient strain (LA02Deltadld, with GlpK-GlpD overexpressed) produced 32 g/liter of d-lactate from 40 g/liter of glycerol at a yield of 85% of the theoretical maximum and with a chiral purity higher than 99.9%. This strain exhibited maximum volumetric and specific productivities for d-lactate production of 1.5 g/liter/h and 1.25 g/g cell mass/h, respectively. The engineered homolactic route generates 1 to 2 mol of ATP per mol of d-lactate and is redox balanced, thus representing a viable metabolic pathway.

The Availability of Information on Induced Lactation in Malaysia.

PubMed

Rahim, Norsyamlina Che Abdul; Sulaiman, Zaharah; Ismail, Tengku Alina Tengku

2017-08-01

Induced lactation is a method of stimulating the production of breast milk in women who have not gone through the process of pregnancy. Recent advances in technology have given such women the opportunity to breastfeed adopted children. Previous studies conducted in Western countries have explored the breastfeeding of adopted children, as well as the experiences, successes and challenges of this process. However, research on procedures for breastfeeding adopted children is lacking in Malaysia. The authors have therefore reviewed literature related to induced lactation in Malaysia to fill this gap. Of the 30 related articles identified, 19 described the breastfeeding practices and experiences of adoptive mothers in Malaysia. Out of 19 articles, there were four journal articles, five circulars and regulations, two books, two post-graduate theses, four blogs posts and forum discussions, and two online newspaper articles. Medical information relating to induced lactation procedures was also reviewed, showing that there was a lack of scientific studies focusing on induced lactation practices among adoptive mothers. Information on religious, specifically Islamic, perspectives on breastfeeding and child adoption laws was gathered from websites, social networks, blogs, magazines and online news sources. In consideration of recent advancements in medical technology and the dire need among Malaysians, it is crucial that evidence-based, accurate and reliable information on induced lactation is made available to professionals and other individuals in this country.

The Availability of Information on Induced Lactation in Malaysia

PubMed Central

Rahim, Norsyamlina Che Abdul; Sulaiman, Zaharah; Ismail, Tengku Alina Tengku

2017-01-01

Induced lactation is a method of stimulating the production of breast milk in women who have not gone through the process of pregnancy. Recent advances in technology have given such women the opportunity to breastfeed adopted children. Previous studies conducted in Western countries have explored the breastfeeding of adopted children, as well as the experiences, successes and challenges of this process. However, research on procedures for breastfeeding adopted children is lacking in Malaysia. The authors have therefore reviewed literature related to induced lactation in Malaysia to fill this gap. Of the 30 related articles identified, 19 described the breastfeeding practices and experiences of adoptive mothers in Malaysia. Out of 19 articles, there were four journal articles, five circulars and regulations, two books, two post-graduate theses, four blogs posts and forum discussions, and two online newspaper articles. Medical information relating to induced lactation procedures was also reviewed, showing that there was a lack of scientific studies focusing on induced lactation practices among adoptive mothers. Information on religious, specifically Islamic, perspectives on breastfeeding and child adoption laws was gathered from websites, social networks, blogs, magazines and online news sources. In consideration of recent advancements in medical technology and the dire need among Malaysians, it is crucial that evidence-based, accurate and reliable information on induced lactation is made available to professionals and other individuals in this country. PMID:28951685

In vivo Raman measurement of levofloxacin lactate in blood using a nanoparticle-coated optical fiber probe

PubMed Central

Liu, Shupeng; Rong, Ming; Zhang, Heng; Chen, Na; Pang, Fufei; Chen, Zhenyi; Wang, Tingyun; Yan, Jianshe

2016-01-01

Monitoring drug concentrations in vivo is very useful for adjusting a drug dosage during treatment and for drug research. Specifically, cutting-edge “on-line” drug research relies on knowing how drugs are metabolized or how they interact with the blood in real-time. Thus, this study explored performing in vivo Raman measurements of the model drug levofloxacin lactate in the blood using a nanoparticle-coated optical fiber probe (optical fiber nano-probe). The results show that we were able to measure real-time changes in the blood concentration of levofloxacin lactate, suggesting that this technique could be helpful for performing drug analyses and drug monitoring in a clinical setting without repeatedly withdrawing blood from patients. PMID:27231590

Field Demonstration and Validation of a New Device for Measuring Groundwater and Perchlorate Fluxes at IHDIV-NSWC, Indian Head, MD

DTIC Science & Technology

2006-07-01

in bioremediation (such as lactate, citrate, benzoate , phenols, etc). Site Study Objectives • demonstrate and validate the PFM as an innovative...contaminants and alcohol tracers. However, organic acids (e.g., benzoate ) can be used as the PFM resident racers. We modified zeolites and GAC with a...bioremediation (such as lactate, citrate, benzoate , phenols, etc). 1.2. Objectives of the Demonstration The specific objectives of this

Metabolic interrogation as a tool to optimize chemotherapeutic regimens.

PubMed

Sandulache, Vlad C; Chen, Yunyun; Feng, Lei; William, William N; Skinner, Heath D; Myers, Jeffrey N; Meyn, Raymond E; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A; Fuller, Clifton D; Konopleva, Marina Y; Lai, Stephen Y

2017-03-14

Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines.Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies.

Metabolic interrogation as a tool to optimize chemotherapeutic regimens

PubMed Central

Feng, Lei; William, William N.; Skinner, Heath D.; Myers, Jeffrey N.; Meyn, Raymond E.; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A.; Fuller, Clifton D.; Konopleva, Marina Y.; Lai, Stephen Y.

2017-01-01

Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC). We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines. Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies. PMID:28184025

miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Yaguang; Cheng, Chuanyao; Lu, Hong, E-mail: honglu6512@163.com

miR-4458, a new tumor-suppressor, was reported to down-regulated in human hepatocellular carcinoma. The expression status, roles and inhibitory mechanisms of miR-4458 in other tumors still need to be clarified. The aim of this study is to investigate the effects of miR-4458 and to elucidate the potential mechanism in colon cancer cells. Using bioinformatic databases, we predicted that hexokinase2 (HK2), a rate-limiting enzyme in the glycolytic pathway, was a target of miR-4458, so the effects of miR-4458 on glycolysis and lactate production was assessed in colon cancer cells. We found that miR-4458 was down-regulated and HK2 was up-regulated in colon cancermore » cells. Overexpression of miR-4458 inhibited proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. Luciferase activity assays showed that HK2 was a direct target of miR-4458. Moreover, knockdown of HK2 by specific RNAi also suppressed proliferation, glycolysis, and lactate production under both normoxic and hypoxic conditions. In conclusion, our findings suggested that miR-4458 inhibited the progression of colon cancer cells by inhibition of glycolysis and lactate production via directly targeting HK2 mRNA. - Highlights: • miR-4458 is down-regulated in colon cancer cells. • miR-4458 suppresses proliferation, glycolysis, and lactate production. • HK2 is a target of miR-4458. • HK2 knockdown inhibits proliferation, glycolysis, and lactate production.« less

Serum lactate predicts resource utilization, but not surgical need, in the emergency department.

PubMed

Richards, Carly; Ishihara, Kelli; Grayson, Cary; Lustik, Michael; Yheulon, Christopher

2018-06-01

Serum lactate is frequently tested in the emergency department (ED) setting to diagnose visceral ischemia and as a marker of end-organ perfusion. It is highly nonspecific, and levels can be affected by both kidney and liver function. In this retrospective chart review, we aim to demonstrate that serum lactate is overused in the ED setting and predicts resource utilization but not the need for surgical intervention. ED records with a chief complaint of "abdominal pain" were queried for the preceding 12 mo. We excluded pregnant patients, patients aged less than 18 years, and patients for whom a blood count and chemistry were not obtained. Vital signs, laboratory values, resource utilization, and outcome of the visit were obtained. Logistic regression models were developed to correct for confounding associations. A total of 1003 records were obtained initially with 753 patients (75%) included in the study. Serum lactate was drawn in 118 patients (15%) and was elevated in 19 patients (16% of those drawn). Utilization of computed tomography imaging was associated with lactate utilization (P < 0.001). Patients in whom lactate was drawn were more likely to have a general surgery consult (51% versus 34%, P < 0.001) and to be admitted to the hospital (P < 0.001). The use of serum lactate in the workup of patients with abdominal pain should be targeted at patients who have signs of sepsis and based on the index of suspicion for specific disease processes such as mesenteric ischemia. Published by Elsevier Inc.

Simultaneous detection of valine and lactate using MEGA-PRESS editing in pyogenic brain abscess.

PubMed

Lange, Thomas; Ko, Cheng-Wen; Lai, Ping-Hong; Dacko, Michael; Tsai, Shang-Yueh; Buechert, Martin

2016-12-01

Valine and lactate have been recognized as important metabolic markers to diagnose brain abscess by means of MRS. However, in vivo unambiguous detection and quantification is hampered by macromolecular contamination. In this work, MEGA-PRESS difference editing of valine and lactate is proposed. The method is validated in vitro and applied for quantitative in vivo experiments in one healthy subject and two brain abscess patients. It is demonstrated that with this technique the overlapping lipid signal can be reduced by more than an order of magnitude and thus the robustness of valine and lactate detection in vivo can be enhanced. Quantification of the two abscess MEGA-PRESS spectra yielded valine/lactate concentration ratios of 0.10 and 0.27. These ratios agreed with the concentration ratios determined from concomitantly acquired short-T E PRESS data and were in line with literature values. The quantification accuracy of lactate (as measured with Cramér-Rao lower bounds in LCModel processing) was better for MEGA-PRESS than for short-T E PRESS in all acquired in vivo datasets. The Cramér-Rao lower bounds of valine were only better for MEGA-PRESS in one of the two abscess cases, while in the other case coediting of isoleucine confounded the quantification in the MEGA-PRESS analysis. MEGA-PRESS and short-T E PRESS should be combined for unambiguous quantification of amino acids in abscess measurements. Simultaneous valine/lactate MEGA-PRESS editing might benefit the distinction of brain abscesses from tumors, and further categorization of bacteria with reasonable sensitivity and specificity. Copyright © 2016 John Wiley & Sons, Ltd.

Milk oligosaccharides over time of lactation from different dog breeds.

PubMed

Macias Rostami, Shirin; Bénet, Thierry; Spears, Julie; Reynolds, Arleigh; Satyaraj, Ebenezer; Sprenger, Norbert; Austin, Sean

2014-01-01

The partnership of humans and dogs goes back to over 10'000 years, yet relatively little is known about a dog's first extra-uterine nutrition particularly when it comes to milk oligosaccharides. We set out to identify and quantify milk oligosaccharides over the course of lactation from different dog breeds (Labrador retriever, Schnauzer and 3 Alaskan husky crossbreeds). To this end, 2 different chromatographic methods with fluorescence and mass spectrometry detection were developed and one was validated for quantification. Besides lactose and lactose-sulphate, we identified 2 different trisaccharides composed of 3 hexose units, 3'sialyllactose (3'SL), 6'sialyllactose (6'SL), 2'fucosyllactose (2'FL), and a tetrasaccharide composed of 2 hexoses, an N-acetylhexosamine and a deoxyhexose. 3'SL was present at the highest levels in milk of all dog breeds starting at around 7.5 g/L and dropping to about 1.5 g/L in the first 10 days of lactation. 6'SL was about 10 times less abundant and 2'FL and the tetrasaccharide had rather varying levels in the milk of the different breeds with the tetrasaccharide only detectable in the Alaskan husky crossbreeds. The longitudinal and quantitative data of milk oligosaccharides from different dog breeds are an important basis to further our understanding on their specific biological roles and also on the specific nutritional requirements of lactating puppies.

Milk Oligosaccharides over Time of Lactation from Different Dog Breeds

PubMed Central

Macias Rostami, Shirin; Bénet, Thierry; Spears, Julie; Reynolds, Arleigh; Satyaraj, Ebenezer; Sprenger, Norbert; Austin, Sean

2014-01-01

The partnership of humans and dogs goes back to over 10'000 years, yet relatively little is known about a dog's first extra-uterine nutrition particularly when it comes to milk oligosaccharides. We set out to identify and quantify milk oligosaccharides over the course of lactation from different dog breeds (Labrador retriever, Schnauzer and 3 Alaskan husky crossbreeds). To this end, 2 different chromatographic methods with fluorescence and mass spectrometry detection were developed and one was validated for quantification. Besides lactose and lactose-sulphate, we identified 2 different trisaccharides composed of 3 hexose units, 3′sialyllactose (3′SL), 6′sialyllactose (6′SL), 2′fucosyllactose (2′FL), and a tetrasaccharide composed of 2 hexoses, an N-acetylhexosamine and a deoxyhexose. 3′SL was present at the highest levels in milk of all dog breeds starting at around 7.5 g/L and dropping to about 1.5 g/L in the first 10 days of lactation. 6′SL was about 10 times less abundant and 2′FL and the tetrasaccharide had rather varying levels in the milk of the different breeds with the tetrasaccharide only detectable in the Alaskan husky crossbreeds. The longitudinal and quantitative data of milk oligosaccharides from different dog breeds are an important basis to further our understanding on their specific biological roles and also on the specific nutritional requirements of lactating puppies. PMID:24924915

Enzyme mechanisms for pyruvate-to-lactate flux attenuation: a study of Sherpas, Quechuas, and hummingbirds.

PubMed

Hochachka, P W; Stanley, C; McKenzie, D C; Villena, A; Monge, C

1992-10-01

During incremental exercise to fatigue under hypobaric hypoxia, Andean Quechua natives form and accumulate less plasma lactate than do lowlanders under similar conditions. This phenomenon of low lactate accumulation despite hypobaric hypoxia, first discovered some half century ago, is known in Quechuas to be largely unaffected by acute exposure to hypoxia or by acclimatization to sea level conditions. Earlier Nuclear Magnetic Resonance (NMR) spectroscopy and metabolic biochemistry studies suggest that closer coupling of energy demand and energy supply in Quechuas allows given changes in work rate with relatively modest changes in muscle adenylate and phosphagen concentrations, thus tempering the activation of glycolytic flux to pyruvate--a coarse control mechanism operating at the level of overall pathway flux. Later studies of enzyme activities in skeletal muscles of Quechuas and of Sherpas have identified a finely-tuned control mechanism which by adaptive modifications of a few key enzymes apparently serves to specifically attenuate pyruvate flux to lactate.

Properties of lactate dehydrogenase from the isopod, Saduria entomon.

PubMed

Mulkiewicz, E; Zietara, M S; Stachowiak, K; Skorkowski, E F

2000-07-01

Saduria entomon lactate dehydrogenase (LDH-A4*) from thorax muscle was purified about 89 fold to specific activity 510 micromol NADH/min/mg using Cibacron Blue 3GA Agarose and Oxamate-Agarose chromatographies. The enzyme is a tetramer, with molecular weight of 140 kDa for the native enzyme and 36 kDa for the subunit. The isoelectric point was at pH 5.7. The enzyme possesses high heat stability (T50 = 71.5 degrees C). The optimum pH for pyruvate reduction reaction was 6.5, while for lactate oxidation one, the maximum activity was at pH 9.1. The Km for pyruvate was minimal at 5 degrees C, the average environmental temperature of the isopod. The Km values determined at 30 degrees C and optimal pH for pyruvate reduction and lactate oxidation were 0.18 and 90.04 mM, respectively. Amino acid compositional analyses showed the strongest resemblance of the isopod isoenzyme to cod (Gadus morhua) LDH-C4.

Ectoparasite Caligus rogercresseyi modifies the lactate response in Atlantic salmon (Salmo salar) and Coho salmon (Oncorhynchus kisutch).

PubMed

Vargas-Chacoff, L; Muñoz, J L P; Hawes, C; Oyarzún, R; Pontigo, J P; Saravia, J; González, M P; Mardones, O; Labbé, B S; Morera, F J; Bertrán, C; Pino, J; Wadsworth, S; Yáñez, A

2017-08-30

Although Caligus rogercresseyi negatively impacts Chilean salmon farming, the metabolic effects of infection by this sea louse have never been completely characterized. Therefore, this study analyzed lactate responses in the plasma, as well as the liver/muscle lactate dehydrogenase (LDH) activity and gene expression, in Salmo salar and Oncorhynchus kisutch infested by C. rogercresseyi. The lactate responses of Atlantic and Coho salmon were modified by the ectoparasite. Both salmon species showed increasing in plasma levels, whereas enzymatic activity increased in the muscle but decreased in the liver. Gene expression was overexpressed in both Coho salmon tissues but only in the liver for Atlantic salmon. These results suggest that salmonids need more energy to adapt to infection, resulting in increased gene expression, plasma levels, and enzyme activity in the muscles. The responses differed between both salmon species and over the course of infection, suggesting potential species-specific responses to sea-lice infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Enzymatic Kinetic Properties of the Lactate Dehydrogenase Isoenzyme C4 of the Plateau Pika (Ochotona curzoniae)

PubMed Central

Wang, Yang; Wei, Lian; Wei, Dengbang; Li, Xiao; Xu, Lina; Wei, Linna

2016-01-01

Testis-specific lactate dehydrogenase (LDH-C4) is one of the lactate dehydrogenase (LDH) isozymes that catalyze the terminal reaction of pyruvate to lactate in the glycolytic pathway. LDH-C4 in mammals was previously thought to be expressed only in spermatozoa and testis and not in other tissues. Plateau pika (Ochotona curzoniae) belongs to the genus Ochotona of the Ochotonidea family. It is a hypoxia-tolerant species living in remote mountain areas at altitudes of 3000–5000 m above sea level on the Qinghai-Tibet Plateau. Surprisingly, Ldh-c is expressed not only in its testis and sperm, but also in somatic tissues of plateau pika. To shed light on the function of LDH-C4 in somatic cells, Ldh-a, Ldh-b, and Ldh-c of plateau pika were subcloned into bacterial expression vectors. The pure enzymes of Lactate Dehydrogenase A4 (LDH-A4), Lactate Dehydrogenase B4 (LDH-B4), and LDH-C4 were prepared by a series of expression and purification processes, and the three enzymes were identified by the method of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and native polyacrylamide gel electrophoresis (PAGE). The enzymatic kinetics properties of these enzymes were studied by Lineweaver-Burk double-reciprocal plots. The results showed the Michaelis constant (Km) of LDH-C4 for pyruvate and lactate was 0.052 and 4.934 mmol/L, respectively, with an approximate 90 times higher affinity of LDH-C4 for pyruvate than for lactate. At relatively high concentrations of lactate, the inhibition constant (Ki) of the LDH isoenzymes varied: LDH-A4 (Ki = 26.900 mmol/L), LDH-B4 (Ki = 23.800 mmol/L), and LDH-C4 (Ki = 65.500 mmol/L). These data suggest that inhibition of lactate by LDH-A4 and LDH-B4 were stronger than LDH-C4. In light of the enzymatic kinetics properties, we suggest that the plateau pika can reduce reliance on oxygen supply and enhance its adaptation to the hypoxic environments due to increased anaerobic glycolysis by LDH-C4. PMID:26751442

The prevalence and clinical relevance of hyperkalaemia in calves with neonatal diarrhoea.

PubMed

Trefz, Florian M; Lorch, Annette; Feist, Melanie; Sauter-Louis, Carola; Lorenz, Ingrid

2013-03-01

One hundred and twenty-four calves with neonatal diarrhoea were investigated in order to assess the prevalence of hyperkalaemia and the associated clinical signs. Hyperkalaemia (potassium concentration >5.8mmol/L) was recognized in 42 (34%) calves and was more closely associated with dehydration than with decreases in base excess or venous blood pH. In 75 calves with normal blood concentrations of D-lactate (i.e. ⩽3.96mmol/L), K concentrations were moderately correlated with base excess values (r=-0.48, P<0.001). In contrast, no significant correlation was observed in 49 calves with elevated D-lactate. Only three hyperkalaemic calves had bradycardia and a weak positive correlation was found between heart rate and K concentrations (r=0.22, P=0.014). Ten of the 124 calves had cardiac arrhythmia and of these seven had hyperkalaemia indicating that cardiac arrhythmia had a low sensitivity (17%) but a high specificity (96%) as a predictor of hyperkalaemia. In a subset of 34 calves with base excess values ⩽-5mmol/L and D-lactate concentrations <5mmol/L (of which 22 had hyperkalaemia), changes in posture/ability to stand could be mainly explained by elevations of K concentrations (P<0.001) and to a lesser extent by increases in L-lactate concentrations (P=0.024). Skeletal muscle weakness due to hyperkalaemia alongside hypovolaemia may produce a clinical picture that is similar to that in calves with marked D-lactic acidosis. However, since reductions in the strength of the palpebral reflex are closely correlated with D-lactate concentrations, a prompt palpebral reflex can assist the clinical prediction of hyperkalaemia in calves presenting with a distinct impairment in their ability to stand (specificity 99%, sensitivity 29%). Copyright © 2012 Elsevier Ltd. All rights reserved.

Determination of protein and amino acid requirements of lactating sows using a population-based factorial approach.

PubMed

Strathe, A V; Strathe, A B; Theil, P K; Hansen, C F; Kebreab, E

2015-08-01

Determination of appropriate nutritional requirements is essential to optimize the productivity and longevity of lactating sows. The current recommendations for requirements do not consider the large variation between animals. Therefore, the aim of this study was to determine the amino acid recommendations for lactating sows using a stochastic modeling approach that integrates population variation and uncertainty of key parameters into establishing nutritional recommendations for lactating sows. The requirement for individual sows was calculated using a factorial approach by adding the requirement for maintenance and milk. The energy balance of the sows was either negative or zero depending on feed intake being a limiting factor. Some parameters in the model were sow-specific and others were population-specific, depending on state of knowledge. Each simulation was for 1000 sows repeated 100 times using Monte Carlo simulation techniques. BW, back fat thickness of the sow, litter size (LS), average litter gain (LG), dietary energy density and feed intake were inputs to the model. The model was tested using results from the literature, and the values were all within ±1 s.d. of the estimated requirements. Simulations were made for a group of low- (LS=10 (s.d.=1), LG=2 kg/day (s.d.=0.6)), medium- (LS=12 (s.d.=1), LG=2.5 kg/day (s.d.=0.6)) and high-producing (LS=14 (s.d.=1), LG=3.5 kg/day (s.d.=0.6)) sows, where the average requirement was the result. In another simulation, the requirements were estimated for each week of lactation. The results were given as the median and s.d. The average daily standardized ileal digestible (SID) protein and lysine requirements for low-, medium- and high-producing sows were 623 (CV=2.5%) and 45.1 (CV=4.8%); 765 (CV=4.9%) and 54.7 (CV=7.0%); and 996 (CV=8.5%) and 70.8 g/day (CV=9.6%), respectively. The SID protein and lysine requirements were lowest at week 1, intermediate at week 2 and 4 and the highest at week 3 of lactation. The model is a valuable tool to develop new feeding strategies by taking into account the variable requirement between groups of sows and changes during lactation. The inclusion of between-sow variation gives information on safety margins when developing new dietary recommendations of amino acids and protein for lactating sows.

Maternal peanut exposure during pregnancy and lactation reduces peanut allergy risk in offspring.

PubMed

López-Expósito, Iván; Song, Ying; Järvinen, Kirsi M; Srivastava, Kamal; Li, Xiu-Min

2009-11-01

Maternal allergy is believed to be a risk factor for peanut allergy (PNA) in children. However, there is no direct evidence of maternal transmission of PNA susceptibility, and it is unknown whether maternal peanut exposure affects the development of PNA in offspring. To investigate the influence of maternal PNA on offspring reactions to the first peanut exposure, and whether maternal low-dose peanut exposure during pregnancy and lactation influences these reactions and peanut sensitization in a murine model. Five-week-old offspring of PNA C3H/HeJ mothers (PNA-Ms) were challenged intragastrically with peanut (first exposure), and reactions were determined. In a subset of the experiment, PNA-Ms were fed a low dose of peanut (PNA-M/PN) or not fed peanut (PNA-M/none) during pregnancy and lactation. Their 5-week-old offspring were challenged intragastrically with peanut, and reactions were determined. In another subset of the experiment, offspring of PNA-M/PN or PNA-M/none were sensitized with peanut intragastrically for 6 weeks, and serum peanut-specific antibodies were determined. PNA-M offspring exhibited anaphylactic reactions at first exposure to peanut that were associated with peanut-specific IgG(1) levels and prevented by a platelet activation factor antagonist. In a subset experiment, PNA-M/PN offspring showed significantly reduced first-exposure peanut reactions, increased IgG(2a), and reduced mitogen-stimulated splenocyte cytokine production compared with PNA-M/none offspring. In an additional experiment, PNA-M/PN offspring showed reduction of peanut-specific IgE to active peanut sensitization. We show for the first time maternal transmission of susceptibility to first-exposure peanut reactions and active peanut sensitization. Low-dose peanut exposure during pregnancy and lactation reduced this risk.

The effect of mineral-based alkaline water on hydration status and the metabolic response to short-term anaerobic exercise.

PubMed

Chycki, Jakub; Zając, Tomasz; Maszczyk, Adam; Kurylas, Anna

2017-09-01

Previously it was demonstrated that mineralization and alkalization properties of mineral water are important factors influencing acid-base balance and hydration in athletes. The purpose of this study was to investigate the effects of drinking different types of water on urine pH, specific urine gravity, and post-exercise lactate utilization in response to strenuous exercise. Thirty-six male soccer players were divided into three intervention groups, consuming around 4.0 l/day of different types of water for 7 days: HM (n=12; highly mineralized water), LM (n=12; low mineralized water), and CON (n=12; table water). The athletes performed an exercise protocol on two occasions (before and after intervention). The exercise protocol consisted of 5 bouts of intensive 60-s (120% VO 2max ) cycling separated by 60 s of passive rest. Body composition, urinalysis and lactate concentration were evaluated - before (t0), immediately after (t1), 5' (t2), and 30' (t3) after exercise. Total body water and its active transport (TBW - total body water / ICW - intracellular water / ECW - extracellular water) showed no significant differences in all groups, at both occasions. In the post-hydration state we found a significant decrease of specific urine gravity in HM (1021±4.2 vs 1015±3.8 g/L) and LM (1022±3.1 vs 1008±4.2 g/L). We also found a significant increase of pH and lactate utilization rate in LM. In conclusion, the athletes hydrated with alkaline, low mineralized water demonstrated favourable changes in hydration status in response to high-intensity interval exercise with a significant decrease of specific urine gravity, increased urine pH and more efficient utilization of lactate after supramaximal exercise.

Antagonism of V1b receptors promotes maternal motivation to retrieve pups in the MPOA and impairs pup-directed behavior during maternal defense in the mpBNST of lactating rats.

PubMed

Bayerl, Doris S; Kaczmarek, Veronika; Jurek, Benjamin; van den Burg, Erwin H; Neumann, Inga D; Gaßner, Barbara M; Klampfl, Stefanie M; Bosch, Oliver J

2016-03-01

Recent studies using V1b receptor (V1bR) knockout mice or central pharmacological manipulations in lactating rats highlighted the influence of this receptor for maternal behavior. However, its role in specific brain sites known to be important for maternal behavior has not been investigated to date. In the present study, we reveal that V1bR mRNA (qPCR) and protein levels (Western blot) within either the medial preoptic area (MPOA) or the medial-posterior part of the bed nucleus of the stria terminalis (mpBNST) did not differ between virgin and lactating rats. Furthermore, we characterized the effects of V1bR blockade via bilateral injections of the receptor subtype-specific antagonist SSR149415 within the MPOA or the mpBNST on maternal behavior (maternal care under non-stress and stress conditions, maternal motivation to retrieve pups in a novel environment, maternal aggression) and anxiety-related behavior in lactating rats. Blocking V1bR within the MPOA increased pup retrieval, whereas within the mpBNST it decreased pup-directed behavior, specifically licking/grooming the pups, during the maternal defense test. In addition, immediately after termination of the maternal defense test, V1bR antagonism in both brain regions reduced nursing, particularly arched back nursing. Anxiety-related behavior was not affected by V1bR antagonism in either brain region. In conclusion our data indicate that V1bR antagonism significantly modulates different aspects of maternal behavior in a brain region-dependent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Carcinogenicity and Immunotoxicity of Embedded Depleted Uranium and Heavy-Metal Tungsten Alloy in Rodents

DTIC Science & Technology

2006-10-01

local metal- induced toxicity daily for two weeks following surgery and weekly thereafter for the duration of the study. Task 1 - Determine whether...A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor...4 months, no signs of local or systemic toxic- ity were observed (Peuster et al. 2003). Studies on health effects of Ni and Co are more numerous

Inflammatory mediators in mastitis and lactation insufficiency.

PubMed

Ingman, Wendy V; Glynn, Danielle J; Hutchinson, Mark R

2014-07-01

Mastitis is a common inflammatory disease during lactation that causes reduced milk supply. A growing body of evidence challenges the central role of pathogenic bacteria in mastitis, with disease severity associated with markers of inflammation rather than infection. Inflammation in the mammary gland may be triggered by microbe-associated molecular patterns (MAMPs) as well as danger-associated molecular patterns (DAMPs) binding to pattern recognition receptors such as the toll-like receptors (TLRs) on the surface of mammary epithelial cells and local immune cell populations. Activation of the TLR4 signalling pathway and downstream nuclear factor kappa B (NFkB) is critical to mediating local mammary gland inflammation and systemic immune responses in mouse models of mastitis. However, activation of NFkB also induces epithelial cell apoptosis and reduced milk protein synthesis, suggesting that inflammatory mediators activated during mastitis promote partial involution. Perturbed milk flow, maternal stress and genetic predisposition are significant risk factors for mastitis, and could lead to a heightened TLR4-mediated inflammatory response, resulting in increased susceptibility and severity of mastitis disease in the context of low MAMP abundance. Therefore, heightened host inflammatory signalling may act in concert with pathogenic or commensal bacterial species to cause both the inflammation associated with mastitis and lactation insufficiency. Here, we present an alternate paradigm to the widely held notion that breast inflammation is driven principally by infectious bacterial pathogens, and suggest there may be other therapeutic strategies, apart from the currently utilised antimicrobial agents, that could be employed to prevent and treat mastitis in women.

Riboflavin uptake transporter Slc52a2 (RFVT2) is upregulated in the mouse mammary gland during lactation.

PubMed

Wu, Alex Man Lai; Dedina, Liana; Dalvi, Pooja; Yang, Mingdong; Leon-Cheon, John; Earl, Brian; Harper, Patricia A; Ito, Shinya

2016-04-01

While it is well recognized that riboflavin accumulates in breast milk as an essential vitamin for neonates, transport mechanisms for its milk excretion are not well characterized. The multidrug efflux transporter ABCG2 in the apical membrane of milk-producing mammary epithelial cells (MECs) is involved with riboflavin excretion. However, it is not clear whether MECs possess other riboflavin transport systems, which may facilitate its basolateral uptake into MECs. We report here that transcripts encoding the second (SLC52A2) and third (SLC52A3) member of the recently discovered family of SLC52A riboflavin uptake transporters are expressed in milk fat globules from human breast milk. Furthermore, Slc52a2 and Slc52a3 mRNA are upregulated in the mouse mammary gland during lactation. Importantly, the induction ofSlc52a2, which was the major Slc52a riboflavin transporter in the lactating mammary gland, was also observed at the protein level. Subcellular localization studies showed that green fluorescent protein-tagged mouse SLC52A2 mainly localized to the cell membrane, with no preferential distribution to the apical or basolateral membrane in polarized kidney MDCK cells. These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk. Copyright © 2016 the American Physiological Society.

Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting.

PubMed

Frith, Kelly-Anne; Fogel, Ronen; Goldring, J P Dean; Krause, Robert G E; Khati, Makobetsa; Hoppe, Heinrich; Cromhout, Mary E; Jiwaji, Meesbah; Limson, Janice L

2018-05-03

Early detection is crucial for the effective treatment of malaria, particularly in those cases infected with Plasmodium falciparum. There is a need for diagnostic devices with the capacity to distinguish P. falciparum from other strains of malaria. Here, aptamers generated against targeted species-specific epitopes of P. falciparum lactate dehydrogenase (rPfLDH) are described. Two classes of aptamers bearing high binding affinity and specificity for recombinant P. falciparum lactate dehydrogenase (rPfLDH) and P. falciparum-specific lactate dehydrogenase epitopic oligopeptide (LDHp) were separately generated. Structurally-relevant moieties with particular consensus sequences (GGTAG and GGCG) were found in aptamers reported here and previously published, confirming their importance in recognition of the target, while novel moieties particular to this work (ATTAT and poly-A stretches) were identified. Aptamers with diagnostically-supportive functions were synthesized, prime examples of which are the aptamers designated as LDHp 1, LDHp 11 and rLDH 4 and rLDH 15 in work presented herein. Of the sampled aptamers raised against the recombinant protein, rLDH 4 showed the highest binding to the target rPfLDH in the ELONA assay, with both rLDH 4 and rLDH 15 indicating an ability to discriminate between rPfLDH and rPvLDH. LDHp 11 was generated against a peptide selected as a unique P. falciparum LDH peptide. The aptamer, LDHp 11, like antibodies against the same peptide, only detected rPfLDH and discriminated between rPfLDH and rPvLDH. This was supported by affinity binding experiments where only aptamers generated against a unique species-specific epitope showed an ability to preferentially bind to rPfLDH relative to rPvLDH rather than those generated against the whole recombinant protein. In addition, rLDH 4 and LDHp 11 demonstrated in situ binding to P. falciparum cells during confocal microscopy. The utilization and application of LDHp 11, an aptamer generated against a unique species-specific epitope of P. falciparum LDH indicated the ability to discriminate between recombinant P. falciparum and Plasmodium vivax LDH. This aptamer holds promise as a biorecognition element in malaria diagnostic devices for the detection, and differentiation, of P. falciparum and P. vivax malaria infections. This study paves the way to explore aptamer generation against targeted species-specific epitopes of other Plasmodium species.

The work patterns of lactating women in Madura.

PubMed

Launer, L J

1993-08-01

Little is known about the work patterns of mildly malnourished lactating women: are they modified to accommodate the demands of lactation? What factors influence their pattern of work during this period of nutritional stress? These questions were addressed using quantitative and qualitative data collected from 36 randomly selected women living in a poor community in Madura, Indonesia. Work patterns of the lactating women and their family members were documented for the first 12 months post-partum. Changes in work activity were analysed within four time periods corresponding to Madurese views on development during infancy: the vulnerable neonatal (birth-40 days), early (6-12 wk) and mid (13-31 wk) stages and the independent late (32-54 wk) stage. Quantitative data suggest that women did adjust work patterns to accommodate the demands of lactation and that these adjustments went beyond the neonatal stage. Mothers curtailed their participation in high- and low-energy income-generating activities, modified their conditions of work to promote maternal-infant proximity and conserved energy while performing specific activities. These patterns were most common through the mid infancy stage. Data are presented that describe how cultural values supporting maternal-infant proximity, intra- and inter-familial work exchanges, season and resources played a role in the type of accommodations mothers were able to make to breast-feed. These data suggest that even in relatively poor environments alterations in work patterns that may be favourable to lactation are possible, particularly when cultural concepts of infancy support such a trade-off.

Validity of Lactate Thresholds in Inline Speed Skating.

PubMed

Hecksteden, Anne; Heinze, Tobias; Faude, Oliver; Kindermann, Wilfried; Meyer, Tim

2015-09-01

Lactate thresholds are commonly used as estimates of the highest workload where lactate production and elimination are in equilibrium (maximum lactate steady state [MLSS]). However, because of the high static load on propulsive muscles, lactate kinetics in inline speed skating may differ significantly from other endurance exercise modes. Therefore, the discipline-specific validity of lactate thresholds has to be verified. Sixteen competitive inline-speed skaters (age: 30 ± 10 years; training per week: 10 ± 4 hours) completed an exhaustive stepwise incremental exercise test (start 24 km·h, step duration 3 minutes, increment 2 km·h) to determine individual anaerobic threshold (IAT) and the workload corresponding to a blood lactate concentration of 4 mmol·L (LT4) and 2-5 continuous load tests of (up to) 30 minutes to determine MLSS. The IAT and LT4 correlated significantly with MLSS, and the mean differences were almost negligible (MLSS 29.5 ± 2.5 km·h; IAT 29.2 ± 2.0 km·h; LT4 29.6 ± 2.3 km·h; p > 0.1 for all differences). However, the variability of differences was considerable resulting in 95% limits of agreement in the upper range of values known from other endurance disciplines (2.6 km·h [8.8%] for IAT and 3.1 km·h [10.3%] for LT4). Consequently, IAT and LT4 may be considered as valid estimates of the MLSS in inline speed skating, but verification by means of a constant load test should be considered in cases of doubt or when optimal accuracy is needed (e.g., in elite athletes or scientific studies).

Increased circulating D-lactate levels predict risk of mortality after hemorrhage and surgical trauma in baboons.

PubMed

Sobhian, Babak; Kröpfl, Albert; Hölzenbein, Thomas; Khadem, Anna; Redl, Heinz; Bahrami, Soheyl

2012-05-01

Patients with hemorrhagic shock and/or trauma are at risk of developing colonic ischemia associated with bacterial translocation that may lead to multiple organ failure and death. Intestinal ischemia is difficult to diagnose noninvasively. The present retrospective study was designed to determine whether circulating plasma D-lactate is associated with mortality in a clinically relevant two-hit model in baboons. Hemorrhagic shock was induced in anesthetized baboons (n = 24) by controlled bleeding (mean arterial pressure, 40 mmHg), base excess (maximum -5 mmol/L), and time (maximum 3 h). To mimic clinical setting more closely, all animals underwent a surgical trauma after resuscitation including midshaft osteotomy stabilized with reamed femoral interlocking nailing and were followed for 7 days. Hemorrhagic shock/surgical trauma resulted in 66% mortality by day 7. In nonsurvivor (n = 16) hemorrhagic shock/surgical trauma baboons, circulating D-lactate levels were significantly increased (2-fold) at 24 h compared with survivors (n = 8), whereas the early increase during hemorrhage and resuscitation declined during the early postresuscitation phase with no difference between survivors and nonsurvivors. Moreover, D-lactate levels remained elevated in the nonsurvival group until death, whereas it decreased to baseline in survivors. Prediction of death (receiver operating characteristic test) by D-lactate was accurate with an area under the curve (days 1-3 after trauma) of 0.85 (95% confidence interval, 0.72-0.93). The optimal D-lactate cutoff value of 25.34 μg/mL produced sensitivity of 73% to 99% and specificity of 50% to 83%. Our data suggest that elevation of plasma D-lactate after 24 h predicts an increased risk of mortality after hemorrhage and trauma.

Early lactate clearance for predicting active bleeding in critically ill patients with acute upper gastrointestinal bleeding: a retrospective study.

PubMed

Wada, Tomoki; Hagiwara, Akiyoshi; Uemura, Tatsuki; Yahagi, Naoki; Kimura, Akio

2016-08-01

Not all patients with upper gastrointestinal bleeding (UGIB) require emergency endoscopy. Lactate clearance has been suggested as a parameter for predicting patient outcomes in various critical care settings. This study investigates whether lactate clearance can predict active bleeding in critically ill patients with UGIB. This single-center, retrospective, observational study included critically ill patients with UGIB who met all of the following criteria: admission to the emergency department (ED) from April 2011 to August 2014; had blood samples for lactate evaluation at least twice during the ED stay; and had emergency endoscopy within 6 h of ED presentation. The main outcome was active bleeding detected with emergency endoscopy. Classification and regression tree (CART) analyses were performed using variables associated with active bleeding to derive a prediction rule for active bleeding in critically ill UGIB patients. A total of 154 patients with UGIB were analyzed, and 31.2 % (48/154) had active bleeding. In the univariate analysis, lactate clearance was significantly lower in patients with active bleeding than in those without active bleeding (13 vs. 29 %, P < 0.001). Using the CART analysis, a prediction rule for active bleeding is derived, and includes three variables: lactate clearance; platelet count; and systolic blood pressure at ED presentation. The rule has 97.9 % (95 % CI 90.2-99.6 %) sensitivity with 32.1 % (28.6-32.9 %) specificity. Lactate clearance may be associated with active bleeding in critically ill patients with UGIB, and may be clinically useful as a component of a prediction rule for active bleeding.

Attentive processes, blood lactate and CrossFit®.

PubMed

Perciavalle, Valentina; Marchetta, Nunzio Salvatore; Giustiniani, Salvatore; Borbone, Carlo; Perciavalle, Vincenzo; Petralia, Maria Cristina; Buscemi, Andrea; Coco, Marinella

2016-11-01

To analyze the influences of blood lactate produced during a specific session of CrossFit® on intensity and selectivity of attention. The first was evaluated by measuring the reaction time and the second by analyzing divided attention with a dual task. Fifteen male professionals of CrossFit® volunteered in the study. The training session was the Workout Of the Day (WOD) called 15.5, marked as: 27-21-15-9 repetitions (without recovery) in term of calories measured by using a rowing ergometer (e.g. 27 rowed calories) and in term of barbell full squats (raising a weight of 43 kg for men and of 29.5 kg for women). Blood lactate, blood glucose, reaction time, execution time of a dual task, number of errors and number of omissions were measured at rest, at the conclusion of the session and 15 minutes after its end. The levels of the blood lactate before the start of the session were considerably higher than those which normally occur at rest (<2 mmol /L), with a mean value of 4.5 mmol /l (± 1.99 SD). At the end of the workout session the blood lactate exhibited a significant increase, reaching a mean value of 13.8 mmol /l (± 1.18 SD) and then returning to values similar to the initial ones after 15 minutes. Blood glucose did not exhibit any statistically significant differences during the session. Reaction time, execution time, number of errors and number of omissions exhibited a significant worsening concomitantly with the increase in blood lactate. Athletes practicing CrossFit®, with high levels of blood lactate even at rest, should consequently have attentional performances somewhat limited.

High-throughput metataxonomic characterization of the raw milk microbiota identifies changes reflecting lactation stage and storage conditions.

PubMed

Doyle, Conor J; Gleeson, David; O'Toole, Paul W; Cotter, Paul D

2017-08-16

Low temperature is used to control the growth of bacteria in milk, both pre- and post-pasteurization. As the duration of refrigerated storage extends, psychrotrophs dominate the milk microbiota, that can produce heat stable lipases which negatively impact the organoleptic qualities of milk. Here we examine the influence that refrigeration temperature (2°C, 4°C and 6°C) and storage duration (96h) have on the microbiota composition (16S profiling) of raw bulk tank milk (BTM). To reflect a proposed change to current farming practices, raw milk was blended after each milking (8 milkings) and stored for five consecutive days in each temperature-specific tank. Here 16S rRNA-based microbiota compositional analysis was performed after milk was collected on day 1 and again after the final addition of milk at day 5. In addition to assessing the impact of the duration and temperature of storage, the influence of lactation stage, i.e. mid- versus late-lactation, on the microbiota of the blended BTM was also examined. Overall, both temperature and length of storage had surprisingly little influence on the raw milk microbiota, other than an increase in proportions of Gammaproteobacteria in the blended milk samples collected after pooling on day 5, and in samples stored at 6°C. However, lactation stage had a considerable influence on microbiota composition, with milk from mid-lactation containing higher proportions of Bacteroides, Faecalibacterium, Campylobacter and Rhodanobacter, and late-lactation milk containing higher proportions of Actinobacteria. Overall, the study demonstrates that current temperature and storage duration practises impact the microbiota of raw milk, but these impacts are modest relative to the more considerable differences between mid and late-lactation milk. Copyright © 2017 Elsevier B.V. All rights reserved.

Correcting the anion gap for hypoalbuminaemia does not improve detection of hyperlactataemia

PubMed Central

Dinh, C H; Ng, R; Grandinetti, A; Joffe, A; Chow, D C

2006-01-01

Background An elevated lactate level reflects impaired tissue oxygenation and is a predictor of mortality. Studies have shown that the anion gap is inadequate as a screen for hyperlactataemia, particularly in critically ill and trauma patients. A proposed explanation for the anion gap's poor sensitivity and specificity in detecting hyperlactataemia is that the serum albumin is frequently low. This study therefore, sought to compare the predictive values of the anion gap and the anion gap corrected for albumin (cAG) as an indicator of hyperlactataemia as defined by a lactate ⩾2.5 mmol/l. Methods A retrospective review of 639 sets of laboratory values from a tertiary care hospital. Patients' laboratory results were included in the study if serum chemistries and lactate were drawn consecutively. The sensitivity, specificity, and predictive values were obtained. A receiver operator characteristics curve (ROC) was drawn and the area under the curve (AUC) was calculated. Results An anion gap ⩾12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 79%, and 58%, respectively, and a cAG ⩾12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 59%, 66%, and 69%, respectively. The ROC curves between anion gap and cAG as a predictor of hyperlactataemia were almost identical. The AUC was 0.757 and 0.750, respectively. Conclusions The sensitivities, specificities, and predictive values of the anion gap and cAG were inadequate in predicting the presence of hyperlactataemia. The cAG provides no additional advantage over the anion gap in the detection of hyperlactataemia. PMID:16858097

Cumulative Risk of Bovine Mastitis Treatments in Denmark, Finland, Norway and Sweden

PubMed Central

Valde, JP; Lawson, LG; Lindberg, A; Agger, JF; Saloniemi, H; Østerås, O

2004-01-01

Data from the national dairy cow recording systems during 1997 were used to calculate lactation-specific cumulative risk of mastitis treatments and cumulative risk of removal from the herds in Denmark, Finland Norway and Sweden. Sweden had the lowest risk of recorded mastitis treatments during 305 days of lactation and Norway had the highest risk. The incidence risk of recorded mastitis treatments during 305 days of lactation in Denmark, Finland, Norway and Sweden was 0.177, 0.139, 0.215 and 0.127 for first parity cows and 0.228, 0.215, 0.358 and 0.204 for parities higher than three, respectively. The risk of a first parity cow being treated for mastitis was almost 3 times higher at calving in Norway than in Sweden. The period with the highest risk for mastitis treatments was from 2 days before calving until 14 days after calving and the highest risk for removal was from calving to 10 days after calving in all countries. The study clearly demonstrated differences in bovine mastitis treatment patterns among the Nordic countries. The most important findings were the differences in treatment risks during different lactations within each country, as well as differences in strategies with respect to the time during lactation mastitis was treated. PMID:15663080

Cumulative risk of bovine mastitis treatments in Denmark, Finland, Norway and Sweden.

PubMed

Valde, J P; Lawson, L G; Lindberg, A; Agger, J F; Saloniemi, H; Osterås, O

2004-01-01

Data from the national dairy cow recording systems during 1997 were used to calculate lactation-specific cumulative risk of mastitis treatments and cumulative risk of removal from the herds in Denmark, Finland Norway and Sweden. Sweden had the lowest risk of recorded mastitis treatments during 305 days of lactation and Norway had the highest risk. The incidence risk of recorded mastitis treatments during 305 days of lactation in Denmark, Finland, Norway and Sweden was 0.177, 0.139, 0.215 and 0.127 for first parity cows and 0.228, 0.215, 0.358 and 0.204 for parities higher than three, respectively. The risk of a first parity cow being treated for mastitis was almost 3 times higher at calving in Norway than in Sweden. The period with the highest risk for mastitis treatments was from 2 days before calving until 14 days after calving and the highest risk for removal was from calving to 10 days after calving in all countries. The study clearly demonstrated differences in bovine mastitis treatment patterns among the Nordic countries. The most important findings were the differences in treatment risks during different lactations within each country, as well as differences in strategies with respect to the time during lactation mastitis was treated.

Monitoring In-Vivo the Mammary Gland Microstructure during Morphogenesis from Lactation to Post-Weaning Using Diffusion Tensor MRI.

PubMed

Nissan, Noam; Furman-Haran, Edna; Shapiro-Feinberg, Myra; Grobgeld, Dov; Degani, Hadassa

2017-09-01

Lactation and the return to the pre-conception state during post-weaning are regulated by hormonal induced processes that modify the microstructure of the mammary gland, leading to changes in the features of the ductal / glandular tissue, the stroma and the fat tissue. These changes create a challenge in the radiological workup of breast disorder during lactation and early post-weaning. Here we present non-invasive MRI protocols designed to record in vivo high spatial resolution, T 2 -weighted images and diffusion tensor images of the entire mammary gland. Advanced imaging processing tools enabled tracking the changes in the anatomical and microstructural features of the mammary gland from the time of lactation to post-weaning. Specifically, by using diffusion tensor imaging (DTI) it was possible to quantitatively distinguish between the ductal / glandular tissue distention during lactation and the post-weaning involution. The application of the T 2 -weighted imaging and DTI is completely safe, non-invasive and uses intrinsic contrast based on differences in transverse relaxation rates and water diffusion rates in various directions, respectively. This study provides a basis for further in-vivo monitoring of changes during the mammary developmental stages, as well as identifying changes due to malignant transformation in patients with pregnancy associated breast cancer (PABC).

[Interest of lactate micro-dosage in scalp and umbilical cord in cases of abnormal fetal heart rate during labor. Prospective study on 162 patients].

PubMed

Paris, A; Maurice-Tison, S; Coatleven, F; Vandenbossche, F; Dallay, D; Horovitz, J

2012-06-01

To compare the interest of lactate microanalysis with pH measurement (Gold Standard procedure) in cord blood and fetal scalp blood samples for the assessment of abnormal fetal heart rate (FHR) during labour. A prospective observational study conducted from July 1st 2007 till March 31st 2008 on 162 patients with abnormal FHR during labour. Sampling failure for scalp lactate was less than 1 % compared to a failure of 10.5 % for scalp pH (P<0.001). There was a good correlation between pH and lactates in fetal scalp blood samples and in cord blood samples, between lactate in the last fetal scalp sample and in cord blood. When there was umbilical acidosis (pH≤7.15 or lactate≥5mmol/L), Apgar score at 5 minutes was significantly lower than when there was no acidosis (4.66±3.59 versus 8.35±2.73 for pH ; 6.6±3.77 versus 8.45±2.58 for lactate). The specificity of the lactate in the umbilical cord artery (≥5 mmol/laws) was 76.4 % for predicting an Apgar score at 5 minutes less than 7 ; 79.7 % for predicting the need for immediate neonatal care ; 77.3 % for predicting an hospital stay in neonatal unit. These figures were generally worse but close to those found for a threshold value of umbilical artery pH≤7.15. The values of lactate in cord blood and fetal scalp blood samples were comparable to pH values (Gold standard procedure). This method is easy to perform and is an attractive alternative to pH for monitoring fetal asphyxia. It is our opinion that the combination of the two methods is of interest. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose.

PubMed

Wang, Qingzhao; Ingram, Lonnie O; Shanmugam, K T

2011-11-22

Lactic acid, an attractive, renewable chemical for production of biobased plastics (polylactic acid, PLA), is currently commercially produced from food-based sources of sugar. Pure optical isomers of lactate needed for PLA are typically produced by microbial fermentation of sugars at temperatures below 40 °C. Bacillus coagulans produces L(+)-lactate as a primary fermentation product and grows optimally at 50 °C and pH 5, conditions that are optimal for activity of commercial fungal cellulases. This strain was engineered to produce D(-)-lactate by deleting the native ldh (L-lactate dehydrogenase) and alsS (acetolactate synthase) genes to impede anaerobic growth, followed by growth-based selection to isolate suppressor mutants that restored growth. One of these, strain QZ19, produced about 90 g L(-1) of optically pure D(-)-lactic acid from glucose in < 48 h. The new source of D-lactate dehydrogenase (D-LDH) activity was identified as a mutated form of glycerol dehydrogenase (GlyDH; D121N and F245S) that was produced at high levels as a result of a third mutation (insertion sequence). Although the native GlyDH had no detectable activity with pyruvate, the mutated GlyDH had a D-LDH specific activity of 0.8 μmoles min(-1) (mg protein)(-1). By using QZ19 for simultaneous saccharification and fermentation of cellulose to D-lactate (50 °C and pH 5.0), the cellulase usage could be reduced to 1/3 that required for equivalent fermentations by mesophilic lactic acid bacteria. Together, the native B. coagulans and the QZ19 derivative can be used to produce either L(+) or D(-) optical isomers of lactic acid (respectively) at high titers and yields from nonfood carbohydrates.

Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose

PubMed Central

Wang, Qingzhao; Ingram, Lonnie O.; Shanmugam, K. T.

2011-01-01

Lactic acid, an attractive, renewable chemical for production of biobased plastics (polylactic acid, PLA), is currently commercially produced from food-based sources of sugar. Pure optical isomers of lactate needed for PLA are typically produced by microbial fermentation of sugars at temperatures below 40 °C. Bacillus coagulans produces L(+)-lactate as a primary fermentation product and grows optimally at 50 °C and pH 5, conditions that are optimal for activity of commercial fungal cellulases. This strain was engineered to produce D(−)-lactate by deleting the native ldh (L-lactate dehydrogenase) and alsS (acetolactate synthase) genes to impede anaerobic growth, followed by growth-based selection to isolate suppressor mutants that restored growth. One of these, strain QZ19, produced about 90 g L-1 of optically pure D(−)-lactic acid from glucose in < 48 h. The new source of D-lactate dehydrogenase (D-LDH) activity was identified as a mutated form of glycerol dehydrogenase (GlyDH; D121N and F245S) that was produced at high levels as a result of a third mutation (insertion sequence). Although the native GlyDH had no detectable activity with pyruvate, the mutated GlyDH had a D-LDH specific activity of 0.8 μmoles min-1 (mg protein)-1. By using QZ19 for simultaneous saccharification and fermentation of cellulose to D-lactate (50 °C and pH 5.0), the cellulase usage could be reduced to 1/3 that required for equivalent fermentations by mesophilic lactic acid bacteria. Together, the native B. coagulans and the QZ19 derivative can be used to produce either L(+) or D(−) optical isomers of lactic acid (respectively) at high titers and yields from nonfood carbohydrates. PMID:22065761

Retention in care of HIV-infected pregnant and lactating women starting ART under Option B+ in rural Mozambique.

PubMed

Llenas-García, Jara; Wikman-Jorgensen, Philip; Hobbins, Michael; Mussa, Manuel Aly; Ehmer, Jochen; Keiser, Olivia; Mbofana, Francisco; Wandeler, Gilles

2016-08-01

In 2013, Mozambique adopted Option B+, universal lifelong antiretroviral therapy (ART) for all pregnant and lactating women, as national strategy for prevention of mother-to-child transmission of HIV. We analysed retention in care of pregnant and lactating women starting Option B+ in rural northern Mozambique. We compared ART outcomes in pregnant ('B+ pregnant'), lactating ('B+ lactating') and non-pregnant non-lactating women of childbearing age starting ART according to clinical and/or immunological criteria ('own health') between July 2013 and June 2014. Lost to follow-up was defined as no contact >180 days after the last visit. Multivariable competing risk models were adjusted for type of facility (type 1 vs. peripheral type 2 health centre), age, WHO stage and time from HIV diagnosis to ART. Over 333 person-years of follow-up (243 'B+ pregnant', 65'B+ lactating' and 317 'own health' women), 3.7% of women died and 48.5% were lost to follow-up. 'B+ pregnant' and 'B+ lactating' women were more likely to be lost in the first year (57% vs. 56.9% vs. 31.6%; P < 0.001) and to have no follow-up after the first visit (42.4% vs. 29.2% vs. 16.4%; P < 0.001) than 'own health' women. In adjusted analyses, risk of being lost to follow-up was higher in 'B+ pregnant' (adjusted subhazard ratio [asHR]: 2.77; 95% CI: 2.18-3.50; P < 0.001) and 'B+ lactating' (asHR: 1.94; 95% CI: 1.37-2.74; P < 0.001). Type 2 health centre was the only additional significant risk factor for loss to follow-up. Retention among PLW starting option B+ ART was poor and mainly driven by early losses. The success of Option B+ for prevention of mother-to-child transmission of HIV in rural settings with weak health systems will depend on specific improvements in counselling and retention measures, especially at the beginning of treatment. © 2016 John Wiley & Sons Ltd.

Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development.

PubMed

Rao Barkur, Rajashekar; Bairy, Laxminarayana K

2015-01-01

Widespread use of heavy metal lead (Pb) for various commercial purposes has resulted in the environmental contamination caused by this metal. The studies have shown a definite relationship between low level lead exposure during early brain development and deficit in children's cognitive functions. This study investigated the passive avoidance learning and spatial learning in male rat pups exposed to lead through their mothers during specific periods of early brain development. Experimental male rats were divided into 5 groups: i) the normal control group (NC) (N = 12) consisted of rat offspring born to mothers who were given normal drinking water throughout gestation and lactation, ii) the pre-gestation lead exposed group (PG) (N = 12) consisted of rat offspring, mothers of these rats had been exposed to 0.2% lead acetate in the drinking water for 1 month before conception, iii) the gestation lead exposed group (G) (N = 12) contained rat offspring born to mothers who had been exposed to 0.2% lead acetate in the drinking water throughout gestation, iv) the lactation lead exposed group (L) (N = 12) had rat offspring, mothers of these rats exposed to 0.2% lead acetate in the drinking water throughout lactation and v) the gestation and lactation lead exposed group (GL) (N = 12) contained rat offspring, mothers of these rats were exposed to 0.2% lead acetate throughout gestation and lactation. The study found deficit in passive avoidance learning in the G, L and GL groups of rats. Impairment in spatial learning was found in the PG, G, L and GL groups of rats. Interestingly, the study found that gestation period only and lactation period only lead exposure was sufficient to cause deficit in learning and memory in rats. The extent of memory impairment in the L group of rats was comparable with the GL group of rats. So it can be said that postnatal period of brain development is more sensitive to neurotoxicity compared to prenatal exposure. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

The diagnostic value of cerebrospinal fluid lactate for post-neurosurgical bacterial meningitis: a meta-analysis.

PubMed

Xiao, Xiong; Zhang, Yang; Zhang, Liwei; Kang, Peng; Ji, Nan

2016-09-13

Bacterial meningitis is not rare in post-neurosurgical patients. If patients are not treated promptly, the mortality rate can reach 20 to 50 %. The concentration of cerebrospinal fluid (CSF) lactate has been reported to be helpful in the diagnosis of bacterial meningitis; however, no systematic evaluations have investigated CSF from a postoperative perspective. In this study, we performed a systematic evaluation and meta-analysis of the efficacy of using CSF lactate concentrations in the diagnosis of post-neurosurgical bacterial meningitis. We retrieved studies that investigated the diagnostic value of CSF lactate for the diagnosis of post-neurosurgical bacterial meningitis by searching PubMed, EBSCO, the Cochrane Library and ClinicalTrials.gov. All these databases were searched from inception to November 2015. We used Quality Assessment of Diagnostic Accuracy Studies (QUADAS), a tool for the quality assessment of diagnostic accuracy, to evaluate the quality of the included studies. The Meta-DiSc 1.4 and Review Manager 5.3 software programs were used to analyze the included studies. Forest plots and summary receiver operating characteristics (SROC) curves were also drawn. Five studies, involving a total of 404 post-neurosurgical patients, were selected from 1,672 articles according to the inclusion criteria. The quality of the five included studies was assessed using QUADAS, and the related results are presented in tables. The meta-analysis revealed the following diagnostic values regarding CSF lactate for post-neurosurgical bacterial meningitis: a pooled sensitivity of 0.92 (95 % CI 0.85-0.96), a pooled specificity of 0.88 (95 % CI 0.84-0.92 with significant heterogeneity), a diagnostic odds ratio of 83.09 (95 % CI 36.83-187.46), an area under the curve (AUCSROC) of 0.9601, an SE(AUC) of 0.0122, a Q* of 0.9046 and an SE(Q*) of 0.0179. The meta-analysis indicated that the CSF lactate concentration has relatively high sensitivity and specificity for the diagnosis of post-neurosurgical bacterial meningitis and thus has relatively good efficacy.

Microdialysis Monitoring of CSF Parameters in Severe Traumatic Brain Injury Patients: A Novel Approach

PubMed Central

Thelin, Eric P.; Nelson, David W.; Ghatan, Per Hamid; Bellander, Bo-Michael

2014-01-01

Background: Neuro-intensive care following traumatic brain injury (TBI) is focused on preventing secondary insults that may lead to irreversible brain damage. Microdialysis (MD) is used to detect deranged cerebral metabolism. The clinical usefulness of the MD is dependent on the regional localization of the MD catheter. The aim of this study was to analyze a new method of continuous cerebrospinal fluid (CSF) monitoring using the MD technique. The method was validated using conventional laboratory analysis of CSF samples. MD-CSF and regional MD-Brain samples were correlated to patient outcome. Materials and Methods: A total of 14 patients suffering from severe TBI were analyzed. They were monitored using (1) a MD catheter (CMA64-iView, n = 7448 MD samples) located in a CSF-pump connected to the ventricular drain and (2) an intraparenchymal MD catheter (CMA70, n = 8358 MD samples). CSF-lactate and CSF-glucose levels were monitored and were compared to MD-CSF samples. MD-CSF and MD-Brain parameters were correlated to favorable (Glasgow Outcome Score extended, GOSe 6–8) and unfavorable (GOSe 1–5) outcome. Results: Levels of glucose and lactate acquired with the CSF-MD technique could be correlated to conventional levels. The median MD recovery using the CMA64 catheter in CSF was 0.98 and 0.97 for glucose and lactate, respectively. Median MD-CSF (CMA 64) lactate (p = 0.0057) and pyruvate (p = 0.0011) levels were significantly lower in the favorable outcome group compared to the unfavorable group. No significant difference in outcome was found using the lactate:pyruvate ratio (LPR), or any of the regional MD-Brain monitoring in our analyzed cohort. Conclusion: This new technique of global MD-CSF monitoring correlates with conventional CSF levels of glucose and lactate, and the MD recovery is higher than previously described. Increase in lactate and pyruvate, without any effect on the LPR, correlates to unfavorable outcome, perhaps related to the presence of erythrocytes in the CSF. PMID:25228896

DdlN from Vancomycin-Producing Amycolatopsis orientalis C329.2 Is a VanA Homologue with d-Alanyl-d-Lactate Ligase Activity

PubMed Central

Marshall, C. Gary; Wright, Gerard D.

1998-01-01

Vancomycin-resistant enterococci acquire high-level resistance to glycopeptide antibiotics through the synthesis of peptidoglycan terminating in d-alanyl-d-lactate. A key enzyme in this process is a d-alanyl-d-alanine ligase homologue, VanA or VanB, which preferentially catalyzes the synthesis of the depsipeptide d-alanyl-d-lactate. We report the overexpression, purification, and enzymatic characterization of DdlN, a VanA and VanB homologue encoded by a gene of the vancomycin-producing organism Amycolatopsis orientalis C329.2. Evaluation of kinetic parameters for the synthesis of peptides and depsipeptides revealed a close relationship between VanA and DdlN in that depsipeptide formation was kinetically preferred at physiologic pH; however, the DdlN enzyme demonstrated a narrower substrate specificity and commensurately increased affinity for d-lactate in the C-terminal position over VanA. The results of these functional experiments also reinforce the results of previous studies that demonstrated that glycopeptide resistance enzymes from glycopeptide-producing bacteria are potential sources of resistance enzymes in clinically relevant bacteria. PMID:9791137

Comparative effect of lidocaine and bupivacaine on glucose uptake and lactate production in the perfused working rat heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cronau, L.H. Jr.; Merin, R.G.; Aboulish, E.

1986-03-01

It has been suggested that at equivalent therapeutic concentrations, lidocaine and bupivacaine may have different cardiotoxic potency. In the isolated working rat heart preparation, the effect of a range of lidocaine and bupivacaine concentrations on glucose uptake and lactate production (LP) were observed. Insulin was added, 10 ..mu../L, to Ringer's solution containing /sup 3/H-labeled glucose to measure the glycolytic flux (GF). The effect of the local anesthetics on LP at the indicated concentrations were similar. Lidocaine appears to depress the glycolytic flux from exogenous glucose to a lesser degree. Bupivacaine, 10 mg/L, depresses VO/sub 2/ to a greater degree thanmore » does lidocaine, 40 mg/L.« less

Detection of 11 beta-hydroxysteroid dehydrogenase type 1, the glucocorticoid and mineralocorticoid receptor in various adipose tissue depots of dairy cows supplemented with conjugated linoleic acids.

PubMed

Friedauer, K; Dänicke, S; Schulz, K; Sauerwein, H; Häussler, S

2015-10-01

Early lactating cows mobilize adipose tissue (AT) to provide energy for milk yield and maintenance and are susceptible to metabolic disorders and impaired immune response. Conjugated linoleic acids (CLA), mainly the trans-10, cis-12 isomer, reduce milk fat synthesis and may attenuate negative energy balance. Circulating glucocorticoids (GC) are increased during parturition in dairy cows and mediate differentiating and anti-inflammatory effects via glucocorticoid (GR) and mineralocorticoid receptors (MR) in the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). Activated GC are the main ligands for both receptors in AT; therefore, we hypothesized that tissue-specific GC metabolism is effected by varying amounts of GR, MR and 11βHSD1 and/or their localization within AT depots. Furthermore, the lipolytic and antilipogenic effects of CLA might influence the GC/GR/MR system in AT. Therefore, we aimed to localize GR and MR as well as the expression pattern and activity of 11βHSD1 in different AT depots during early lactation in dairy cows and to identify potential effects of CLA. Primiparous German Holstein cows were divided into a control (CON) and a CLA group. From day 1 post-partum (p.p.) until sample collection, the CLA group was fed with 100 g/d CLA (contains 10 g each of the cis-9, trans-11 and the trans-10, cis-12-CLA isomers). CON cows (n = 5 each) were slaughtered on day 1, 42 and 105 p.p., while CLA cows (n = 5 each) were slaughtered on day 42 and 105 p.p. Subcutaneous fat from tailhead, withers and sternum, and visceral fat from omental, mesenteric and retroperitoneal depots were sampled. The localization of GR and 11βHSD1 in mature adipocytes - being already differentiated - indicates that GC promote other effects via GR than differentiation. Moreover, MR were observed in the stromal vascular cell fraction and positively related to the pre-adipocyte marker Pref-1. However, only marginal CLA effects were observed in this study. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Village women lead the way: SARTHI's experience.

PubMed

Khanna, R

1992-01-01

The grassroots nongovernmental organization Social Action for Rural and Tribal Inhabitants of India (SARTHI) has evolved, since its founding in 1980, from a project-oriented group aimed at addressing the shortage of drinking water and fuel wood to a broad-based women's health program. Starting in 1988, local women were trained as Women Health Workers to provide nutrition education to pregnant and lactating women and encourage tetanus immunization. Also undertaken was a study to validate locally used traditional medicines. About 80% were found to have healing properties, and systematic cultivation of these plants began on common lands obtained from the village council. Since local women came to trust the health workers and confided in them about gynecologic concerns, these workers were subsequently trained to take a medical history and perform pelvic and vaginal examinations. At monthly workshops, the women health workers receive updated training in gynecology and discuss issues that have arisen in the villages, e.g., domestic violence. Role playing is the central training modality, and health workers are urged to share their personal experiences as well as those of their clients. The women health workers now view their primary role as that of empowering other women by responding to their specific needs and serving as catalysts for social change in women's status.

Nutritional status of lactating women in Bogor district, Indonesia: cross-sectional dietary intake in three economic quintiles and comparison with pre-pregnant women.

PubMed

Madanijah, Siti; Rimbawan, Rimbawan; Briawan, Dodik; Zulaikhah, Zulaikhah; Andarwulan, Nuri; Nuraida, Lilis; Sundjaya, Tonny; Murti, Laksmi; Bindels, Jacques

2016-07-01

The way in which women accommodate for their increased nutritional needs during the lactation period is poorly investigated. In a cross-sectional study involving 220 lactating women (LW), equally distributed in economic quintiles (Q2, Q3, Q4), we investigated whether habitual dietary intake of LW differed from that of 200 pre-pregnant women (PPW) studied using the same methodology. Differences in dietary intake and nutrition sufficiency according to economic status were also investigated. Dietary intake data were collected using 2×24-h dietary recalls and FFQ. Energy, protein, Fe, Ca, Zn and vitamins A and C intakes were calculated utilising local food composition tables and were compared against Indonesian recommendations for adequacy. Energy and protein intakes 25 % of LW. For Q2-LW, this proportion was >50 %, except for protein. LW across all studied economic quintiles approximately doubled their vegetable intake, and 71 % of LW indicated a belief that this enhances lactation performance. Biochemical status parameters were analysed in a subset of forty-five women. Anaemia as well as Fe, Zn and Se deficiencies were prevalent among LW, supporting the nutrient intake deficiency data. Despite increasing intakes in LW compared with PPW, habitual diets in the study area do not provide for daily nutrient requirements in substantial proportions for both LW and PPW across all investigated economic groups.

Quadriceps oxygenation during isometric exercise in sailing.

PubMed

Vogiatzis, I; Tzineris, D; Athanasopoulos, D; Georgiadou, O; Geladas, N

2008-01-01

The aim of the present study was to investigate why blood lactate after prolonged quadriceps contraction during hiking is only marginally increased. Eight sailors performed five 3-min hiking bouts interspersed with 5-s recovery periods. Whole body oxygen uptake, heart rate and lactate were recorded, along with continuous-wave near-infrared spectroscopy measures of quadriceps oxygenation. The time for 50% re-oxygenation was also assessed as an indication of the degree of localized oxygen delivery stress. Hiking elicited a significant (p = 0.001) increase in mean (+/- SD) heart rate (124 +/- 10 beats . min (-1)) which was accompanied by a disproportionately low oxygen uptake (12 +/- 2 ml.kg(-1).min(-1)). Lactate was significantly (p = 0.001) increased throughout hiking manoeuvres, though post-exercise it remained low (3.2 +/- 0.9 mmol.l(-1)). During the hiking bouts mean quadriceps oxygenation was significantly (p = 0.001) reduced compared to baseline (by 33 +/- 5%), indicating an imbalance between muscle oxygen accessibility and oxygen demand. During rest intervals quadriceps oxygenation was partially restored. After the end of the final bout the time for 50 % re-oxygenation was only 8 +/- 2 s, whereas recovery of quadriceps oxygenation and oxygen uptake was completed within 3 min. We conclude that the observed low lactate could be attributed to the small oxygen and energy deficits during hiking as the muscles' oxygen accessibility is presumably partially restored during the brief rest intervals.

Transport of pyruvate and lactate in yeast mitochondria.

PubMed

Briquet, M

1977-02-07

Evidence for the existence of mediated transport of pyruvate and lactate in isolated mitochondria of Saccharomyces cerevisiae is presented. 1. The mitochondrial oxidation of pyruvate is specifically inhibited by the monocarboxylic oxoacids alpha-ketoisocaproate and by alpha-cyano-3-hydroxycinnamate, while pyruvate and malate dehydrogenases activities are not inhibited. 2. The stimulation of the mitochondrial oxidations of succinate, alpha-ketoglutarate and citrate by pyruvate are also inhibited by alpha-cyano-3-hydroxycinnamate. 3. The [14C]pyruvate uptake by yeast mitochondria follows saturation kinetics and is completely inhibited by alpha-cyano-3-hydroxycinnamate. 4. Large amplitude passive swellings of mitochondria of the wild type and of cytoplasmic rho- and rho-n mutants are induced by isoosmotic ammonium pyruvate and lactate. These pH-dependent swellings are inhibited by alpha-cyano-3-hydroxycinnamate suggesting that the carrier system is not coded by mitochondrial DNA.

Specific Inhibition of Hepatic Lactate Dehydrogenase Reduces Oxalate Production in Mouse Models of Primary Hyperoxaluria.

PubMed

Lai, Chengjung; Pursell, Natalie; Gierut, Jessica; Saxena, Utsav; Zhou, Wei; Dills, Michael; Diwanji, Rohan; Dutta, Chaitali; Koser, Martin; Nazef, Naim; Storr, Rachel; Kim, Boyoung; Martin-Higueras, Cristina; Salido, Eduardo; Wang, Weimin; Abrams, Marc; Dudek, Henryk; Brown, Bob D

2018-06-15

Primary hyperoxalurias (PHs) are autosomal recessive disorders caused by the overproduction of oxalate leading to calcium oxalate precipitation in the kidney and eventually to end-stage renal disease. One promising strategy to treat PHs is to reduce the hepatic production of oxalate through substrate reduction therapy by inhibiting liver-specific glycolate oxidase (GO), which controls the conversion of glycolate to glyoxylate, the proposed main precursor to oxalate. Alternatively, diminishing the amount of hepatic lactate dehydrogenase (LDH) expression, the proposed key enzyme responsible for converting glyoxylate to oxalate, should directly prevent the accumulation of oxalate in PH patients. Using RNAi, we provide the first in vivo evidence in mammals to support LDH as the key enzyme responsible for converting glyoxylate to oxalate. In addition, we demonstrate that reduction of hepatic LDH achieves efficient oxalate reduction and prevents calcium oxalate crystal deposition in genetically engineered mouse models of PH types 1 (PH1) and 2 (PH2), as well as in chemically induced PH mouse models. Repression of hepatic LDH in mice did not cause any acute elevation of circulating liver enzymes, lactate acidosis, or exertional myopathy, suggesting further evaluation of liver-specific inhibition of LDH as a potential approach for treating PH1 and PH2 is warranted. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats.

PubMed

Cost, Katherine Tombeau; Lobell, Thomas D; Williams-Yee, Zari N; Henderson, Sherryl; Dohanich, Gary

2014-01-01

Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42 days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring. © 2013.

Genetic parameters across lactation for feed intake, fat- and protein-corrected milk, and liveweight in first-parity Holstein cattle.

PubMed

Manzanilla Pech, C I V; Veerkamp, R F; Calus, M P L; Zom, R; van Knegsel, A; Pryce, J E; De Haas, Y

2014-09-01

Breeding values for dry matter intake (DMI) are important to optimize dairy cattle breeding goals for feed efficiency. However, generally, only small data sets are available for feed intake, due to the cost and difficulty of measuring DMI, which makes understanding the genetic associations between traits across lactation difficult, let alone the possibility for selection of breeding animals. However, estimating national breeding values through cheaper and more easily measured correlated traits, such as milk yield and liveweight (LW), could be a first step to predict DMI. Combining DMI data across historical nutritional experiments might help to expand the data sets. Therefore, the objective was to estimate genetic parameters for DMI, fat- and protein-corrected milk (FPCM) yield, and LW across the entire first lactation using a relatively large data set combining experimental data across the Netherlands. A total of 30,483 weekly records for DMI, 49,977 for FPCM yield, and 31,956 for LW were available from 2,283 Dutch Holstein-Friesian first-parity cows between 1990 and 2011. Heritabilities, covariance components, and genetic correlations were estimated using a multivariate random regression model. The model included an effect for year-season of calving, and polynomials for age of cow at calving and days in milk (DIM). The random effects were experimental treatment, year-month of measurement, and the additive genetic, permanent environmental, and residual term. Additive genetic and permanent environmental effects were modeled using a third-order orthogonal polynomial. Estimated heritabilities ranged from 0.21 to 0.40 for DMI, from 0.20 to 0.43 for FPCM yield, and from 0.25 to 0.48 for LW across DIM. Genetic correlations between DMI at different DIM were relatively low during early and late lactation, compared with mid lactation. The genetic correlations between DMI and FPCM yield varied across DIM. This correlation was negative (up to -0.5) between FPCM yield in early lactation and DMI across the entire lactation, but highly positive (above 0.8) when both traits were in mid lactation. The correlation between DMI and LW was 0.6 during early lactation, but decreased to 0.4 during mid lactation. The highest correlations between FPCM yield and LW (0.3-0.5) were estimated during mid lactation. However, the genetic correlations between DMI and either FPCM yield or LW were not symmetric across DIM, and differed depending on which trait was measured first. The results of our study are useful to understand the genetic relationship of DMI, FPCM yield, and LW on specific days across lactation. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Use of dietary supplements by pregnant and lactating women in North America1234

PubMed Central

Picciano, Mary Frances; McGuire, Michelle K

2009-01-01

Nutrient requirements increase during periods of growth and development such as pregnancy and lactation. In response, many clinicians recommend dietary supplements during these important periods of the life cycle. Although there exist some recommendations concerning the need for a limited number of nutrients in supplemental form (eg, iron, folic acid, and iodine), there is a relative paucity of data concerning the use of dietary supplements during pregnancy and lactation. Limited data suggest, however, that usage is dependent on demographic, sociologic, and economic factors. Thus, it is possible that the nation's most at-risk populations may be those who are least likely to comply with these recommendations. As researchers continue to study what is meant by “optimal nutrition” during pregnancy and lactation, it is likely that additional recommendations concerning dietary supplements will emerge. For example, it is possible that increased consumption of some of the long-chain polyunsaturated fatty acids during pregnancy or lactation may impart a benefit to infant health. Understanding better the population dynamics related to supplement use during these periods will be critical in implementation of campaigns designed to encourage appropriate use—and discourage inappropriate use—of dietary supplements during these important phases of human reproduction. The purpose of this article is to briefly review what is known about the use of dietary supplements in North America and, more specifically, in pregnant and lactating women. In addition, information concerning barriers to supplement use is discussed as are current recommendations for dietary supplement consumption during these periods of the life cycle. PMID:19073789

Holsteins favor heifers, not bulls: biased milk production programmed during pregnancy as a function of fetal sex.

PubMed

Hinde, Katie; Carpenter, Abigail J; Clay, John S; Bradford, Barry J

2014-01-01

Mammalian females pay high energetic costs for reproduction, the greatest of which is imposed by lactation. The synthesis of milk requires, in part, the mobilization of bodily reserves to nourish developing young. Numerous hypotheses have been advanced to predict how mothers will differentially invest in sons and daughters, however few studies have addressed sex-biased milk synthesis. Here we leverage the dairy cow model to investigate such phenomena. Using 2.39 million lactation records from 1.49 million dairy cows, we demonstrate that the sex of the fetus influences the capacity of the mammary gland to synthesize milk during lactation. Cows favor daughters, producing significantly more milk for daughters than for sons across lactation. Using a sub-sample of this dataset (N = 113,750 subjects) we further demonstrate that the effects of fetal sex interact dynamically across parities, whereby the sex of the fetus being gestated can enhance or diminish the production of milk during an established lactation. Moreover the sex of the fetus gestated on the first parity has persistent consequences for milk synthesis on the subsequent parity. Specifically, gestation of a daughter on the first parity increases milk production by ∼ 445 kg over the first two lactations. Our results identify a dramatic and sustained programming of mammary function by offspring in utero. Nutritional and endocrine conditions in utero are known to have pronounced and long-term effects on progeny, but the ways in which the progeny has sustained physiological effects on the dam have received little attention to date.

Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex

PubMed Central

Hinde, Katie; Carpenter, Abigail J.; Clay, John S.; Bradford, Barry J.

2014-01-01

Mammalian females pay high energetic costs for reproduction, the greatest of which is imposed by lactation. The synthesis of milk requires, in part, the mobilization of bodily reserves to nourish developing young. Numerous hypotheses have been advanced to predict how mothers will differentially invest in sons and daughters, however few studies have addressed sex-biased milk synthesis. Here we leverage the dairy cow model to investigate such phenomena. Using 2.39 million lactation records from 1.49 million dairy cows, we demonstrate that the sex of the fetus influences the capacity of the mammary gland to synthesize milk during lactation. Cows favor daughters, producing significantly more milk for daughters than for sons across lactation. Using a sub-sample of this dataset (N = 113,750 subjects) we further demonstrate that the effects of fetal sex interact dynamically across parities, whereby the sex of the fetus being gestated can enhance or diminish the production of milk during an established lactation. Moreover the sex of the fetus gestated on the first parity has persistent consequences for milk synthesis on the subsequent parity. Specifically, gestation of a daughter on the first parity increases milk production by ∼445 kg over the first two lactations. Our results identify a dramatic and sustained programming of mammary function by offspring in utero. Nutritional and endocrine conditions in utero are known to have pronounced and long-term effects on progeny, but the ways in which the progeny has sustained physiological effects on the dam have received little attention to date. PMID:24498270

Validation of a novel wearable, wireless technology to estimate oxygen levels and lactate threshold power in the exercising muscle.

PubMed

Farzam, Parisa; Starkweather, Zack; Franceschini, Maria A

2018-04-01

There is a growing interest in monitoring muscle oxygen saturation (SmO 2 ), which is a localized measure of muscle oxidative metabolism and can be acquired continuously and noninvasively using near-infrared spectroscopy (NIRS) methods. Most NIRS systems are cumbersome, expensive, fiber coupled devices, with use limited to lab settings. A novel, low cost, wireless, wearable has been developed for use in athletic training. In this study, we evaluate the advantages and limitations of this new simple continuous-wave (CW) NIRS device with respect to a benchtop, frequency-domain near-infrared spectroscopy (FDNIRS) system. Oxygen saturation and hemoglobin/myoglobin concentration in the exercising muscles of 17 athletic individuals were measured simultaneously with the two systems, while subjects performed an incremental test on a stationary cycle ergometer. In addition, blood lactate concentration was measured at the end of each increment with a lactate analyzer. During exercise, the correlation coefficients of the SmO 2 and hemoglobin/myoglobin concentrations between the two systems were over 0.70. We also found both systems were insensitive to the presence of thin layers of varying absorption, mimicking different skin colors. Neither system was able to predict the athletes' lactate threshold power accurately by simply using SmO 2 thresholds. Instead, the proprietary software of the wearable device was able to predict the athletes' lactate threshold power within half of one power increment of the cycling test. These results indicate this novel wearable device may provide a physiological indicator of athlete's exertion. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Breast pain in lactating mothers.

PubMed

Leung, S Sf

2016-08-01

The number of new mothers who breastfeed has increased dramatically over the last three decades. There is a concern that the present related medical service may be inadequate. Breast pain is the most common complaint among lactating mothers who seek medical help. This study aimed to investigate this problem. Medical records of women who presented with breast pain to a private clinic run by a doctor who was trained as an International Lactation Consultant were reviewed over a period of 6 months in 2015. Most patients were self-referred after chatting online. Assessment included characteristics and duration of pain, treatment prior to consultation, feeding practices, mother's diet, and breast examination. Any site of blockage was identified and relieved. Those with persistent pain were given antibiotics. When there were signs of abscess or abscess that could not be drained, they were referred to a breast surgeon. A total of 69 patients were seen of whom 45 had been breastfeeding for more than 1 month. Pain was experienced for longer than 7 days in 22 women. Antifungal or antibacterial treatment had been unsuccessful in 31 women prior to consultation. The diagnoses were engorgement in five women, blocked duct in 35, mastitis in 13, breast abscess in six, poor positioning and latch in seven, nipple cracks in two, and skin infection in one. Oral antibiotics were prescribed to 21 patients and local antifungal treatment was given to one patient only. Blocked duct was the most common cause of breast pain in lactating mothers. Without prompt relief it is possible that it will progress to mastitis/breast abscess or the mother may discontinue breastfeeding. This may be a suitable time for Hong Kong to set up one or more public full-time breastfeeding clinics to provide a better service to lactating mothers and to facilitate professional training and research.

21 CFR 184.1207 - Calcium lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... lactic acid with calcium carbonate or calcium hydroxide. (b) The ingredient meets the specifications of... manufacturing practice. (d) Prior sanctions for this ingredient different from the uses established in this...

21 CFR 184.1207 - Calcium lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... lactic acid with calcium carbonate or calcium hydroxide. (b) The ingredient meets the specifications of... manufacturing practice. (d) Prior sanctions for this ingredient different from the uses established in this...

21 CFR 184.1207 - Calcium lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... lactic acid with calcium carbonate or calcium hydroxide. (b) The ingredient meets the specifications of... manufacturing practice. (d) Prior sanctions for this ingredient different from the uses established in this...

Impacts of Maternal Nutrition on Vascularity of Nutrient Transferring Tissues during Gestation and Lactation

PubMed Central

Vonnahme, Kimberly A.; Lemley, Caleb O.; Caton, Joel S.; Meyer, Allison M.

2015-01-01

As the demand for food increases with exponential growth in the world population, it is imperative that we understand how to make livestock production as efficient as possible in the face of decreasing available natural resources. Moreover, it is important that livestock are able to meet their metabolic demands and supply adequate nutrition to developing offspring both during pregnancy and lactation. Specific nutrient supplementation programs that are designed to offset deficiencies, enhance efficiency, and improve nutrient supply during pregnancy can alter tissue vascular responses, fetal growth, and postnatal offspring outcomes. This review outlines how vascularity in nutrient transferring tissues, namely the maternal gastrointestinal tract, the utero-placental tissue, and the mammary gland, respond to differing nutritional planes and other specific nutrient supplementation regimes. PMID:25984740

Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and β-Arrestin-1-Regulated Lactate Metabolism.

PubMed

Dong, Jun-Hong; Wang, Yi-Jing; Cui, Min; Wang, Xiao-Jing; Zheng, Wen-Shuai; Ma, Ming-Liang; Yang, Fan; He, Dong-Fang; Hu, Qiao-Xia; Zhang, Dao-Lai; Ning, Shang-Lei; Liu, Chun-Hua; Wang, Chuan; Wang, Yue; Li, Xiang-Yao; Yi, Fan; Lin, Amy; Kahsai, Alem W; Cahill, Thomas Joseph; Chen, Zhe-Yu; Yu, Xiao; Sun, Jin-Peng

2017-04-15

Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful. We used specific β-adrenergic agonists, as well as β 2 -adrenergic receptor (β2AR) and arrestin knockout models, to study the effects of adaptive β2AR activation on cognitive function using Morris water maze and object recognition experiments. We used molecular and cell biological approaches to elucidate the signaling subnetworks. We observed that the duration of the adaptive β2AR activation determines its consequences on learning and memory. Short-term formoterol treatment, for 3 to 5 days, improved cognitive function; however, prolonged β2AR activation, for more than 6 days, produced harmful effects. We identified the activation of several signaling networks downstream of β2AR, as well as an essential role for arrestin and lactate metabolism in promoting cognitive ability. Whereas Gs-protein kinase A-cyclic adenosine monophosphate response element binding protein signaling modulated monocarboxylate transporter 1 expression, β-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a β-arrestin-1/phospho-mitogen-activated protein kinase/hypoxia-inducible factor-1α ternary complex to upregulate lactate metabolism in astrocyte-derived U251 cells. Conversely, long-term treatment with formoterol led to the desensitization of β2ARs, which was responsible for its decreased beneficial effects. Our results not only revealed that β-arrestin-1 regulated lactate metabolism to contribute to β2AR functions in improved memory formation, but also indicated that the appropriate management of one specific stress pathway, such as through the clinical drug formoterol, may exert beneficial effects on cognitive abilities. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

TRIENNIAL LACTATION SYMPOSIUM/BOLFA:Historical perspectives of lactation biology in the late 20th and early 21st centuries.

PubMed

Collier, R J; Bauman, D E

2017-12-01

The latter half of the 20th century and the early portion of the 21st century will be recognized as the "Golden Age" of lactation biology. This period corresponded with the rise of systemic, metabolomic, molecular, and genomic biology. It includes the discovery of the structure of DNA and ends with the sequencing of the complete genomes of humans and all major domestic animal species including the dairy cow. This included the ability to identify polymorphisms in the nucleic acid sequence, which can be tied to specific differences in cellular, tissue, and animal performance. Before this period, classical work using endocrine ablation and replacement studies identified the mammary gland as an endocrine-dependent organ. In the early 1960s, the development of RIA and radioreceptor assays permitted the study of the relationship between endocrine patterns and mammary function. The ability to measure nucleic acid content of tissues opened the door to study of the factors regulating mammary growth. The development of high-speed centrifugation in the 1960s allowed separation of specific cell organelles and their membranes. The development of transmission and scanning electron microscopy permitted the study of the relationship between structure and function in the mammary secretory cell. The availability of radiolabeled metabolites provided the opportunity to investigate the metabolic pathways and their regulation. The development of concepts regarding the coordination of metabolism to support lactation integrated our understanding of nutrient partitioning and homeostasis. The ability to produce recombinant molecules and organisms permitted enhancement of lactation in farm animal species and the production of milk containing proteins of value to human medicine. These discoveries and others contributed to vastly increased dairy farm productivity in the United States and worldwide. This review will include the discussion of the centers of excellence and scientists who labored in these fields to produce the harvest of knowledge we enjoy today.

Growth advantage of Streptococcus thermophilus over Lactobacillus bulgaricus in vitro and in the gastrointestinal tract of gnotobiotic rats.

PubMed

Ben-Yahia, L; Mayeur, C; Rul, F; Thomas, M

2012-09-01

The yoghurt bacteria, Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus, are alleged to have beneficial effects on human health. The objective of this study was to characterise growth, biochemical activity and competitive behaviour of these two bacteria in vitro and in vivo. S. thermophilus LMD-9 and L. bulgaricus ATCC 11842 growth and lactate production were monitored in different media and in the gastrointestinal tract (GIT) of germ-free rats. In vitro, particularly in milk, S. thermophilus had a selective growth advantage over L. bulgaricus. The GIT of germ-free rats not supplemented with lactose was colonised by S. thermophilus but not by L. bulgaricus. Both bacteria were able to colonise the GIT of germ-free rats supplemented with 45 g/l lactose in their drinking water. However, if germ-free rats were inoculated with a mixture of the two bacteria and were supplemented with lactose, S. thermophilus rapidly and extensively colonised the GIT (1010 cfu/g faeces) at the expense of L. bulgaricus, which remained in most cases at levels <102 cfu/g faeces. S. thermophilus specifically produced L-lactate, while L. bulgaricus produced only D-lactate, both in vitro and in vivo. S. thermophilus showed competitive and growth advantage over L. bulgaricus in vitro as well as in vivo in the GIT of germ-free rats and, accordingly, L-lactate was the main lactate isomer produced.

Oxytocin receptor mRNA expression in rat brain: implications for behavioral integration and reproductive success.

PubMed

Ostrowski, N L

1998-11-01

The nonapeptide, oxytocin (OT), has been implicated in a wide range of physiological, behavioral and pharmacological effects related to learning and memory, parturition and lactation, maternal and sexual behavior, and the formation of social attachments. Specific G-protein linked membrane bound OT receptors mediate OTs effects. The unavailability of highly selective pharmacological ligands that discriminate the OT receptor from the highly homologous vasopressin receptors (V1a, V1b and V2 subtypes) has made it difficult to confirm specific effects of oxytocin, particularly in brain regions where OT and multiple AVP receptor subtypes may be coexpressed. Here, data on the oxytocin receptor (OTR) messenger ribonucleic acid (mRNA) localization in brain are presented in the context of a model that proposes a reproductive state-dependent role for steroid-hormone restructuring of neural circuits, and a role for oxytocin in the integration of neural transmission in pathways subserving: (1) steroid-sensitive reproductive behaviors; (2) learning; and (3) reinforcement. It is hypothesized that social attachments emerge as a consequence of a conditioned association between OT-related activity in these pathways and the eliciting stimulus.

Pathogen-group specific association between CXCR1 polymorphisms and subclinical mastitis in dairy heifers.

PubMed

Verbeke, Joren; Piepers, Sofie; Peelman, Luc; Van Poucke, Mario; De Vliegher, Sarne

2012-08-01

The chemokine (C-X-C motif) receptor 1 (CXCR1) gene encodes the homonymous receptor for interleukin 8 (IL8) on polymorphonuclear neutrophilic leucocytes (PMNL). Binding causes migration from blood to milk, activation and prolonged survival of PMNL, a crucial process in the innate immune defence of the bovine mammary gland against invading mastitis-causing pathogens. The main objective of this study was to screen the entire coding region of the CXCR1 gene for polymorphisms and to analyse their association with udder health of dairy heifers. One-hundred-and-forty Belgian Holstein heifers originating from 20 commercial dairy farms were genotyped by DNA sequencing. Detailed phenotypic data on udder health was available including quarter bacteriological culture results and somatic cell count (SCC) in early lactation and composite milk SCC during first lactation. In total, 16 polymorphisms (including 8 missense mutations) were detected. Polymorphism c.980A>G was associated with pathogen-group specific IMI: heifers with genotype AG were less likely to have an IMI due to major mastitis pathogens compared with heifers with genotype GG but did not have less IMI by coagulase-negative staphylococci, so-called minor pathogens. CXCR1 genotype was neither associated with quarter SCC in early lactation nor with composite SCC during lactation. Although mastitis susceptibility is influenced by many factors, some genetic polymorphisms potentially have major effects on udder health of heifers, as was shown here. These results trigger us to further study the relationship between CXCR1 polymorphisms and mastitis susceptibility in both observational and experimental trials.

Supplementation of Mice with Specific Nondigestible Oligosaccharides during Pregnancy or Lactation Leads to Diminished Sensitization and Allergy in the Female Offspring.

PubMed

Hogenkamp, Astrid; Knippels, Leon M J; Garssen, Johan; van Esch, Betty C A M

2015-05-01

The maternal environment and early life exposure affect immune development in offspring. We investigated whether development of food allergy in offspring is affected by supplementing pregnant or lactating sensitized or nonsensitized mice with a mixture of nondigestible oligosaccharides. Dams were sensitized intragastrically with ovalbumin before mating, with use of cholera toxin (CT) as an adjuvant. Nonsensitized dams received CT only. Dams were fed a control diet or a diet supplemented with short-chain galacto oligosaccharides (scGOSs), long-chain fructo oligosaccharides (lcFOSs), and pectin-derived acidic oligosaccharides (pAOSs) in a ratio of 9:1:2 at a dose of 2% during pregnancy or lactation, resulting in 7 experimental groups. After weaning, offspring were fed a control diet and ovalbumin-CT sensitized. Acute allergic skin responses (ASRs), shock symptoms, body temperature, and specific plasma immunoglobulins were measured upon intradermal ovalbumin challenge. Th2/Th1- and regulatory T cells were analyzed with use of quantitative polymerase chain reaction and flow cytometric analysis in spleen, mesenteric lymph nodes, and blood. Supplementing sensitized pregnant or lactating dams with scGOS/lcFOS/pAOS resulted in lower ASRs in the offspring [offspring of sensitized female mice fed experimental diet during pregnancy (S-Preg): 48 ± 2.1 μm; offspring of sensitized female mice fed experimental diet during lactation (S-Lact): 60 ± 6.2 μm] compared with the sensitized control group (119 ± 13.9 μm). In the S-Lact group, this coincided with an absence of shock symptoms compared with the offspring of sensitized female mice fed control food during pregnancy and lactation (S-Con) and S-Preg groups, and lower ovalbumin-IgG1 [S-Con: 3.8 ± 0.1 arbitrary units (AUs); S-Preg: 3.3 ± 0.1 AUs; S-Lact: 2.4 ± 0.1 AUs] and higher ovalbumin-IgG2a concentrations (S-Con: 1.1 ± 0.1 AUs; S-Preg: 0.8 ± 0.1 AUs; S-Lact: 2.0 ± 0.1 AUs). Supplementing nonsensitized pregnant or lactating dams with scGOS/lcFOS/pAOS resulted in lower plasma ovalbumin-IgE [offspring of nonsensitized female mice fed experimental diet during pregnancy (NS-Preg): 1.6 ± 0.4 AUs; offspring of nonsensitized female mice fed experimental diet during lactation (NS-Lact): 0.3 ± 0.1 AUs vs. offspring of nonsensitized female mice fed control food during pregnancy and lactation (NS-Con): 3.1 ± 0.6 AUs] and ovalbumin-IgG1 (NS-Lact: 2.3 ± 0.3 AUs vs. NS-Con: 3.4 ± 0.3 AUs) concentrations in offspring. Ovalbumin-IgG2a plasma concentrations were higher in offspring of scGOS/lcFOS/pAOS-supplemented dams (NS-Preg: 1.1 ± 0.1 AUs; NS-Lact: 1.1 ± 0.1 AUs) than in those of unsupplemented, nonsensitized controls (0.4 ± 0.0 AUs). These data show impaired sensitization in offspring of scGOS/lcFOS/pAOS-supplemented mice. A number of the analyzed variables are differentially affected by whether supplementation occurs during pregnancy or lactation, and the outcome of dietary supplementation is affected by whether the mother has been sensitized to ovalbumin and CT. © 2015 American Society for Nutrition.

LDHk, an unusual oxygen-sensitive lactate dehydrogenase expressed in human cancer.

PubMed Central

Anderson, G R; Kovacik, W P

1981-01-01

An unusual isozyme of lactate dehydrogenase (LDH; L-lactate:NAD+ oxidoreductase, EC 1.1.1.27), LDHk, has been described in cells transformed by the Kirsten murine sarcoma virus (KiMSV). This isozyme appears to contain one or more subunits encoded by the transforming gene of KiMSV and is readily distinguished from other isozymes of LDH. Specifically, it is more basic than other LDH isozymes, has an apparent subunit structure of (35,000)4(22,000)1, is essentially inactive if assayed under a normal atmosphere, and is strongly inhibited by GTP and various related compounds. We have examined human cancer and normal tissue controls for expression of an activity like LDHk. In 11 out of 16 human carcinomas, LDHk activity was increased 10- to 500-fold over the level seen in adjoining nontumor tissue. In contrast, other LDH isozymes were increased by only 2- to 5-fold. Images PMID:6942426

Neurotoxicity Induced by Bupivacaine via T-Type Calcium Channels in SH-SY5Y Cells

PubMed Central

Wen, Xianjie; Xu, Shiyuan; Liu, Hongzhen; Zhang, Quinguo; Liang, Hua; Yang, Chenxiang; Wang, Hanbing

2013-01-01

There is concern regarding neurotoxicity induced by the use of local anesthetics. A previous study showed that an overload of intracellular calcium is involved in the neurotoxic effect of some anesthetics. T-type calcium channels, which lower the threshold of action potentials, can regulate the influx of calcium ions. We hypothesized that T-type calcium channels are involved in bupivacaine-induced neurotoxicity. In this study, we first investigated the effects of different concentrations of bupivacaine on SH-SY5Y cell viability, and established a cell injury model with 1 mM bupivacaine. The cell viability of SH-SY5Y cells was measured following treatment with 1 mM bupivacaine and/or different dosages (10, 50, or 100 µM) of NNC 55-0396 dihydrochloride, an antagonist of T-type calcium channels for 24 h. In addition, we monitored the release of lactate dehydrogenase, cytosolic Ca2+ ([Ca2+]i), cell apoptosis and caspase-3 expression. SH-SY5Y cells pretreated with different dosages (10, 50, or 100 µM) of NNC 55-0396 dihydrochloride improved cell viability, reduced lactate dehydrogenase release, inhibited apoptosis, and reduced caspase-3 expression following bupivacaine exposure. However, the protective effect of NNC 55-0396 dihydrochloride plateaued. Overall, our results suggest that T-type calcium channels may be involved in bupivacaine neurotoxicity. However, identification of the specific subtype of T calcium channels involved requires further investigation. PMID:23658789

Genes Involved in the Astrocyte-Neuron Lactate Shuttle (ANLS) Are Specifically Regulated in Cortical Astrocytes Following Sleep Deprivation in Mice

PubMed Central

Petit, Jean-Marie; Gyger, Joël; Burlet-Godinot, Sophie; Fiumelli, Hubert; Martin, Jean-Luc; Magistretti, Pierre J.

2013-01-01

Study Objectives: There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called “astrocyte-neuron lactate shuttle” (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. Design: 6-hour instrumental sleep deprivation (TSD). Setting: Animal sleep research laboratory. Participants: Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Interventions: Basal sleep recordings and sleep deprivation achieved using a modified cage where animals were gently forced to move. Measurements and Results: Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, α-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. Conclusions: This study shows that TSD induces the expression of genes associated with ANLS specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle. Citation: Petit JM; Gyger J; Burlet-Godinot S; Fiumelli H; Martin JL; Magistretti PJ. Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice. SLEEP 2013;36(10):1445-1458. PMID:24082304

The effect of mineral-based alkaline water on hydration status and the metabolic response to short-term anaerobic exercise

PubMed Central

Chycki, Jakub; Zając, Tomasz; Kurylas, Anna

2017-01-01

Previously it was demonstrated that mineralization and alkalization properties of mineral water are important factors influencing acid-base balance and hydration in athletes. The purpose of this study was to investigate the effects of drinking different types of water on urine pH, specific urine gravity, and post-exercise lactate utilization in response to strenuous exercise. Thirty-six male soccer players were divided into three intervention groups, consuming around 4.0 l/day of different types of water for 7 days: HM (n=12; highly mineralized water), LM (n=12; low mineralized water), and CON (n=12; table water). The athletes performed an exercise protocol on two occasions (before and after intervention). The exercise protocol consisted of 5 bouts of intensive 60-s (120% VO2max) cycling separated by 60 s of passive rest. Body composition, urinalysis and lactate concentration were evaluated – before (t0), immediately after (t1), 5’ (t2), and 30’ (t3) after exercise. Total body water and its active transport (TBW – total body water / ICW – intracellular water / ECW – extracellular water) showed no significant differences in all groups, at both occasions. In the post-hydration state we found a significant decrease of specific urine gravity in HM (1021±4.2 vs 1015±3.8 g/L) and LM (1022±3.1 vs 1008±4.2 g/L). We also found a significant increase of pH and lactate utilization rate in LM. In conclusion, the athletes hydrated with alkaline, low mineralized water demonstrated favourable changes in hydration status in response to high-intensity interval exercise with a significant decrease of specific urine gravity, increased urine pH and more efficient utilization of lactate after supramaximal exercise. PMID:29158619

Kinetic characterization of recombinant Bacillus coagulans FDP-activated l-lactate dehydrogenase expressed in Escherichia coli and its substrate specificity.

PubMed

Jiang, Ting; Xu, Yanbing; Sun, Xiucheng; Zheng, Zhaojuan; Ouyang, Jia

2014-03-01

Bacillus coagulans is a homofermentative, acid-tolerant and thermophilic sporogenic lactic acid bacterium, which is capable of producing high yields of optically pure lactic acid. The l-(+)-lactate dehydrogenase (l-LDH) from B. coagulans is considered as an ideal biocatalyst for industrial production. In this study, the gene ldhL encoding a thermostable l-LDH was amplified from B. coagulans NL01 genomic DNA and successfully expressed in Escherichia coli BL21 (DE3). The recombinant enzyme was partially purified and its enzymatic properties were characterized. Sequence analysis demonstrated that the l-LDH was a fructose 1,6-diphosphate-activated NAD-dependent lactate dehydrogenase (l-nLDH). Its molecular weight was approximately 34-36kDa. The Km and Vmax values of the purified l-nLDH for pyruvate were 1.91±0.28mM and 2613.57±6.43μmol(minmg)(-1), respectively. The biochemical properties of l-nLDH showed that the specific activity were up to 2323.29U/mg with optimum temperature of 55°C and pH of 6.5 in the pyruvate reduction and 351.01U/mg with temperature of 55°C and pH of 11.5 in the lactate oxidation. The enzyme also showed some activity in the absence of FDP, with a pH optimum of 4.0. Compared to other lactic acid bacterial l-nLDHs, the enzyme was found to be relatively stable at 50°C. Ca(2+), Ba(2+), Mg(2+) and Mn(2+) ions had activated effects on the enzyme activity, and the enzyme was greatly inhibited by Ni(2+) ion. Besides these, l-nLDH showed the higher specificity towards pyruvate esters, such as methyl pyruvate and ethyl pyruvate. Copyright © 2014 Elsevier Inc. All rights reserved.

Longitudinal data analysis of polymorphisms in the κ-casein and β-lactoglobulin genes shows differential effects along the trajectory of the lactation curve in tropical dairy goats.

PubMed

Cardona, Samir Julián Calvo; Cadavid, Henry Cardona; Corrales, Juan David; Munilla, Sebastián; Cantet, Rodolfo J C; Rogberg-Muñoz, Andrés

2016-09-01

The κ-casein (CSN-3) and β-lactoglobulin (BLG) genes are extensively polymorphic in ruminants. Several association studies have estimated the effects of polymorphisms in these genes on milk yield, milk composition, and cheese-manufacturing properties. Usually, these results are based on production integrated over the lactation curve or on cross-sectional studies at specific days in milk (DIM). However, as differential expression of milk protein genes occurs over lactation, the effect of the polymorphisms may change over time. In this study, we fitted a mixed-effects regression model to test-day records of milk yield and milk quality traits (fat, protein, and total solids yields) from Colombian tropical dairy goats. We used the well-characterized A/B polymorphisms in the CSN-3 and BLG genes. We argued that this approach provided more efficient estimators than cross-sectional designs, given the same number and pattern of observations, and allowed exclusion of between-subject variation from model error. The BLG genotype AA showed a greater performance than the BB genotype for all traits along the whole lactation curve, whereas the heterozygote showed an intermediate performance. We observed no such constant pattern for the CSN-3 gene between the AA homozygote and the heterozygote (the BB genotype was absent from the sample). The differences among the genotypic effects of the BLG and the CSN-3 polymorphisms were statistically significant during peak and mid lactation (around 40-160 DIM) for the BLG gene and only for mid lactation (80-145 DIM) for the CSN-3 gene. We also estimated the additive and dominant effects of the BLG locus. The locus showed a statistically significant additive behavior along the whole lactation trajectory for all quality traits, whereas for milk yield the effect was not significant at later stages. In turn, we detected a statistically significant dominance effect only for fat yield in the early and peak stages of lactation (at about 1-45 DIM). The longitudinal analysis of test-day records allowed us to estimate the differential effects of polymorphisms along the lactation curve, pointing toward stages that could be affected by the gene. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Energy expenditures and food intakes of lactating women in Guatemala.

PubMed

Schutz, Y; Lechtig, A; Bradfield, R B

1980-04-01

Total energy expenditures and intakes were simultaneously assessed in 18 free-ranging lactating women (10 months postpartum) and compared to six similarly-sized, nonlactating, nonpregnant but multiparous women living in the same rural villages in the Guatemalan highlands. Energy intakes were estimated by the 24-hr recall method for each of 4 consecutive days. Energy expenditures were determined for 2 days by monitoring heart rate throughout the day and relating heart rate to oxygen consumption by individually-determined regression lines. The mean energy intake for the 4 consecutive days was estimated to be 1929 +/- 360 kcal/day (39.2 kcal/kg per day) for the lactating group; and 1876 +/- 404 kcal/day (38.3 kcal/kg per day) for the nonlactating group. The 2-day mean energy expenditures were estimated to be 2007 +/- 292 kcal/day for the lactating women (41.8 kcal/kg per day) and 1966 +/- 382 kcal/day for the lactating women (40.1 kcal/kg per day). The way of life of both groups was judged "moderately active" by 1973 FAO/WHO classifications. Most of the lactating women had been losing weight progressively during the past 6 months. Over the 10-week period prior to our measurnth) (P less than 0.01) than in the nonlactating group (-35 g/month) (ns). The high correlation (r = 0.87) between weight loss and the reduction in the sum of the three skinfolds suggested adipose tissue loss. There were no significant differences between the two groups in terms of daily energy intake, daily energy expenditure, the energy cost of specific activities throughout the day. The slope of the heart rate/oxygen consumption regressions suggest adequate cardiorespiratory fitness. This study suggests that the energy cost of lactation was met to a greater extent by fat loss than by either increased energy intake, reduced energy expenditure, or both.

From genes to milk: genomic organization and epigenetic regulation of the mammary transcriptome.

PubMed

Lemay, Danielle G; Pollard, Katherine S; Martin, William F; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J Bruce; Rijnkels, Monique

2013-01-01

Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival.

From Genes to Milk: Genomic Organization and Epigenetic Regulation of the Mammary Transcriptome

PubMed Central

Lemay, Danielle G.; Pollard, Katherine S.; Martin, William F.; Freeman Zadrowski, Courtneay; Hernandez, Joseph; Korf, Ian; German, J. Bruce; Rijnkels, Monique

2013-01-01

Even in genomes lacking operons, a gene's position in the genome influences its potential for expression. The mechanisms by which adjacent genes are co-expressed are still not completely understood. Using lactation and the mammary gland as a model system, we explore the hypothesis that chromatin state contributes to the co-regulation of gene neighborhoods. The mammary gland represents a unique evolutionary model, due to its recent appearance, in the context of vertebrate genomes. An understanding of how the mammary gland is regulated to produce milk is also of biomedical and agricultural importance for human lactation and dairying. Here, we integrate epigenomic and transcriptomic data to develop a comprehensive regulatory model. Neighborhoods of mammary-expressed genes were determined using expression data derived from pregnant and lactating mice and a neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3 in the mouse mammary gland and liver tissue during lactation. We found that neighborhoods of genes in regions of uniquely active chromatin in the lactating mammary gland, compared with liver tissue, were extremely rare. Rather, genes in most neighborhoods were suppressed during lactation as reflected in their expression levels and their location in regions of silenced chromatin. Chromatin silencing was largely shared between the liver and mammary gland during lactation, and what distinguished the mammary gland was mainly a small tissue-specific repertoire of isolated, expressed genes. These findings suggest that an advantage of the neighborhood organization is in the collective repression of groups of genes via a shared mechanism of chromatin repression. Genes essential to the mammary gland's uniqueness are isolated from neighbors, and likely have less tolerance for variation in expression, properties they share with genes responsible for an organism's survival. PMID:24086428

The effect of trace mineral fortification level and source on performance of dairy cattle.

PubMed

Nocek, J E; Socha, M T; Tomlinson, D J

2006-07-01

Five hundred seventy-three cows, balanced by parity and 305-d mature equivalent at dry off, were assigned to 1 of 4 treatments: 1) 75% complexed trace minerals (CTM; 75C): Zn, Mn, Cu, and Co supplied at 75% of NRC (2001) guidelines by Zn-, Mn-, and Cu-specific AA complexes, and cobalt glucoheptonate; 2) 100% inorganic (100I): Zn, Mn, Cu, and Co supplied at 100% of NRC (2001) requirements by sulfate sources; 3) 100% complexed (100C): Zn, Mn, Cu, and Co supplied at 100% of NRC (2001) requirements by CTM; and 4) complexed/ inorganic (C/I): Zn and Cu supplied at 100% of NRC (2001) requirements using a combination of CTM and sulfates and Co and Mn supplied with sources at 9.1 and 3.3 times NRC (2001) requirements using a combination of CTM and sulfates. All percentages of Zn, Cu, Mn, and Co relative to NRC (2001) reflect supplemental contributions and do not include basal diet contributions. Experimental periods were dry period 1, full lactation 1, dry period 2, and 200 d into the subsequent lactation. Reproductive, health, and production information was collected during both lactations. Claw evaluations were conducted at trial start, 150 d into lactation 1, at the end of lactation 1, and 150 d into lactation 2. During lactation 1, C/I cows produced more milk, fat-corrected milk, energy-corrected milk, and fat than 100I cows. During lactation 2, yields of milk, fat-corrected milk, energy-corrected milk, fat, and protein were higher for 100C and C/I cows than for 75C or 100I cows. Fat percentage was highest for 100C cows with no treatment effect on protein content. During lactations 1 and 2, C/I cows had fewer days to first estrus than cows receiving the other treatments. During lactation 2, C/ I cows had fewer services per conception and days open. There were no significant effects of treatment on health. White line separation incidence was lower for 100I cows than 75C cows, whereas heel erosion was higher for the 100I cows than for the C/I cows. Fortification of trace elements with inorganic and complexed sources at or above NRC requirements improved reproductive and productive performance. In addition, cows can be supplemented with CTM at 75% of NRC requirements with no reduction in performance compared with supplementing at 100% of NRC requirements using only sulfate sources of Zn, Mn, Cu, and Co.

Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1).

PubMed

Madaan, Ankush; Nadeau-Vallée, Mathieu; Rivera, Jose Carlos; Obari, Dima; Hou, Xin; Sierra, Estefania Marin; Girard, Sylvie; Olson, David M; Chemtob, Sylvain

2017-01-01

Uterine inflammatory processes trigger prolabor pathways and orchestrate on-time labor onset. Although essential for successful labor, inflammation needs to be regulated to avoid uncontrolled amplification and resolve postpartum. During labor, myometrial smooth muscle cells generate ATP mainly via anaerobic glycolysis, resulting in accumulation of lactate. Aside from its metabolic function, lactate has been shown to activate a G protein-coupled receptor, GPR81, reported to regulate inflammation. We therefore hypothesize that lactate produced during labor may act via GPR81 in the uterus to exert in a feedback manner antiinflammatory effects, to resolve or mitigate inflammation. We sought to investigate the role of lactate produced during labor and its receptor, GPR81, in regulating inflammation in the uterus. We investigated the expression of GPR81 in the uterus and the pharmacological role of lactate acting via GPR81 during labor, using shRNA-GPR81 and GPR81 -/- mice. (1) Uterine lactate levels increased substantially from 2 to 9 mmol/L during labor. (2) Immunohistological analysis revealed expression of GPR81 in the uterus with high expression in myometrium. (3) GPR81 expression increased during gestation, and peaked near labor. (4) In primary myometrial smooth muscle cell and ex vivo uteri from wild-type mice, lactate decreased interleukin-1β-induced transcription of key proinflammatory Il1b, Il6, Ccl2, and Pghs2; suppressive effects of lactate were not observed in cells and tissues from GPR81 -/- mice. (5) Conversely, proinflammatory gene expression was augmented in the uterus at term in GPR81 -/- mice and wild-type mice treated intrauterine with lentiviral-encoded shRNA-GPR81; GPR81 silencing also induced proinflammatory gene transcription in the uterus when labor was induced by endotoxin (lipopolysaccharide). (6) Importantly, administration to pregnant mice of a metabolically stable specific GPR81 agonist, 3,5-dihydroxybenzoic acid, decreased endotoxin-induced uterine inflammation, preterm birth, and associated neonatal mortality. Collectively, our data uncover a novel link between the anaerobic glycolysis and the control of uterine inflammation wherein the high levels of lactate produced during labor act on uterine GPR81 to down-regulate key proinflammatory genes. This discovery may represent a novel feedback mechanism to regulate inflammation during labor, and conveys a potential rationale for the use of GPR81 agonists to attenuate inflammation and resulting preterm birth. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of test-strategies for estimating probability of low prevalence of paratuberculosis in Danish dairy herds.

PubMed

Sergeant, E S G; Nielsen, S S; Toft, N

2008-06-15

Paratuberculosis is a chronic infection affecting cattle and other ruminants. In the dairy industry, losses due to paratuberculosis can be substantial in infected herds and several countries have implemented national programmes based on herd-classification to manage the disease. The aim of this study was to develop a method to estimate the probability of low within-herd prevalence of paratuberculosis for Danish dairy herds. A stochastic simulation model was developed using the R programming environment. Features of this model included: use of age-specific estimates of test-sensitivity and specificity; use of a distribution of observed values (rather than a fixed, low value) for design prevalence; and estimates of the probability of low prevalence (PrLow) based on a specific number of test-positive animals, rather than for a result less than or equal to a specified cut-point number of reactors. Using this model, five herd-testing strategies were evaluated: (1) milk-ELISA on all lactating cows; (2) milk-ELISA on lactating cows4 years old; (4) faecal culture on all lactating cows; and (5) milk-ELISA plus faecal culture in series on all lactating cows. The five testing strategies were evaluated using observed milk-ELISA results from 19 Danish dairy herds as well as for simulated results from the same herds assuming that they were uninfected. Whole-herd milk-ELISA was the preferred strategy, and considered the most cost-effective strategy of the five alternatives. The five strategies were all efficient in detecting infection, i.e. estimating a low PrLow in infected herds, however, PrLow estimates for milk-ELISA on age-cohorts were too low in simulated uninfected herds and the strategies involving faecal culture were too expensive to be of practical interest. For simulated uninfected herds, whole-herd milk-ELISA resulted in median PrLow values>0.9 for most herds, depending on herd size and age-structure. None of the strategies provided enough power to establish a high PrLow in smaller herds, or herds with a younger age-structure. Despite this, it appears as if the method is a useful approach for herd-classification for most herds in the Danish dairy industry.

The use of complementary and alternative medicines during breastfeeding: results from the Herbal supplements in Breastfeeding InvesTigation (HaBIT).

PubMed

Bettiol, Alessandra; Lombardi, Niccolò; Marconi, Ettore; Crescioli, Giada; Bonaiuti, Roberto; Maggini, Valentina; Gallo, Eugenia; Mugelli, Alessandro; Firenzuoli, Fabio; Ravaldi, Claudia; Vannacci, Alfredo

2018-05-16

Use of complementary and alternative medicines (CAMs) during breastfeeding is commonly increasing, mainly due to their presumed higher safety compared to conventional medications. Indeed, CAMs can cause serious adverse effects, and high-quality evidence supporting their use during lactation is limited. In Italy, specific investigations on the attitude of lactating women towards CAMs are lacking. The Herbal supplements in Breastfeeding InvesTigation (HaBIT) aimed to explore the attitudes and knowledge on CAMs among lactating women. A web-based survey was conducted over a six-year period among lactating women resident in Tuscany (Italy). Data on lactating behavior, CAMs use during pregnancy or breastfeeding, and women knowledge about CAMs' efficacy and safety were collected. 388 lactating women answered the questionnaire; the majority of them were primiparae with high education level. Two-hundred and four women declared to have been CAMs users during breastfeeding. Moreover, the 61 and 48% of subjects reported CAMs use also before and during pregnancy. A significant proportion of subjects were unable to correctly identify the type of CAMs they were using. The 73% of women were convinced that CAMs had higher or comparable safety than conventional medications; nevertheless, 65% of women admitted to have no scientific information about the potential risks of CAMs, and 14 CAMs users reported to have experienced side effects. These results claim the necessity that healthcare providers amplify their role to increase nursing women' awareness about CAMs. Further research is needed to support the evidence base of non-pharmaceutical approaches for symptom control during breastfeeding. This article is protected by copyright. All rights reserved.

High serum lactate as an adjunct in the early prediction of anastomotic leak following oesophagectomy.

PubMed

Ip, B; Ng, K T; Packer, S; Paterson-Brown, S; Couper, G W

2017-10-01

Anastomotic leak (AL) following oesophagectomy carries a high mortality and morbidity. Early detection and intervention is required for a successful outcome. We have examined the role of a high postoperative serum lactate in predicting which patients are at risk of developing an anastomotic leak(AL). All patients who underwent transthoracic oesophagectomy over a 3-year period were identified from a prospectively collected database. Medical records were reviewed to identify the highest serum lactate recorded from blood gas analysis over each 24hr post-operative period. Patients who underwent transhiatal and left thoraco-abdominal oesophagectomies were excluded. Patients who developed a chyle leak were excluded. Of a total of 136 oesophagectomies included for analysis, 18 developed an AL (13.2%). Of these patients, 10 underwent thoracoscopic oesophageal mobilization with cervical anastomosis and the rest an Ivor Lewis procedure. Predictive factors for AL included neoadjuvant chemotherapy (15/18 83.3% vs 55/118 46.6% p = 0.0046) and number of positive lymph nodes (mean 4.2 vs control mean 2.3 p = 0.045). Overall net fluid balance was comparable between the 2 groups, although AL patients received slightly more fluid on Day 3. High lactate levels on days 1-3 were associated with an AL. Using a Day 2 lactate of 1.7 mmol/L, the sensitivity of predicting AL was 72% and specificity 88%. The mean lag time using existing diagnostic modalities was 7.9 days. A serum lactate of >1.7 mmol/l on day 2 should raise the possibility of a potential AL. Such patients should be selected for more intensive monitoring, optimization and selective gastroscopy. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Glycolysis-mediated control of blood-brain barrier development and function.

PubMed

Salmina, Alla B; Kuvacheva, Natalia V; Morgun, Andrey V; Komleva, Yulia K; Pozhilenkova, Elena A; Lopatina, Olga L; Gorina, Yana V; Taranushenko, Tatyana E; Petrova, Lyudmila L

2015-07-01

The blood-brain barrier (BBB) consists of differentiated cells integrating in one ensemble to control transport processes between the central nervous system (CNS) and peripheral blood. Molecular organization of BBB affects the extracellular content and cell metabolism in the CNS. Developmental aspects of BBB attract much attention in recent years, and barriergenesis is currently recognized as a very important and complex mechanism of CNS development and maturation. Metabolic control of angiogenesis/barriergenesis may be provided by glucose utilization within the neurovascular unit (NVU). The role of glycolysis in the brain has been reconsidered recently, and it is recognized now not only as a process active in hypoxic conditions, but also as a mechanism affecting signal transduction, synaptic activity, and brain development. There is growing evidence that glycolysis-derived metabolites, particularly, lactate, affect barriergenesis and functioning of BBB. In the brain, lactate produced in astrocytes or endothelial cells can be transported to the extracellular space via monocarboxylate transporters (MCTs), and may act on the adjoining cells via specific lactate receptors. Astrocytes are one of the major sources of lactate production in the brain and significantly contribute to the regulation of BBB development and functioning. Active glycolysis in astrocytes is required for effective support of neuronal activity and angiogenesis, while endothelial cells regulate bioavailability of lactate for brain cells adjusting its bidirectional transport through the BBB. In this article, we review the current knowledge with regard to energy production in endothelial and astroglial cells within the NVU. In addition, we describe lactate-driven mechanisms and action of alternative products of glucose metabolism affecting BBB structural and functional integrity in developing and mature brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal protein restriction during lactation induces early and lasting plasma metabolomic and hepatic lipidomic signatures of the offspring in a rodent programming model.

PubMed

Martin Agnoux, Aurore; El Ghaziri, Angélina; Moyon, Thomas; Pagniez, Anthony; David, Agnès; Simard, Gilles; Parnet, Patricia; Qannari, El Mostafa; Darmaun, Dominique; Antignac, Jean-Philippe; Alexandre-Gouabau, Marie-Cécile

2018-05-01

Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. However, the exact mechanisms underlying offspring metabolic adaptations are not yet fully understood. Specifically, it remains unclear whether the gestation or the lactation is the more vulnerable period to modify offspring metabolic flexibility. We investigated in a rodent model of intrauterine growth restriction (IUGR) induced by maternal protein restriction (R) during gestation which time window of maternal undernutrition (gestation, lactation or gestation-lactation) has more impact on the male offspring metabolomics phenotype. Plasma metabolome and hepatic lipidome of offspring were characterized through suckling period and at adulthood using liquid chromatography-high-resolution mass spectrometry. Multivariate analysis of these fingerprints highlighted a persistent metabolomics signature in rats suckled by R dams, with a clear-cut discrimination from offspring fed by control (C) dams. Pups submitted to a nutritional switch at birth presented a metabolomics signature clearly distinct from that of pups nursed by dams maintained on a consistent perinatal diet. Control rats suckled by R dams presented transiently higher branched-chain amino acid (BCAA) oxidation during lactation besides increased fatty acid (FA) β-oxidation, associated with preserved insulin sensitivity and lesser fat accretion that persisted throughout their life. In contrast, IUGR rats displayed permanently impaired β-oxidation, associated to increased glucose or BCAA oxidation at adulthood, depending on the fact that pups experienced slow postnatal or catch-up growth, as suckled by R or C dams, respectively. Taken together, these findings provide evidence for a significant contribution of the lactation period in metabolic programming. Copyright © 2018 Elsevier Inc. All rights reserved.

TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Late gestation heat stress of dairy cattle programs dam and daughter milk production.

PubMed

Dahl, G E; Tao, S; Laporta, J

2017-12-01

Anticipated increases in the world population to 9 billion people will lead to increased demand for food. Dairy products represent one of the most sustainable animal sources of food protein because ruminants can utilize byproduct and forage feeds unsuitable for human consumption. Continued improvements in productivity will depend on deeper understanding of the biology of lactation, including developmental programming of tissues critical to that process. Although prenatal programming of postnatal phenotype is well documented for growth, behavior, and disease, there may also be instances of "programming" that last for a specific physiological stage (e.g., lactation). We distinguish between these 2 terms by the use of developmental programming to describe a permanent effect, whereas the more general term is used to describe nonpermanent impacts on the mammary gland. Despite this complexity, here we review the evidence that exposure to elevated temperature and humidity during late gestation can program reduced yields in the subsequent lactation, largely through effects at the mammary gland. Furthermore, we provide emerging evidence that adult capacity for milk synthesis can be programmed in the calf that dam is carrying by events during fetal life occurring 2 yr before. Specifically, calves born to dams that are heat stressed for the final 6 wk of gestation produce 19% less milk in lactation relative to calves from dams provided with evaporative cooling. Importantly, the increased milk yield in animals derived from dams under evaporative cooling occurred without a greater decline in BW that accompanies negative energy balance during early lactation. Therefore, the increase in milk production suggests an increase in the efficiency of conversion of feed to milk. These data indicate that a brief period of heat stress late in development reduces the physiological efficiency of the cow in a coordinated manner to result in a substantial decline in productivity. It is likely that this programming effect would be observed across genetic lines and result in poor sustainability of milk production. Milk will continue to be an important source of high-quality, human-edible food and technologies that improve the efficiency of production will be critical to enhance sustainability. These data provide compelling support for the concept that programming impacts on the dam and the developing fetus will play a role in optimizing the efficiency of production.

Physiological stress responses in big gamefish after capture: observations on plasma chemistry and blood factors.

PubMed

Wells, R M; McIntyre, R H; Morgan, A K; Davie, P S

1986-01-01

The plasma electrolytes, Na+, K+, Ca2+, Cl- and osmolarities had high values in capture-stressed big gamefish. Blood metabolites measured after stress showed glucose and lactate elevations. The activity of the plasma enzymes alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase and lactate dehydrogenase suggested tissue disruptions following severe capture stress. Haematocrit values and methaemoglobin were high in capture-stressed gamefish. The plasma chemistry of resting and capture-stressed snapper (Chrysophrys auratus) was studied for comparison. Specific differences in plasma biochemistry appeared to be the result of different strategies of fish behaviour during capture.

Evaluation of hyperketonemia risk period and screening protocols for early-lactation dairy cows.

PubMed

Mahrt, A; Burfeind, O; Heuwieser, W

2015-05-01

The objectives of this study were to describe the onset of hyperketonemia, the number of positive hyperketonemia test results, and the duration of the longest hyperketonemic period during the first 42 d in milk (DIM) in dairy cows. Furthermore, we set out to evaluate test characteristics of single and repeated measurements of β-hydroxybutyric acid (BHBA) during this period to diagnose hyperketonemia. Using an electronic handheld meter, 252 cows from 3 farms were tested twice weekly for hyperketonemia (blood BHBA ≥1.2 mmol/L) during the first 42 DIM, resulting in 12 test results per cow (i.e., in lactation wk 0.5 to 6). Prevalence and incidence of hyperketonemia were calculated for the 12 examination days and the 42-d period, respectively. Test characteristics for the diagnosis of hyperketonemia were calculated for 4 different testing scenarios (testing all cows 1, 2, 3, or 6 times during the first 42 DIM) and 2 different gold-standard definitions (BHBA ≥1.2 mmol/L at least once during the observation period or BHBA ≥1.2 mmol/L at least twice during the observation period). Mean prevalence of hyperketonemia was 11.8%, ranging from 9.6% in lactation wk 0.5 and 2.0 to 14.6% in lactation wk 5.5. In total, 134 cows (53.2%) had at least 1 positive hyperketonemia test result during the whole 42-d period. Of these cows, 46.3% had only 1 positive result. The median first positive hyperketonemia test result was in lactation wk 2.0 [interquartile range (IQR) 1.0-3.5]. Median frequency of positive test results in cows affected by hyperketonemia was 2 positive test results (IQR 1-3). Median duration of the longest hyperketonemic period per cow affected was 1 examination interval (3-4 d; IQR 1-2). Considering a minimum of 1 positive hyperketonemia test result during the first 42 DIM as the gold standard, sensitivity of a single BHBA measurement during this period to diagnose hyperketonemia was 21%. A weekly testing protocol had a sensitivity of 72%. Specificity was 100% in both cases. Considering a minimum of 2 positive hyperketonemia test results as the gold standard, sensitivity and specificity of a single BHBA measurement during the first 42 DIM were 33 and 97%, respectively. A weekly testing protocol provided sensitivity and specificity of 91 and 83%, respectively. We conclude that the risk period for hyperketonemia lasts at least until lactation wk 6, which should be considered when planning hyperketonemia screening programs. Test characteristics of screening protocols depend on testing frequency. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ethyl lactate-EDTA composite system enhances the remediation of the cadmium-contaminated soil by autochthonous willow (Salix x aureo-pendula CL 'J1011') in the lower reaches of the Yangtze River.

PubMed

Li, Jiahua; Sun, Yuanyuan; Yin, Ying; Ji, Rong; Wu, Jichun; Wang, Xiaorong; Guo, Hongyan

2010-09-15

In order to explore a practical approach to the remediation of the cadmium (Cd)-contaminated soil in the lower reaches of the Yangtze River, we evaluated the effects of a local willow (Salix x aureo-pendula CL 'J1011') of absorbing, accumulating, and translocating Cd; and assessed the potential of chelator ethylenediaminetetraacetic acid (EDTA) in combination with ethyl lactate for enhancing the efficiency of the willow in removing Cd in two water-culture growth chamber trials and a field one. The willow showed a high tolerance to Cd in growth chamber trial 1 where the Cd concentration in the medium reached up to 25 mg L(-1) medium, and the bioaccumulation factors (BAFs) of the shoots for Cd rose from 3.8 to 7.4 as the Cd concentration in the medium was elevated from 5 to 25 mg L(-1) medium. In growth chamber trial 2, the average Cd removal rates in two treatments with EDTA and ethyl lactate (molar ratios of EDTA to ethyl lactate=68/39 and 53.5/53.5, respectively) reached 0.71 mg d(-1) pot(-1) for the duration of Day 5-8 and 0.59 mg d(-1) pot(-1) for that of Day 8-11, which were 5- and 4-fold of their counterparts in the control, respectively. In the field trial, for the remediational duration of 45 days, three treatments-willow alone, willow combined with EDTA, and willow combined with EDTA and ethyl lactate-led to decreases in the Cd concentration in soil by 5%, 20%, and 29%, respectively; increases in that in the leaves by 14.6%, 56.7%, and 146.5%, respectively; and increases in that in the stems by 15.6%, 41.2%, and 87.4%, respectively, compared to their counterparts on Day 0. These results indicate that EDTA combined with ethyl lactate significantly enhanced the efficiency of willow in removing Cd from the soil. Therefore, a phytoextration system consisting of the autochthonous willow, EDTA, and ethyl lactate has high potential for the remediation of the Cd-polluted soil in the lower reaches of the Yangtze River. Copyright 2010 Elsevier B.V. All rights reserved.

Glucose and lactate as metabolic constraints on presynaptic transmission at an excitatory synapse.

PubMed

Lucas, Sarah J; Michel, Christophe B; Marra, Vincenzo; Smalley, Joshua L; Hennig, Matthias H; Graham, Bruce P; Forsythe, Ian D

2018-05-01

Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission. Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic transmission through a reduction in the number of functional synaptic vesicle release sites and a slowing of vesicle pool replenishment, without a consistent change in release probability. Metabolic function is compromised in many pathological conditions (e.g. stroke, traumatic brain injury and neurodegeneration). Knowledge of how synaptic transmission is constrained by metabolic stress, especially during intense brain activity, will provide insights to improve cognition following pathological insults. The synapse has high energy demands, which increase during intense activity. Presynaptic ATP production depends on substrate availability and usage will increase during activity, which in turn could influence transmitter release and information transmission. We investigated transmitter release at the mouse calyx of Held synapse using glucose or lactate (10, 1 or 0 mm) as the extracellular substrates while inducing metabolic stress. High-frequency stimulation (HFS) and recovery paradigms evoked trains of EPSCs monitored under voltage-clamp. Whilst postsynaptic intracellular ATP was stabilised by diffusion from the patch pipette, depletion of glucose increased EPSC depression during HFS and impaired subsequent recovery. Computational modelling of these data demonstrated a reduction in the number of functional release sites and slowed vesicle pool replenishment during metabolic stress, with little change in release probability. Directly depleting presynaptic terminal ATP impaired transmitter release in an analogous manner to glucose depletion. In the absence of glucose, presynaptic terminal metabolism could utilise lactate from the aCSF and this was blocked by inhibition of monocarboxylate transporters (MCTs). MCT inhibitors significantly suppressed transmission in low glucose, implying that lactate is a presynaptic substrate. Additionally, block of glycogenolysis accelerated synaptic transmission failure in the absence of extracellular glucose, consistent with supplemental supply of lactate by local astrocytes. We conclude that both glucose and lactate support presynaptic metabolism and that limited availability, exacerbated by high-intensity firing, constrains presynaptic ATP, impeding transmission through a reduction in functional presynaptic release sites as vesicle recycling slows when ATP levels are low. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Systematic Review on N-3 and N-6 Polyunsaturated Fatty Acid Intake in European Countries in Light of the Current Recommendations – Focus on Specific Population Groups

PubMed Central

Sioen, Isabelle; van Lieshout, Lilou; Eilander, Ans; Fleith, Mathilde; Lohner, Szimonetta; Szommer, Alíz; Petisca, Catarina; Eussen, Simone; Forsyth, Stewart; Calder, Philip C.; Campoy, Cristina; Mensink, Ronald P.

2017-01-01

Background Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation. Summary The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically. Results The evaluations were done against recommendations of the European Food Safety Authority. Key Messages Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6–12 months, 6 in children 1–3 years, 11 in children 4–9 years, 8 in adolescents 10–18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean α-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe. PMID:28190013

Systematic Review on N-3 and N-6 Polyunsaturated Fatty Acid Intake in European Countries in Light of the Current Recommendations - Focus on Specific Population Groups.

PubMed

Sioen, Isabelle; van Lieshout, Lilou; Eilander, Ans; Fleith, Mathilde; Lohner, Szimonetta; Szommer, Alíz; Petisca, Catarina; Eussen, Simone; Forsyth, Stewart; Calder, Philip C; Campoy, Cristina; Mensink, Ronald P

2017-01-01

Earlier reviews indicated that in many countries adults, children and adolescents consume on an average less polyunsaturated fatty acids (PUFAs) than recommended by the Food and Agriculture Organisation/World Health Organisation. The intake of total and individual n-3 and n-6 PUFAs in European infants, children, adolescents, elderly and pregnant/lactating women was evaluated systematically. The evaluations were done against recommendations of the European Food Safety Authority. Key Messages: Fifty-three studies from 17 different European countries reported an intake of total n-3 and n-6 PUFAs and/or individual n-3 or n-6 PUFAs in at least one of the specific population groups: 10 in pregnant women, 4 in lactating women, 3 in infants 6-12 months, 6 in children 1-3 years, 11 in children 4-9 years, 8 in adolescents 10-18 years and 11 in elderly >65 years. Mean linoleic acid intake was within the recommendation (4 energy percentage [E%]) in 52% of the countries, with inadequate intakes more likely in lactating women, adolescents and elderly. Mean α-linolenic acid intake was within the recommendation (0.5 E%) in 77% of the countries. In 26% of the countries, mean eicosapentaenoic acid and/or docosahexaenoic acid intake was as recommended. These results indicate that intake of n-3 and n-6 PUFAs may be suboptimal in specific population groups in Europe. © 2017 S. Karger AG, Basel.

Local foods can meet micronutrient needs for women in urban Burkina Faso, but only if rarely consumed micronutrient-dense foods are included in daily diets: A linear programming exercise.

PubMed

Arimond, Mary; Vitta, Bineti S; Martin-Prével, Yves; Moursi, Mourad; Dewey, Kathryn G

2018-01-01

Women of reproductive age are at nutritional risk due to their need for nutrient-dense diets. Risk is further elevated in resource-poor environments. In one such environment, we evaluated feasibility of meeting micronutrient needs of women of reproductive age using local foods alone or using local foods and supplements, while minimizing cost. Based on dietary recall data from Ouagadougou, we used linear programming to identify the lowest cost options for meeting 10 micronutrient intake recommendations, while also meeting energy needs and following an acceptable macronutrient intake pattern. We modeled scenarios with maximum intake per food item constrained at the 75th percentile of reported intake and also with more liberal maxima based on recommended portions per day, with and without the addition of supplements. Some scenarios allowed only commonly consumed foods (reported on at least 10% of recall days). We modeled separately for pregnant, lactating, and nonpregnant, nonlactating women. With maxima constrained to the 75th percentile, all micronutrient needs could be met with local foods but only when several nutrient-dense but rarely consumed items were included in daily diets. When only commonly consumed foods were allowed, micronutrient needs could not be met without supplements. When larger amounts of common animal-source foods were allowed, all needs could be met for nonpregnant, nonlactating women but not for pregnant or lactating women, without supplements. We conclude that locally available foods could meet micronutrient needs but that to achieve this, strategies would be needed to increase consistent availability in markets, consistent economic access, and demand. © 2017 John Wiley & Sons Ltd.

Use of admission serum lactate and sodium levels to predict mortality in necrotizing soft-tissue infections.

PubMed

Yaghoubian, Arezou; de Virgilio, Christian; Dauphine, Christine; Lewis, Roger J; Lin, Matthew

2007-09-01

Simple admission laboratory values can be used to classify patients with necrotizing soft-tissue infection (NSTI) into high and low mortality risk groups. Chart review. Public teaching hospital. All patients with NSTI from 1997 through 2006. Variables analyzed included medical history, admission vital signs, laboratory values, and microbiologic findings. Data analyses included univariate and classification and regression tree analyses. Mortality. One hundred twenty-four patients were identified with NSTI. The overall mortality rate was 21 of 124 (17%). On univariate analysis, factors associated with mortality included a history of cancer (P = .03), intravenous drug abuse (P < .001), low systolic blood pressure on admission (P = .03), base deficit (P = .009), and elevated white blood cell count (P = .06). On exploratory classification and regression tree analysis, admission serum lactate and sodium levels were predictors of mortality, with a sensitivity of 100%, specificity of 28%, positive predictive value of 23%, and negative predictive value of 100%. A serum lactate level greater than or equal to 54.1 mg/dL (6 mmol/L) alone was associated with a 32% mortality, whereas a serum sodium level greater than or equal to 135 mEq/L combined with a lactate level less than 54.1 mg/dL was associated with a mortality of 0%. Mortality for NSTIs remains high. A simple model, using admission serum lactate and serum sodium levels, may help identify patients at greatest risk for death.

Th-POK regulates mammary gland lactation through mTOR-SREBP pathway.

PubMed

Zhang, Rui; Ma, Huimin; Gao, Yuan; Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial; Liu, Xiaolong; Ge, Gaoxiang

2018-02-01

The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation.

Th-POK regulates mammary gland lactation through mTOR-SREBP pathway

PubMed Central

Wu, Yanjun; Qiao, Yuemei; Geng, Ajun; Cai, Cheguo; Han, Yingying; Zeng, Yi Arial

2018-01-01

The Th-inducing POK (Th-POK, also known as ZBTB7B or cKrox) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. Here we show that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands that is upregulated at late pregnancy and lactation. Lineage restrictedly expressed Th-POK exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Th-POK is not required for mammary epithelial cell fate determination. Mammary gland morphogenesis in puberty and alveologenesis in pregnancy are phenotypically normal in the Th-POK-deficient mice. However, Th-POK-deficient mice are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. As a result, Th-POK knockout mice are unable to efficiently secret milk lipid and to nurse the offspring. Such defect is mainly attributed to the malfunctioned mammary epithelial cells, but not the tissue microenvironment in the Th-POK deficient mice. Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the lactating mammary glands. Conversely, insulin induces Th-POK expression. Thus, Th-POK functions as an important feed-forward regulator of insulin signaling in mammary gland lactation. PMID:29420538

Comparison of effects on macrophage cultures of glass fibre, glass powder, and chrysotile asbestos

PubMed Central

Beck, E. G.; Holt, P. F.; Manojlović, N.

1972-01-01

Beck, E. G., Holt, P. F., and Manojlović, N. (1972).Brit. J. industr. Med.,29, 280-286. Comparison of effects on macrophage cultures of glass fibre, glass powder, and chrysotile asbestos. The effects on macrophage cultures of glass fibre, glass powder, and chrysotile asbestos are compared. Glass fibre behaves like chrysotile in producing an increase in cell membrane permeability in cultured macrophages. This is demonstrable by the increase in lactic dehydrogenase activity in the supernatant fluid. The metabolism, measured by lactate production, is not reduced as it is when quartz is phagocytosed. Glass powder behaves like the inert dust corundum, producing little change in the number of cells stained by erythrosin B and a small increase in lactate dehydrogenase activity, both being in the range of the control. There is an increase in lactate production as a result of higher metabolism due to phagocytosis. Dusts may produce two basic effects, namely a toxic effect and change in cell membrane permeability. A non-specific effect on the cell membrane due to the slow and sometimes incomplete process of ingestion of long fibres is probably a function of the morphology, particularly the length of the fibres. A primary specific effect induced by some dusts immediately follows contact with the cell membrane. Images PMID:4339803

[Changes in the rates of glucose consumption and lactate release by cells in perfused and nonperfused cultures].

PubMed

Berestovskaia, N G; Akatov, V S; Lavrovskaia, V P

1993-01-01

The energetic state of Chinese hamster fibroblasts was investigated under stationary cultural conditions and under condition of culture medium perfusion immediately above the cells. Specific rates of glucose utilization and lactate formation under the former conditions (1.88 +/- 0.2) x 10(-13) and (4.3 +/- 0.56) x 10(-13) Mole/cell/h at the logarithmic growth phase, and (0.21 +/- 0.08) x 10(-13) and (0.58 +/- 0.06) x 10(-13) Mole/cell/h at the stationary phase, respectively. In the perfused culture, specific rates of glucose utilization and formation of lactate are (4.86 +/- 0.56) x 10(-13) and (11.0 +/- 1.8) x 10(-13) Mole/cell/h at the logarithmic growth phase, and (1.57 +/- 0.14) x 10(-13) and (4.11 +/- 0.5) x 10(-13) Mole/cell/h at the stationary phase, respectively. It has been proposed that under conditions of stationary culture the fall of the rates, as the culture reaches the survival phase, is due to diffusion-dependent limitations of mass transfer between the medium and the culture. Under perfusion conditions, the fall of the rates can be explained by some deficiency of necessary components and by excessive amounts of metabolic products in the multilayer structure.

Are arterial, muscle and working limb lactate exchange data obtained on men at altitude consistent with the hypothesis of an intracellular lactate shuttle?

PubMed

Brooks, G A

1999-01-01

The "Lactate Shuttle" Hypothesis posits that lactate removal requires exchange among producing and consuming cells. The "Intra-cellular Lactate Shuttle" hypothesis posits that lactate exchange occurs among compartments within cells, and that mitochondria are the major sites of cellular lactate disposal. Thus, cells with high mitochondrial densities (cardiocytes, myocytes, hepatocytes) are those which participate in lactate clearance. The model of an Intracellular Lactate Shuttle recognizes that the Keq for LDH is 3.6 x 10(4) M-1; thus, glycolysis results in cytosolic lactate production regardless of the intracellular PO2. The model also requires presence of a mitochondrial monocarboxylate transporter (MCT) that allows uptake of lactate as well as pyruvate, and intra-mitochondrial LDH whose function is linked to the ETC, and which permits lactate-->pyruvate conversion and oxidation. Recently, we have shown that liver, heart and muscle mitochondria readily oxidize lactate and contain LDH and MCT1. Accordingly, we have concluded that lactate is the predominant monocarboxylate oxidized by mitochondria in vivo. The model of an "Intra-cellular Lactate Shuttle" is consistent with many of the observations on men at sea level and altitude. The observations include: oxidation is the primary fate of lactate disposal during rest and exercise; lactate production and oxidation occur simultaneously within resting and working muscle; increasing [lactate]a increases muscle lactate extraction, and that by increasing SaO2 acclimatization reduces blood [lactate].

Lactate shuttles in nature.

PubMed

Brooks, G A

2002-04-01

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously under fully aerobic conditions. "Cell-cell" and "intracellular lactate shuttle" concepts describe the roles of lactate in the delivery of oxidative and gluconeogenic substrates, as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges between white-glycolytic and red-oxidative fibres within a working muscle bed, between working skeletal muscle and heart, and between tissues of net lactate release and gluconeogenesis. Lactate exchange between astrocytes and neurons that is linked to glutamatergic signalling in the brain is an example of a lactate shuttle supporting cell-cell signalling. Lactate uptake by mitochondria and pyruvate-lactate exchange in peroxisomes are examples of intracellular lactate shuttles. Lactate exchange between sites of production and removal is facilitated by monocarboxylate transport proteins, of which there are several isoforms, and, probably, also by scaffolding proteins. The mitochondrial lactate-pyruvate transporter appears to work in conjunction with mitochondrial lactate dehydrogenase, which permits lactate to be oxidized within actively respiring cells. Hence mitochondria function to establish the concentration and proton gradients necessary for cells with high mitochondrial densities (e.g. cardiocytes) to take up and oxidize lactate. Arteriovenous difference measurements on working cardiac and skeletal muscle beds as well as NMR spectral analyses of these tissues show that lactate is formed and oxidized within the cells of formation in vivo. Glycolysis and lactate oxidation within cells permits high flux rates and the maintenance of redox balance in the cytosol and mitochondria. Other examples of intracellular lactate shuttles include lactate uptake and oxidation in sperm mitochondria and the facilitation of beta-oxidation in peroxisomes by pyruvate-lactate exchange. An ancient origin to the utility of lactate shuttling is implied by the observation that mitochondria of Saccharomyces cerevisiae contain flavocytochrome b(2), a lactate-cytochrome c oxidoreductase that couples lactate dehydrogenation to the reduction of cytochrome c. The presence of cell-cell and intracellular lactate shuttles gives rise to the notion that glycolytic and oxidative pathways can be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.

Extraskeletal Ewing's sarcoma family of tumors in adults: prognostic factors and clinical outcome.

PubMed

Tural, Deniz; Molinas Mandel, Nil; Dervisoglu, Sergulen; Oner Dincbas, Fazilet; Koca, Sedat; Colpan Oksuz, Didem; Kantarci, Fatih; Turna, Hande; Selcukbiricik, Fatih; Hiz, Murat

2012-05-01

The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewing's sarcoma. Data of patients with extraskeletal Ewing's sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥ 8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8 ≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewing's sarcoma.

Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

PubMed

Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M

2013-03-01

The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

Meningitis in adult patients with a negative direct cerebrospinal fluid examination: value of cytochemical markers for differential diagnosis

PubMed Central

2011-01-01

Introduction The objective of this study was to determine the ability of various parameters commonly used for the diagnosis of acute meningitis to differentiate between bacterial and viral meningitis, in adult patients with a negative direct cerebrospinal fluid (CSF) examination. Methods This was a prospective study, started in 1997, including all patients admitted to the emergency unit with acute meningitis and a negative direct CSF examination. Serum and CSF samples were taken immediately on admission. The patients were divided into two groups according to the type of meningitis: bacterial (BM; group I) or viral (VM; group II). The CSF parameters investigated were cytology, protein, glucose, and lactate; the serum parameters evaluated were C-reactive protein and procalcitonin. CSF/serum glucose and lactate ratios were also assessed. Results Of the 254 patients with meningitis with a negative direct CSF examination, 35 had BM and 181, VM. The most highly discriminative parameters for the differential diagnosis of BM proved to be CSF lactate, with a sensitivity of 94%, a specificity of 92%, a negative predictive value of 99%, a positive predictive value of 82% at a diagnostic cut-off level of 3.8 mmol/L (area under the curve (AUC), 0.96; 95% confidence interval (CI), 0.95 to 1), and serum procalcitonin, with a sensitivity of 95%, a specificity of 100%, a negative predictive value of 100%, and a positive predictive value of 97% at a diagnostic cut-off level of 0.28 ng/ml (AUC, 0.99; 95% CI, 0.99 to 1). Conclusions Serum procalcitonin and CSF lactate concentrations appear to be the most highly discriminative parameters for the differential diagnosis of BM and VM. PMID:21645387

Kinetics and methane gas yields of selected C1 to C5 organic acids in anaerobic digestion.

PubMed

Yang, Yu; Chen, Qian; Guo, Jialiang; Hu, Zhiqiang

2015-12-15

Volatile fatty acids (VFAs) and other short-chain organic acids such as lactic and pyruvic acids are intermediates in anaerobic organic degradation. In this study, anaerobic degradation of seven organic acids in salt form was investigated, including formate (C1), acetate (C2), propionate (C3), pyruvate (C3), lactate (C3), butyrate (C4), and valerate (C5). Microbial growth kinetics on these organic acids were determined individually at 37 °C through batch anaerobic digestion tests by varying substrate concentrations from 250 to 4000 mg COD/L. The cumulative methane generation volume was determined real-time by respirometry coupled with gas chromatographic analysis while methane yield and related kinetics were calculated. The methane gas yields (fe, mg CH4 COD/mg substrate COD) from anaerobic degradation of formate, acetate, propionate, pyruvate, lactate, butyrate, and valerate were 0.44 ± 0.27, 0.58 ± 0.05, 0.53 ± 0.18, 0.24 ± 0.05, 0.17 ± 0.05, 0.43 ± 0.15, 0.49 ± 0.11, respectively. Anaerobic degradation of formate showed self-substrate inhibition at the concentrations above 3250 mg COD/L. Acetate, propionate, pyruvate, butyrate, lactate, and valerate did not inhibit methane production at the highest concentrations tested (i.e., 4000 mg COD/L). Microbes growing on acetate had the highest overall specific growth rate (0.30 d(-1)) in methane production. For comparison, the specific microbial growth rates on formate, propionate, pyruvate, butyrate, lactate, and valerate for methane production were 0.10, 0.06, 0.08, 0.07, 0.05, 0.15 d(-1), respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Systemic and local bactericidal potentiality in late lactation Holstein-Friesian cows following a combined antibiotics and Enterococcus faecium SF68 dry-cow treatment.

PubMed

Tiantong, Attapol; Piamya, Piya; Chen, Shuen-Ei; Liu, Wen-Bor; Chang, Fang-Yu; Lin, Pei-Chi; Nagahata, Hajime; Chang, Chai-Ju

2015-08-01

Antibiotic dry-cow treatment contributes a major part to the total use of antibiotics in dairy herds. Enterococcus faecium strain SF68 (SF68) was of human origin but has been authorized in EU as probiotic feed additive. In the present study, one of the front and rear quarters of twelve late lactation Holstein-Friesian cows were infused once with a commercial antibiotic dry-cow formula (antibiotics quarter) on the first milk-stasis day (d 1), when the contrallateral quarters were infused with 5 x 10(8)-CFU SF68 plus half-dose antibiotic dry-cow formula (SF68/antibiotics quarter) meanwhile. Gelatinase level and cellular reactive oxygen species (ROS) production capacity were measured for blood and quarter secretion. The results showed that the count of blood total leukocytes minorly decreased on d 3 only but the microscopic somatic cell count (MSCC) continuously increased up to d 7, especially in SF68/antibiotics quarters. Plasma level of gelatinase A remained similar up to d 7 but gelatinase B was not detectable in plasma throughout the study. The level of gelatinase A in quarter secretion increased up to d 7 but gelatinase B increased even more drastically, especially in SF68/antibiotics quarters. The ROS production capacity of blood leukocytes increased temporarily only on d 3, but that of milk cells continuously increased up to d 7, especially in SF68/antitiotics quarters. Overall, late lactation Holstein-Friesian cows were systemically adaptable to the combined antibiotics and SF68 dry-cow treatment, while the local bactericidal potentiality in mammary gland was actively responsive to additional SF68 intramammary treatment.

Evaluating the Efficacy of GLUT Inhibitors Using a Seahorse Extracellular Flux Analyzer.

PubMed

Wei, Changyong; Heitmeier, Monique; Hruz, Paul W; Shanmugam, Mala

2018-01-01

Glucose is metabolized through anaerobic glycolysis and aerobic oxidative phosphorylation (OXPHOS). Perturbing glucose uptake and its subsequent metabolism can alter both glycolytic and OXPHOS pathways and consequently lactate and/or oxygen consumption. Production and secretion of lactate, as a consequence of glycolysis, leads to acidification of the extracellular medium. Molecular oxygen is the final electron acceptor in the electron transport chain, facilitating oxidative phosphorylation of ADP to ATP. The alterations in extracellular acidification and/or oxygen consumption can thus be used as indirect readouts of glucose metabolism and assessing the impact of inhibiting glucose transport through specific glucose transporters (GLUTs). The Seahorse bioenergetics analyzer can measure both the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). The proposed methodology affords a robust, high-throughput method to screen for GLUT inhibition in cells engineered to express specific GLUTs, providing live cell read-outs upon GLUT inhibition.

Comparative transcriptome analysis reveals different molecular mechanisms of Bacillus coagulans 2-6 response to sodium lactate and calcium lactate during lactic acid production.

PubMed

Qin, Jiayang; Wang, Xiuwen; Wang, Landong; Zhu, Beibei; Zhang, Xiaohua; Yao, Qingshou; Xu, Ping

2015-01-01

Lactate production is enhanced by adding calcium carbonate or sodium hydroxide during fermentation. However, Bacillus coagulans 2-6 can produce more than 180 g/L L-lactic acid when calcium lactate is accumulated, but less than 120 g/L L-lactic acid when sodium lactate is formed. The molecular mechanisms by which B. coagulans responds to calcium lactate and sodium lactate remain unclear. In this study, comparative transcriptomic methods based on high-throughput RNA sequencing were applied to study gene expression changes in B. coagulans 2-6 cultured in non-stress, sodium lactate stress and calcium lactate stress conditions. Gene expression profiling identified 712 and 1213 significantly regulated genes in response to calcium lactate stress and sodium lactate stress, respectively. Gene ontology assignments of the differentially expressed genes were performed. KEGG pathway enrichment analysis revealed that 'ATP-binding cassette transporters' were significantly affected by calcium lactate stress, and 'amino sugar and nucleotide sugar metabolism' was significantly affected by sodium lactate stress. It was also found that lactate fermentation was less affected by calcium lactate stress than by sodium lactate stress. Sodium lactate stress had negative effect on the expression of 'glycolysis/gluconeogenesis' genes but positive effect on the expression of 'citrate cycle (TCA cycle)' genes. However, calcium lactate stress had positive influence on the expression of 'glycolysis/gluconeogenesis' genes and had minor influence on 'citrate cycle (TCA cycle)' genes. Thus, our findings offer new insights into the responses of B. coagulans to different lactate stresses. Notably, our RNA-seq dataset constitute a robust database for investigating the functions of genes induced by lactate stress in the future and identify potential targets for genetic engineering to further improve L-lactic acid production by B. coagulans.

Exogenous lactate supply affects lactate kinetics of rainbow trout, not swimming performance

PubMed Central

Omlin, Teye; Langevin, Karolanne

2014-01-01

Intense swimming causes circulatory lactate accumulation in rainbow trout because lactate disposal (Rd) is not stimulated as strongly as lactate appearance (Ra). This mismatch suggests that maximal Rd is limited by tissue capacity to metabolize lactate. This study uses exogenous lactate to investigate what constrains maximal Rd and minimal Ra. Our goals were to determine how exogenous lactate affects: 1) Ra and Rd of lactate under baseline conditions or during graded swimming, and 2) exercise performance (critical swimming speed, Ucrit) and energetics (cost of transport, COT). Results show that exogenous lactate allows swimming trout to boost maximal Rd lactate by 40% and reach impressive rates of 56 μmol·kg−1·min−1. This shows that the metabolic capacity of tissues for lactate disposal is not responsible for setting the highest Rd normally observed after intense swimming. Baseline endogenous Ra (resting in normoxic water) is not significantly reduced by exogenous lactate supply. Therefore, trout have an obligatory need to produce lactate, either as a fuel for oxidative tissues and/or from organs relying on glycolysis. Exogenous lactate does not affect Ucrit or COT, probably because it acts as a substitute for glucose and lipids rather than extra fuel. We conclude that the observed 40% increase in Rd lactate is made possible by accelerating lactate entry into oxidative tissues via monocarboxylate transporters (MCTs). This observation together with the weak expression of MCTs and the phenomenon of white muscle lactate retention show that lactate metabolism of rainbow trout is significantly constrained by transmembrane transport. PMID:25121611

Influence of phytase added to a vegetarian diet on bone metabolism in pregnant and lactating sows.

PubMed

Liesegang, A; Loch, L; Bürgi, E; Risteli, J

2005-01-01

The purpose of the study was to find out if the supplementation of phytase to a diet of gestating and lactating sows has any effects on performance and bone parameters of the animals. Forty primiparous gilts were assigned into four groups: group A with phytase [4.2 g total phosphorus (P)/kg (gestation) and 4.5 g total P/kg (lactation)], group B without phytase (with phytase supplementation in diet for rearing) and same P content as group A, group C without phytase and higher P contents [5.0 g total P/kg (gestation) and 5.5 g total P/kg (lactation)] and group D with the same diet as group B (no phytase during the rearing). A 6-phytase was used in this trial (750 FTU/kg diet). The four diets were fed during gestation and lactation. Faeces were collected to determine apparent digestibility of minerals. Blood samples were taken to analyse minerals and bone markers. After weaning the sows were slaughtered and the bones of one hind leg were prepared to measure bone mineral density (BMD) and bone mineral content (BMC) of the tibia. Bone ash and mineral content of the phalanx III were determined. Mean P concentrations in serum decreased during gestation and lactation. But there were no significant differences between the groups. Bone formation marker bone-specific alkaline phosphatase decreased at the beginning of lactation whereas bone resorption marker serum crosslaps increased. The BMD and BMC of the tibia were slightly higher in the groups fed higher concentrations of P and phytase. The ash and mineral contents of the phalanx were the highest for the group fed the highest concentration of P. The apparent digestibility of P increased during gestation mostly in group A (57%--> 69%). In conclusion, high P content and addition of phytase to the diet induced a slightly higher ash content of the bones. It is of high importance, that sows during gestation absorb enough P, to avoid lamenesses and sudden fractures. As not many studies with phytase have been performed during gestation and lactation in sows yet, we can recommend, that phytase as supplement can be used to keep P in the diet at a lower level without negative consequences for bone health.

Effects of alfalfa and orchardgrass on digestion by dairy cows.

PubMed

Holden, L A; Glenn, B P; Erdman, R A; Potts, W E

1994-09-01

The effects of alfalfa and orchardgrass diets of similar NDF content on ruminal digestion and digesta kinetics as measured using radiolabeled herbage were evaluated in Holstein cows. Two dry and two lactating cows, fitted with ruminal and duodenal cannulas, were fed 12 times daily at restricted and ad libitum intakes, respectively, in a crossover design. Diets were 65:35 and 55:45 hay: concentrate in DM for alfalfa and orchardgrass, respectively, with approximately 19% CP and 42% NDF. The DMI by lactating cows was greater for the alfalfa diet than for the orchardgrass diet. Ruminal and apparent total tract digestibilities of NDF and ADF were less for cows consuming the alfalfa diet than for those on the orchardgrass diet. Particle size of ruminal digesta, based on specific activity from a ruminal pulse-dose of 14C-labeled alfalfa or orchardgrass, did not decrease consistently with time and was greater than fecal particle size, suggesting selective retention of large digesta particles before passage. Ruminal and total tract fractional passage rates of indigestible NDF, based on 14C-labeled forage, did not differ as a result of forage or lactation stage, but NDF gut fill was greater in lactating than in dry cows, indicating that changes in gut fill were related more to differences in intake than to passage rate.

Voluntary exercise in pregnant rats improves post-lactation maternal bone parameters but does not affect offspring outcomes in early life.

PubMed

Rosa, B V; Blair, H T; Vickers, M H; Morel, P C; Cockrem, J F; Firth, E C

2012-12-01

The objectives of this study were to examine the effects of voluntary exercise during pregnancy on maternal post-lactation bone parameters and offspring growth. Pregnant Wistar rats were housed in conventional cages (control), or were housed in raised cages requiring them to rise to an erect, bipedal stance to obtain food/water, throughout pregnancy. Dual energy X-ray absorptiometry and peripheral quantitative computed tomography scans were performed pre-mating and post-weaning. Maternal stress was assessed by fecal corticosterone measurement. Offspring weights were assessed at postnatal days 1 and 25 (weaning). Changes in bone mineral over the pregnancy/lactation period were site-specific. Exercise did not affect loss of bone mineral from the lumbar spine, but did attenuate the loss of trabecular bone mineral from the tibial metaphysis and enhance the strength strain index and cross-sectional moment of inertia at the tibial diaphysis (P≤0.05) in dams in the exercised group. Fecal corticosterone did not differ between dam groups. There were no significant differences in offspring weight between the exercised and control group at either time point. Voluntary exercise in the pregnant rat can improve some post-lactation bone parameters and does not adversely affect early postnatal outcomes of the offspring.

Functional significance of brain glycogen in sustaining glutamatergic neurotransmission.

PubMed

Sickmann, Helle M; Walls, Anne B; Schousboe, Arne; Bouman, Stephan D; Waagepetersen, Helle S

2009-05-01

The involvement of brain glycogen in sustaining neuronal activity has previously been demonstrated. However, to what extent energy derived from glycogen is consumed by astrocytes themselves or is transferred to the neurons in the form of lactate for oxidative metabolism to proceed is at present unclear. The significance of glycogen in fueling glutamate uptake into astrocytes was specifically addressed in cultured astrocytes. Moreover, the objective was to elucidate whether glycogen derived energy is important for maintaining glutamatergic neurotransmission, induced by repetitive exposure to NMDA in co-cultures of cerebellar neurons and astrocytes. In the astrocytes it was shown that uptake of the glutamate analogue D-[3H]aspartate was impaired when glycogen degradation was inhibited irrespective of the presence of glucose, signifying that energy derived from glycogen degradation is important for the astrocytic compartment. By inhibiting glycogen degradation in co-cultures it was evident that glycogen provides energy to sustain glutamatergic neurotransmission, i.e. release and uptake of glutamate. The relocation of glycogen derived lactate to the neuronal compartment was investigated by employing d-lactate, a competitive substrate for the monocarboxylate transporters. Neurotransmitter release was affected by the presence of d-lactate indicating that glycogen derived energy is important not only in the astrocytic but also in the neuronal compartment.

Is Breast Best? Examining the effects of alcohol and cannabis use during lactation.

PubMed

Brown, R A; Dakkak, H; Seabrook, J A

2018-05-23

Maternal drug use during lactation may have adverse effects on the health of their children. Two common drugs used during this period are alcohol and cannabis. A literature search was conducted using PubMed, CINAHL, Nursing and Allied Health, and Google Scholar with the following search terms: marijuana, cannabis, THC, alcohol, ethanol, breastfeeding, lactation, and breastmilk. The search strategy was restricted to papers since the year 2000, and limited to English language journals. Reference lists were also used to capture any articles that were missed from the database searches. In total, 19 articles were found related to alcohol and breastfeeding (n = 17 original research papers; n = 2 systematic reviews), and 4 articles were specific to cannabis (n = 2 original papers; n = 2 systematic reviews). The most common outcomes associated with alcohol consumption and breastfeeding included changes in sleep patterns, reduced milk production and flow, lower milk intake, and impaired immune function. Maternal outcomes related to cannabis consumption included panic attacks, delayed response time, increased heart rate, reduced short-term memory, dizziness, and impaired motor performance; infant outcomes associated with maternal cannabis use and breastfeeding were reduced muscular tonus, poor sucking, and growth delay and restriction. Mothers should be advised to refrain from substance use during the lactation period for the health and safety of their children.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pestov, Nikolay B., E-mail: korn@mail.ibch.ru; Dmitriev, Ruslan I.; Kostina, Maria B.

Highlights: Black-Right-Pointing-Pointer Full-length secretory pathway Ca-ATPase (SPCA2) cloned from rat duodenum. Black-Right-Pointing-Pointer ATP2C2 gene (encoding SPCA2) exists only in genomes of Tetrapoda. Black-Right-Pointing-Pointer Rat and pig SPCA2 are expressed in intestines, lung and some secretory glands. Black-Right-Pointing-Pointer Subcellular localization of SPCA2 may depend on tissue type. Black-Right-Pointing-Pointer In rat duodenum, SPCA2 is localized in plasma membrane-associated compartments. -- Abstract: Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2),more » the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1. The rat SPCA2 sequence is also highly homologous to putative human protein KIAA0703, however, the latter seems to have an aberrant N-terminus originating from intron 2. The tissue-specificity of SPCA2 expression is different from ubiquitous SPCA1. Rat SPCA2 transcripts were detected predominantly in gastrointestinal tract, lung, trachea, lactating mammary gland, skin and preputial gland. In the newborn pig, the expression profile is very similar with one remarkable exception: porcine bulbourethral gland gave the strongest signal. Upon overexpression in cultured cells, SPCA2 shows an intracellular distribution with remarkable enrichment in Golgi. However, in vivo SPCA2 may be localized in compartments that differ among various tissues: it is intracellular in epidermis, but enriched in plasma membranes of the intestinal epithelium. Analysis of SPCA2 sequences from various vertebrate species argue that ATP2C2 gene radiated from ATP2C1 (encoding SPCA1) during adaptation of tetrapod ancestors to terrestrial habitats.« less

[Bone histomorphometry of lactating and no lactating hyperthyroid rats].

PubMed

Serakides, Rogéria; Ocarino, Natália de Melo; Magalhães, Fernanda do Carmo; Souza, Cíntia de Almeida; Leite, Eveline Dias; Freitas, Edmilson Santos de

2008-06-01

The objective of this study was to verify if hyperthyroidism potentiates the osteopenia lactational. 24 adult female rats were distributed in four groups: euthyroid no lactating (control), euthyroid lactating, hyperthyroid no lactating and hyperthyroid lactating. 20 days after gestation, all the animals were necropsied. The thoracic and lumbar vertebrae, the femur and tibia were decalcified and processed for histomorphometric analysis. The euthyroid lactating group presented intense osteopenia in the studied bones. In the hyperthyroid no lactating group, there was not any change in trabecular bone percentage in none of the analyzed bone. In the hyperthyroid lactating group, there was osteopenia in the tibia and femur, similar to the one in the euthyroid lactating group. But the trabecular bone percentage in all the vertebral bodies was significantly larger in comparison with the euthyroid lactating group. It was concluded that the hyperthyroidism does not potentiate the osteopenia lactational in female rats, but it minimizes the vertebral osteopenia once it stimulates the osteoblastic activity.

Basal glycogenolysis in mouse skeletal muscle: in vitro model predicts in vivo fluxes

NASA Technical Reports Server (NTRS)

Lambeth, Melissa J.; Kushmerick, Martin J.; Marcinek, David J.; Conley, Kevin E.

2002-01-01

A previously published mammalian kinetic model of skeletal muscle glycogenolysis, consisting of literature in vitro parameters, was modified by substituting mouse specific Vmax values. The model demonstrates that glycogen breakdown to lactate is under ATPase control. Our criteria to test whether in vitro parameters could reproduce in vivo dynamics was the ability of the model to fit phosphocreatine (PCr) and inorganic phosphate (Pi) dynamic NMR data from ischemic basal mouse hindlimbs and predict biochemically-assayed lactate concentrations. Fitting was accomplished by optimizing four parameters--the ATPase rate coefficient, fraction of activated glycogen phosphorylase, and the equilibrium constants of creatine kinase and adenylate kinase (due to the absence of pH in the model). The optimized parameter values were physiologically reasonable, the resultant model fit the [PCr] and [Pi] timecourses well, and the model predicted the final measured lactate concentration. This result demonstrates that additional features of in vivo enzyme binding are not necessary for quantitative description of glycogenolytic dynamics.

A lactate electrochemical biosensor with a titanate nanotube as direct electron transfer promoter

NASA Astrophysics Data System (ADS)

Yang, Mingli; Wang, Jin; Li, Huaqing; Zheng, Jian-Guo; Wu, Nianqiang Nick

2008-02-01

Hydrogen titanate (H2Ti3O7) nanotubes (TNTs) have been synthesized by a one-step hydrothermal processing. Lactate oxidase (LOx) enzyme has been immobilized on the three-dimensional porous TNT network to make an electrochemical biosensor for lactate detection. Cyclic voltammetry and amperometry tests reveal that the LOx enzyme, which is supported on TNTs, maintains their substrate-specific catalytic activity. The nanotubes offer the pathway for direct electron transfer between the electrode surface and the active redox centers of LOx, which enables the biosensor to operate at a low working potential and to avoid the influence of the presence of O2 on the amperometric current response. The biosensor exhibits a sensitivity of 0.24 µA cm-2 mM-1, a 90% response time of 5 s, and a linear response in the range from 0.5 to 14 mM and the redox center of enzyme obviates the need of redox mediators for electrochemical enzymatic sensors, which is attractive for the development of reagentless biosensors.

Exercise responses in patients with chronically high creatine kinase levels.

PubMed

Cooper, Christopher B; Dolezal, Brett A; Neufeld, Eric V; Shieh, Perry; Jenner, John R; Riley, Marshall

2017-08-01

Elevated serum creatine kinase (CK) is often taken to reflect muscle disease, but many individuals have elevated CK without a specific diagnosis. How elevated CK reflects muscle metabolism during exercise is not known. Participants (46 men, 48 women) underwent incremental exercise testing to assess aerobic performance, cardiovascular response, and ventilatory response. Serum lactate, ammonia, and CK were measured at rest, 4 minutes into exercise, and 2 minutes into recovery. High-CK and control subjects demonstrated similar aerobic capacities and cardiovascular responses to incremental exercise. Those with CK ≥ 300 U/L exhibited significantly higher lactate and ammonia levels after maximal exercise, together with increased ventilatory responses, whereas those with CK ≥200 U/L but ≤ 300 U/L did not. We recommend measurement of lactate and ammonia profiles during a maximal incremental exercise protocol to help identify patients who warrant muscle biopsy to rule out myopathy. Muscle Nerve 56: 264-270, 2017. © 2016 Wiley Periodicals, Inc.

A Stand-Alone Synbiotic Treatment for the Prevention of D-Lactic Acidosis in Short Bowel Syndrome

PubMed Central

Takahashi, Kazuhiro; Terashima, Hideo; Kohno, Keisuke; Ohkohchi, Nobuhiro

2013-01-01

Synbiotics are combinations of probiotics and prebiotics that have recently been used in the context of various gastrointestinal diseases, including infectious enteritis, inflammatory bowel disease, and bowel obstruction. We encountered a patient with recurrent D-lactic acidosis who was treated successfully for long periods using synbiotics. The patient was diagnosed as having short bowel syndrome and had recurrent episodes of neurologic dysfunction due to D-lactic acidosis. In addition to fasting, the patient had been treated with antibiotics to eliminate D-lactate–producing bacteria. After the failure of antibiotic treatment, a stand-alone synbiotic treatment was started, specifically Bifidobacterium breve Yakult and Lactobacillus casei Shirota as probiotics, and galacto-oligosaccharide as a prebiotic. Serum D-lactate levels declined, and the patient has been recurrence-free for 3 years without dietary restriction. Synbiotics allowed the reduction in colonic absorption of D-lactate by both prevention of D-lactate–producing bacterial overgrowth and stimulation of intestinal motility, leading to remission of D-lactate acidosis. PMID:23701144

Blood cell transcriptomic-based early biomarkers of adverse programming effects of gestational calorie restriction and their reversibility by leptin supplementation

PubMed Central

Konieczna, Jadwiga; Sánchez, Juana; Palou, Mariona; Picó, Catalina; Palou, Andreu

2015-01-01

The challenge of preventing major chronic diseases requires reliable, early biomarkers. Gestational mild undernutrition in rats is enough to program the offspring to develop later pathologies; the intake of leptin, a breastmilk component, during lactation may reverse these programming effects. We used these models to identify, in peripheral blood mononuclear cells (PBMCs), transcriptomic-based early biomarkers of programmed susceptibility to later disorders, and explored their response to neonatal leptin intake. Microarray analysis was performed in PBMCs from the offspring of control and 20% gestational calorie-restricted dams (CR), and CR-rats supplemented with physiological doses of leptin throughout lactation. Notably, leptin supplementation normalised 218 of the 224 mRNA-levels identified in PBMCs associated to undernutrition during pregnancy. These markers may be useful for early identification and subsequent monitoring of individuals who are at risk of later diseases and would specifically benefit from the intake of appropriate amounts of leptin during lactation. PMID:25766068

Committee Opinion No. 637: Marijuana Use During Pregnancy and Lactation.

PubMed

2015-07-01

Cannabis sativa (marijuana) is the illicit drug most commonly used during pregnancy. The self-reported prevalence of marijuana use during pregnancy ranges from 2% to 5% in most studies. A growing number of states are legalizing marijuana for medicinal or recreational purposes, and its use by pregnant women could increase even further as a result. Because of concerns regarding impaired neurodevelopment, as well as maternal and fetal exposure to the adverse effects of smoking, women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Obstetrician-gynecologists should be discouraged from prescribing or suggesting the use of marijuana for medicinal purposes during preconception, pregnancy, and lactation. Pregnant women or women contemplating pregnancy should be encouraged to discontinue use of marijuana for medicinal purposes in favor of an alternative therapy for which there are better pregnancy-specific safety data. There are insufficient data to evaluate the effects of marijuana use on infants during lactation and breastfeeding, and in the absence of such data, marijuana use is discouraged.

Committee Opinion No. 722: Marijuana Use During Pregnancy and Lactation.

PubMed

2017-10-01

Cannabis sativa (marijuana) is the illicit drug most commonly used during pregnancy. The self-reported prevalence of marijuana use during pregnancy ranges from 2% to 5% in most studies. A growing number of states are legalizing marijuana for medicinal or recreational purposes, and its use by pregnant women could increase even further as a result. Because of concerns regarding impaired neurodevelopment, as well as maternal and fetal exposure to the adverse effects of smoking, women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Obstetrician-gynecologists should be discouraged from prescribing or suggesting the use of marijuana for medicinal purposes during preconception, pregnancy, and lactation. Pregnant women or women contemplating pregnancy should be encouraged to discontinue use of marijuana for medicinal purposes in favor of an alternative therapy for which there are better pregnancy-specific safety data. There are insufficient data to evaluate the effects of marijuana use on infants during lactation and breastfeeding, and in the absence of such data, marijuana use is discouraged.

Committee Opinion Summary NO. 722: Marijuana Use During Pregnancy and Lactation.

PubMed

2017-10-01

Cannabis sativa (marijuana) is the illicit drug most commonly used during pregnancy. The self-reported prevalence of marijuana use during pregnancy ranges from 2% to 5% in most studies. A growing number of states are legalizing marijuana for medicinal or recreational purposes, and its use by pregnant women could increase even further as a result. Because of concerns regarding impaired neurodevelopment, as well as maternal and fetal exposure to the adverse effects of smoking, women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Obstetrician-gynecologists should be discouraged from prescribing or suggesting the use of marijuana for medicinal purposes during preconception, pregnancy, and lactation. Pregnant women or women contemplating pregnancy should be encouraged to discontinue use of marijuana for medicinal purposes in favor of an alternative therapy for which there are better pregnancy-specific safety data. There are insufficient data to evaluate the effects of marijuana use on infants during lactation and breastfeeding, and in the absence of such data, marijuana use is discouraged.

Hypertonic sodium lactate reverses brain oxygenation and metabolism dysfunction after traumatic brain injury.

PubMed

Millet, A; Cuisinier, A; Bouzat, P; Batandier, C; Lemasson, B; Stupar, V; Pernet-Gallay, K; Crespy, T; Barbier, E L; Payen, J F

2018-06-01

The mechanisms by which hypertonic sodium lactate (HSL) solution act in injured brain are unclear. We investigated the effects of HSL on brain metabolism, oxygenation, and perfusion in a rodent model of diffuse traumatic brain injury (TBI). Thirty minutes after trauma, anaesthetised adult rats were randomly assigned to receive a 3 h infusion of either a saline solution (TBI-saline group) or HSL (TBI-HSL group). The sham-saline and sham-HSL groups received no insult. Three series of experiments were conducted up to 4 h after TBI (or equivalent) to investigate: 1) brain oedema using diffusion-weighted magnetic resonance imaging and brain metabolism using localized 1 H-magnetic resonance spectroscopy (n = 10 rats per group). The respiratory control ratio was then determined using oxygraphic analysis of extracted mitochondria, 2) brain oxygenation and perfusion using quantitative blood-oxygenation-level-dependent magnetic resonance approach (n = 10 rats per group), and 3) mitochondrial ultrastructural changes (n = 1 rat per group). Compared with the TBI-saline group, the TBI-HSL and the sham-operated groups had reduced brain oedema. Concomitantly, the TBI-HSL group had lower intracellular lactate/creatine ratio [0.049 (0.047-0.098) vs 0.097 (0.079-0.157); P < 0.05], higher mitochondrial respiratory control ratio, higher tissue oxygen saturation [77% (71-79) vs 66% (55-73); P < 0.05], and reduced mitochondrial cristae thickness in astrocytes [27.5 (22.5-38.4) nm vs 38.4 (31.0-47.5) nm; P < 0.01] compared with the TBI-saline group. Serum sodium and lactate concentrations and serum osmolality were higher in the TBI-HSL than in the TBI-saline group. These findings indicate that the hypertonic sodium lactate solution can reverse brain oxygenation and metabolism dysfunction after traumatic brain injury through vasodilatory, mitochondrial, and anti-oedema effects. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Effects of evaporative cooling on the regulation of body water and milk production in crossbred Holstein cattle in a tropical environment

NASA Astrophysics Data System (ADS)

Chaiyabutr, N.; Chanpongsang, S.; Suadsong, S.

2008-09-01

The aim of this study was to determine how evaporative cooling modifies body function with respect to water metabolism and other variables relevant to milk synthesis in crossbred cattle. The study was conducted on two groups of 0.875HF:0.125RS crossbred Holstein cattle (87.5%) housed in an open-sided barn with a tiled roof (non-cooled animals) and in a close-sided barn under an evaporative cooling system (cooled animals). The maximum ambient temperature and relative humidity for the non-cooled group were 33°C and 61%, with the corresponding values for the evaporatively cooled barn being 28°C and 84%, respectively. The temperature humidity index (THI) of under non-cooled conditions was higher ( P < 0.05) than that in the cooled barn. Rectal temperatures and respiration rates of non-cooled animals were higher ( P < 0.05) than those of cooled animals. Daily dry matter intake (DMI) of cooled animals was higher while water intakes were lower ( P < 0.05) than those of non-cooled animals. The mean absolute values of plasma volume, blood volume, and extracellular fluid (ECF) of cooled animals were significantly higher ( P < 0.05) than those of non-cooled animals throughout all stages of lactation. Milk yields of cooled animals were higher by 42%, 36% and 79% on average than those of non-cooled animals during early-, mid- and late-lactation, respectively. The decline in milk yields as lactation advances was markedly apparent in late-lactating non-cooled animals, while no significant changes in milk composition at different stages of lactation were observed in either group. Mean arterial plasma concentrations, arteriovenous concentration differences (A-V differences) and the extraction ratio across the mammary gland for acetate, glucose and triglyceride of cooled animals were not significantly different compared with values for non-cooled animals. No differences were seen in plasma hormonal levels for triiodotyronine (T3) and insulin-like growth factor-1 (IGF-1), but plasma cortisol and thyroxine (T4) levels tended to be lower in non-cooled animals. This study suggests that low cooling temperature accompanied by high humidity influences a galactopoietic effect, in part through increases in ECF, blood volume and plasma volume in association with an increase in DMI, which partitions the distribution of nutrients to the mammary gland for milk synthesis. Cooled animals were unable to maintain high milk yield as lactation advances even though a high level of body fluids was maintained during long-term cooled exposure. The decline in milk yield, coinciding with a decrease in net energy for lactation as lactation advances, could be attributed to a local change within the mammary gland.

Cumulative lactate and hospital mortality in ICU patients

PubMed Central

2013-01-01

Background Both hyperlactatemia and persistence of hyperlactatemia have been associated with bad outcome. We compared lactate and lactate-derived variables in outcome prediction. Methods Retrospective observational study. Case records from 2,251 consecutive intensive care unit (ICU) patients admitted between 2001 and 2007 were analyzed. Baseline characteristics, all lactate measurements, and in-hospital mortality were recorded. The time integral of arterial blood lactate levels above the upper normal threshold of 2.2 mmol/L (lactate-time-integral), maximum lactate (max-lactate), and time-to-first-normalization were calculated. Survivors and nonsurvivors were compared and receiver operating characteristic (ROC) analysis were applied. Results A total of 20,755 lactate measurements were analyzed. Data are srpehown as median [interquartile range]. In nonsurvivors (n = 405) lactate-time-integral (192 [0–1881] min·mmol/L) and time-to-first normalization (44.0 [0–427] min) were higher than in hospital survivors (n = 1846; 0 [0–134] min·mmol/L and 0 [0–75] min, respectively; all p < 0.001). Normalization of lactate <6 hours after ICU admission revealed better survival compared with normalization of lactate >6 hours (mortality 16.6% vs. 24.4%; p < 0.001). AUC of ROC curves to predict in-hospital mortality was the largest for max-lactate, whereas it was not different among all other lactate derived variables (all p > 0.05). The area under the ROC curves for admission lactate and lactate-time-integral was not different (p = 0.36). Conclusions Hyperlactatemia is associated with in-hospital mortality in a heterogeneous ICU population. In our patients, lactate peak values predicted in-hospital mortality equally well as lactate-time-integral of arterial blood lactate levels above the upper normal threshold. PMID:23446002

Changes in blood flow and cellular metabolism at a myofascial trigger point with trigger point release (ischemic compression): a proof-of-principle pilot study

PubMed Central

Moraska, Albert F.; Hickner, Robert C.; Kohrt, Wendy M.; Brewer, Alan

2012-01-01

Objective To demonstrate proof-of-principle measurement for physiological change within an active myofascial trigger point (MTrP) undergoing trigger point release (ischemic compression). Design Interstitial fluid was sampled continuously at a trigger point before and after intervention. Setting A biomedical research clinic at a university hospital. Participants Two subjects from a pain clinic presenting with chronic headache pain. Interventions A single microdialysis catheter was inserted into an active MTrP of the upper trapezius to allow for continuous sampling of interstitial fluid before and after application of trigger point therapy by a massage therapist. Main Outcome Measures Procedural success, pain tolerance, feasibility of intervention during sample collection, determination of physiologically relevant values for local blood flow, as well as glucose and lactate concentrations. Results Both patients tolerated the microdialysis probe insertion into the MTrP and treatment intervention without complication. Glucose and lactate concentrations were measured in the physiological range. Following intervention, a sustained increase in lactate was noted for both subjects. Conclusions Identifying physiological constituents of MTrP’s following intervention is an important step toward understanding pathophysiology and resolution of myofascial pain. The present study forwards that aim by showing proof-of-concept for collection of interstitial fluid from an MTrP before and after intervention can be accomplished using microdialysis, thus providing methodological insight toward treatment mechanism and pain resolution. Of the biomarkers measured in this study, lactate may be the most relevant for detection and treatment of abnormalities in the MTrP. PMID:22975226

Risk Factors Predicting Infectious Lactational Mastitis: Decision Tree Approach versus Logistic Regression Analysis.

PubMed

Fernández, Leónides; Mediano, Pilar; García, Ricardo; Rodríguez, Juan M; Marín, María

2016-09-01

Objectives Lactational mastitis frequently leads to a premature abandonment of breastfeeding; its development has been associated with several risk factors. This study aims to use a decision tree (DT) approach to establish the main risk factors involved in mastitis and to compare its performance for predicting this condition with a stepwise logistic regression (LR) model. Methods Data from 368 cases (breastfeeding women with mastitis) and 148 controls were collected by a questionnaire about risk factors related to medical history of mother and infant, pregnancy, delivery, postpartum, and breastfeeding practices. The performance of the DT and LR analyses was compared using the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity and accuracy of both models were calculated. Results Cracked nipples, antibiotics and antifungal drugs during breastfeeding, infant age, breast pumps, familial history of mastitis and throat infection were significant risk factors associated with mastitis in both analyses. Bottle-feeding and milk supply were related to mastitis for certain subgroups in the DT model. The areas under the ROC curves were similar for LR and DT models (0.870 and 0.835, respectively). The LR model had better classification accuracy and sensitivity than the DT model, but the last one presented better specificity at the optimal threshold of each curve. Conclusions The DT and LR models constitute useful and complementary analytical tools to assess the risk of lactational infectious mastitis. The DT approach identifies high-risk subpopulations that need specific mastitis prevention programs and, therefore, it could be used to make the most of public health resources.

Circular RNA of cattle casein genes are highly expressed in bovine mammary gland.

PubMed

Zhang, ChunLei; Wu, Hui; Wang, YanHong; Zhu, ShiQi; Liu, JunQiang; Fang, XingTang; Chen, Hong

2016-06-01

Recent studies have revealed that, in addition to hormones and other protein factors, noncoding RNA molecules play an important regulatory role in milk protein synthesis. Circular RNAs (circRNAs) are universally expressed noncoding RNA species that have been proposed recently to regulate the expression of their parental genes. In the present study, the deep RNA-sequencing technique known as RNA-seq was used to compare expression profiles of circRNAs from 2 pooled RNA samples from cow mammary gland on d 90 and 250 postpartum and to identify the key circRNAs involved in lactation. A total of 4,804 and 4,048 circRNAs were identified in the cow mammary gland on d 90 and 250 postpartum, respectively, of which only 2,231 circRNAs were co-expressed at both lactation stages, suggesting high stage specificity in the circRNAs. The enrichment of some Gene Ontology terms for the circRNA parental genes differed between lactation stages. Among the top 10 enriched Gene Ontology terms, vesicle, endoplasmic reticulum, and mitochondrial lumen were more common on lactation d 90. All 4 casein-coding genes (CSN1S1, CSN1S2, CSN2, and CSN3) produced circRNAs in the cattle mammary gland. In total, 80 circRNAs were identified from these 4 genes; circRNAs from CSN1S1 had very high abundance, and 3 of them accounted for 36% of all the circRNAs expressed in the mammary gland on lactation d 90. Three circRNAs from CSN1S1, 1 circRNA from CSN1S2, and 1 circRNA from CSN2 were all more highly expressed on lactation d 90 than on lactation d 250, as confirmed by quantitative PCR. These circRNAs had several target sites for the microRNA miR-2284 family and were predicted to target CSN1S1 and CSN2 mRNA, suggesting their potential involvement in regulating expression of the casein genes. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.

PubMed

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. Copyright 2009 S. Karger AG, Basel.

Dopamine-Regulated Adrenocorticotropic Hormone Secretion in Lactating Rats: Functional Plasticity of Melanotropes

PubMed Central

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E.; Nagy, György M.; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and β-lipotropin in corticotropes of the anterior lobe, and to α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence α-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in α-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by α-methyl-p-tyrosine (αMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma α-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both αMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. PMID:19641299

Ketones and lactate increase cancer cell “stemness”, driving recurrence, metastasis and poor clinical outcome in breast cancer

PubMed Central

Tsirigos, Aristotelis; Lin, Zhao; Pavlides, Stephanos; Wang, Chengwang; Flomenberg, Neal; Knudsen, Erik S; Howell, Anthony; Pestell, Richard G

2011-01-01

Previously, we showed that high-energy metabolites (lactate and ketones) “fuel” tumor growth and experimental metastasis in an in vivo xenograft model, most likely by driving oxidative mitochondrial metabolism in breast cancer cells. To mechanistically understand how these metabolites affect tumor cell behavior, here we used genome-wide transcriptional profiling. Human breast cancer cells (MCF7) were cultured with lactate or ketones, and then subjected to transcriptional analysis (exon-array). Interestingly, our results show that treatment with these high-energy metabolites increases the transcriptional expression of gene profiles normally associated with “stemness”, including genes upregulated in embryonic stem (ES) cells. Similarly, we observe that lactate and ketones promote the growth of bonafide ES cells, providing functional validation. The lactate- and ketone-induced “gene signatures” were able to predict poor clinical outcome (including recurrence and metastasis) in human breast cancer patients. Taken together, our results are consistent with the idea that lactate and ketone utilization in cancer cells promotes the “cancer stem cell” phenotype, resulting in significant decreases in patient survival. One possible mechanism by which high-energy metabolites might induce stemness is by increasing the pool of Acetyl-CoA, leading to increased histone acetylation and elevated gene expression. Thus, our results mechanistically imply that clinical outcome in breast cancer could simply be determined by epigenetics and energy metabolism, rather than by the accumulation of specific “classical” gene mutations. We also suggest that high-risk cancer patients (identified by the lactate/ketone gene signatures) could be treated with new therapeutics that target oxidative mitochondrial metabolism, such as the anti-oxidant and “mitochondrial poison” metformin. Finally, we propose that this new approach to personalized cancer medicine be termed “metabolo-genomics,” which incorporates features of both (1) cell metabolism and (2) gene transcriptional profiling. This powerful new approach directly links cancer cell metabolism with clinical outcome, and suggests new therapeutic strategies for inhibiting the TCA cycle and mitochondrial oxidative phosphorylation in cancer cells. PMID:21512313

Partial nucleotide sequences, and routine typing by polymerase chain reaction-restriction fragment length polymorphism, of the brown trout (Salmo trutta) lactate dehydrogenase, LDH-C1*90 and *100 alleles.

PubMed

McMeel, O M; Hoey, E M; Ferguson, A

2001-01-01

The cDNA nucleotide sequences of the lactate dehydrogenase alleles LDH-C1*90 and *100 of brown trout (Salmo trutta) were found to differ at position 308 where an A is present in the *100 allele but a G is present in the *90 allele. This base substitution results in an amino acid change from aspartic acid at position 82 in the LDH-C1 100 allozyme to a glycine in the 90 allozyme. Since aspartic acid has a net negative charge whilst glycine is uncharged, this is consistent with the electrophoretic observation that the LDH-C1 100 allozyme has a more anodal mobility relative to the LDH-C1 90 allozyme. Based on alignment of the cDNA sequence with the mouse genomic sequence, a local primer set was designed, incorporating the variable position, and was found to give very good amplification with brown trout genomic DNA. Sequencing of this fragment confirmed the difference in both homozygous and heterozygous individuals. Digestion of the polymerase chain reaction products with BslI, a restriction enzyme specific for the site difference, gave one, two and three fragments for the two homozygotes and the heterozygote, respectively, following electrophoretic separation. This provides a DNA-based means of routine screening of the highly informative LDH-C1* polymorphism in brown trout population genetic studies. Primer sets presented could be used to sequence cDNA of other LDH* genes of brown trout and other species.

Maternal Dietary Supplementation with Oligofructose-Enriched Inulin in Gestating/Lactating Rats Preserves Maternal Bone and Improves Bone Microarchitecture in Their Offspring

PubMed Central

Diaz-Castro, Javier; López-Aliaga, Inmaculada; Rueda, Ricardo

2016-01-01

Nutrition during pregnancy and lactation could exert a key role not only on maternal bone, but also could influence the skeletal development of the offspring. This study was performed in rats to assess the relationship between maternal dietary intake of prebiotic oligofructose-enriched inulin and its role in bone turnover during gestation and lactation, as well as its effect on offspring peak bone mass/architecture during early adulthood. Rat dams were fed either with standard rodent diet (CC group), calcium-fortified diet (Ca group), or prebiotic oligofructose-enriched inulin supplemented diet (Pre group), during the second half of gestation and lactation. Bone mineral density (BMD) and content (BMC), as well as micro-structure of dams and offspring at different stages were analysed. Dams in the Pre group had significantly higher trabecular thickness (Tb.Th), trabecular bone volume fraction (BV/TV) and smaller specific bone surface (BS/BV) of the tibia in comparison with CC dams. The Pre group offspring during early adulthood had an increase of the lumbar vertebra BMD when compared with offspring of CC and Ca groups. The Pre group offspring also showed significant increase versus CC in cancellous and cortical structural parameters of the lumbar vertebra 4 such as Tb.Th, cortical BMD and decreased BS/BV. The results indicate that oligofructose-enriched inulin supplementation can be considered as a plausible nutritional option for protecting against maternal bone loss during gestation and lactation preventing bone fragility and for optimizing peak bone mass and architecture of the offspring in order to increase bone strength. PMID:27115490

Monotreme Lactation Protein Is Highly Expressed in Monotreme Milk and Provides Antimicrobial Protection

PubMed Central

Enjapoori, Ashwantha Kumar; Grant, Tom R.; Nicol, Stewart C.; Lefèvre, Christophe M.; Nicholas, Kevin R.; Sharp, Julie A.

2014-01-01

Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female’s abdomen. Milk is the sole source of nutrition and immune protection for the developing young until weaning. Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. We propose that MLP evolved specifically in the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples. PMID:25245409

Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio

PubMed Central

Quintard, Hervé; Patet, Camille; Zerlauth, Jean-Baptiste; Suys, Tamarah; Bouzat, Pierre; Pellerin, Luc; Meuli, Reto; Magistretti, Pierre J.

2016-01-01

Abstract Energy dysfunction is associated with worse prognosis after traumatic brain injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL) improves energy metabolism after TBI. Here, we specifically examined whether the efficacy of HL (3h infusion, 30–40 μmol/kg/min) in improving brain energetics (using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found CMD glucose increase during HL was significant only in the subgroup of patients with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08–0.19] mmol/L, p < 0.001; vs. +0.04 [–0.05–0.13] in those with normal LPR, p = 0.33, mixed-effects model). In contrast, CMD glucose increase was independent from baseline CBF (coefficient +0.13 [0.04–0.21] mmol/L when global CBF was <32.5 mL/100 g/min vs. +0.09 [0.04–0.14] mmol/L at normal CBF, both p < 0.005) and systemic glucose. Our data suggest that improvement of brain energetics upon HL seems predominantly dependent on baseline cerebral metabolic state and support the concept that CMD LPR – rather than CBF – could be used as a diagnostic indication for systemic lactate supplementation following TBI. PMID:26421521

Weather and landscape factors affect white-tailed deer neonate survival at ecologically important life stages in the Northern Great Plains

USGS Publications Warehouse

Michel, Eric S.; Jenks, Jonathan A.; Kaskie, Kyle D.; Klaver, Robert W.; Jensen, William F.

2018-01-01

Offspring survival is generally more variable than adult survival and may limit population growth. Although white-tailed deer neonate survival has been intensively investigated, recent work has emphasized how specific cover types influence neonate survival at local scales (single study area). These localized investigations have often led to inconsistences within the literature. Developing specific hypotheses describing the relationships among environmental, habitat, and landscape factors influencing white-tailed deer neonate survival at regional scales may allow for detection of generalized patterns. Therefore, we developed 11 hypotheses representing the various effects of environmental (e.g., winter and spring weather), habitat (e.g., hiding and escape cover types), and landscape factors (e.g., landscape configuration regardless of specific cover type available) on white-tailed deer neonate survival up to one-month and from one- to three-months of age. At one-month, surviving fawns experienced a warmer lowest recorded June temperature and more June precipitation than those that perished. At three-months, patch connectance (percent of patches of the corresponding patch type that are connected within a predefined distance) positively influenced survival. Our results are consistent with white-tailed deer neonate ecology: increased spring temperature and precipitation are likely associated with a flush of nutritional resources available to the mother, promoting increased lactation efficiency and neonate growth early in life. In contrast, reduced spring temperature with increased precipitation place neonates at risk to hypothermia. Increased patch connectance likely reflects increased escape cover available within a neonate’s home range after they are able to flee from predators. If suitable escape cover is available on the landscape, then managers could focus efforts towards manipulating landscape configuration (patch connectance) to promote increased neonate survival while monitoring spring weather to assess potential influences on current year survival.

Comparative Transcriptome Analysis Reveals Different Molecular Mechanisms of Bacillus coagulans 2-6 Response to Sodium Lactate and Calcium Lactate during Lactic Acid Production

PubMed Central

Qin, Jiayang; Wang, Xiuwen; Wang, Landong; Zhu, Beibei; Zhang, Xiaohua; Yao, Qingshou; Xu, Ping

2015-01-01

Lactate production is enhanced by adding calcium carbonate or sodium hydroxide during fermentation. However, Bacillus coagulans 2-6 can produce more than 180 g/L L-lactic acid when calcium lactate is accumulated, but less than 120 g/L L-lactic acid when sodium lactate is formed. The molecular mechanisms by which B. coagulans responds to calcium lactate and sodium lactate remain unclear. In this study, comparative transcriptomic methods based on high-throughput RNA sequencing were applied to study gene expression changes in B. coagulans 2-6 cultured in non-stress, sodium lactate stress and calcium lactate stress conditions. Gene expression profiling identified 712 and 1213 significantly regulated genes in response to calcium lactate stress and sodium lactate stress, respectively. Gene ontology assignments of the differentially expressed genes were performed. KEGG pathway enrichment analysis revealed that ‘ATP-binding cassette transporters’ were significantly affected by calcium lactate stress, and ‘amino sugar and nucleotide sugar metabolism’ was significantly affected by sodium lactate stress. It was also found that lactate fermentation was less affected by calcium lactate stress than by sodium lactate stress. Sodium lactate stress had negative effect on the expression of ‘glycolysis/gluconeogenesis’ genes but positive effect on the expression of ‘citrate cycle (TCA cycle)’ genes. However, calcium lactate stress had positive influence on the expression of ‘glycolysis/gluconeogenesis’ genes and had minor influence on ‘citrate cycle (TCA cycle)’ genes. Thus, our findings offer new insights into the responses of B. coagulans to different lactate stresses. Notably, our RNA-seq dataset constitute a robust database for investigating the functions of genes induced by lactate stress in the future and identify potential targets for genetic engineering to further improve L-lactic acid production by B. coagulans. PMID:25875592

Lactate: link between glycolytic and oxidative metabolism.

PubMed

Brooks, George A

2007-01-01

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilised continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges (i) between white-glycolytic and red-oxidative fibres within a working muscle bed; (ii) between working skeletal muscle and heart; and (iii) between tissues of net lactate release and gluconeogenesis. Lactate shuttles exist in diverse tissues including in the brain, where a shuttle between astrocytes and neurons is linked to glutamatergic signalling. Because lactate, the product of glycogenolysis and glycolysis, is disposed of by oxidative metabolism, lactate shuttling unites the two major processes of cellular energy transduction. Lactate disposal is mainly through oxidation, especially during exercise when oxidation accounts for 70-75% of removal and gluconeogenesis the remainder. Lactate flux occurs down proton and concentration gradients that are established by the mitochondrial lactate oxidation complex. Marathon running is a power activity requiring high glycolytic and oxidative fluxes; such activities require lactate shuttling. Knowledge of the lactate shuttle is yet to be imparted to the sport.

A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat

PubMed Central

Zambrano, E; Bautista, C J; Deás, M; Martínez-Samayoa, P M; González-Zamorano, M; Ledesma, H; Morales, J; Larrea, F; Nathanielsz, P W

2006-01-01

Extensive epidemiological and experimental evidence indicates that a sub-optimal environment during fetal and neonatal development in both humans and animals may programme offspring susceptibility to later development of chronic diseases including obesity and diabetes that are the result of altered carbohydrate metabolism. We determined the effects of protein restriction during pregnancy and/or lactation on growth, serum leptin, and glucose and insulin responses to a glucose tolerance test in male and female offspring at 110 days postnatal life. We fed Wistar rats a normal control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. Female but not male R pups weighed less than C at birth. After delivery, mothers received the C or R diet during lactation to provide four offspring groups: CC (first letter maternal pregnancy diet and second maternal lactation diet), RR, CR and RC. All offspring were fed ad libitum with C diet after weaning. Relative food intake correlated inversely with weight. Offspring serum leptin correlated with body weight and relative, but not absolute, food intake in both male and female pups. Serum leptin was reduced in RR female pups compared with CC and increased in RC males compared with CC at 110 days of age. Offspring underwent a glucose tolerance test (GTT) at 110 days postnatal life. Female RR and CR offspring showed a lower insulin to glucose ratio than CC. At 110 days of age male RR and CR also showed some evidence of increased insulin sensitivity. Male but not female RC offspring showed evidence of insulin resistance compared with CC. Cholesterol was similar and triglycerides (TG) higher in male compared with female CC. Cholesterol and TG were higher in males than females in RR, CR and RC (P < 0.05). Cholesterol and TG did not differ between groups in females. Cholesterol and TG were elevated in RC compared with CC males. Nutrient restriction in lactation increased relative whole protein and decreased whole lipid in both males and females. RC females showed decreased relative levels of protein and increased fat. We conclude that maternal protein restriction during either pregnancy and/or lactation alters postnatal growth, appetitive behaviour, leptin physiology, TG and cholesterol concentrations and modifies glucose metabolism and insulin resistance in a sex- and time window of exposure-specific manner. PMID:16339179

Lactate: Brain Fuel in Human Traumatic Brain Injury: A Comparison with Normal Healthy Control Subjects

PubMed Central

Martin, Neil A.; Horning, Michael A.; McArthur, David L.; Hovda, David A.; Vespa, Paul; Brooks, George A.

2015-01-01

Abstract We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-2H2]glucose, that is, D2-glucose, and [3-13C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as 13CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-13C]lactate tracer and 13C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75–80% of 13CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the injured brain. Undiminished cerebral lactate fractional extraction and uptake suggest that arterial lactate supplementation may be used to compensate for decreased CMRgluc following TBI. PMID:25594628

MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother

PubMed Central

Alsaweed, Mohammed; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

2015-01-01

Human milk (HM) is the optimal source of nutrition, protection and developmental programming for infants. It is species-specific and consists of various bioactive components, including microRNAs, small non-coding RNAs regulating gene expression at the post-transcriptional level. microRNAs are both intra- and extra-cellular and are present in body fluids of humans and animals. Of these body fluids, HM appears to be one of the richest sources of microRNA, which are highly conserved in its different fractions, with milk cells containing more microRNAs than milk lipids, followed by skim milk. Potential effects of exogenous food-derived microRNAs on gene expression have been demonstrated, together with the stability of milk-derived microRNAs in the gastrointestinal tract. Taken together, these strongly support the notion that milk microRNAs enter the systemic circulation of the HM fed infant and exert tissue-specific immunoprotective and developmental functions. This has initiated intensive research on the origin, fate and functional significance of milk microRNAs. Importantly, recent studies have provided evidence of endogenous synthesis of HM microRNA within the human lactating mammary epithelium. These findings will now form the basis for investigations of the role of microRNA in the epigenetic control of normal and aberrant mammary development, and particularly lactation performance. PMID:26529003

Identification of activin A and follistatin in human milk.

PubMed

Luisi, Stefano; Calonaci, Giulia; Florio, Pasquale; Lombardi, Ilaria; De Felice, Claudio; Bagnoli, Franco; Petraglia, Felice

2002-09-01

Activin A is a dimeric protein member of the transforming growth factor-beta (TGF-beta) family: it is synthesized by a variety of organs and follistatin is an activin-binding protein. A sensitive and specific assays for bioactive dimeric activin A and follistatin have recently allowed to measure these proteins in blood and other biological fluids, giving a new insights into their possible physiological role. Since human breast is able to produce activin A, the aim of the present study was to evaluate whether it and follistatin are measurable in breast milk of women during lactation. Concentrations of activin A and follistatin were measured in milk samples collected at 3, 5 and 30 days after delivery by using specific and sensitive two-site ELISAs. For the first time the presence of immunoreactive activin A and follistatin in human milk has been shown; no significant different concentration between the third and the fifth day after delivery was found. Furthermore, no difference of activin A and follistatin concentration between the whole and the skim milk or between spontaneous delivery and cesarean section was found. Milk activin A and follistatin concentrations after 1 month of lactation were significantly decreased (P < 0.01). Activin A and follistatin are present in human milk in high concentrations in the first week of lactation, while decrease after a month suggesting a possible role as growth factors in human milk.

Effects of bovine necrotic vulvovaginitis on productivity in a dairy herd in Israel.

PubMed

Blum, S; Mazuz, M; Brenner, J; Friedgut, O; Koren, O; Goshen, T; Elad, D

2008-05-01

Bovine necrotic vulvovaginitis (BNVV) is characterized by the development of a necrotic vulvovaginal lesion, almost exclusively in post-parturient first-lactation cows, associated with Porphyromonas levii. The scope of this survey was to evaluate the impact of BNVV on herd productivity as a means to rationally evaluate the resources that should be allocated in dealing with the syndrome. During an outbreak of BNVV in a dairy herd, following the introduction of a large number of cows from another farm, the impact of the animals' origin (local or transferred) and BNVV (positive or negative) upon involuntary culling rate, milk yield and days between pregnancies were assessed. The results indicated that the number of days between pregnancies was significantly higher in first-lactation cows with BNVV but was not influenced by the other independent variables. None of the other variables included in this survey had any effect on the involuntary culling rate and milk yield.

Inhibiting Sperm Pyruvate Dehydrogenase Complex and Its E3 Subunit, Dihydrolipoamide Dehydrogenase Affects Fertilization in Syrian Hamsters

PubMed Central

Sailasree, Purnima; Singh, Durgesh K.; Kameshwari, Duvurri B.; Shivaji, Sisinthy

2014-01-01

Background/Aims The importance of sperm capacitation for mammalian fertilization has been confirmed in the present study via sperm metabolism. Involvement of the metabolic enzymes pyruvate dehydrogenase complex (PDHc) and its E3 subunit, dihydrolipoamide dehydrogenase (DLD) in hamster in vitro fertilization (IVF) via in vitro sperm capacitation is being proposed through regulation of sperm intracellular lactate, pH and calcium. Methodology and Principal Findings Capacitated hamster spermatozoa were allowed to fertilize hamster oocytes in vitro which were then assessed for fertilization, microscopically. PDHc/DLD was inhibited by the use of the specific DLD-inhibitor, MICA (5-methoxyindole-2-carboxylic acid). Oocytes fertilized with MICA-treated (MT) [and thus PDHc/DLD-inhibited] spermatozoa showed defective fertilization where 2nd polar body release and pronuclei formation were not observed. Defective fertilization was attributable to capacitation failure owing to high lactate and low intracellular pH and calcium in MT-spermatozoa during capacitation. Moreover, this defect could be overcome by alkalinizing spermatozoa, before fertilization. Increasing intracellular calcium in spermatozoa pre-IVF and in defectively-fertilized oocytes, post-fertilization rescued the arrest seen, suggesting the role of intracellular calcium from either of the gametes in fertilization. Parallel experiments carried out with control spermatozoa capacitated in medium with low extracellular pH or high lactate substantiated the necessity of optimal sperm intracellular lactate levels, intracellular pH and calcium during sperm capacitation, for proper fertilization. Conclusions This study confirms the importance of pyruvate/lactate metabolism in capacitating spermatozoa for successful fertilization, besides revealing for the first time the importance of sperm PDHc/ DLD in fertilization, via the modulation of sperm intracellular lactate, pH and calcium during capacitation. In addition, the observations made in the IVF studies in hamsters suggest that capacitation failures could be a plausible cause of unsuccessful fertilization encountered during human assisted reproductive technologies, like IVF and ICSI. Our studies indicate a role of sperm capacitation in the post-penetration events during fertilization. PMID:24852961

No Evidence for a Trade-Off between Reproductive Investment and Immunity in a Rodent

PubMed Central

Xu, Yan-Chao; Yang, Deng-Bao; Wang, De-Hua

2012-01-01

Life history theory assumes there are trade-offs between competing functions such as reproduction and immunity. Although well studied in birds, studies of the trade-offs between reproduction and immunity in small mammals are scarce. Here we examined whether reduced immunity is a consequence of reproductive effort in lactating Brandt's voles (Lasiopodomys brandtii). Specifically, we tested the effects of lactation on immune function (Experiment I). The results showed that food intake and resting metabolic rate (RMR) were higher in lactating voles (6≤ litter size ≤8) than that in non-reproductive voles. Contrary to our expectation, lactating voles also had higher levels of serum total Immunoglobulin G (IgG) and anti-keyhole limpet hemocyanin (KLH) IgG and no change in phytohemagglutinin (PHA) response and anti-KLH Immunoglobulin M (IgM) compared with non-reproductive voles, suggesting improved rather than reduced immune function. To further test the effect of differences in reproductive investment on immunity, we compared the responses between natural large (n≥8) and small litter size (n≤6) (Experiment II) and manipulated large (11–13) and small litter size (2–3) (Experiment III). During peak lactation, acquired immunity (PHA response, anti-KLH IgG and anti-KLH IgM) was not significantly different between voles raising large or small litters in both experiments, despite the measured difference in reproductive investment (greater litter size, litter mass, RMR and food intake in the voles raising larger litters). Total IgG was higher in voles with natural large litter size than those with natural small litter size, but decreased in the enlarged litter size group compared with control and reduced group. Our results showed that immune function is not suppressed to compensate the high energy demands during lactation in Brandt's voles and contrasting the situation in birds, is unlikely to be an important aspect mediating the trade-off between reproduction and survival. PMID:22649512

Two separate pathways for d-lactate oxidation by Saccharomyces cerevisiae mitochondria which differ in energy production and carrier involvement.

PubMed

Pallotta, Maria Luigia; Valenti, Daniela; Iacovino, Michelina; Passarella, Salvatore

2004-02-15

In this work we looked at whether and how mitochondria isolated from Saccharomyces cerevisiae (SCM) oxidize d-lactate. We found that: (1). externally added d-lactate causes oxygen uptake by SCM with P/O ratio equal to 1.5; in the presence of antimycin A (AA), P/O ratio was 1.8, differently in the presence of the non-penetrant alpha-cyanocinnamate (alpha-CCN-) no P/O ratio could be measured. Consistently, mitochondrial electrical membrane potential (deltapsi) generation was found, due to externally added d-lactate in the presence of antimycin A, but not of alpha-CCN-. (2). SCM oxidize d-lactate in two different manners: (i). via inner membrane d-lactate dehydrogenase which leads to d-lactate oxidation without driving deltapsi generation and ATP synthesis and (ii). via the matrix d-lactate dehydrogenase, which drives deltapsi generation and ATP synthesis by using taken up d-lactate. (3). Pyruvate newly synthesised in the mitochondrial matrix is exported via the novel d-lactate/pyruvate antiporter. d-Lactate/pyruvate antiport proved to regulate the rate of pyruvate efflux in vitro. (4). The existence of the d-lactate/H+ symporter is also proposed as shown by mitochondrial swelling. The d-lactate carriers and d-lactate dehydrogenases could account for the removal of the toxic methylglyoxal from cytosol, as well as for the d-lactate-dependent gluconeogenesis.

Blood lactate clearance after maximal exercise depends on active recovery intensity.

PubMed

Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

2014-06-01

High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05). Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

Rapid in vivo apparent diffusion coefficient mapping of hyperpolarized (13) C metabolites.

PubMed

Koelsch, Bertram L; Reed, Galen D; Keshari, Kayvan R; Chaumeil, Myriam M; Bok, Robert; Ronen, Sabrina M; Vigneron, Daniel B; Kurhanewicz, John; Larson, Peder E Z

2015-09-01

Hyperpolarized (13) C magnetic resonance allows for the study of real-time metabolism in vivo, including significant hyperpolarized (13) C lactate production in many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport lactate out of cells. Thus, the ability to not only measure the production of hyperpolarized (13) C lactate but also understand its compartmentalization using diffusion-weighted MR will provide unique information for improved tumor characterization. We used a bipolar, pulsed-gradient, double spin echo imaging sequence to rapidly generate diffusion-weighted images of hyperpolarized (13) C metabolites. Our methodology included a simultaneously acquired B1 map to improve apparent diffusion coefficient (ADC) accuracy and a diffusion-compensated variable flip angle scheme to improve ADC precision. We validated this sequence and methodology in hyperpolarized (13) C phantoms. Next, we generated ADC maps of several hyperpolarized (13) C metabolites in a normal rat, rat brain tumor, and prostate cancer mouse model using both preclinical and clinical trial-ready hardware. ADC maps of hyperpolarized (13) C metabolites provide information about the localization of these molecules in the tissue microenvironment. The methodology presented here allows for further studies to investigate ADC changes due to disease state that may provide unique information about cancer aggressiveness and metastatic potential. © 2014 Wiley Periodicals, Inc.

Association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002-2008).

PubMed

Zacher, Laurie A; Berg, John; Shaw, Scott P; Kudej, Raymond K

2010-04-15

To determine whether changes in presurgical plasma lactate concentration (before and after initial fluid resuscitation and gastric decompression) were associated with short-term outcome for dogs with gastric dilatation-volvulus (GDV). Retrospective case series. 64 dogs. Medical records were reviewed, and signalment, history, resuscitative treatments, serial presurgical lactate concentrations, surgical findings, and short-term outcome were obtained for dogs with confirmed GDV. 36 of 40 (90%) dogs with an initial lactate concentration 9.0 mmol/L). Within HIL dogs, there was no difference in mean +/- SD initial lactate concentration between survivors and nonsurvivors (10.6 +/- 2.3 mmol/L vs 11.2 +/- 2.3 mmol/L, respectively); however, there were significant differences in post-treatment lactate concentration, absolute change in lactate concentration, and percentage change in lactate concentration following resuscitative treatment. By use of optimal cutoff values within HIL dogs, survival rates for dogs with final lactate concentration > 6.4 mmol/L (23%), absolute change in lactate concentration 4 mmol/L (86%), or percentage change in lactate concentration > 42.5% (100%). Calculating changes in plasma lactate concentration following initial treatment in dogs with GDV may assist in determining prognosis and identifying patients that require more aggressive treatment.

A comparative proteomic analysis of Bacillus coagulans in response to lactate stress during the production of L-lactic acid.

PubMed

Wang, Xiuwen; Qin, Jiayang; Wang, Landong; Xu, Ping

2014-12-01

The growth rate and maximum biomass of Bacillus coagulans 2-6 were inhibited by lactate; inhibition by sodium lactate was stronger than by calcium lactate. The differences of protein expressions by B. coagulans 2-6 under the lactate stress were determined using two-dimensional electrophoresis coupled with mass spectrometric identification. Under the non-stress condition, calcium lactate stress and sodium lactate stress, the number of detected protein spots was 1,571 ± 117, 1,281 ± 231 and 904 ± 127, respectively. Four proteins with high expression under lactate stress were identified: lactate dehydrogenase, cysteine synthase A, aldo/keto reductase and ribosomal protein L7/L12. These proteins are thus potential targets for the reconstruction of B. coagulans to promote its resistance to lactate stress.

Subcellular storage compartments of bacteriopheophorbide sensitizers

NASA Astrophysics Data System (ADS)

Moser, Joerg G.; Dembeck, U.; Hubert, M.; Spengler, Bernhard; Bayer, Rainer; Wagner, Birgit

1994-03-01

Fluorescence colocalization with the Golgi specific stain, NBD-ceramide, and the mitochondrial localizing stain, Rhodamine 123, confirmed the earlier assumption that the Golgi apparatus is one of the prominent storage compartments for bacteriopheophorbide esters in OAT 75 SCLC cells and several amelanotic melanoma cell lines (A375, Melur SP18, SkAMel 25). Furthermore, a diffuse staining of mitochondria, of non-structured cytoplasm, and an additional storage in melanine vesicles of the amelanotic melanoma cells suggests further storage compartments with quantitatively different contributions to the phototoxicity of bacteriochlorophyll-derived photosensitizers. Independent observations of early phototoxic effects on microfilamentous networks, enzymatic activities (succinate dehydrogenase, lactate dehydrogenase), and redistribution phenomena following primary uptake of the sensitizers let us assume that only a part of the 108 molecules taken up by a cell contribute directly to phototoxicity. Thus it may be asked if a proper subcellular positioning of only a few sensitizer molecules may have similar phototoxic effects as the huge amounts stored at apparently ineffective sites.

In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons.

PubMed

Mächler, Philipp; Wyss, Matthias T; Elsayed, Maha; Stobart, Jillian; Gutierrez, Robin; von Faber-Castell, Alexandra; Kaelin, Vincens; Zuend, Marc; San Martín, Alejandro; Romero-Gómez, Ignacio; Baeza-Lehnert, Felipe; Lengacher, Sylvain; Schneider, Bernard L; Aebischer, Patrick; Magistretti, Pierre J; Barros, L Felipe; Weber, Bruno

2016-01-12

Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

BIOKID: Randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991

PubMed Central

Nau, Barbara; Schmitt, Claus P; Almeida, Margarida; Arbeiter, Klaus; Ardissino, Gianluigi; Bonzel, Klaus E; Edefonti, Alberto; Fischbach, Michel; Haluany, Karin; Misselwitz, Joachim; Kemper, Markus J; Rönnholm, Kai; Wygoda, Simone; Schaefer, Franz

2004-01-01

Background Peritoneal dialysis (PD) is the preferred dialysis modality in children. Its major drawback is the limited technique survival due to infections and progressive ultrafiltration failure. Conventional PD solutions exert marked acute and chronic toxicity to local tissues. Prolonged exposure is associated with severe histopathological alterations including vasculopathy, neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial cell layer. Recently, more biocompatible PD solutions containing reduced amounts of toxic glucose degradation products (GDPs) and buffered at neutral pH have been introduced into clinical practice. These solutions contain lactate, bicarbonate or a combination of both as buffer substance. Increasing evidence from clinical trials in adults and children suggests that the new PD fluids may allow for better long-term preservation of peritoneal morphology and function. However, the relative importance of the buffer in neutral-pH, low-GDP fluids is still unclear. In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD fluids. The BIOKID trial is designed to clarify the clinical significance of the buffer choice in biocompatible PD fluids. Methods/design The objective of the study is to test the hypothesis that bicarbonate based PD solutions may allow for a better preservation of peritoneal transport characteristics in children than solutions containing lactate buffer. Secondary objectives are to assess any impact of the buffer system on acid-base status, peritoneal tissue integrity and the incidence and severity of peritonitis. After a run-in period of 2 months during which a targeted cohort of 60 patients is treated with a conventional, lactate buffered, acidic, GDP containing PD fluid, patients will be stratified according to residual renal function and type of phosphate binding medication and randomized to receive either the lactate-containing Balance solution or the bicarbonate-buffered Bicavera® solution for a period of 10 months. Patients will be monitored by monthly physical and laboratory examinations. Peritoneal equilibration tests, 24-h dialysate and urine collections will be performed 4 times. Peritoneal biopsies will be obtained on occasion of intraabdominal surgery. Changes in small solute transport rates, markers of peritoneal tissue turnover in the effluent, acid-base status and peritonitis rates and severity will be analyzed. PMID:15485574

Comparison of lactate and bicarbonate buffered haemofiltration fluids: use in critically ill patients.

PubMed

Thomas, A N; Guy, J M; Kishen, R; Geraghty, I F; Bowles, B J; Vadgama, P

1997-06-01

To compare acid-base balance, lactate concentration, and haemodynamic and O2 transport variables during haemofiltration with replacement fluid containing 44.5 mmol/l Na+ lactate or 40 mmol/l Na+ HCO3- and 3 mmol/l lactic acid. A prospective, randomized trial. A multidisciplinary, adult intensive care unit in a university hospital. Forty acidotic patients who required haemofiltration, were dependent on mechanical ventilation, and had PA catheters in situ. During haemofiltration patients received lactate or bicarbonate replacement fluid at a mean rate of 1.7 l/h (SD 0.3). Arterial blood gases, plasma lactate, and haemodynamic and O2 transport variables were measured before and after 12 and 24 h haemofiltration. Ultrafiltrate was collected for lactate estimation. As means (SD). The net gain of lactate was 63 mmol/h (12 mmol) with Na+ lactate and 0 mmol/h (0.3 mmol) with Na+ HCO3-. There was a significant increase in pH and [lactate] in both groups, but [lactate] was higher in patients receiving lactate. Twenty-one patients survived to ICU discharge, these patients were significantly less acidotic after filtration (lactate group: 0 h: pH 7.23 (0.09), [lactate] 2.4 mmol/l (1.7); 12 h: pH 7.34 (0.09), [lactate] 4.7 mmol/l (2.4); 24 h: pH 7.36 (0.07), [lactate] 4.7 mmol (2.7). HCO3 group: 0 h: pH 7.23 (0.09), [lactate] 2.3 (1.3); 12 h: pH 7.32 (0.06), [lactate] 2.9 mmol/l (1.8); 24 h: pH 7.35 (0.08), [lactate] 2.8 mmol/l (2.0). Base deficit: survivors: 0 h: 9 mmol/l (4); 12 h: 2 mmol/l (3). Non-survivors: 0 h: 10 mmol/l (3); 12 h: 6 mmol/l (3)). Haemodynamic and O2 transport variables were not significantly affected by treatment group or outcome. The degree of correction of acidosis during the first 24 h of haemofiltration was determined by patients outcome but was not affected by the substitution of bicarbonate- for lactate-containing replacement fluids.

Changes in Plasma Progesterone Levels in the Caudal Vena Cava and the Jugular Vein and Luteinizing Hormone Secretion Pattern After Feeding in Lactating and Non-lactating Dairy Cows

PubMed Central

ENDO, Natsumi; NAGAI, Kiyosuke; TANAKA, Tomomi; KAMOMAE, Hideo

2012-01-01

Abstract The present study was designed to assess progesterone profiles at the secreted (caudal vena cava) and circulating levels (jugular vein) and luteinizing hormone (LH) secretion pattern in lactating and non-lactating cows with reference to feeding. Four lactating and four non-lactating cycling Holstein cows were examined. Blood samples were collected simultaneously from the caudal vena cava (via a catheter inserted from the coccygeal vein) and the jugular vein every 15 min for 12 h (0500–1700 h) during the functional luteal phase. Cows were fed 50% of the daily diet 6 h after the start of blood sampling. During the 12-h sampling period, mean progesterone concentrations in the caudal vena cava did not differ between lactating and non-lactating cows (49.0 ± 2.9 and 53.3 ± 3.7 ng/ml; mean ± SE), whereas mean progesterone concentrations in the jugular vein in lactating cows were higher than those in non-lactating cows (6.4 ± 0.1 and 5.6 ± 0.1 ng/ml, P < 0.001). Lactating cows had a higher frequency of LH pulses than non-lactating cows (7.0 ± 0.7 and 4.3 ± 0.9 pulses/12 h, P<0.05). The influence of feeding was not observed on LH profiles but was observed on progesterone profiles in both veins. Progesterone concentrations in the caudal vena cava increased after feeding in both groups. Progesterone concentrations in the jugular vein decreased after feeding in lactating cows but not in non-lactating cows. These results indicate the difference in feeding-related changes in progesterone dynamics between lactating and non-lactating cows. PMID:23171608

Partial reconstruction of in vitro gluconeogenesis arising from mitochondrial l-lactate uptake/metabolism and oxaloacetate export via novel L-lactate translocators.

PubMed

De Bari, Lidia; Atlante, Anna; Valenti, Daniela; Passarella, Salvatore

2004-05-15

In the light of the occurrence of L-lactate dehydrogenase inside the mitochondrial matrix, we looked at whether isolated rat liver mitochondria can take up and metabolize L-lactate, and provide oxaloacetate outside mitochondria, thus contributing to a partial reconstruction of gluconeogenesis in vitro. We found that: (1) L-lactate (10 mM), added to mitochondria in the presence of a cocktail of glycolysis/gluconeogenesis enzymes and cofactors, can lead to synthesis of glyceraldehyde-3-phosphate at a rate of about 7 nmol/min per mg mitochondrial protein. (2) Three novel translocators exist to mediate L-lactate traffic across the inner mitochondrial membrane. An L-lactate/H+ symporter was identified by measuring fluorimetrically the rate of endogenous pyridine nucleotide reduction. Consistently, L-lactate oxidation was found to occur with P/O ratio=3 (where P/O ratio is the ratio of mol of ATP synthesized to mol of oxygen atoms reduced to water during oxidative phosphorylation) and with generation of membrane potential. Proton uptake, which occurred as a result of addition of L-lactate to RLM together with electron flow inhibitors, and mitochondrial swelling in ammonium L-lactate solutions were also monitored. L-Lactate/oxaloacetate and L-lactate/pyruvate anti-porters were identified by monitoring photometrically the appearance of L-lactate counter-anions outside mitochondria. These L-lactate translocators, which are distinct from the monocarboxylate carrier, were found to differ from each other in V(max) values and in inhibition and pH profiles, and proved to regulate mitochondrial L-lactate metabolism in vitro. The role of lactate/mitochondria interactions in gluconeogenesis is discussed.

Effects of high and low blood lactate concentrations on sweat lactate response.

PubMed

Green, J M; Bishop, P A; Muir, I H; McLester, J R; Heath, H E

2000-11-01

Sweat lactate results from eccrine gland metabolism, however, the possible clearance of blood lactate through sweat has not been resolved. On separate days in an environmental chamber (32 +/- 1 C) 12 subjects completed a constant load (CON) (30 min at 40% VO2 max) and an interval cycling trial (INT) (15 one-min intervals at 80% VO2 max, each separated by one min rest) each designed to elicit different blood lactate responses. Each 30 min cycling trial was preceded by 15 min warm-up (30 watts) and followed by 15 min passive rest. Sweat and blood were analyzed for lactate concentration at 15, 25, 35, 45, and 60 min during CON and INT. Total body water loss was used to calculate sweat rate (ml/hr). Blood lactate was significantly greater (p < or = 0.05) at 25, 35, 45, and 60 min during INT compared to CON (approximately 5 mmol/L vs 1.5 mmol/L). Sweat lactate was not significantly different (p>0.05) between trials at any time (approximately 10 mmol/L). Sweat rates (approximately 600ml/hr) and estimated total lactate secretion were not significantly different (CON vs. INT) (p > 0.05). Elevated blood lactate was not associated with changes in sweat lactate concentration. Sweat lactate seems to originate in eccrine glands independent of blood lactate.

Lactate is a preferential oxidative energy substrate over glucose for neurons in culture.

PubMed

Bouzier-Sore, Anne-Karine; Voisin, Pierre; Canioni, Paul; Magistretti, Pierre J; Pellerin, Luc

2003-11-01

The authors investigated concomitant lactate and glucose metabolism in primary neuronal cultures using 13C- and 1H-NMR spectroscopy. Neurons were incubated in a medium containing either [1-13C]glucose and different unlabeled lactate concentrations, or unlabeled glucose and different [3-13C]lactate concentrations. Overall, 13C-NMR spectra of cellular extracts showed that more 13C was incorporated into glutamate when lactate was the enriched substrate. Glutamate 13C-enrichment was also found to be much higher in lactate-labeled than in glucose-labeled conditions. When glucose and lactate concentrations were identical (5.5 mmol/L), relative contributions of glucose and lactate to neuronal oxidative metabolism amounted to 21% and 79%, respectively. Results clearly indicate that when neurons are in the presence of both glucose and lactate, they preferentially use lactate as their main oxidative substrate.

A Review of Worksite Lactation Accommodations.

PubMed

Hilliard, Elizabeth Dianne

2017-01-01

The purpose of this review was to examine workplace lactation accommodations, and their association with breastfeeding duration, and identify strategies occupational health professionals can use to promote lactation improvements. This study included literature published from 1985 through 2015 and listed in PubMed and CINAHL. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 articles were identified for review. Presence of a corporate lactation program, on-site child care, and return to work/telephone lactation consultation were consistently associated with breastfeeding at 6 months. Other breastfeeding accommodations (i.e., lactation spaces, lactation breaks, worksite lactation policies, and supervisor/coworker support) were not consistently associated with breastfeeding duration. Occupational health professionals can play key roles in improving the effectiveness of lactation accommodations. Assuring adequate implementation of accommodations, increasing communication and marketing of accommodations, and promoting supervisor and coworker support are areas that occupational health professionals should explore for improving lactation duration.

Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Final rule.

PubMed

2014-12-04

The Food and Drug Administration (FDA) is amending its regulations governing the content and format of the "Pregnancy," "Labor and delivery," and "Nursing mothers" subsections of the "Use in Specific Populations" section of the labeling for human prescription drug and biological products. The final rule requires the removal of the pregnancy categories A, B, C, D, and X from all human prescription drug and biological product labeling. For human prescription drug and biological products subject to the Agency's 2006 Physician Labeling Rule, the final rule requires that the labeling include a summary of the risks of using a drug during pregnancy and lactation, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and lactation. The final rule eliminates the "Labor and delivery" subsection because information about labor and delivery is included in the "Pregnancy" subsection. The final rule requires that the labeling include relevant information about pregnancy testing, contraception, and infertility for health care providers prescribing for females and males of reproductive potential. The final rule creates a consistent format for providing information about the risks and benefits of prescription drug and/or biological product use during pregnancy and lactation and by females and males of reproductive potential. These revisions will facilitate prescriber counseling for these populations.

Investigating high-concentration monoclonal antibody powder suspension in nonaqueous suspension vehicles for subcutaneous injection.

PubMed

Bowen, Mayumi; Armstrong, Nick; Maa, Yuh-Fun

2012-12-01

Developing high-concentration monoclonal antibody (mAb) liquid formulations for subcutaneous (s.c.) administration is challenging because increased viscosity makes injection difficult. To overcome this obstacle, we investigated a nonaqueous powder suspension approach. Three IgG1 mAbs were spray dried and suspended at different concentrations in Miglyol® 840, benzyl benzoate, or ethyl lactate. Suspensions were characterized for viscosity, particle size, and syringeability; physical stability was visually inspected. Suspensions generally outperformed liquid solutions for injectability despite higher viscosity at the same mAb concentrations. Powder formulations and properties had little effect on viscosity or injectability. Ethyl lactate suspensions had lowest viscosity (<20 cP) and lowest syringe injection glide force (<15 N) at mAb concentrations as high as 333 mg/mL (500 mg powder/mL). Inverse gas chromatography analysis indicated that the vehicle was the most important factor impacting suspension performance. Ethyl lactate rendered greater heat of sorption (suggesting strong particle-suspension vehicle interaction may reduce particle-particle self-association, leading to low suspension viscosity and glide force) but lacked the physical suspension stability exhibited by the other vehicles. Specific mixtures of ethyl lactate and Miglyol® 840 improved overall performance in high mAb concentration suspensions. This study demonstrated the viability of high mAb concentration (>300 mg/mL) in suspension formulations for s.c. administration. Copyright © 2012 Wiley Periodicals, Inc.

Prognostic significance of blood lactate and lactate clearance in trauma patients.

PubMed

Régnier, Marie-Alix; Raux, Mathieu; Le Manach, Yannick; Asencio, Yves; Gaillard, Johann; Devilliers, Catherine; Langeron, Olivier; Riou, Bruno

2012-12-01

Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

No change in energy efficiency in lactation: Insights from a longitudinal study.

PubMed

Bender, Richard L; Williams, Heather S; Dufour, Darna L

2017-11-01

Lactation is the most energy-demanding phase of reproduction for human females, but it is still unclear how women in different environments are able to meet this additional energy demand. Previous studies have investigated whether changes in metabolism could have an energy-sparing effect in lactation, with conflicting results. Here, we asked whether increased energy efficiency in physical activity serves as an energy-sparing mechanism in lactation. We used a longitudinal design with a control group. Participants were 33 well-nourished, exclusively breastfeeding women and 29 non-pregnant, non-lactating (NPNL) controls aged 32 ± 4 years. Lactating women were measured at peak- and post-lactation. NPNL controls completed a baseline measurement and a follow-up visit. Energy efficiency in physical activity was assessed using a graded submaximal exercise test and calculated as delta efficiency (change in work accomplished over change in energy expended) and gross efficiency (work accomplished over energy expended). There was no significant change in either delta efficiency or gross efficiency from peak to post lactation in lactating women, and no significant difference in delta efficiency between lactating women and NPNL controls at any time period. However, lactating women showed greater between-visit variation in delta efficiency than the NPNL controls. Additionally, 79% of lactating participants lost weight between visits (mean weight loss -3.6 ± 2.3kg), consistent with a mobilization of body tissues to support lactation. We found no support for the idea that lactating women undergo an increase in energy efficiency to support the energy costs of lactation. © 2017 Wiley Periodicals, Inc.

Effects of various forms of calcium on body weight and bone turnover markers in women participating in a weight loss program.

PubMed

Wagner, Ginger; Kindrick, Shirley; Hertzler, Steven; DiSilvestro, Robert A

2007-10-01

This study examined the effects of calcium intake on body weight, body fat, and markers of bone turnover in pre-menopausal adult women undergoing a 12 week weight loss program of diet and exercise. Subjects were prescribed a 12 week diet with a 500 Kcal restriction containing about 750 mg calcium/day, exercised 3 times/week, and were given either placebo capsules, capsules of calcium lactate or calcium phosphate (daily dose about 800 mg calcium), or low fat milk (daily dose about 800 mg calcium). Subjects completed and returned daily diet diaries weekly. Daily calcium intake in mg from diet records + supplement assignment was: 788 +/- 175 (placebo), 1698 +/- 210 (Ca lactate), 1566 +/- 250 (Ca phosphate), 1514 +/- 225 (milk)(no significant differences among the calcium and milk groups). Each group had statistically significant changes in body weight (p < 0.01), but there were no significant differences among groups for the weight loss: 5.8 +/- 0.8 kg (placebo), 4.1 +/- 0.7 kg (Ca lactate), 5.4 +/- 1.3 kg (Ca phosphate), 4.2 +/- 0.8 kg (milk). Body fat was changed significantly in each group (p < 0.01), with milk group showing a little less change than the other groups. Serum bone specific alkaline phophatase activity, a bone synthesis marker, increased similarly in all groups (p < 0.001 within groups, no significance for changes among groups). In contrast, the Ca lactate group, but not other groups, had a drop in urine values for alpha helical peptide, a bone resorption marker (p < 0.05). For the conditions of this study, increased calcium intake, by supplement or milk, did not enhance loss of body weight or fat, though calcium lactate supplementation lowered values for a marker of bone degradation.

Use of Videoconferencing for Lactation Consultation: An Online Cross-Sectional Survey of Mothers' Acceptance in the United States.

PubMed

Habibi, Mona F; Springer, Cary M; Spence, Marsha L; Hansen-Petrik, Melissa B; Kavanagh, Katherine F

2018-05-01

Suboptimal breastfeeding duration and exclusivity rates are a public health concern. Therefore, there is a need for identifying effective tools for use in interventions targeting specific barriers to optimal breastfeeding outcomes. Research aim: This study aimed to assess the relationship between acceptance of remote lactation consultation using videoconferencing and (a) maternal demographic factors, (b) technology acceptance subscales, (c) maternal learning style preferences, and (d) other potentially explanatory maternal factors. This was a cross-sectional, online study. English-speaking mothers of at least 18 years of age, with an infant age 4 months or younger, and who reported initiating breastfeeding were eligible to participate. Mothers were recruited from 27 randomly selected states. One hundred one mothers completed the survey, resulting in a response rate of 71%. The main outcome was acceptance of videoconferencing use for lactation consultation. No significant differences were found in acceptance by maternal demographic factors or learning style preferences. Acceptance was significantly related to perceived ease of use ( r = .680, p < .001), perceived usefulness/extrinsic motivation ( r = .774, p < .001), intrinsic motivation ( r = .689, p < .001), desire for control of privacy ( r = -.293, p < .01), and mother's perception of the infant father's/maternal partner's acceptance of videoconferencing for lactation consultation ( r = .432, p < .001). Only perceived usefulness/extrinsic motivation and maternal age remained in the final regression model ( R 2 = .616, p < .001). Although perceived usefulness/extrinsic motivation was positively associated with acceptance, maternal age was inversely related. This sample of mothers indicated general acceptance of videoconferencing for lactation consultation, with younger mothers and those perceiving it to be more useful demonstrating greater acceptance.

Assessing the information in the Summaries of Product Characteristics for the use of medicines in pregnancy and lactation

PubMed Central

Arguello, Blanca; Salgado, Teresa M; Fernandez-Llimos, Fernando

2015-01-01

Aims To assess the completeness and applicability of information for the use of medicines in pregnancy and lactation contained in European Summaries of Product Characteristics (SmPCs). Methods SmPCs available on the EMA website in April 2011 were retrieved, and information on the use of medicines during pregnancy and lactation was analyzed. A form was designed to extract information regarding drug concentrations crossing the placenta, excretion of the drug in milk, the existence of pre-clinical and clinical studies and clinical experience describing the use of the medicine in pregnancy and lactation, medicine effects on human fertility, medicines use in women of child-bearing potential and specific recommendations for use during pregnancy and breastfeeding. SmPCs were classified as containing ‘conclusive’ or ‘ambiguous’ information depending on whether (or not) they provided clear instructions regarding medicine use in pregnancy and lactation. Results Of the 534 SmPCs, 89.3% did not mention whether the drug crossed the placenta, 67.6% indicated that there was no clinical experience during pregnancy and in 61.4% it was unknown whether the medicine was excreted in human milk. Recommendations for medicine use during pregnancy and breastfeeding were ambiguous in 57.0% and 16.5% of the SmPCs, respectively, and medicine use was restricted in over 90% SmPCs for both pregnancy and breastfeeding, despite no information supporting these restrictions being reported. The time elapsed since a SmPCs first approval was not associated with an increase in information quality. Conclusions Important information deficits on the use of medicines during pregnancy and breastfeeding were found in European SmPCs. PMID:25224071

Assessing the information in the Summaries of Product Characteristics for the use of medicines in pregnancy and lactation.

PubMed

Arguello, Blanca; Salgado, Teresa M; Fernandez-Llimos, Fernando

2015-03-01

To assess the completeness and applicability of information for the use of medicines in pregnancy and lactation contained in European Summaries of Product Characteristics (SmPCs). SmPCs available on the EMA website in April 2011 were retrieved, and information on the use of medicines during pregnancy and lactation was analyzed. A form was designed to extract information regarding drug concentrations crossing the placenta, excretion of the drug in milk, the existence of pre-clinical and clinical studies and clinical experience describing the use of the medicine in pregnancy and lactation, medicine effects on human fertility, medicines use in women of child-bearing potential and specific recommendations for use during pregnancy and breastfeeding. SmPCs were classified as containing 'conclusive' or 'ambiguous' information depending on whether (or not) they provided clear instructions regarding medicine use in pregnancy and lactation. Of the 534 SmPCs, 89.3% did not mention whether the drug crossed the placenta, 67.6% indicated that there was no clinical experience during pregnancy and in 61.4% it was unknown whether the medicine was excreted in human milk. Recommendations for medicine use during pregnancy and breastfeeding were ambiguous in 57.0% and 16.5% of the SmPCs, respectively, and medicine use was restricted in over 90% SmPCs for both pregnancy and breastfeeding, despite no information supporting these restrictions being reported. The time elapsed since a SmPCs first approval was not associated with an increase in information quality. Important information deficits on the use of medicines during pregnancy and breastfeeding were found in European SmPCs. © 2014 The British Pharmacological Society.

Exposure of Lactating Dairy Cows to Acute Pre-Ovulatory Heat Stress Affects Granulosa Cell-Specific Gene Expression Profiles in Dominant Follicles

PubMed Central

Vanselow, Jens; Vernunft, Andreas; Koczan, Dirk; Spitschak, Marion; Kuhla, Björn

2016-01-01

High environmental temperatures induce detrimental effects on various reproductive processes in cattle. According to the predicted global warming the number of days with unfavorable ambient temperatures will further increase. The objective of this study was to investigate effects of acute heat stress during the late pre-ovulatory phase on morphological, physiological and molecular parameters of dominant follicles in cycling cows during lactation. Eight German Holstein cows in established lactation were exposed to heat stress (28°C) or thermoneutral conditions (15°C) with pair-feeding for four days. After hormonal heat induction growth of the respective dominant follicles was monitored by ultrasonography for two days, then an ovulatory GnRH dose was given and follicular steroid hormones and granulosa cell-specific gene expression profiles were determined 23 hrs thereafter. The data showed that the pre-ovulatory growth of dominant follicles and the estradiol, but not the progesterone concentrations tended to be slightly affected. mRNA microarray and hierarchical cluster analysis revealed distinct expression profiles in granulosa cells derived from heat stressed compared to pair-fed animals. Among the 255 affected genes heatstress-, stress- or apoptosis associated genes were not present. But instead, we found up-regulation of genes essentially involved in G-protein coupled signaling pathways, extracellular matrix composition, and several members of the solute carrier family as well as up-regulation of FST encoding follistatin. In summary, the data of the present study show that acute pre-ovulatory heat stress can specifically alter gene expression profiles in granulosa cells, however without inducing stress related genes and pathways and suggestively can impair follicular growth due to affecting the activin-inhibin-follistatin system. PMID:27532452

Exposure of Lactating Dairy Cows to Acute Pre-Ovulatory Heat Stress Affects Granulosa Cell-Specific Gene Expression Profiles in Dominant Follicles.

PubMed

Vanselow, Jens; Vernunft, Andreas; Koczan, Dirk; Spitschak, Marion; Kuhla, Björn

2016-01-01

High environmental temperatures induce detrimental effects on various reproductive processes in cattle. According to the predicted global warming the number of days with unfavorable ambient temperatures will further increase. The objective of this study was to investigate effects of acute heat stress during the late pre-ovulatory phase on morphological, physiological and molecular parameters of dominant follicles in cycling cows during lactation. Eight German Holstein cows in established lactation were exposed to heat stress (28°C) or thermoneutral conditions (15°C) with pair-feeding for four days. After hormonal heat induction growth of the respective dominant follicles was monitored by ultrasonography for two days, then an ovulatory GnRH dose was given and follicular steroid hormones and granulosa cell-specific gene expression profiles were determined 23 hrs thereafter. The data showed that the pre-ovulatory growth of dominant follicles and the estradiol, but not the progesterone concentrations tended to be slightly affected. mRNA microarray and hierarchical cluster analysis revealed distinct expression profiles in granulosa cells derived from heat stressed compared to pair-fed animals. Among the 255 affected genes heatstress-, stress- or apoptosis associated genes were not present. But instead, we found up-regulation of genes essentially involved in G-protein coupled signaling pathways, extracellular matrix composition, and several members of the solute carrier family as well as up-regulation of FST encoding follistatin. In summary, the data of the present study show that acute pre-ovulatory heat stress can specifically alter gene expression profiles in granulosa cells, however without inducing stress related genes and pathways and suggestively can impair follicular growth due to affecting the activin-inhibin-follistatin system.

Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice.

PubMed

Petit, Jean-Marie; Gyger, Joël; Burlet-Godinot, Sophie; Fiumelli, Hubert; Martin, Jean-Luc; Magistretti, Pierre J

2013-10-01

There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. 6-hour instrumental sleep deprivation (TSD). Animal sleep research laboratory. Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Basal sleep recordings and sleep deprivation achieved using a modified cage where animals were gently forced to move. Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, α-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. This study shows that TSD induces the expression of genes associated with ANLS specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

Lactate is oxidized outside of the mitochondrial matrix in rodent brain.

PubMed

Herbst, Eric A F; George, Mitchell A J; Brebner, Karen; Holloway, Graham P; Kane, Daniel A

2018-05-01

The nature and existence of mitochondrial lactate oxidation is debated in the literature. Obscuring the issue are disparate findings in isolated mitochondria, as well as relatively low rates of lactate oxidation observed in permeabilized muscle fibres. However, respiration with lactate has yet to be directly assessed in brain tissue with the mitochondrial reticulum intact. To determine if lactate is oxidized in the matrix of brain mitochondria, oxygen consumption was measured in saponin-permeabilized mouse brain cortex samples, and rat prefrontal cortex and hippocampus (dorsal) subregions. While respiration in the presence of ADP and malate increased with the addition of lactate, respiration was maximized following the addition of exogenous NAD + , suggesting maximal lactate metabolism involves extra-matrix lactate dehydrogenase. This was further supported when NAD + -dependent lactate oxidation was significantly decreased with the addition of either low-concentration α-cyano-4-hydroxycinnamate or UK-5099, inhibitors of mitochondrial pyruvate transport. Mitochondrial respiration was comparable between glutamate, pyruvate, and NAD + -dependent lactate oxidation. Results from the current study demonstrate that permeabilized brain is a feasible model for assessing lactate oxidation, and support the interpretation that lactate oxidation occurs outside the mitochondrial matrix in rodent brain.

General Requirement for Harvesting Antennae at Ca2+ and H+ Channels and Transporters

PubMed Central

Martínez, Cristián; Kalise, Dante; Barros, L. Felipe

2010-01-01

The production and dissipation of energy in cells is intimately linked to the movement of small molecules in and out of enzymes, channels, and transporters. An analytical model of diffusion was described previously, which was used to estimate local effects of these proteins acting as molecular sources. The present article describes a simple but more general model, which can be used to estimate the local impact of proteins acting as molecular sinks. The results show that the enzymes, transporters, and channels, whose substrates are present at relatively high concentrations like ATP, Na+, glucose, lactate, and pyruvate, do not operate fast enough to deplete their vicinity to a meaningful extent, supporting the notion that for these molecules the cytosol is a well-mixed compartment. One specific consequence of this analysis is that the well-documented cross-talk existing between the Na+/K+ ATPase and the glycolytic machinery should not be explained by putative changes in local ATP concentration. In contrast, Ca2+ and H+ transporters like the Na+/Ca2+ exchanger NCX and the Na+/H+ exchanger NHE, show experimental rates of transport that are two to three orders of magnitude faster than the rates at which the aqueous phase may possibly feed their binding sites. This paradoxical result implies that Ca2+ and H+ transporters do not extract their substrates directly from the bulk cytosol, but from an intermediate “harvesting” compartment located between the aqueous phase and the transport site. PMID:20877432

In VivoLactate Editing with Simultaneous Detection of Choline, Creatine, NAA, and Lipid Singlets at 1.5 T Using PRESS Excitation with Applications to the Study of Brain and Head and Neck Tumors

NASA Astrophysics Data System (ADS)

Star-Lack, Josh; Spielman, Daniel; Adalsteinsson, Elfar; Kurhanewicz, John; Terris, David J.; Vigneron, Daniel B.

1998-08-01

Two T2-independentJ-difference lactate editing schemes for the PRESS magnetic resonance spectroscopy localization sequence are introduced. The techniques, which allow for simultaneous acquisition of the lactate doublet (1.3 ppm) and edited singlets upfield of and including choline (3.2 ppm), exploit the dependence of the in-phase intensity of the methyl doublet upon the time interval separating two inversion (BASING) pulses applied to its coupling partner after initial excitation. Editing method 1, which allows for echo times TE =n/J(n= 1, 2, 3, …), alters the BASING carrier frequency for each of two cycles so that, for one cycle, the quartet is inverted, whereas, for the other cycle, the quartet is unaffected. Method 2, which also provides water suppression, allows for editing for TE > 1/Jby alternating, between cycles, the time interval separating the inversion pulses. Experimental results were obtained at 1.5 T using a Shinnar Le-Roux-designed maximum phase inversion pulse with a filter transition bandwidth of 55 Hz. Spectra were acquired from phantoms andin vivofrom the human brain and neck. In a neck muscle study, the lipid suppression factor, achieved partly through the use of a novel phase regularization algorithm, was measured to be over 103. Spectra acquired from a primary brain and a metastatic neck tumor demonstrated the presence of lactate and choline signals consistent with abnormal spectral patterns. The advantages and limitations of the methods are analyzed theoretically and experimentally, and significance of the results is discussed.

Has the mammary gland a protective mechanism against overexposure to triiodothyronine during the peripartum period? The prolactin pulse down-regulates mammary type I deiodinase responsiveness to norepinephrine.

PubMed

Anguiano, B; Rojas-Huidobro, R; Delgado, G; Aceves, C

2004-11-01

Peripartum is a crucial period for mammary gland final differentiation and the onset of lactation. Although the 'trigger' for lactogenesis depends on several hormones, a key factor is the peripartum prolactin (PRL) pulse whose deletion results in a failure to initiate milk production. Other hormones having a critical role during this period but exerting a contrary effect are the thyronines. A transitory hypothyroidism occurs at peripartum in serum and several other extrathyroidal tissues, whereas the induction of hyperthyroidism during late pregnancy is associated with the absence of lactation after delivery. We analyzed the mammary gland during pregnancy and lactation for: (a) the type and amount of thyroid receptors (TRs), (b) the local triiodothyronine (T3) generation catalyzed by type I deiodinase (Dio1), (c) the Dio1 response to norepinephrine (NE) and (d) the effect on Dio1 and TRs of blocking the PRL pulse at peripartum. Our data showed that during pregnancy the mammary gland contains Dio1 in low amounts associated with the highest expression of TRalpha1; whereas during lactation the gland shows high levels of both Dio1 and TRalpha1. However, at peripartum, both TRs and Dio1 decrease, and Dio1 becomes refractory to NE. This refractoriness disappears when the PRL pulse is blocked by the dopamine agonist bromocriptine. This blockade is also accompanied by a significant decrease in cyclin D1 expression. Our data suggested that the peripartum PRL pulse is part of a protective mechanism against precocious differentiation and/or premature involution of the alveolar epithelium due to T3 overexposure.

Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives.

PubMed

Westhoff, T H; Franke, N; Schmidt, S; Vallbracht-Israng, K; Zidek, W; Dimeo, F; van der Giet, M

2007-06-01

Aerobic physical exercise is broadly recommended as a helpful adjunct to obtain blood pressure control in hypertension. Beta-blockade interacts with heart rate, sympathetic tone, maximal workload and local lactate production. In the present randomized-controlled study, we compared the cardiovascular effects of an endurance training programme in elderly hypertensives with or without beta-blockers and developed a first approach to determine a lactate-based training heart rate in presence of beta-blockade. Fifty-two patients (23 with beta-blocker, 29 without beta-blocker) > or =60 years with systolic 24-h ambulatory blood pressure (ABP) > or =140 mm Hg and/or antihypertensive treatment were randomly assigned to sedentary activity or a heart-rate controlled 12-week treadmill exercise programme (lactate 2.0 mmol/l). In the exercise group, the training significantly decreased systolic and diastolic 24-h ABP, blood pressure on exertion (100 W) and increased endothelium-dependent vasodilation (flow-mediated vasodilation, FMD) and physical performance both in the presence and absence of beta-blockade (P<0.05 each). The extent of ABP reduction did not significantly differ in the presence or absence of beta-blockade (Delta systolic ABP 10.6+/-10.5 vs 10.6+/-8.8 mm Hg, Delta diastolic ABP 5.7+/-8.6 vs 5.8+/-4.0 mm Hg). Mean training heart rate was significantly lower in the patients on beta-blockers (97.2+/-7.7 vs 118.3+/-7.5/min, P<0.001). Lactate-based aerobic endurance training evokes comparable cardiovascular benefits in the presence and absence of beta-blockade including a marked improvement of endothelial function. In the present study, target training heart rate with beta-blockers is about 18% lower than without.

Resting blood lactate in individuals with sickle cell disease

PubMed Central

Petto, Jefferson; de Jesus, Jaqueline Brito; Vasques, Leila Monique Reis; Pinheiro, Renata Leão Silva; Oliveira, Aila Mascarenhas; Spinola, Kelly Aparecida Borges; Silva, Wellington dos Santos

2011-01-01

Background The most common hereditary hemoglobin disorder, affecting 20 million individuals worldwide, is sickle cell disease. The vascular obstruction resulting from the sickling of cells in this disease can produce local hypoxemia, pain crises and infarction in several tissues, including the bones, spleen, kidneys and lungs. Objective To determine red blood group genes in a Brazilian populations. Methods The present study is characterized as a case control study, with the aim of identifying the baseline blood lactate concentration in individuals with hemoglobin SS and SC diseases. One-way ANOVA with the Tukey post-test was used to analyze the results and a p-value < 0.05 was considered significant. Calculations were made using the INSTAT statistical program. The graphs were generated using the ORING program. The study sample was composed of 31 men and women residing in the city of Santo Antônio de Jesus, Bahia, Brazil. The individuals were divided into two groups: Group GC of 16 subjects who did not present with any type of structural hemoglobinopathy; and Group GE composed of 15 individuals with ages between 2 and 35 years old, who had the SS and SC genotypes. Sample analyses were performed with 3 mL of blood during fasting. Results The baseline blood lactate concentration of the SS and SC individuals was higher than that of the control group (p<0.001) with means of 4.86 ± 0.95; 3.30 ± 0.33; 1.31 ± 0.08 IU/L for SS, SC and controls, respectively. This corroborates the initial research hypothesis. Conclusion The baseline blood lactate of SS and SC individuals is 3 to 4 times higher than that of healthy subjects, probably due to the fact that these patients have a metabolic deviation to the anaerobic pathway. PMID:23284239

Lactation and changes in maternal metabolic risk factors.

PubMed

Gunderson, Erica P; Lewis, Cora E; Wei, Gina S; Whitmer, Rachel A; Quesenberry, Charles P; Sidney, Steve

2007-03-01

To examine the relationship between duration of lactation and changes in maternal metabolic risk factors. This 3-year prospective study examined changes in metabolic risk factors among lactating women from preconception to postweaning and among nonlactating women from preconception to postdelivery, in comparison with nongravid women. Of 1,051 (490 black, 561 white) women who attended two consecutive study visits in years 7 (1992-1993) and 10 (1995-1996), 942 were nongravid and 109 had one interim birth. Of parous women, 48 (45%) did not lactate, and 61 (55%) lactated and weaned before year 10. The lactated and weaned women were subdivided by duration of lactation into less than 3 months and 3 months or more. Multiple linear regression models estimated mean 3-year changes in metabolic risk factors adjusted for age, race, parity, education, and behavioral covariates. Both parous women who did not lactate and parous women who lactated and weaned gained more weight (+5.6, +4.4 kg) and waist girth (+5.3, +4.9 cm) than nongravid women over the 3-year interval; P<.001. Low-density lipoprotein cholesterol (+6.7 mg/dL, P<.05) and fasting insulin (+2.6 microunits, P=.06) increased more for parous women who did not lactate than for nongravid and parous women who lactated and weaned. High-density lipoprotein cholesterol decrements for both parous women who did not lactate and parous women who lactated and weaned were 4.0 mg/dL greater than for nongravid women (P<.001). Among parous, lactated and weaned women, lactation for 3 months or longer was associated with a smaller decrement in high-density lipoprotein cholesterol (-1.3 mg/dL versus -7.3 mg/dL for less than 3 months; P<.01). Lactation may attenuate unfavorable metabolic risk factor changes that occur with pregnancy, with effects apparent after weaning. As a modifiable behavior, lactation may affect women's future risk of cardiovascular and metabolic diseases. II.

Adipose tissue remodeling in late-lactation dairy cows during feed-restriction-induced negative energy balance.

PubMed

Contreras, G Andres; Thelen, Kyan; Schmidt, Sarah E; Strieder-Barboza, Clarissa; Preseault, Courtney L; Raphael, William; Kiupel, Matti; Caron, John; Lock, Adam L

2016-12-01

Excessive rates of demand lipolysis in the adipose tissue (AT) during periods of negative energy balance (NEB) are associated with increased susceptibility to disease and limited lactation performance. Lipolysis induces a remodeling process within AT that is characterized by an inflammatory response, cellular proliferation, and changes in the extracellular matrix (ECMT). The adipose tissue macrophage (ATM) is a key component of the inflammatory response. Infiltration of ATM-forming cellular aggregates was demonstrated in transition cows, suggesting that ATM trafficking and phenotype changes may be associated with disease. However, it is currently unknown if ATM infiltration occurs in dairy cows only during NEB states related to the transition period or also during NEB-induced lipolysis at other stages of lactation. The objective of this study was to evaluate changes in ATM trafficking and inflammatory phenotypes, and the expression of genetic markers of AT remodeling in healthy late-lactation cows during feed restriction-induced NEB. After a 14-d (d -14 to d -1) preliminary period, Holstein cows were randomly assigned to 1 of 2 feeding protocols, ad libitum (AL) or feed restriction (FR), for 4 d (d 1-4). Caloric intake was reduced in FR to achieve a targeted energy balance of -15 Mcal/d of net energy for lactation. Omental and subcutaneous AT samples were collected laparoscopically to harvest stromal vascular fraction (SVF) cells on d -3 and 4. The FR induced a NEB of -14.1±0.62 Mcal/d of net energy for lactation, whereas AL cows remained in positive energy balance (3.2±0.66 Mcal/d of NE L ). The FR triggered a lipolytic response reflected in increased plasma nonesterified fatty acids (0.65±0.05 mEq/L on d 4), enhanced phosphorylation of hormone sensitive lipase, and reduced adipocyte diameter. Flow cytometry and immunohistochemistry analysis revealed that on d 4, FR cows had increased numbers of CD172a + , an ATM (M1 and M2) surface marker, cells in SVF that were localized in aggregates. However, FR did not alter the number of SVF cells expressing M1 markers (CD14 and CD11c) or M2 markers (CD11b and CD163). This finding contrasts with the predominately M1 phenotype observed previously in ATM from clinically diseased cows. No changes were observed in the expression of ECMT-related or cell proliferation markers. In summary, an acute 4-d lipolytic stimulus in late-lactation dairy cows led to ATM infiltration with minimal changes in inflammatory phenotype and no changes in ECMT. These results underscore that physiological changes related to parturition, the onset of lactation, extended periods of lipolysis, or a combination of these can induce intense AT remodeling with enhanced ATM inflammatory phenotype expression that may impair the metabolic function of AT in transition dairy cattle. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Lactation and reproduction*

PubMed Central

Thomson, A. M.; Hytten, F. E.; Black, A. E.

1975-01-01

The authors review the literature on the effect of lactation on fertility in the absence of contraception and on the effects of contraceptive measures on lactation. They examine data from several countries on the intervals between births and on the return of menstruation and ovulation after childbirth, comparing lactating with nonlactating women. They conclude that lactation is an inefficient contraceptive for the individual, but that in populations sustained lactation is associated with reduced fertility. Possible physiological mechanisms causing lactation amenorrhoea are discussed. Though much of the literature on the effect of contraceptives on lactation is inadequate, there is general agreement that the estrogen component of hormonal preparations has an adverse effect on lactation, but that progestins alone do not. Many questions remain. Is this effect seen in established lactation, or only in the puerperal period? Is it a direct pharmacological effect, or are pill-users the mothers least motivated to maintain breast-feeding? Does a close relationship exist between hormones given and lactation performance? The authors comment on some of the technical deficiencies of previous studies in this field and discuss practical possibilities of, and limitations to, obtaining adequate scientific information in the future. PMID:1084804

Alcohol consumption decreases lactate clearance in acutely injured patients☆

PubMed Central

Dezman, Zachary D.W.; Comer, Angela C.; Narayan, Mayur; Scalea, Thomas M.; Hirshon, Jon Mark; Smith, Gordon S.

2017-01-01

Introduction Alcohol, a common risk factor for injury, has direct toxic effects on the liver. The use of lactate clearance has been well described as an indicator of the adequacy of resuscitation in injured patients. We investigated whether acutely injured patients with positive blood alcohol content (+BAC) had less lactate clearance than sober patients. Methods We conducted a retrospective cohort study of acutely injured patients treated at an urban Level 1 trauma centre between January 2010 and December 2012. Blood alcohol and venous lactate levels were measured on all patients at the time of arrival. Study subjects were patients transported directly from the scene of injury, who had an elevated lactate concentration on arrival (≥3.0 mmol/L) and at least one subsequent lactate measurement within 24 h after admission. Lactate clearance ([Lactate1 − Lactate2]/Lactate1) was calculated for all patients. Chi-squared tests were used to compare values from sober and intoxicated subjects. Lactate clearance was plotted against alcohol levels and stratified by age and Injury Severity Score (ISS). Results Serial lactate concentration measurements were obtained in 3910 patients; 1674 of them had +BAC. Patients with +BAC were younger (mean age: 36.6 [SD 14.7] vs 41.0 [SD 19.9] years [p = 0.0001]), were more often male (83.4% vs 75.9% [p = 0.0001]), had more minor injuries (ISS < 9) (33.8% vs 27.1% [p = 0.0001]), had a lower in-hospital mortality rate (1.4% vs 3.9% [p = 0.0001]), but also had lower average lactate clearance (37.8% vs 47.6% [p = 0.0001]). The lactate clearance of the sober patients (47.6 [SD 33.5]) was twice that of those with +BAC >400 (23.5 [SD 6.5]). Lactate clearance decreased with increasing BAC irrespective of age and ISS. Conclusions In a large group of acutely injured patients, a dose-dependent decrease in lactate clearance was seen in those with elevated BAC. This relationship will cause a falsely elevated lactate reading or prolong lactate clearance and should be taken into account when evaluating patients with +BAC. PMID:27025567

Lactation persistency as a component trait of the selection index and increase in reliability by using single nucleotide polymorphism in net merit defined as the first five lactation milk yields and herd life.

PubMed

Togashi, K; Hagiya, K; Osawa, T; Nakanishi, T; Yamazaki, T; Nagamine, Y; Lin, C Y; Matsumoto, S; Aihara, M; Hayasaka, K

2012-08-01

We first sought to clarify the effects of discounted rate, survival rate, and lactation persistency as a component trait of the selection index on net merit, defined as the first five lactation milks and herd life (HL) weighted by 1 and 0.389 (currently used in Japan), respectively, in units of genetic standard deviation. Survival rate increased the relative economic importance of later lactation traits and the first five lactation milk yields during the first 120 months from the start of the breeding scheme. In contrast, reliabilities of the estimated breeding value (EBV) in later lactation traits are lower than those of earlier lactation traits. We then sought to clarify the effects of applying single nucleotide polymorphism (SNP) on net merit to improve the reliability of EBV of later lactation traits to maximize their increased economic importance due to increase in survival rate. Net merit, selection accuracy, and HL increased by adding lactation persistency to the selection index whose component traits were only milk yields. Lactation persistency of the second and (especially) third parities contributed to increasing HL while maintaining the first five lactation milk yields compared with the selection index whose only component traits were milk yields. A selection index comprising the first three lactation milk yields and persistency accounted for 99.4% of net merit derived from a selection index whose components were identical to those for net merit. We consider that the selection index comprising the first three lactation milk yields and persistency is a practical method for increasing lifetime milk yield in the absence of data regarding HL. Applying SNP to the second- and third-lactation traits and HL increased net merit and HL by maximizing the increased economic importance of later lactation traits, reducing the effect of first-lactation milk yield on HL (genetic correlation (rG) = -0.006), and by augmenting the effects of the second- and third-lactation milk yields on HL (rG = 0.118 and 0.257, respectively).

Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation.

PubMed

Aubert, Agnès; Costalat, Robert; Magistretti, Pierre J; Pellerin, Luc

2005-11-08

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans.

Functional interaction between bicarbonate transporters and carbonic anhydrase modulates lactate uptake into mouse cardiomyocytes.

PubMed

Peetz, Jan; Barros, L Felipe; San Martín, Alejandro; Becker, Holger M

2015-07-01

Blood-derived lactate is a precious energy substrate for the heart muscle. Lactate is transported into cardiomyocytes via monocarboxylate transporters (MCTs) together with H(+), which couples lactate uptake to cellular pH regulation. In this study, we have investigated how the interplay between different acid/base transporters and carbonic anhydrases (CA), which catalyze the reversible hydration of CO2, modulates the uptake of lactate into isolated mouse cardiomyocytes. Lactate transport was estimated both as lactate-induced acidification and as changes in intracellular lactate levels measured with a newly developed Förster resonance energy transfer (FRET) nanosensor. Recordings of intracellular pH showed an increase in the rate of lactate-induced acidification when CA was inhibited by 6-ethoxy-2-benzothiazolesulfonamide (EZA), while direct measurements of lactate flux demonstrated a decrease in MCT transport activity, when CA was inhibited. The data indicate that catalytic activity of extracellular CA increases lactate uptake and counteracts intracellular lactate-induced acidification. We propose a hypothetical model, in which HCO3 (-), formed from cell-derived CO2 at the outer surface of the cardiomyocyte plasma membrane by membrane-anchored, extracellular CA, is transported into the cell via Na(+)/HCO3 (-) cotransport to counteract intracellular acidification, while the remaining H(+) stabilizes extracellular pH at the surface of the plasma membrane during MCT activity to enhance lactate influx into cardiomyocytes.

Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation

PubMed Central

Aubert, Agnès; Costalat, Robert; Magistretti, Pierre J.; Pellerin, Luc

2005-01-01

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans. PMID:16260743

Longitudinal Profiling of the Tissue-Specific Expression of Genes Related with Insulin Sensitivity in Dairy Cows during Lactation Focusing on Different Fat Depots

PubMed Central

Saremi, Behnam; Winand, Sarah; Friedrichs, Paula; Kinoshita, Asako; Rehage, Jürgen; Dänicke, Sven; Häussler, Susanne; Breves, Gerhard; Mielenz, Manfred; Sauerwein, Helga

2014-01-01

In dairy cows the milk associated energy output in early lactation exceeds the input via voluntary feed intake. To spare glucose for mammary lactose synthesis, peripheral insulin sensitivity (IS) is reduced and fat mobilization is stimulated. For these processes a link between IS and the endocrine functions of adipose tissue (AT) is likely; we thus aimed to characterise the mRNA expression from bovine AT derived proteins and receptors that are related to IS according to the literature in metabolically active tissues plus systemic IS throughout lactation. Conjugated linoleic acids (CLA) reduce milk fat thus decreasing the milk drain of energy and potentially dampening lipolysis, but may also affect IS. Subcutaneous (s.c.) AT and liver from pluriparous cows receiving either control fat or CLA supplement (100 g/day from 1 to 182 days in milk each) were biopsied covering week −3 to 36 relative to parturition. In an additional trial with primiparous cows treated analogously and slaughtered on days in milk 1, 42 or 105, samples from liver, udder, skeletal muscle and 3 visceral and 3 s.c. AT were obtained and assayed for mRNA abundance of adiponectin, its receptors, leptin, leptin receptor, PPARγ, PPARγ2, IL-6, and TNF-α. In pluriparous animals, the mRNA abundance of most of the target genes decreased after parturition in s.c. AT but increased in liver. In primiparous cows, AT depot specific differences were mostly related to retroperitoneal AT; adiponectin receptor 1 and TNF-α were affected predominantly. CLA effects in primiparous cows were largely limited to decreased PPARγ2 mRNA abundance in udder tissue. In pluriparous cows, insulin secretion was increased by CLA resulting in decreased systemic IS but without consistent changes in tissue target mRNA abundance. The temporal gene expression profiles from the adipokines and related receptors support their coactive function in adapting to the needs of lactation. PMID:24465964

Evaluation of different models to segregate Pelibuey and Katahdin ewes into resistant or susceptible to gastrointestinal nematodes.

PubMed

Palomo-Couoh, Jovanny Gaspar; Aguilar-Caballero, Armando Jacinto; Torres-Acosta, Juan Felipe de Jesús; Magaña-Monforte, Juan Gabriel

2016-12-01

This study evaluated four models based on the number of eggs per gram of faeces (EPG) to segregate Pelibuey or Katahdin ewes during the lactation period into resistant or susceptible to gastrointestinal nematodes (GIN) in tropical Mexico. Nine hundred and thirty EPG counts of Pelibuey ewes and 710 of Katahdin ewes were obtained during 10 weeks of lactation. Ewes were segregated into resistant, intermediate and susceptible, using their individual EPG every week. Then, data of every ewe was used to provide a reference classification, which included all the EPG values of each animal. Then, four models were evaluated against such reference. Model 1 was based on the 10-week mean EPG count ± 2 SE. Models 2, 3 and 4 were based on the mean EPG count of 10, 5 and 2 weeks of lactation. The cutoff points for the segregation of ewe in those three models were the quartiles ≤Q1 (low elimination) and ≥Q3 (high elimination). In all the models evaluated, the ewes classified as resistant had lower EPG than intermediates and susceptible (P < 0.001) while ewes classified as susceptible had higher EPG than intermediate and resistant (P < 0.001). According to J Youden test, models presented concordance with the reference group (>70 %). Model 3 tended to show higher sensitivity and specificity with the reference data, but no difference was found with other models. The present study showed that the phenotypic marker EPG might serve to identify and segregate populations of adult ewes during the lactation period. All models used served to segregate Pelibuey and Katahdin ewes into resistant, intermediate and susceptible. The model 3 (mean of 5 weeks) could be used because it required less sampling effort without losing sensitivity or specificity in the segregation of animals. However, model 2 (mean of 2 weeks) was less labour-intensive.

Associative patterns among anaerobic fungi, methanogenic archaea, and bacterial communities in response to changes in diet and age in the rumen of dairy cows.

PubMed

Kumar, Sanjay; Indugu, Nagaraju; Vecchiarelli, Bonnie; Pitta, Dipti W

2015-01-01

The rumen microbiome represents a complex microbial genetic web where bacteria, anaerobic rumen fungi (ARF), protozoa and archaea work in harmony contributing to the health and productivity of ruminants. We hypothesized that the rumen microbiome shifts as the dairy cow advances in lactations and these microbial changes may contribute to differences in productivity between primiparous (first lactation) and multiparous (≥second lactation) cows. To this end, we investigated shifts in the ruminal ARF and methanogenic communities in both primiparous (n = 5) and multiparous (n = 5) cows as they transitioned from a high forage to a high grain diet upon initiation of lactation. A total of 20 rumen samples were extracted for genomic DNA, amplified using archaeal and fungal specific primers, sequenced on a 454 platform and analyzed using QIIME. Community comparisons (Bray-Curtis index) revealed the effect of diet (P < 0.01) on ARF composition, while archaeal communities differed between primiparous and multiparous cows (P < 0.05). Among ARF, several lineages were unclassified, however, phylum Neocallimastigomycota showed the presence of three known genera. Abundance of Cyllamyces and Caecomyces shifted with diet, whereas Orpinomyces was influenced by both diet and age. Methanobrevibacter constituted the most dominant archaeal genus across all samples. Co-occurrence analysis incorporating taxa from bacteria, ARF and archaea revealed syntrophic interactions both within and between microbial domains in response to change in diet as well as age of dairy cows. Notably, these interactions were numerous and complex in multiparous cows, supporting our hypothesis that the rumen microbiome also matures with age to sustain the growing metabolic needs of the host. This study provides a broader picture of the ARF and methanogenic populations in the rumen of dairy cows and their co-occurrence implicates specific relationships between different microbial domains in response to diet and age.

High-intensity exercise training induces morphological and biochemical changes in skeletal muscles.

PubMed

Toti, L; Bartalucci, A; Ferrucci, M; Fulceri, F; Lazzeri, G; Lenzi, P; Soldani, P; Gobbi, P; La Torre, A; Gesi, M

2013-12-01

IN THE PRESENT STUDY WE INVESTIGATED THE EFFECT OF TWO DIFFERENT EXERCISE PROTOCOLS ON FIBRE COMPOSITION AND METABOLISM OF TWO SPECIFIC MUSCLES OF MICE: the quadriceps and the gastrocnemius. Mice were run daily on a motorized treadmill, at a velocity corresponding to 60% or 90% of the maximal running velocity. Blood lactate and body weight were measured during exercise training. We found that at the end of training the body weight significantly increased in high-intensity exercise mice compared to the control group (P=0.0268), whereas it decreased in low-intensity exercise mice compared to controls (P=0.30). In contrast, the food intake was greater in both trained mice compared to controls (P < 0.0001 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively). These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls (P=0.03 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively); in particular, blood lactate levels after high-intensity exercise were significantly lower than those measured in low-intensity exercise mice (P=0.0044). Immunoblotting analysis demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial enzymes contained within gastrocnemius and quadriceps muscles. These changes were associated with an increase in the amount of slow fibres in both these muscles of high-intensity exercise mice, as revealed by the counts of slow fibres stained with specific antibodies (P < 0.0001 for the gastrocnemius; P=0.0002 for the quadriceps). Our results demonstrate that high-intensity exercise, in addition to metabolic changes consisting of a decrease in blood lactate and body weight, induces an increase in the mitochondrial enzymes and slow fibres in different skeletal muscles of mice, which indicates an exercise-induced increase in the aerobic metabolism.

Role of Monocarboxylate Transporters in Drug Delivery to the Brain

PubMed Central

Vijay, Nisha; Morris, Marilyn E.

2014-01-01

Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors. PMID:23789956

Lactate metabolism and its effects on glucose metabolism in an excised neural tissue.

PubMed

Larrabee, M G

1995-04-01

Chains of lumbar sympathetic ganglia, excised from 15-day-old chicken embryos, were incubated for 4 h at 36 degrees C in a bicarbonate-buffered physiological salt solution containing 5.5 mM glucose and equilibrated with 5% CO2-95% O2. [U-14C]Glucose and [U-14C]lactate were used as tracers to measure the products of glucose and lactate metabolism, respectively, including CO2, lactate, and constituents of the tissue. When 5 mM lactate was added to bathing solution containing 5.5 mM glucose, lactate carbon displaced 50-70% of the glucose carbon otherwise used for CO2 production and provided about three times as much carbon for CO2 as did glucose. The lactate addition increased the total carbon incorporated into CO2 and into constituents of the tissue above those observed with glucose alone and also increased the lactate released to the bathing solution from [U-14C]-glucose. The latter increase was evidently due to an interference with reuptake of the lactate released from the ganglion cells, not to an increase in the cellular release itself. When the volume of bathing solution was increased 10-fold relative to that of the tissue, the average output of CO2 from [U-14C]glucose during a 4-h incubation was decreased by 50% when 5 mM lactate was present but was not affected significantly in the absence of added lactate. It is concluded that the effect of changing volume in the presence of lactate was due to the effects of lactate on glucose metabolism described above and resulted from a lower average lactate concentration in the smaller volume than in the larger one, due to metabolic depletion of the added lactate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Systemic Metabolic Fuels on Glucose and Lactate Levels in the Brain Extracellular Compartment of the Mouse

PubMed Central

Béland-Millar, Alexandria; Larcher, Jeremy; Courtemanche, Justine; Yuan, Tina; Messier, Claude

2017-01-01

Classic neuroenergetic research has emphasized the role of glucose, its transport and its metabolism in sustaining normal neural function leading to the textbook statement that it is the necessary and sole metabolic fuel of the mammalian brain. New evidence, including the Astrocyte-to-Neuron Lactate Shuttle hypothesis, suggests that the brain can use other metabolic substrates. To further study that possibility, we examined the effect of intraperitoneally administered metabolic fuels (glucose, fructose, lactate, pyruvate, ß-hydroxybutyrate, and galactose), and insulin, on blood, and extracellular brain levels of glucose and lactate in the adult male CD1 mouse. Primary motor cortex extracellular levels of glucose and lactate were monitored in freely moving mice with the use of electrochemical electrodes. Blood concentration of these same metabolites were obtained by tail vein sampling and measured with glucose and lactate meters. Blood and extracellular fluctuations of glucose and lactate were monitored for a 2-h period. We found that the systemic injections of glucose, fructose, lactate, pyruvate, and ß-hydroxybutyrate increased blood lactate levels. Apart for a small transitory rise in brain extracellular lactate levels, the main effect of the systemic injection of glucose, fructose, lactate, pyruvate, and ß-hydroxybutyrate was an increase in brain extracellular glucose levels. Systemic galactose injections produced a small rise in blood glucose and lactate but almost no change in brain extracellular lactate and glucose. Systemic insulin injections led to a decrease in blood glucose and a small rise in blood lactate; however brain extracellular glucose and lactate monotonically decreased at the same rate. Our results support the concept that the brain is able to use alternative fuels and the current experiments suggest some of the mechanisms involved. PMID:28154523

"The way to break the taboo is to do the taboo thing" breastfeeding in public and citizen-activism in the UK.

PubMed

Boyer, Kate

2011-03-01

Like other forms of infant feeding, breastfeeding is a fundamental act of care. Yet despite being the recommended way of feeding babies, breastfeeding is not always easy to do. In addition to lack of support, bio-physical problems and the need to return to work; discomfort with breastfeeding in public is a factor shaping infant feeding choice (and the decision to stop breastfeeding specifically). With increased awareness of breast milk's health benefits in recent years, there has been a rise in efforts to make breastfeeding in public more commonplace and socially acceptable (including through lactation advocacy or "lactivism"). This paper considers breastfeeding in public and lactation advocacy in the UK through interviews with lactation activists, non-activist breastfeeding mothers, and participant-observation at two breastfeeding picnics held in 2009. Building on existing scholarship in Geography, I suggest that lactivism can be understood as an effort to expand the boundaries of where care-work is allowed to take place: thus constituting a form of "care-work activism". Copyright © 2010 Elsevier Ltd. All rights reserved.

Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells.

PubMed

Shishido, Yurina; Baba, Takashi; Sato, Tetsuya; Shima, Yuichi; Miyabayashi, Kanako; Inoue, Miki; Akiyama, Haruhiko; Kimura, Hiroshi; Kanai, Yoshiakira; Ishihara, Yasuhiro; Haraguchi, Shogo; Miyazaki, Akira; Rozman, Damjana; Yamazaki, Takeshi; Choi, Man-Ho; Ohkawa, Yasuyuki; Suyama, Mikita; Morohashi, Ken-Ichirou

2017-02-02

SRY, a sex-determining gene, induces testis development in chromosomally female (XX) individuals. However, mouse XX Sertoli cells carrying Sry (XX/Sry Sertoli cells) are incapable of fully supporting germ cell development, even when the karyotype of the germ cells is XY. While it has therefore been assumed that XX/Sry Sertoli cells are not functionally equivalent to XY Sertoli cells, it has remained unclear which specific functions are affected. To elucidate the functional difference, we compared the gene expression of XY and XX/Sry Sertoli cells. Lactate and cholesterol metabolisms, essential for nursing the developing germ cells, were down-regulated in XX/Sry cells, which appears to be caused at least in part by the differential expression of histone modification enzymes SMCX/SMCY (H3K4me3 demethylase) and UTX/UTY (H3K27me3 demethylase) encoded by the sex chromosomes. We suggest that down-regulation of lactate and cholesterol metabolism that may be due to altered epigenetic modification affects the nursing functions of XX/Sry Sertoli cells.

Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells

PubMed Central

Shishido, Yurina; Baba, Takashi; Sato, Tetsuya; Shima, Yuichi; Miyabayashi, Kanako; Inoue, Miki; Akiyama, Haruhiko; Kimura, Hiroshi; Kanai, Yoshiakira; Ishihara, Yasuhiro; Haraguchi, Shogo; Miyazaki, Akira; Rozman, Damjana; Yamazaki, Takeshi; Choi, Man-Ho; Ohkawa, Yasuyuki; Suyama, Mikita; Morohashi, Ken-ichirou

2017-01-01

SRY, a sex-determining gene, induces testis development in chromosomally female (XX) individuals. However, mouse XX Sertoli cells carrying Sry (XX/Sry Sertoli cells) are incapable of fully supporting germ cell development, even when the karyotype of the germ cells is XY. While it has therefore been assumed that XX/Sry Sertoli cells are not functionally equivalent to XY Sertoli cells, it has remained unclear which specific functions are affected. To elucidate the functional difference, we compared the gene expression of XY and XX/Sry Sertoli cells. Lactate and cholesterol metabolisms, essential for nursing the developing germ cells, were down-regulated in XX/Sry cells, which appears to be caused at least in part by the differential expression of histone modification enzymes SMCX/SMCY (H3K4me3 demethylase) and UTX/UTY (H3K27me3 demethylase) encoded by the sex chromosomes. We suggest that down-regulation of lactate and cholesterol metabolism that may be due to altered epigenetic modification affects the nursing functions of XX/Sry Sertoli cells. PMID:28150810

21 CFR 862.1440 - Lactate dehydrogenase test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Systems § 862.1440 Lactate dehydrogenase test system. (a) Identification. A lactate dehydrogenase test system is a device intended to measure the activity of the enzyme lactate dehydrogenase in serum. Lactate... hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction...

Glymphatic clearance controls state-dependent changes in brain lactate concentration.

PubMed

Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2017-06-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

Glymphatic clearance controls state-dependent changes in brain lactate concentration

PubMed Central

Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2016-01-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep–wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport. PMID:27481936

Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia

PubMed Central

Harris, Ashley D; Roberton, Victoria H; Huckle, Danielle L; Saxena, Neeraj; Evans, C John; Murphy, Kevin; Hall, Judith E; Bailey, Damian M; Mitsis, Georgios; Edden, Richard A E; Wise, Richard G

2012-01-01

Purpose To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using MRS during hypoxia. Methods A respiratory protocol consisting of 10 min baseline normoxia, 20 min inspiratory hypoxia and ending with 10 min normoxic recovery was used, throughout which lactate-edited MRS was performed. This was repeated four times in three subjects. A separate session was performed to measure blood lactate. Impulse response functions using end-tidal oxygen and blood lactate as system inputs and cerebral lactate as the system output were examined to describe the dynamics of the cerebral lactate response to a hypoxic challenge. Results The average lactate increase was 20%±15% during the last half of the hypoxic challenge. Significant changes in cerebral lactate concentration were observed after 400s. The average relative increase in blood lactate was 188%±95%. The temporal dynamics of cerebral lactate concentration was reproducibly demonstrated with 200s time bins of MRS data (coefficient of variation 0.063±0.035 between time bins in normoxia). The across subject coefficient of variation was 0.333. Conclusions The methods for measuring the dynamics of the cerebral lactate response developed here would be useful to further investigate the brain’s response to hypoxia. PMID:23197421

Reliability of the Lactate Scout point-of-care instrument for the determination of blood L-lactate concentration in sheep.

PubMed

Kaynar, Ozgur; Karapinar, Tolga; Hayirli, Armagan; Baydar, Ersoy

2015-12-01

Data on accuracy and precision of the Lactate Scout point-of-care (POC) analyzer in ovine medicine are lacking. The purpose of the study was to assess the reliability of the Lactate Scout in sheep. Fifty-seven sheep at varying ages with various diseases were included. Blood lactate concentration in samples collected from the jugular vein was measured immediately on the Lactate Scout. Plasma L-lactate concentration was measured by the Cobas autoanalyzer as the reference method. Data were subjected to Student's t-test, Passing-Bablok regression, and Bland-Altman plot analyses for comparison and assessment of accuracy, precision, and reliability. Plasma l-lactate concentration was consistently lower than blood L-lactate concentration (3.06 ± 0.24 vs 3.3 ± 0.3 mmol/L, P < .0001). There was a positive correlation between plasma and blood L-lactate concentrations (r = .98, P < .0001). The Lactate Scout had 99% accuracy and 98% precision with the reference method. Blood (Y) and plasma (X) L-lactate concentrations were fitted to Y = 0.28 + 1.00 · X, with a residual standard deviation of 0.31 and a negligible deviation from the identity line (P = .93). The bias was fitted to Y = 0.10 + 0.05 · X, with Sy.x of 0.44 (P < .07). The Lactate Scout has high accuracy and precision, with a negligible bias. It is a reliable POC analyzer to assess L-lactate concentration in ovine medicine. © 2015 American Society for Veterinary Clinical Pathology.

Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis.

PubMed

Scott, Halden F; Brou, Lina; Deakyne, Sara J; Fairclough, Diane L; Kempe, Allison; Bajaj, Lalit

2016-03-01

To evaluate whether lactate clearance and normalization during emergency care of pediatric sepsis is associated with lower rates of persistent organ dysfunction. This was a prospective cohort study of 77 children <18 years of age in the emergency department with infection and acute organ dysfunction per consensus definitions. In consented patients, lactate was measured 2 and/or 4 hours after an initial lactate; persistent organ dysfunction was assessed through laboratory and physician evaluation at 48 hours. A decrease of ≥ 10% from initial to final level was considered lactate clearance; a final level < 2 mmol/L was considered lactate normalization. Relative risk (RR) with 95% CIs, adjusted in a log-binomial model, was used to evaluate associations between lactate clearance/normalization and organ dysfunction. Lactate normalized in 62 (81%) patients and cleared in 70 (91%). The primary outcome, persistent 48-hour organ dysfunction, was present in 32 (42%). Lactate normalization was associated with decreased risk of persistent organ dysfunction (RR 0.46, 0.29-0.73; adjusted RR 0.47, 0.29-0.78); lactate clearance was not (RR 0.70, 0.35-1.41; adjusted RR 0.75, 0.38-1.50). The association between lactate normalization and decreased risk of persistent organ dysfunction was retained in the subgroups with initial lactate ≥ 2 mmol/L and hypotension. In children with sepsis and organ dysfunction, lactate normalization within 4 hours was associated with decreased persistent organ dysfunction. Serial lactate level measurement may provide a useful prognostic tool during the first hours of resuscitation in pediatric sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Lameness Prevalence and Risk Factors in Large Dairy Farms in Upstate New York. Model Development for the Prediction of Claw Horn Disruption Lesions

PubMed Central

Foditsch, Carla; Oikonomou, Georgios; Machado, Vinícius Silva; Bicalho, Marcela Luccas; Ganda, Erika Korzune; Lima, Svetlana Ferreira; Rossi, Rodolfo; Ribeiro, Bruno Leonardo; Kussler, Arieli; Bicalho, Rodrigo Carvalho

2016-01-01

The main objectives of this prospective cohort study were a) to describe lameness prevalence at drying off in large high producing New York State herds based on visual locomotion score (VLS) and identify potential cow and herd level risk factors, and b) to develop a model that will predict the probability of a cow developing claw horn disruption lesions (CHDL) in the subsequent lactation using cow level variables collected at drying off and/or available from farm management software. Data were collected from 23 large commercial dairy farms located in upstate New York. A total of 7,687 dry cows, that were less than 265 days in gestation, were enrolled in the study. Farms were visited between May 2012 and March 2013, and cows were assessed for body condition score (BCS) and VLS. Data on the CHDL events recorded by the farm employees were extracted from the Dairy-Comp 305 database, as well as information regarding the studied cows’ health events, milk production, and reproductive records throughout the previous and subsequent lactation period. Univariable analyses and mixed multivariable logistic regression models were used to analyse the data at the cow level. The overall average prevalence of lameness (VLS > 2) at drying off was 14%. Lactation group, previous CHDL, mature equivalent 305-d milk yield (ME305), season, BCS at drying off and sire PTA for strength were all significantly associated with lameness at the drying off (cow-level). Lameness at drying off was associated with CHDL incidence in the subsequent lactation, as well as lactation group, previous CHDL and ME305. These risk factors for CHDL in the subsequent lactation were included in our predictive model and adjusted predicted probabilities for CHDL were calculated for all studied cows. ROC analysis identified an optimum cut-off point for these probabilities and using this cut-off point we could predict CHDL incidence in the subsequent lactation with an overall specificity of 75% and sensitivity of 59%. Using this approach, we would have detected 33% of the studied population as being at risk, eventually identifying 59% of future CHDL cases. Our predictive model could help dairy producers focusing their efforts on CHDL reduction by implementing aggressive preventive measures for high risk cows. PMID:26795970

The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep.

PubMed

Liesegang, A; Risteli, J; Wanner, M

2006-06-01

The goal of the present study was to compare mobilization rate of calcium (Ca) from bone in pregnant and lactating goats and sheep. Blood samples were collected from goats and sheep monthly during pregnancy and at 1, 2, and 4 weeks postpartum (pp) and monthly during lactation until 6 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography at the same intervals as the blood was taken. Bone resorption was assessed by immunoassays quantitating two epitopes of the carboxyterminal telopeptide of type I collagen (ICTP, CTX). Bone formation was estimated by quantifying serum osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25-dihydroxy vitamin D (1,25-VITD) concentrations were determined in serum. Mean ICTP and CTX concentrations of both animal species increased the first week after parturition. By the second week pp, the concentrations of both markers had decreased toward early gestation levels. In contrast, mean OC concentrations continually decreased until the 1st week pp. By the 2nd week pp, the mean concentrations of OC started to increase again. Mean bAP activities decreased during gestation and reached a nadir in the first week pp in goats and 4 weeks pp in sheep. Afterwards, mean bAP activities increased again in goats and sheep. 1,25-VITD concentrations peaked the first week pp and returned to early gestation values thereafter. Total BMC and BMD decreased from the 4th month of pregnancy until the 1st week pp in both species. Afterwards, BMC increased throughout the first month pp in goats and the first 3 months pp in sheep. BMD levels of sheep and goats returned to prepartum levels during lactation. The resorptive phase of bone remodeling is accelerated at parturition and in early lactation and is uncoupled from the process of bone formation. This allows the animal to achieve Ca homeostasis at the expense of bone. Increased bone remodeling during lactation may represent physiological mechanisms to help replace the maternal skeleton lost as the animal adapted to enormously increased Ca losses to the fetus and milk in late gestation and early lactation.

Total lactate dehydrogenase activity of tail muscle is not cold-adapted in nocturnal lizards from cool-temperate habitats.

PubMed

Hare, K M; Miller, J H; Clark, A G; Daugherty, C H

2005-12-01

The dependence of metabolic processes on temperature constrains the behavior, physiology and ecology of many ectothermic animals. The evolution of nocturnality in lizards, especially in temperate regions, requires adaptations for activity at low temperatures when optimal body temperatures are unlikely to be obtained. We examined whether nocturnal lizards have cold-adapted lactate dehydrogenase (LDH). LDH was chosen as a representative metabolic enzyme. We measured LDH activity of tail muscle in six lizard species (n=123: three nocturnal, two diurnal and one crepuscular) between 5 and 35 degrees C and found no differences in LDH-specific activity or thermal sensitivity among the species. Similarly, the specific activity and thermal sensitivity of LDH were similar between skinks and geckos. Similar enzyme activities among nocturnal and diurnal lizards indicate that there is no selection of temperature specific LDH enzyme activity at any temperature. As many nocturnal lizards actively thermoregulate during the day, LDH may be adapted for a broad range of temperatures rather than adapted specifically for the low temperatures encountered when the animals are active. The total activity of LDH in tropical and temperate lizards is not cold-adapted. More data are required on biochemical adaptations and whole animal thermal preferences before trends can be established.

Thermal Preference Ranges Correlate with Stable Signals of Universal Stress Markers in Lake Baikal Endemic and Holarctic Amphipods

PubMed Central

Axenov-Gribanov, Denis; Bedulina, Daria; Shatilina, Zhanna; Jakob, Lena; Vereshchagina, Kseniya; Lubyaga, Yulia; Gurkov, Anton; Shchapova, Ekaterina; Luckenbach, Till; Lucassen, Magnus; Sartoris, Franz Josef; Pörtner, Hans-Otto; Timofeyev, Maxim

2016-01-01

Temperature is the most pervasive abiotic environmental factor for aquatic organisms. Fluctuations in temperature range lead to changes in metabolic performance. Here, we aimed to identify whether surpassing the thermal preference zones is correlated with shifts in universal cellular stress markers of protein integrity, responses to oxidative stress and lactate content, as indicators of anaerobic metabolism. Exposure of the Lake Baikal endemic amphipod species Eulimnogammarus verrucosus (Gerstfeldt, 1858), Ommatogammarus flavus (Dybowski, 1874) and of the Holarctic amphipod Gammarus lacustris Sars 1863 (Amphipoda, Crustacea) to increasing temperatures resulted in elevated heat shock protein 70 (Hsp70) and lactate content, elevated antioxidant enzyme activities (i.e., catalase and peroxidase), and reduced lactate dehydrogenase and glutathione S-transferase activities. Thus, the zone of stability (absence of any significant changes) of the studied molecular and biochemical markers correlated with the behaviorally preferred temperatures. We conclude that the thermal behavioral responses of the studied amphipods are directly related to metabolic processes at the cellular level. Thus, the determined thermal ranges may possibly correspond to the thermal optima. This relationship between species-specific behavioral reactions and stress response metabolism may have significant ecological consequences that result in a thermal zone-specific distribution (i.e., depths, feed spectrum, etc.) of species. As a consequence, by separating species with different temperature preferences, interspecific competition is reduced, which, in turn, increases a species’ Darwinian fitness in its environment. PMID:27706227

The Ca2+/H+ antiporter TMEM165 expression, localization in the developing, lactating and involuting mammary gland parallels the secretory pathway Ca2+ATPase (SPCA1)

USDA-ARS?s Scientific Manuscript database

Plasma membrane Ca2+-ATPase 2 (PMCA2) knockout mice showed that ~ 60 % of calcium in milk is transported across the mammary cells apical membrane by PMCA2. The remaining milk calcium is thought to arrive via the secretory pathway through the actions of secretory pathway Ca2+-ATPase’s 1 and/or 2 (SP...

Inhibition of lactation.

PubMed

Llewellyn-Jones, D

1975-01-01

The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows.

PubMed

González, Felix Diaz; Muiño, Rodrigo; Pereira, Víctor; Campos, Rómulo; Benedito, José Luis

2011-09-01

Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 µmol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea.

Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations

PubMed Central

Dienel, Gerald A

2014-01-01

Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as ‘preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte–neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted. PMID:25204393

Measurements of lactate in exhaled breath condensate at rest and after maximal exercise in young and healthy subjects.

PubMed

Marek, E M; Volke, J; Hawener, I; Platen, P; Mückenhoff, K; Marek, W

2010-03-01

Arterial lactate concentrations, taken as indicators of physical fitness, in athletes as well as in patients with cardio-respiratory or metabolic diseases, are measured invasively from arterialized ear lobe blood. Currently developed micro enzyme detectors permit a non-invasive measurement of hypoxia-related metabolites such as lactate in exhaled breath condensate (EBC). The aim of our study is to prove whether this technology will replace the traditional measurement of lactate in arterialized blood. Therefore, we determined the functional relation between lactate release in EBC and lactate concentration in blood in young and healthy subjects at rest and after exhausting bicycle exercise. During resting conditions as well as after exhausting bicycle exercise, 100 L of exhaled air along with blood samples from the ear lobe was collected after stationary load conditions in 16 healthy subjects. EBC was obtained by cooling the expired air volume with an ECoScreen I (FILT GmbH, Berlin) condenser. The analysis was performed within 90 min using an ECoCheck ampere meter (FILT GmbH, Berlin). Lactate measurements were performed using a bi-enzyme sensor after lactate oxidase-induced oxidation of lactate to pyruvate and H2O2. The rates of lactate release via the exhaled air were calculated from the lactate concentration, the volume and the collection time of the EBC. The functional relation of lactate release in exhaled air and lactate concentration of arterial blood was computed. At rest, the mean lactate concentration in arterialized blood was 0.93 ± 0.30 mmol L(-1). At a resting ventilation of 11.5 ± 3.4 L min(-1), the collection time for 100 L of exhaled air, Ts, was 8.4 ± 2.9 min, and 1.68 ± 0.40 mL EBC was obtained. In EBC, the lactate concentration was 21.4 ± 7.7 µmol L(-1), and the rate of lactate release rate in collected EBC was 4.5 ± 1.7 nmol min(-1). After maximal exercise load (220 ± 20 W), the blood lactate concentration increased to 10.9 ± 1.8 mmol L(-1) and the ventilation increased to 111.6 ± 21.4 L min(-1). The EBC collection time decreased to 3.9 ± 1.9 min, and 1.20 ± 0.44 mL EBC were obtained in the recovery period after termination of exercise. The lactate concentration in EBC increased to 40.3 ± 23.0 µmol L(-1), and the lactate release in EBC increased to 13.6 ± 8.6 nmol min(-1) (p < 0.01). Assuming a volume of 4.3 mL water in 100 L of exhaled air (saturated with water at 37 °C), we calculated a lactate release at rest of 11.5 ± 4.3 nmol min(-1) and 48.6 ± 30.7 nmol min(-1) (p < 0.01) after exhausting exercise. Detectable releases of lactate in exhaled breath condensate were found already under resting conditions. During exhausting external load on a bicycle spiroergometer, an increase in the lactate concentration was found in arterialized blood along with an increased lactate release in EBC. The correlation between expiratory lactate release via EBC and lactate concentration in arterialized blood is studied in pursuing investigations.

Epigenetic Modifications Unlock the Milk Protein Gene Loci during Mouse Mammary Gland Development and Differentiation

PubMed Central

Rijnkels, Monique; Freeman-Zadrowski, Courtneay; Hernandez, Joseph; Potluri, Vani; Wang, Liguo; Li, Wei; Lemay, Danielle G.

2013-01-01

Background Unlike other tissues, development and differentiation of the mammary gland occur mostly after birth. The roles of systemic hormones and local growth factors important for this development and functional differentiation are well-studied. In other tissues, it has been shown that chromatin organization plays a key role in transcriptional regulation and underlies epigenetic regulation during development and differentiation. However, the role of chromatin organization in mammary gland development and differentiation is less well-defined. Here, we have studied the changes in chromatin organization at the milk protein gene loci (casein, whey acidic protein, and others) in the mouse mammary gland before and after functional differentiation. Methodology/Principal Findings Distal regulatory elements within the casein gene cluster and whey acidic protein gene region have an open chromatin organization after pubertal development, while proximal promoters only gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. In contrast, other milk protein genes, such as alpha-lactalbumin, already have an open chromatin organization in the mature virgin gland. Changes in chromatin organization in the casein gene cluster region that are present after puberty persisted after lactation has ceased, while the changes which occurred during pregnancy at the gene promoters were not maintained. In general, mammary gland expressed genes and their regulatory elements exhibit developmental stage- and tissue-specific chromatin organization. Conclusions/Significance A progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the development of the mammary gland. These results support a model in which a chromatin organization is established during pubertal development that is then poised to respond to the systemic hormonal signals of pregnancy and lactation to achieve the full functional capacity of the mammary gland. PMID:23301053

Optimizing productivity, herd structure, environmental performance, and profitability of dairy cattle herds.

PubMed

Liang, D; Cabrera, V E

2015-04-01

This study used the Integrated Farm System Model to simulate the whole farm performance of a representative Wisconsin dairy farm and predict its economic and environmental outputs based on 25 yr of daily local weather data (1986 to 2010). The studied farm, located in southern Wisconsin, had 100 milking cows and 100 ha of cropland with no replacement heifers kept on the farm. Sensitivity analyses were conducted to test the effect of management strategies on energy-corrected milk production (ECM; 4.0% fat and 3.5% protein), net return to management, and greenhouse gas (GHG; including biogenic CO2) emission. The management strategies included (1) target milk production, for which the model optimized available resources to attain, and (2) herd structure, represented by the percentage of first-lactation cows. Weather conditions affected the outputs by changing the farm quantity and the quality of produced feed resources. As expected, when target milk production increased, the ECM increased positively and linearly to a certain level, and then it increased nonlinearly at a decreasing rate, constrained by available feed nutrients. Thereafter, the ECM reached the maximum potential milk production and remained flat regardless of higher target milk production input. Greenhouse gas emissions decreased between 3.4 and 7.3% at different first-lactation cow percentages. As the first-lactation cow percent increased from 15 to 45% in 5% intervals, GHG increased between 9.4 and 11.3% at different levels of target milk production. A high percentage of first-lactation cows reduced the maximum potential milk production. Net return to management had a similar changing trend as ECM. As the target milk production increased from 9,979 to 11,793 kg, the net return to management increased between 31 and 46% at different first-lactation cow percentages. Results revealed a win-win situation when increasing milk production or improving herd structure, which concurrently increased farm net return to management and decreased GHG emissions. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Glucose, Lactate, and Shuttling of Metabolites in Vertebrate Retinas

PubMed Central

Hurley, James B.; Lindsay, Kenneth J.; Du, Jianhai

2016-01-01

The vertebrate retina has specific functions and structures that give it a unique set of constraints on the way in which it can produce and use metabolic energy. The retina’s response to illumination influences its energy requirements, and the retina’s laminated structure influences the extent to which neurons and glia can access metabolic fuels. There are fundamental differences between energy metabolism in retina and that in brain. The retina relies on aerobic glycolysis much more than the brain does, and morphological differences between retina and brain limit the types of metabolic relationships that are possible between neurons and glia. This Mini-Review summarizes the unique metabolic features of the retina with a focus on the role of lactate shuttling. PMID:25801286

Differentials in colostrum feeding among lactating women of block RS Pura of J and K: A lesson for nursing practice.

PubMed

Raina, Sunil Kumar; Mengi, Vijay; Singh, Gurdeep

2012-07-01

Breast feeding is universally and traditionally practicised in India. Experts advocate breast feeding as the best method of feeding young infants. To assess the role of various factors in determining colostrum feeding in block R. S. Pura of district Jammu. A stratified two-stage design with villages as the primary sampling unit and lactating mothers as secondary sampling unit. Villages were divided into different clusters on the basis of population and sampling units were selected by a simple random technique. Breastfeeding is almost universal in R. S. Pura. Differentials in discarding the first milk were not found to be important among various socioeconomic groups and the phenomenon appeared more general than specific.

Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.

PubMed

Koike, Terumoto; Yeung, Jonathan C; Cypel, Marcelo; Rubacha, Matthew; Matsuda, Yasushi; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Keshavjee, Shaf

2011-12-01

Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant. Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs. We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP. Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Relationship between season, lactation number and incidence of clinical mastitis in different stages of lactation in a Holstein dairy farm.

PubMed

Moosavi, Maede; Mirzaei, Abdolah; Ghavami, Mohsen; Tamadon, Amin

2014-01-01

The aim of the present study was to compare the occurrence and duration of clinical mastitis in different seasons, stages of lactation period and parities in a Holstein dairy farm in Iran. A retrospective epidemiological survey from April 2005 to March 2008 was conducted on 884 clinical mastitis cases of 7437 lactations. Data of each case including calendar-date of mastitis onset, days in milk (DIM) of mastitis onset (early: 0-74 DIM; middle: 75-150 DIM, and late ≥ 150 DIM), duration of mastitis, and parity (1, 2, and ≥ 3) were recorded. Based on date of mastitis onset, cases were classified into stages of lactation. Moreover, beginning of mastitis was seasonally categorized. Duration of clinical mastitis after treatment in early lactation was less than late lactation in the first-parity cows (p = 0.005). In early lactation period, the first-parity cows suffered clinical mastitis in days earlier than two other parity groups (p < 0.001). Moreover, in late lactation period, the first-parity cows had clinical mastitis in days later than cows in the third and more parities (p = 0.002). Occurrence of clinical mastitis in summer increased in late lactation period but in winter increased in early lactation period (p = 0.001). In addition, occurrence time of clinical mastitis in summer were in days later than in spring (p = 0.02) and winter (p = 0.03) in early lactation period. In conclusion, occurrence of mastitis in winter and spring during early lactation and in summer during late lactation period were more prevalent especially in lower parities.

Relationship between season, lactation number and incidence of clinical mastitis in different stages of lactation in a Holstein dairy farm

PubMed Central

Moosavi, Maede; Mirzaei, Abdolah; Ghavami, Mohsen; Tamadon, Amin

2014-01-01

The aim of the present study was to compare the occurrence and duration of clinical mastitis in different seasons, stages of lactation period and parities in a Holstein dairy farm in Iran. A retrospective epidemiological survey from April 2005 to March 2008 was conducted on 884 clinical mastitis cases of 7437 lactations. Data of each case including calendar-date of mastitis onset, days in milk (DIM) of mastitis onset (early: 0-74 DIM; middle: 75-150 DIM, and late ≥ 150 DIM), duration of mastitis, and parity (1, 2, and ≥ 3) were recorded. Based on date of mastitis onset, cases were classified into stages of lactation. Moreover, beginning of mastitis was seasonally categorized. Duration of clinical mastitis after treatment in early lactation was less than late lactation in the first-parity cows (p = 0.005). In early lactation period, the first-parity cows suffered clinical mastitis in days earlier than two other parity groups (p < 0.001). Moreover, in late lactation period, the first-parity cows had clinical mastitis in days later than cows in the third and more parities (p = 0.002). Occurrence of clinical mastitis in summer increased in late lactation period but in winter increased in early lactation period (p = 0.001). In addition, occurrence time of clinical mastitis in summer were in days later than in spring (p = 0.02) and winter (p = 0.03) in early lactation period. In conclusion, occurrence of mastitis in winter and spring during early lactation and in summer during late lactation period were more prevalent especially in lower parities. PMID:25568687

Different substrates and starter inocula govern microbial community structures in biogas reactors.

PubMed

Satpathy, Preseela; Steinigeweg, Sven; Cypionka, Heribert; Engelen, Bert

2016-01-01

The influence of different starter inocula on the microbial communities in biogas batch reactors fed with fresh maize and maize silage as substrates was investigated. Molecular biological analysis by Denaturing Gradient Gel Electrophoresis (DGGE) of 16S rRNA gene fragments showed that each inoculum bore specific microbial communities with varying predominant phylotypes. Both, bacterial and archaeal DGGE profiles displayed three distinct communities that developed depending on the type of inoculum. Although maize and silage are similar substrates, different communities dominated the lactate-rich silage compared to lactate-free fresh maize. Cluster analysis of DGGE gels showed the communities of the same substrates to be stable with their respective inoculum. Bacteria-specific DGGE analysis revealed a rich diversity with Firmicutes being predominant. The other abundant phylotypes were Bacteroidetes and Synergistetes. Archaea-specific DGGE analysis displayed less diverse community structures, identifying members of the Methanosarcinales as the dominant methanogens present in all the three biogas digesters. In general, the source of inoculum played a significant role in shaping microbial communities. Adaptability of the inoculum to the substrates fed also influenced community compositions which further impacted the rates of biogas production.

Lactic acid-producing yeast cells having nonfunctional L- or D-lactate:ferricytochrome C oxidoreductase cells

DOEpatents

Miller, Matthew [Boston, MA; Suominen, Pirkko [Maple Grove, MN; Aristidou, Aristos [Highland Ranch, CO; Hause, Benjamin Matthew [Currie, MN; Van Hoek, Pim [Camarillo, CA; Dundon, Catherine Asleson [Minneapolis, MN

2012-03-20

Yeast cells having an exogenous lactate dehydrogenase gene ae modified by reducing L- or D-lactate:ferricytochrome c oxidoreductase activity in the cell. This leads to reduced consumption of lactate by the cell and can increase overall lactate yields in a fermentation process. Cells having the reduced L- or D-lactate:ferricytochrome c oxidoreductase activity can be screened for by resistance to organic acids such as lactic or glycolic acid.

Presence of unique glyoxalase III proteins in plants indicates the existence of shorter route for methylglyoxal detoxification

PubMed Central

Ghosh, Ajit; Kushwaha, Hemant R; Hasan, Mohammad R; Pareek, Ashwani; Sopory, Sudhir K; Singla-Pareek, Sneh L

2016-01-01

Glyoxalase pathway, comprising glyoxalase I (GLY I) and glyoxalase II (GLY II) enzymes, is the major pathway for detoxification of methylglyoxal (MG) into D-lactate involving reduced glutathione (GSH). However, in bacteria, glyoxalase III (GLY III) with DJ-1/PfpI domain(s) can do the same conversion in a single step without GSH. Our investigations for the presence of DJ-1/PfpI domain containing proteins in plants have indicated the existence of GLY III-like proteins in monocots, dicots, lycopods, gymnosperm and bryophytes. A deeper in silico analysis of rice genome identified twelve DJ-1 proteins encoded by six genes. Detailed analysis has been carried out including their chromosomal distribution, genomic architecture and localization. Transcript profiling under multiple stress conditions indicated strong induction of OsDJ-1 in response to exogenous MG. A member of OsDJ-1 family, OsDJ-1C, showed high constitutive expression at all developmental stages and tissues of rice. MG depletion study complemented by simultaneous formation of D-lactate proved OsDJ-1C to be a GLY III enzyme that converts MG directly into D-lactate in a GSH-independent manner. Site directed mutagenesis of Cys-119 to Alanine significantly reduces its GLY III activity indicating towards the existence of functional GLY III enzyme in rice—a shorter route for MG detoxification. PMID:26732528

Simultaneous two-voxel localized 1H-observed 13C-edited spectroscopy for in vivo MRS on rat brain at 9.4 T: Application to the investigation of excitotoxic lesions

NASA Astrophysics Data System (ADS)

Doan, Bich-Thuy; Autret, Gwennhael; Mispelter, Joël; Méric, Philippe; Même, William; Montécot-Dubourg, Céline; Corrèze, Jean-Loup; Szeremeta, Frédéric; Gillet, Brigitte; Beloeil, Jean-Claude

2009-05-01

13C spectroscopy combined with the injection of 13C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of 13C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references. Two sequences were developed at 9.4 T: a bi-voxel 1H-( 13C) STEAM-POCE (Proton Observed Carbon Edited) sequence and a bi-voxel 1H-( 13C) PRESS-POCE adiabatically decoupled sequence with Hadamard encoding. Hadamard encoding allows both voxels to be recorded simultaneously, with the same acquisition time as that required for a single voxel. The method was validated in a biological investigation into the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions. Following an excitotoxic quinolinate-induced localized lesion in the rat cortex and the infusion of U- 13C glucose, two 1H-( 13C) spectra of distinct (4 × 4 × 4 mm 3) voxels, one centred on the injured hemisphere and the other on the contralateral hemisphere, were recorded simultaneously. Two 1H bi-voxel spectra were also recorded and showed a significant decrease in N-acetyl aspartate, and an accumulation of lactate in the ipsilateral hemisphere. The 1H-( 13C) spectra could be recorded dynamically as a function of time, and showed a fall in the glutamate/glutamine ratio and the presence of a stable glutamine pool, with a permanent increase of lactate in the ipsilateral hemisphere. This bi-voxel 1H-( 13C) method can be used to investigate simultaneously both brain hemispheres, and to perform dynamic studies. We report here the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions.

Diminution in energy expenditure during lactation.

PubMed Central

Illingworth, P J; Jung, R T; Howie, P W; Leslie, P; Isles, T E

1986-01-01

Energy expenditure at rest and in response to a meal and to an infusion of noradrenaline was measured in 12 lactating women and compared with that in seven bottle feeding women and seven non-pregnant, non-lactating controls. The energy response of the lactating women was remeasured after lactation stopped. During lactation the resting metabolic rate was unaltered but there was a reduced response to infusion of noradrenaline and to a meal, which increased to normal control values after lactation stopped. Such reductions in expenditure were not found in women who had been bottle feeding and were tested at a similar six to eight weeks post partum. These findings suggest that metabolic efficiency is enhanced in lactating women, who may not need to increase energy intake to the extent suggested by current recommended dietary allowances. PMID:3081114

Lactate oxidation coupled to energy production in mitochondria like particles from Setaria digitata, a filarial parasite.

PubMed

Sivan, V M; Raj, R K

1994-10-14

In the filarial parasite, Setaria digitata, the mitochondria like particles (MLP) show NAD reduction with sodium lactate. The MLP also reduces dye and ferricyanide with lactate. The ferricyanide reduction by lactate is found to be sensitive to the cytochrome o inhibitor orthohydroxy diphenyl (OHD) and complex I inhibitor rotenone, modulated by ADP (+) and ATP (-) and inhibited by pyruvate and oxaloacetate. MLP shows lactate oxidation sensitive to OHD, rotenone and sodium malonate. Thus, the lactate utilizing complex system, consisting of an NADH generating MLP bound lactate dehydrogenase and a lactate flavocytochrome reductase tightly linked to complex I and cytochrome o, produces ATP in functional association with fumarate reductase complex and other enzyme systems. Hence, this study provides new dimensions to the study of metabolism in filarial parasites.

Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation-volvulus: 84 dogs (2003-2007).

PubMed

Green, Tiffany I; Tonozzi, Caroline C; Kirby, Rebecca; Rudloff, Elke

2011-02-01

To test whether an initial plasma lactate ≥ 6.0 mmol/L is associated with the presence of macroscopic gastric wall necrosis and overall survival in dogs presenting with gastric dilatation-volvulus (GDV). Additionally, if no association was identified we sought to identify a different predictive initial plasma lactate concentration and to examine whether serial plasma lactate concentrations provide better prediction of survival. Retrospective study over a 5-year period (2003-2007). Urban private referral small animal teaching hospital. Eighty-four client-owned dogs with a diagnosis of GDV and plasma lactate measurements. None. There was no statistically significant relationship found between survival and the presence of macroscopic gastric wall necrosis with the initial plasma lactate ≥ 6 mmol/L. There was a significant relationship between the initial plasma lactate >2.9 mmol/L for predicting necrosis and <4.1 mmol/L for predicting survival to discharge. Forty dogs that had an increased initial plasma lactate (>2.5 mmol/L) also had a subsequent plasma lactate measured within 12 hours of presentation, with 37/40 dogs surviving and 70% of these surviving dogs having the subsequent lactate decrease by ≥ 50% within 12 hours. The 3/40 that died failed to decrease their plasma lactate by ≥ 50% from the initial blood lactate. The results of this study indicate that an initial presenting plasma lactate concentration ≥ 6.0 mmol/L is not predictive of macroscopic gastric wall necrosis or survival in dogs presenting with GDV. A decrease in plasma lactate concentrations ≥ 50% within 12 hours may be a good indicator for survival. Limitations to the study include its retrospective nature, the small number of patients, and the number of dogs that were euthanized rather than allowed to progress to a natural outcome. © Veterinary Emergency and Critical Care Society 2011.

Lactate Parameters Predict Clinical Outcomes in Patients with Nonvariceal Upper Gastrointestinal Bleeding.

PubMed

Lee, Seung Hoon; Min, Yang Won; Bae, Joohwan; Lee, Hyuk; Min, Byung Hoon; Lee, Jun Haeng; Rhee, Poong Lyul; Kim, Jae J

2017-11-01

The predictive role of lactate in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) has been suggested. This study evaluated several lactate parameters in terms of predicting outcomes of bleeding patients and sought to establish a new scoring model by combining lactate parameters and the AIMS65 score. A total of 114 patients with NVUGIB who underwent serum lactate level testing at least twice and endoscopic hemostasis within 24 hours after admission were retrospectively analyzed. The associations between five lactate parameters and clinical outcomes were evaluated and the predictive power of lactate parameter combined AIMS65s (L-AIMS65s) and AIMS56 scoring was compared. The most common cause of bleeding was gastric ulcer (48.2%). Lactate clearance rate (LCR) was associated with 30-day rebleeding (odds ratio [OR], 0.931; 95% confidence interval [CI], 0.872-0.994; P = 0.033). Initial lactate (OR, 1.313; 95% CI, 1.050-1.643; P = 0.017), maximal lactate (OR, 1.277; 95% CI, 1.037-1.573; P = 0.021), and average lactate (OR, 1.535; 95% CI, 1.137-2.072; P = 0.005) levels were associated with 30-day mortality. Initial lactate (OR, 1.213; 95% CI, 1.027-1.432; P = 0.023), maximal lactate (OR, 1.271; 95% CI, 1.074-1.504; P = 0.005), and average lactate (OR, 1.501; 95% CI, 1.150-1.959; P = 0.003) levels were associated with admission over 7 days. Although L-AIMS65s showed the highest area under the curve for prediction of each outcome, differences between L-AIMS65s and AIMS65 did not reach statistical significance. In conclusion, lactate parameters have a prognostic role in patients with NVUGIB. However, they do not increase the predictive power of AIMS65 when combined. © 2017 The Korean Academy of Medical Sciences.

Higher Accuracy of the Lactate Minimum Test Compared to Established Threshold Concepts to Determine Maximal Lactate Steady State in Running.

PubMed

Wahl, Patrick; Zwingmann, Lukas; Manunzio, Christian; Wolf, Jacob; Bloch, Wilhelm

2018-05-18

This study evaluated the accuracy of the lactate minimum test, in comparison to a graded-exercise test and established threshold concepts (OBLA and mDmax) to determine running speed at maximal lactate steady state. Eighteen subjects performed a lactate minimum test, a graded-exercise test (2.4 m·s -1 start,+0.4 m·s -1 every 5 min) and 2 or more constant-speed tests of 30 min to determine running speed at maximal lactate steady state. The lactate minimum test consisted of an initial lactate priming segment, followed by a short recovery phase. Afterwards, the initial load of the subsequent incremental segment was individually determined and was increased by 0.1 m·s -1 every 120 s. Lactate minimum was determined by the lowest measured value (LM abs ) and by a third-order polynomial (LM pol ). The mean difference to maximal lactate steady state was+0.01±0.14 m·s -1 (LM abs ), 0.04±0.15 m·s -1 (LM pol ), -0.06±0.31 m·s 1 (OBLA) and -0.08±0.21 m·s 1 (mDmax). The intraclass correlation coefficient (ICC) between running velocity at maximal lactate steady state and LM abs was highest (ICC=0.964), followed by LM pol (ICC=0.956), mDmax (ICC=0.916) and OBLA (ICC=0.885). Due to the higher accuracy of the lactate minimum test to determine maximal lactate steady state compared to OBLA and mDmax, we suggest the lactate minimum test as a valid and meaningful concept to estimate running velocity at maximal lactate steady state in a single session for moderately up to well-trained athletes. © Georg Thieme Verlag KG Stuttgart · New York.

Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles?

PubMed

Beardsley, D; Holman, S; Gantt, R; Robinson, R A; Lindsey, J; Bazaral, M; Stewart, S F; Stevens, R A

1995-08-01

Recent reports of transient neurologic deficits have raised concern about the potential toxicity of single-dose spinal 5% lidocaine in 7.5% dextrose. Two cases of volunteers who experienced minor local sensory deficits after slow (60 s) injections of 2 mL 5% lidocaine via Whitacre needles are described. One case was a result of a double injection because of a "failed" block. It seemed possible that the neurologic deficit in these cases resulted from neurotoxicity associated with maldistribution of local anesthetic. Using an in vitro spinal model, we investigated drug distribution resulting from injections through side-port spinal needles to determine whether the use of these needles could result in high local concentrations of hyperbaric solutions. A spinal canal model was fabricated using human magnetic resonance measurements. The model was placed in a surgical supine position and filled with lactated Ringer's solution to simulate the specific gravity of cerebral spinal fluid at 22 degrees C. A hyperbaric solution of phthalocyanine blue dye and dextrose (SG 1.042), simulating the anesthetic, was injected through three different needles (27-gauge 4 11/16-in. Whitacre, 25-gauge 3 1/2-in. Whitacre, 25-gauge 3 1/2-in. Quincke). Triplicate injections were done at rapid (2 mL/10 s) and slow (2 mL/60 s) rates, with needle side ports oriented in a sacral and cephalad direction. At slow rates of injection, using 27- or 25-gauge sacrally directed Whitacre needles, injections showed evidence of maldistribution with extrapolated peak sacral lidocaine concentrations reaching 2.0%. In contrast, distribution after slow injection through sacrally directed Quincke needles was uniform.(ABSTRACT TRUNCATED AT 250 WORDS)

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron filings, reaction of ferrous chloride with sodium lactate, or reaction of ferrous sulfate...

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio.

PubMed

Ross, Jaime M; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J; Olson, Lars

2010-11-16

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes.

Workplace Lactation Support in Milwaukee County 5 Years After the Affordable Care Act.

PubMed

Lennon, Tyler; Willis, Earnestine

2017-02-01

Workplace lactation support has become increasingly important because returning to work is associated with discontinuing breastfeeding and women in the workforce are increasing. Research aim: This study examined workplace lactation support among Milwaukee County businesses 5 years after implementation of the Affordable Care Act's Break Time for Nursing Mothers provision. A cross-sectional survey of Milwaukee County businesses was conducted in the summer of 2015 that inquired about workplace policies, lactation spaces, and other lactation resources offered. Business supports were stratified based on employer sizes: large (> 500 employees), medium (50-499 employees), and small (20-49 employees). A lactation amenity score was calculated for each business based on lactation resources available. Three hundred surveys were distributed and 71 businesses voluntarily completed the survey. Small employers were excluded from statistical analysis due to fewer responses ( n = 8). Overall, 87.3% ( n = 55) of respondents reported providing access to a multiuser space for lactation and 65.1% ( n = 41) reported providing a designated lactation space. Large employers ( n = 30) were more likely than medium employers ( n = 33) to provide a designated lactation space for breastfeeding or expressing (86.7% vs. 45.5%, p < .001). Large employers' mean amenity score was significantly higher than that of medium employers (3.37 vs. 2.57, p = .014), and they were also more likely to offer additional supports including access to a lactation consultant, classes, and materials (46.7% vs. 12.1%, p < .01). Large employers provide more lactation support than medium employers in Milwaukee County. All employers, regardless of size, need to increase additional lactation support for women in the workplace.

Identification of diagnostic biomarkers and metabolic pathway shifts of heat-stressed lactating dairy cows.

PubMed

Tian, He; Wang, Weiyu; Zheng, Nan; Cheng, Jianbo; Li, Songli; Zhang, Yangdong; Wang, Jiaqi

2015-07-01

Controlling heat stress (HS) is a global challenge for the dairy industry. However, simple and reliable biomarkers that aid the diagnoses of HS-induced metabolic disorders have not yet been identified. In this work, an integrated metabolomic and lipidomic approach using (1)H nuclear magnetic resonance and ultra-fast LC-MS was employed to investigate the discrimination of plasma metabolic profiles between HS-free and HS lactating dairy cows. Targeted detection using LC-MS in multiple reaction monitoring mode was used to verify the reliability of the metabolites as biomarker candidates. Overall, 41 metabolites were identified as candidates for lactating dairy cows exposed to HS, among which 13 metabolites, including trimethylamine, glucose, lactate, betaine, creatine, pyruvate, acetoacetate, acetone, β-hydroxybutyrate, C16 sphinganine, lysophosphatidylcholine (18:0), phosphatidylcholine (16:0/14:0), and arachidonic acid, had high sensitivity and specificity in diagnosing HS status, and are likely to be the potential biomarkers of HS dairy cows. All of these potentially diagnostic biomarkers were involved in carbohydrate, amino acid, lipid, or gut microbiome-derived metabolism, indicating that HS affected the metabolic pathways in lactating dairy cows. Further research is warranted to evaluate these biomarkers in practical applications and to elucidate the physiological mechanisms of HS-induced metabolic disorders. Heat stress (HS) annually causes huge losses to global dairy industry, including animal performance decrease, metabolic disorder and health problem. So far, physiological mechanisms underlying HS of dairy cows still remain elusive. To our best knowledge, this is the first attempt to elucidate the HS-induced metabolic disorders of dairy cows using integrated (1)H NMR and LC-MS-based metabolic study. The results not only provided potential diagnostic biomarkers for HS lactating dairy cows, but also significantly explored the related physiological mechanisms of metabolic pathway shifts induced by HS environment. This work offers comprehensive insights into the global metabolic alterations of dairy cows exposed to HS and provides a new perspective for further study. Copyright © 2015 Elsevier B.V. All rights reserved.

Failure and preventive costs of mastitis on Dutch dairy farms.

PubMed

van Soest, Felix J S; Santman-Berends, Inge M G A; Lam, Theo J G M; Hogeveen, Henk

2016-10-01

Mastitis is an important disease from an economic perspective, but most cost assessments of mastitis include only the direct costs associated with the disease (e.g., production losses, culling, and treatment), which we call failure costs (FC). However, farmers also invest time and money in controlling mastitis, and these preventive costs (PC) also need to be taken into account. To estimate the total costs of mastitis, we estimated both FC and PC. We combined multiple test-day milk records from 108 Dutch dairy farms with information on applied mastitis prevention measures and farmers' registration of clinical mastitis for individual dairy cows. The aim was to estimate the total costs of mastitis and to give insight into variations between farms. We estimated the average total costs of mastitis to be €240/lactating cow per year, in which FC contributed €120/lactating cow per year and PC contributed another €120/lactating cow per year. Milk production losses, discarded milk, and culling were the main contributors to FC, at €32, €20, and €20/lactating cow per year, respectively. Labor costs were the main contributor to PC, next to consumables and investments, at €82, €34, and €4/lactating cow per year, respectively. The variation between farmers was substantial, and some farmers faced both high FC and PC. This variation may have been due to structural differences between farms, different mastitis-causing pathogens, the time at which preventive action is initiated, stockmanship, or missing measures in PC estimates. We estimated the minimum FC to be €34 per lactating cow per yr. All farmers initiated some preventive action to control or reduce mastitis, indicating that farmers will always have mastitis-related costs, because mastitis will never be fully eradicated from a farm. Insights into both the PC and FC of a specific farm will allow veterinary advisors and farmers to assess whether current udder health strategies are appropriate or whether there is room for improvement from an economic perspective. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Influence of lactation and pregnancy + lactation on mechanical properties and mineral content of the rat femur.

PubMed

Peng, T C; Kusy, R P; Garner, S C; Hirsch, P F; De Blanco, M C

1987-06-01

The quality of bone was assessed from femurs of rats both during lactation and after pregnancy + lactation. Mechanical properties of stiffness, strength, toughness, and ductility were measured, along with standard measurements of dry weight, ash weight, and total bone mineral. No changes occurred during the first week of lactation. During the second and third weeks of lactation all bone parameters except ductility decreased significantly. These data are consistent with bone losing mineral in order to supplement the dietary calcium intake necessary for milk production. In other experiments, femurs were collected from nulliparous rats and from rats that had previously undergone 1-3 pregnancy + lactations. The largest changes in bone mineral and mechanical properties occurred after a single pregnancy + lactation period, although significant further decreases in stiffness and strength occurred after the second pregnancy + lactation. No additional losses occurred following the third pregnancy + lactation. Even 5 months after only one pregnancy + lactation period, the bone quality was still impaired as all bone properties were lower than in nulliparous controls. Because the changes, especially stiffness and strength, were relatively larger than the changes in dry and ash weights of bone, measurements of these mechanical properties provide a more sensitive method to evaluate the quality of bone.

Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows

PubMed Central

Muiño, Rodrigo; Pereira, Víctor; Campos, Rómulo; Benedito, José Luis

2011-01-01

Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 µmol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea. PMID:21897097

Importance of measuring lactate levels in children with sepsis.

PubMed

Anil, Nisha

2017-10-10

Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Brain lactate metabolism: the discoveries and the controversies

PubMed Central

Dienel, Gerald A

2012-01-01

Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an ‘opportunistic', glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain. PMID:22186669

Involvement of monocarboxylate transporter 1 (SLC16A1) in the uptake of l-lactate in human astrocytes.

PubMed

Ideno, Masaya; Kobayashi, Masaki; Sasaki, Shotaro; Futagi, Yuya; Narumi, Katsuya; Furugen, Ayako; Iseki, Ken

2018-01-01

Astrocytes, the most abundant glial cells in the central nervous system (CNS), help neurons survive. Monocarboxylate transporters (MCTs) are reported to transport l-lactate, which is important for CNS physiology and cognitive function. However, it remains unclear which MCT isoform is functionally expressed by human astrocytes. The aim of this study was to establish the contribution of each MCT isoform to l-lactate transport in human astrocytes. The function of l-lactate transport was studied using NHA cells as a human astrocyte model and radiolabeled l-lactate. The expression of MCT in human astrocytes was detected by immunohistochemistry staining. The cellular uptake of l-lactate was found to be pH- and concentration-dependent with a Km value for l-lactate uptake of 0.64mM. This Km was similar to what has been previously established for MCT1-mediated l-lactate uptake. α-Cyano-4- hydroxycinnamate (CHC) and 5-oxoproline, which are both MCT1 inhibitors, were found to significantly inhibit the uptake of l-lactate, suggesting MCT1 is primarily responsible for l-lactate transport. Moreover, MCT1 protein was expressed in human astrocytes. pH-dependent l-lactate transport is mediated by MCT1 in human astrocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... It is prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron filings, reaction of ferrous chloride with sodium lactate, or reaction of ferrous...

21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's Solution...

Blood lactate accumulation in top level swimmers following competition.

PubMed

Bonifazi, M; Martelli, G; Marugo, L; Sardella, F; Carli, G

1993-03-01

The purposes of this study were to evaluate the significance of blood lactate values after competitions and the blood lactate-swimming speed relationship to swimming performances. Auricular blood samples (N = 421) were collected in 203 top level Italian swimmers (116 males and 87 females) at the end of competitions performed in a 25 m swimming pool. The distribution of all lactate values differed between males and females. The lowest lactate values occurred in swimmers performing the longest distances both in males (1500 m) and females (800 m). In swimmers performing freestyle events a relationship between V-4 mM (swimming speed at 4 mmol/l blood lactate value) and competition velocities was observed, in males, at 200, 400 and 1500 m and, in females, at 400 and 800 m. The predicted velocity corresponding to the competition lactate value assessed by the individual blood lactate-swimming speed relationship was found to be highly related to the actual competition velocity. Results suggest that blood lactate values in swimmers are a useful indication of individual aptitudes.

Atherogenicity index and health-related fatty acids in different stages of lactation from Friesian, Jersey and Friesian×Jersey cross cow milk under a pasture-based dairy system.

PubMed

Nantapo, C T W; Muchenje, V; Hugo, A

2014-03-01

The objective of the study was to investigate the effect of stage of lactation on the fatty acid profiles of milk from Friesian, Jersey and Friesian×Jersey cows. Linoleic acid in pastures was highest in the second phase which coincided with mid-lactation days (p<0.05). Highest milk moisture content and lowest fat free dry matter content was seen in early lactation (p<0.05). Higher fat content was observed in late lactation than early lactation. Highest butyric, caproic, linoleic, omega-6 and polyunsaturated fatty acids were observed for milk from Friesian cows. Highest conjugated fatty acids, α-linolenic acid, linoleic acid, saturated fatty acids, polyunsaturated fatty acids, omega-6, and omega-3 were observed in early lactation. Atherogenicity index and desaturase activity indices were highest in late lactation. In conclusion, stage of lactation and genotype affected milk health-related fatty acid profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relationship of milking rate to somatic cell count.

PubMed

Brown, C A; Rischette, S J; Schultz, L H

1986-03-01

Information on milking rate, monthly bucket somatic cell counts, mastitis treatment, and milk production was obtained from 284 lactations of Holstein cows separated into three lactation groups. Significant correlations between somatic cell count (linear score) and other parameters included production in lactation 1 (-.185), production in lactation 2 (-.267), and percent 2-min milk in lactation 2 (.251). Somatic cell count tended to increase with maximum milking rate in all lactations, but correlations were not statistically significant. Twenty-nine percent of cows with milking rate measurements were treated for clinical mastitis. Treated cows in each lactation group produced less milk than untreated cows. In the second and third lactation groups, treated cows had a shorter total milking time and a higher percent 2-min milk than untreated cows, but differences were not statistically significant. Overall, the data support the concept that faster milking cows tend to have higher cell counts and more mastitis treatments, particularly beyond first lactation. However, the magnitude of the relationship was small.

Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers-Applications of the Warburg Effect.

PubMed

Goldberg, Joel S

2011-02-15

It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA.

Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

PubMed

Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

2017-09-16

Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

Single Sodium Pyruvate Ingestion Modifies Blood Acid-Base Status and Post-Exercise Lactate Concentration in Humans

PubMed Central

Olek, Robert A.; Kujach, Sylwester; Wnuk, Damian; Laskowski, Radoslaw

2014-01-01

This study examined the effect of a single sodium pyruvate ingestion on a blood acid-base status and exercise metabolism markers. Nine active, but non-specifically trained, male subjects participated in the double-blind, placebo-controlled, crossover study. One hour prior to the exercise, subjects ingested either 0.1 g·kg−1 of body mass of a sodium pyruvate or placebo. The capillary blood samples were obtained at rest, 60 min after ingestion, and then three and 15 min after completing the workout protocol to analyze acid-base status and lactate, pyruvate, alanine, glucose concentrations. The pulmonary gas exchange, minute ventilation and the heart rate were measured during the exercise at a constant power output, corresponding to ~90% O2max. The blood pH, bicarbonate and the base excess were significantly higher after sodium pyruvate ingestion than in the placebo trial. The blood lactate concentration was not different after the ingestion, but the post-exercise was significantly higher in the pyruvate trial (12.9 ± 0.9 mM) than in the placebo trial (10.6 ± 0.3 mM, p < 0.05) and remained elevated (nonsignificant) after 15 min of recovery. The blood pyruvate, alanine and glucose concentrations, as well as the overall pulmonary gas exchange during the exercise were not affected by the pyruvate ingestion. In conclusion, the sodium pyruvate ingestion one hour before workout modified the blood acid-base status and the lactate production during the exercise. PMID:24841105

Biorecovery of gold as nanoparticles and its catalytic activities for p-nitrophenol degradation.

PubMed

Zhu, Nengwu; Cao, Yanlan; Shi, Chaohong; Wu, Pingxiao; Ma, Haiqin

2016-04-01

Recovery of gold from aqueous solution using simple and economical methodologies is highly desirable. In this work, recovery of gold as gold nanoparticles (AuNPs) by Shewanella haliotis with sodium lactate as electron donor was explored. The results showed that the process was affected by the concentration of biomass, sodium lactate, and initial gold ions as well as pH value. Specifically, the presence of sodium lactate determines the formation of nanoparticles, biomass, and AuCl4 (-) concentration mainly affected the size and dispersity of the products, reaction pH greatly affected the recovery efficiency, and morphology of the products in the recovery process. Under appropriate conditions (5.25 g/L biomass, 40 mM sodium lactate, 0.5 mM AuCl4 (-), and pH of 5), the recovery efficiency was almost 99 %, and the recovered AuNPs were mainly spherical with size range of 10-30 nm (~85 %). Meanwhile, Fourier transforms infrared spectroscopy and X-ray photoelectron spectroscopy demonstrated that carboxyl and amine groups might play an important role in the process. In addition, the catalytic activity of the AuNPs recovered under various conditions was testified by analyzing the reduction rate of p-nitrophenol by borohydride. The biorecovered AuNPs exhibited interesting size and shape-dependent catalytic activity, of which the spherical particle with smaller size showed the highest catalytic reduction activity with rate constant of 0.665 min(-1).

Metabolism of glucose, fructose and lactate in vivo in chronically cannulated foetuses and in suckling lambs.

PubMed Central

Warnes, D M; Seamark, R F; Ballard, F J

1977-01-01

1. Chronically cannulated sheep foetuses and suckling lambs were injected with 14C-labelled glucose, fructose or lactate, and sequential blood samples taken under conditions of minimal stress and without anaesthesia. 2. Gluconeogenesis from lactate was not detectable in foetal sheep, but the pathway was active in suckling lambs. 3. Fructose utilization rates were low in foetal sheep, with no measurable conversion into glucose or lactate. 4. The high rates of irreversible loss of both glucose and lactate in the foetus were decreased in suckling lambs. Radioactivity from labelled glucose entered both the lactate and fructose pools in foetal sheep, and entered the lactate pool in suckling lambs. 5. A model is proposed in which carbon flow between glucose, fructose and lactate has been quantified in foetal sheep. PMID:869907

Electrochemical lactate biosensor based upon chitosan/carbon nanotubes modified screen-printed graphite electrodes for the determination of lactate in embryonic cell cultures.

PubMed

Hernández-Ibáñez, Naiara; García-Cruz, Leticia; Montiel, Vicente; Foster, Christopher W; Banks, Craig E; Iniesta, Jesús

2016-03-15

l-lactate is an essential metabolite present in embryonic cell culture. Changes of this important metabolite during the growth of human embryo reflect the quality and viability of the embryo. In this study, we report a sensitive, stable, and easily manufactured electrochemical biosensor for the detection of lactate within embryonic cell cultures media. Screen-printed disposable electrodes are used as electrochemical sensing platforms for the miniaturization of the lactate biosensor. Chitosan/multi walled carbon nanotubes composite have been employed for the enzymatic immobilization of the lactate oxidase enzyme. This novel electrochemical lactate biosensor analytical efficacy is explored towards the sensing of lactate in model (buffer) solutions and is found to exhibit a linear response towards lactate over the concentration range of 30.4 and 243.9 µM in phosphate buffer solution, with a corresponding limit of detection (based on 3-sigma) of 22.6 µM and exhibits a sensitivity of 3417 ± 131 µAM(-1) according to the reproducibility study. These novel electrochemical lactate biosensors exhibit a high reproducibility, with a relative standard deviation of less than 3.8% and an enzymatic response over 82% after 5 months stored at 4 °C. Furthermore, high performance liquid chromatography technique has been utilized to independently validate the electrochemical lactate biosensor for the determination of lactate in a commercial embryonic cell culture medium providing excellent agreement between the two analytical protocols. Copyright © 2015 Elsevier B.V. All rights reserved.

Two-Voxel Localization Sequence for in Vivo Two-Dimensional Homonuclear Correlation Spectroscopy

NASA Astrophysics Data System (ADS)

Delmas, Florence; Beloeil, Jean-Claude; van der Sanden, Boudewijn P. J.; Nicolay, Klaas; Gillet, Brigitte

2001-03-01

The combination of localized 2D 1H MR correlation spectroscopy and Hadamard encoding allows the simultaneous acquisition of multiple volumes of interest without an increase in the experimental duration, compared to single-voxel acquisition. In the present study, 2D correlation spectra were acquired simultaneously within 20 to 40 min in two voxels located in each hemisphere of the rat brain. An intervoxel distance of 20% of the voxel size was sufficient to limit spatial contamination. The following cerebral metabolites gave detectable crosspeaks: N-acetylaspartate, the glutamate/glutamine pool, aspartate, phosphoethanolamine, glucose, glutathione, taurine, myo-inositols, lactate, threonine, γ-aminobutyric acid, and alanine. Most of the metabolites were measured without contamination of other resonances.

cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, C.K.; Li, X.; Luna, J.

1994-09-15

Lactate and pyruvate are transported across cell membranes by monocarboxylate transporters (MCTs). Here, the authors use the recently cloned cDNA for hamster MCT1 to isolate cDNA and genomic clones for human MCT1. Comparison of the human and hamster amino acid sequences revealed that the proteins are 86% identical. The gene for human MCT1 (gene symbol, SLC16A1) was localized to human chromosome bands 1p13.2-p12 by PCR analysis of panels of human X rodent cell hybrid lines and by fluorescence chromosomal in situ hybridization. 9 refs., 2 figs.

Use of Topical Corticosteroids in Dermatology: An Evidence-based Approach

PubMed Central

Das, Anupam; Panda, Saumya

2017-01-01

Topical corticosteroids (TCs) are the pillars of dermatotherapeutics. These drugs are the “magic molecules,” provided they are used judiciously and appropriately, following a rational prescription. On exhaustive literature search in multiple databases, we found a significant evidence favoring the use of TCs in atopic eczema, localized vitiligo, psoriasis, chronic hand eczema, and localized bullous pemphigoid. However, contrary to conventional wisdom, we did not find any high-level scientific evidence in support of prescribing TCs in cutaneous lichen planus, sarcoidosis, and seborrhoeic dermatitis. Besides, evidence clearly advocates judicious use of mild-to-moderate corticosteroids (if required) in pregnancy and lactation and there is no risk of any fetal abnormality. PMID:28584365

Proton spectral editing in the inhomogeneous radiofrequency field of a surface coil using modified stimulated echoes.

PubMed

Lahrech, H; Briguet, A

1990-11-01

It is shown that the modified stimulated echo sequence, [theta](+/- x +/- y)-t1-[theta](+ x)-t2/2-[2 theta](+ x)-t2/2- [theta](+ x)-t1-Acq(+/- x +/- y), denoted as MSTE[2 theta]x according to the exciter phase of the 2 theta pulse, is able to perform proton spectral editing without difference spectra. On the other hand, this sequence appears to be suitable for spatial localization. Sensitivity and spatial selectivity of MSTE and conventional stimulated echo sequence (STE) are briefly compared. MSTE is applied to editing lactate in the rat brain using the locally restricted excitation of a surface coil.

Falsely increased plasma lactate concentration due to ethylene glycol poisoning in 2 dogs.

PubMed

Hopper, Kate; Epstein, Steven E

2013-01-01

To describe false increases in plasma lactate concentration measured on point-of-care analyzers in 2 dogs with ethylene glycol (EG) intoxication. Two dogs presenting with EG intoxication had extreme increases of plasma lactate concentrations recorded on a point-of-care machine. Laboratory analysis by spectrophotometry of lactate concentration determined these lactate measurements to be erroneous. False increases in plasma lactate concentration were demonstrated in 2 out of 3 point-of-care machines tested. Glycolate, a toxic metabolite of EG, can interfere with the measurement of plasma lactate by some analyzers and this may delay the correct diagnosis of EG toxicity if not recognized. © Veterinary Emergency and Critical Care Society 2012.

Dynamic-SERS Optophysiology: A Nanosensor for Monitoring Cell Secretion Events.

PubMed

Lussier, Félix; Brulé, Thibault; Vishwakarma, Medhavi; Das, Tamal; Spatz, Joachim P; Masson, Jean-François

2016-06-08

We monitored metabolite secretion near living cells using a plasmonic nanosensor. The nanosensor created from borosilicate nanopipettes analogous to the patch clamp was decorated with Au nanoparticles and served as a surface-enhanced Raman scattering (SERS) substrate with addressable location. With this nanosensor, we acquired SERS locally near Madin-Darby canine kidney (MDCKII) epithelial cells, and we detected multiple metabolites, such as pyruvate, lactate, ATP, and urea simultaneously. These plasmonic nanosensors were capable of monitoring metabolites in the extracellular medium with enough sensitivity to detect an increase in metabolite concentration following the lyses of MDCKII cells with a nonionic surfactant. The plasmonic nanosensors also allowed a relative quantification of a chemical gradient for a metabolite near cells, as demonstrated with a decrease in relative lactate to pyruvate concentration further away from the MDCKII cells. This SERS optophysiology technique for the sensitive and nondestructive monitoring of extracellular metabolites near living cells is broadly applicable to different cellular and tissue models and should therefore provide a powerful tool for cellular studies.

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio

PubMed Central

Ross, Jaime M.; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J.; Olson, Lars

2010-01-01

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes. PMID:21041631

Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice.

PubMed

Wendelboe, Mette Høegh; Thomsen, Jesper Skovhus; Henriksen, Kim; Vegger, Jens Bay; Brüel, Annemarie

2016-06-01

In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Lactation stage-dependent expression of transporters in rat whole mammary gland and primary mammary epithelial organoids.

PubMed

Gilchrist, Samuel E; Alcorn, Jane

2010-04-01

Since solute carrier (SLC) and ATP-binding cassette (ABC) transporters play pivotal roles in the transport of both nutrients and drugs into breast milk, drug-nutrient transport interactions at the lactating mammary gland are possible. Our purpose was to characterize lactation stage-dependent changes in transporter expression in rat mammary gland and isolated mammary epithelial organoids (MEO) to provide additional insight for the safe use of maternal medications during breastfeeding. We used quantitative reverse transcription-polymerase chain reaction to assess the temporal expression patterns of SLC and ABC transporters in rat mammary gland and isolated MEO at different stages of lactation. In whole mammary gland five distinct patterns of expression emerged relative to late gestation: (i) decreasing throughout lactation (Mdr1a, Mdr1b, Mrp1, Octn2, Ent2, Ent3, Ncbt2, Mtx1); (ii) prominent increase in early lactation, which may remain elevated or decline with advancing lactation (Octn1, Cnt2, Cnt3, Ent1, Pept1, Pept2); (iii) constant but decreasing later in lactation (Octn3, Dmt1); (iv) increasing until mid-to-late lactation (Oct1, Cnt1); and (v) prominent increase late in lactation (Ncbt1). In isolated MEO (an enriched source of mammary epithelial cells) major differences in expression patterns were noted for Octn3, Ncbt1, and Mtx1, but otherwise were reasonably similar with the whole mammary gland. In conclusion our study augments existing data on transporter expression in the lactating mammary gland. These data should facilitate investigations into lactation-stage dependent changes in drug or nutrient milk-to-serum concentration ratios, the potential for drug- or disease-transporter interactions, and mechanistic studies of transporter function in the lactating mammary gland.

The presence of vaginal Lactobacillus species does not contribute to a measureable difference in amniotic fluid lactate levels collected from the vaginal tract of laboring women.

PubMed

Hall, Beverley; Wong, Diana; Healy, Clare; Tracy, Mark B; Tracy, Sally K; Rawlinson, William D

2017-04-01

Amniotic fluid lactate research is based on the hypothesis that a relationship exists between fatigued uterine muscles and raised concentrations of the metabolite lactate, which is excreted into the amniotic fluid during labor. To assess potentially confounding effects of lactate-producing organisms on amniotic fluid lactate measurements, we aimed to determine if the presence of vaginal Lactobacillus species was associated with elevated levels of amniotic fluid lactate, measured from the vaginal tract of women in labor. Results from this study contribute to a large prospective longitudinal study of amniotic fluid lactate at a teaching hospital in Sydney, Australia. Amniotic fluid lactate measurement was assessed at the time of routine vaginal examination, after membranes had ruptured, using a hand-held lactate meter StatStripXPress (Nova Biomedical). Vaginal swab samples were collected at the time of the first amniotic fluid lactate measurement and stored for later detection and quantification of Lactobacillus species using a TaqMan real-time PCR assay. Swab sample and amniotic fluid lactate results were paired and analyzed. The PCR assay detected Lactobacillus species in 48 of 388 (12%) vaginal swab specimens (8% positive, 4% low positive) collected from women in labor after membranes had ruptured. There was no significant difference in median and mean (respectively) amniotic fluid lactate levels with (8.35 mmol/L; 8.95 mmol/L) or without (8.5 mmol/L; 9.08 mmol/L) Lactobacillus species detected. There was no association between the presence or level of vaginal Lactobacillus species and the measurement of amniotic fluid lactate collected from the vaginal tract of women during labor. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

In Vivo Evidence for Epidermal Growth Factor Receptor (EGFR)-mediated Release of Prolactin from the Pituitary Gland

PubMed Central

Dahlhoff, Maik; Blutke, Andreas; Wanke, Rüdiger; Wolf, Eckhard; Schneider, Marlon R.

2011-01-01

Members of the epidermal growth factor receptor (EGFR/ERBB) system are essential local regulators of mammary gland development and function. Emerging evidence suggests that EGFR signaling may also influence mammary gland activity indirectly by promoting the release of prolactin from the pituitary gland in a MAPK and estrogen receptor-α (ERα)-dependent manner. Here, we report that overexpression of the EGFR ligand betacellulin (BTC) causes a lactating-like phenotype in the mammary gland of virgin female mice including the major hallmarks of lactogenesis. BTC transgenic (BTC-tg) females showed reduced levels of prolactin in the pituitary gland and increased levels of the hormone in the circulation. Furthermore, treatment of BTC-tg females with bromocriptine, an inhibitor of prolactin secretion, blocked the development of the lactation-like phenotype, suggesting that it is caused by central release of prolactin rather than by local actions of BTC in the mammary gland. Introduction of the antimorphic Egfr allele Wa5 also blocked the appearance of the mammary gland alterations, revealing that the phenotype is EGFR-dependent. We detected an increase in MAPK activity, but unchanged phosphorylation of ERα in the pituitary gland of BTC-tg females as compared with control mice. These results provide the first functional evidence in vivo for a role of the EGFR system in regulating mammary gland activity by modulating prolactin release from the pituitary gland. PMID:21914800

Analyte Flux at a Biomaterial–Tissue Interface over Time: Implications for Sensors for Type 1 and 2 Diabetes Mellitus

PubMed Central

Ekberg, Neda Rajamand; Brismar, Kerstin; Malmstedt, Jonas; Hedblad, Mari-Anne; Adamson, Ulf; Ungerstedt, Urban; Wisniewski, Natalie

2010-01-01

Objective The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor–tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Method Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. Results Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. Conclusions Monitoring metabolic changes at a material–tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM. PMID:20920426

Analyte flux at a biomaterial-tissue interface over time: implications for sensors for type 1 and 2 diabetes mellitus.

PubMed

Ekberg, Neda Rajamand; Brismar, Kerstin; Malmstedt, Jonas; Hedblad, Mari-Anne; Adamson, Ulf; Ungerstedt, Urban; Wisniewski, Natalie

2010-09-01

The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor-tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. Monitoring metabolic changes at a material-tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM. © 2010 Diabetes Technology Society.

Analytical performance of three whole blood point-of-care lactate devices compared to plasma lactate comparison methods and a flow-injection mass spectrometry method.

PubMed

Tolan, Nicole V; Wockenfus, Amy M; Koch, Christopher D; Crews, Bridgit O; Dietzen, Dennis J; Karon, Brad S

2017-03-01

Point of care (POC) whole blood lactate testing may facilitate rapid detection of sepsis. We evaluated three POC methods against both plasma lactate comparison methods and a flow-injection mass spectrometric (MS) method. Nova StatStrip, Abbott i-STAT CG4+ and Radiometer ABL90 POC lactate methods were evaluated against the mean of Cobas Integra 400 and Vitros 350 plasma lactate. POC methods were also compared to a flow-injection mass spectrometric assay measuring lactate in ZnSO 4 -precipitated whole blood extracts. Intra- and inter-assay precision was determined using quality control material. Method comparison included specimens from normal donors at rest, after exertion, and after spiking with lactic acid. Intra- and inter-assay coefficient of variation was <5% for i-STAT and ABL90; but ranged from 3.1-8.2% on two StatStrip meters. Mean (±SD) bias between POC and plasma lactate ranged from -0.2±0.9 (i-STAT and ABL90) to -0.4±1.2 (StatStrip) mmol/L. At concentrations >6mmol/L, all POC methods showed proportional negative bias compared to plasma methods; but this bias was not observed when compared to the MS method. Despite proportional negative bias, all POC methods demonstrated acceptable concordance (94-100%) with plasma lactate within the reference interval (<2.3mmol/L) and >4mmol/L, commonly used clinical cut-offs for detection of sepsis. POC lactate methods demonstrate acceptable concordance with plasma lactate across commonly used clinical cut-offs for detection of sepsis. Due to systematic negative bias at higher lactate concentrations, POC and plasma lactate should not be used interchangeably to monitor patients with elevated lactate concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The Effect of Calf Gender on Milk Production in Seasonal Calving Cows and Its Impact on Genetic Evaluations

PubMed Central

Hess, Melanie K.; Hess, Andrew S.; Garrick, Dorian J.

2016-01-01

Gender of the calf whose birth initiates lactation could influence whole lactation milk yield of the dam due to hormonal influences on mammary gland development, or through calf gender effects on gestation length. Fetal gender could influence late lactation yields because cows become pregnant at peak lactation. The effects of calf gender sequences in parities 1–3 were assessed by separately fitting animal models to datasets from New Zealand comprising 274 000 Holstein Friesian and 85 000 Jersey cows, decreasing to 12 000 and 4 000 cows by parity 3. The lactation initiated by the birth of a female rather than a male calf was associated with a 0.33–1.1% (p≤0.05) higher milk yield. Female calf gender had carryover effects associated with higher milk yield in second lactations for Holstein Friesians (0.24%; p = 0.01) and third lactations for Jerseys (1.1%; p = 0.01). Cows giving birth to bull calves have 2 day longer gestations, which reduces lactation length in seasonal calving herds. Adding a covariate for lactation length to the animal model eroded some of these calf gender effects, such that calving a female led to higher milk yield only for second lactation Holstein Friesians (1.6%; p = 0.002). The interval centering method generates lower estimates of whole lactation yield when Wood’s lactation curves are shifted to the right by 2 days for male calves and this explained the higher yield in female calves when differences in lactation length were considered. Correlations of estimated breeding values between models including or excluding calf gender sequence were 1.00 for bulls or cows. Calf gender primarily influences milk yield through increased gestation length of male calves, and bias associated with the interval centering method used to estimate whole lactation milk yields. Including information on calf gender is unlikely to have an effect on selection response in New Zealand dairy cattle. PMID:26974166

Training-induced elevations in extracellular lactate in hippocampus and striatum: Dissociations by cognitive strategy and type of reward.

PubMed

Newman, Lori A; Scavuzzo, Claire J; Gold, Paul E; Korol, Donna L

2017-01-01

Recent evidence suggests that astrocytes convert glucose to lactate, which is released from the astrocytes and supports learning and memory. This report takes a multiple memory perspective to test the role of astrocytes in cognition using real-time lactate measurements during learning and memory. Extracellular lactate levels in the hippocampus or striatum were determined with lactate biosensors while rats were learning place (hippocampus-sensitive) or response (striatum-sensitive) versions of T-mazes. In the first experiment, rats were trained on the place and response tasks to locate a food reward. Extracellular lactate levels in the hippocampus increased beyond those of feeding controls during place training but not during response training. However, striatal lactate levels did not increase beyond those of controls when rats were trained on either the place or the response version of the maze. Because food ingestion itself increased blood glucose and brain lactate levels, the contribution of feeding may have confounded the brain lactate measures. Therefore, we conducted a second similar experiment using water as the reward. A very different pattern of lactate responses to training emerged when water was used as the task reward. First, provision of water itself did not result in large increases in either brain or blood lactate levels. Moreover, extracellular lactate levels increased in the striatum during response but not place learning, whereas extracellular lactate levels in the hippocampus did not differ across tasks. The findings from the two experiments suggest that the relative engagement of the hippocampus and striatum dissociates not only by task but also by reward type. The divergent lactate responses of the hippocampus and striatum in place and response tasks under different reward conditions may reflect ethological constraints tied to foraging for food and water. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.

PubMed

Wiegers, Evita C; Rooijackers, Hanne M; Tack, Cees J; Groenewoud, Hans J M M; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

2017-12-01

Since altered brain lactate handling has been implicated in the development of impaired awareness of hypoglycemia (IAH) in type 1 diabetes, the capacity to transport lactate into the brain during hypoglycemia may be relevant in its pathogenesis. High-intensity interval training (HIIT) increases plasma lactate levels. We compared the effect of HIIT-induced hyperlacticacidemia on brain lactate during hypoglycemia between 1 ) patients with type 1 diabetes and IAH, 2 ) patients with type 1 diabetes and normal awareness of hypoglycemia, and 3 ) healthy participants without diabetes ( n = 6 per group). All participants underwent a hypoglycemic (2.8 mmol/L) clamp after performing a bout of HIIT on a cycle ergometer. Before HIIT (baseline) and during hypoglycemia, brain lactate levels were determined continuously with J-difference-editing 1 H-MRS, and time curves were analyzed using nonlinear mixed-effects modeling. At the beginning of hypoglycemia (after HIIT), brain lactate levels were elevated in all groups but most pronounced in patients with IAH. During hypoglycemia, brain lactate decreased ∼30% below baseline in patients with IAH but returned to baseline levels and remained there in the other two groups. Our results support the concept of enhanced lactate transport as well as increased lactate oxidation in patients with type 1 diabetes and IAH. © 2017 by the American Diabetes Association.

Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

PubMed Central

Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

2016-01-01

ABSTRACT Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling. PMID:26636483

Radiosynthesis and validation of (±)-[18F]-3-fluoro-2-hydroxypropionate ([18F]-FLac) as a PET tracer of lactate to monitor MCT1-dependent lactate uptake in tumors.

PubMed

Van Hée, Vincent F; Labar, Daniel; Dehon, Gwenaël; Grasso, Debora; Grégoire, Vincent; Muccioli, Giulio G; Frédérick, Raphaël; Sonveaux, Pierre

2017-04-11

Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies. It depends on the expression and activity of monocarboxylate transporters (MCTs) at the cell membrane. MCT4 is the main facilitator of lactate export by glycolytic cancer cells, and MCT1 is adapted for lactate uptake by oxidative cancer cells. While MCT1 inhibitor AZD3965 is currently tested in phase I clinical trials and other inhibitors of lactate metabolism have been developed for anticancer therapy, predicting and monitoring a response to the inhibition of lactate uptake is still an unmet clinical need. Here, we report the synthesis, evaluation and in vivo validation of (±)-[18F]-3-fluoro-2-hydroxypropionate ([18F]-FLac) as a tracer of lactate for positron emission tomography. [18F]-FLac offers the possibility to monitor MCT1-dependent lactate uptake and inhibition in tumors in vivo.

Induction of triglyceride accumulation and mitochondrial maintenance in muscle cells by lactate

PubMed Central

Sun, Jingquan; Ye, Xin; Xie, Minhao; Ye, Jianping

2016-01-01

Muscle exercise induces intramuscular triglyceride (TG) accumulation and promotes mitochondrial maintenance in myotubes. However, the mechanism underlying exercise effects remains unknown. In this study, lactic acid was tested as a signaling molecule in C2C12 myotubes to understand the mechanism. Intracellular TG storage was induced in the cells by sodium lactate. The lactate activity was observed with an inhibition of the cAMP-PKA pathway as indicated by a reduction in the phosphorylation status of CREB (pCREB). Induction of pCREB signal by forskolin was blocked by pretreatment of cells with lactate. The impact of lactate on mitochondrial function was examined with a focus on the activities of two enzymes, MCAT (malonylCoA:ACP transferase) and PDH (pyruvate dehydrogenase). The enzyme activities were induced in the cells by lactate. Expression of the lactate receptor (GPR81) and lactate transporters (MCT1/4) were induced as well by lactate. The lactate activities were observed at concentrations between 4–64 mM, and were not dependent on the increase in intracellular pyruvate. Pyruvate treatment did not generate the same effects in the cells. Those results suggest that lactate may induce intramuscular TG storage and mitochondrial maintenance in myotubes through inhibition of the cAMP pathway by activation of GPR81 in a positive feedback manner. PMID:27645401

Cost-effectiveness analysis of early point-of-care lactate testing in the emergency department.

PubMed

Ward, Michael J; Self, Wesley H; Singer, Adam; Lazar, Danielle; Pines, Jesse M

2016-12-01

To determine the cost-effectiveness of implementing a point-of-care (POC) Lactate Program in the emergency department (ED) for patients with suspected sepsis to identify patients who can benefit from early resuscitation. We constructed a cost-effectiveness model to examine an ED with 30 000 patients annually. We evaluated a POC lactate program screening patients with suspected sepsis for an elevated lactate ≥4 mmol/L. Those with elevated lactate levels are resuscitated and their lactate clearance is evaluated by serial POC lactate measurements. The POC Lactate Program was compared with a Usual Care Strategy in which all patients with sepsis and an elevated lactate are admitted to the intensive care unit. Costs were estimated from the 2014 Medicare Inpatient and National Physician Fee schedules, and hospital and industry estimates. In the base-case, the POC Lactate Program cost $39.53/patient whereas the Usual Care Strategy cost $33.20/patient. The screened patients in the POC arm resulted in 1.07 quality-adjusted life years for an incremental cost-effectiveness ratio of $31 590 per quality-adjusted life year gained, well below accepted willingness-to-pay-thresholds. Implementing a POC Lactate Program for screening ED patients with suspected sepsis is a cost-effective intervention to identify patients responsive to early resuscitation. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiosynthesis and validation of (±)-[18F]-3-fluoro-2-hydroxypropionate ([18F]-FLac) as a PET tracer of lactate to monitor MCT1-dependent lactate uptake in tumors

PubMed Central

Van Hée, Vincent F.; Labar, Daniel; Dehon, Gwenaël; Grasso, Debora; Grégoire, Vincent; Muccioli, Giulio G

2017-01-01

Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies. It depends on the expression and activity of monocarboxylate transporters (MCTs) at the cell membrane. MCT4 is the main facilitator of lactate export by glycolytic cancer cells, and MCT1 is adapted for lactate uptake by oxidative cancer cells. While MCT1 inhibitor AZD3965 is currently tested in phase I clinical trials and other inhibitors of lactate metabolism have been developed for anticancer therapy, predicting and monitoring a response to the inhibition of lactate uptake is still an unmet clinical need. Here, we report the synthesis, evaluation and in vivo validation of (±)-[18F]-3-fluoro-2-hydroxypropionate ([18F]-FLac) as a tracer of lactate for positron emission tomography. [18F]-FLac offers the possibility to monitor MCT1-dependent lactate uptake and inhibition in tumors in vivo. PMID:28107190

l-Lactate metabolism in HEP G2 cell mitochondria due to the l-lactate dehydrogenase determines the occurrence of the lactate/pyruvate shuttle and the appearance of oxaloacetate, malate and citrate outside mitochondria.

PubMed

Pizzuto, Roberto; Paventi, Gianluca; Porcile, Carola; Sarnataro, Daniela; Daniele, Aurora; Passarella, Salvatore

2012-09-01

As part of an ongoing study of l-lactate metabolism both in normal and in cancer cells, we investigated whether and how l-lactate metabolism occurs in mitochondria of human hepatocellular carcinoma (Hep G2) cells. We found that Hep G2 cell mitochondria (Hep G2-M) possess an l-lactate dehydrogenase (ml-LDH) restricted to the inner mitochondrial compartments as shown by immunological analysis, confocal microscopy and by assaying ml-LDH activity in solubilized mitochondria. Cytosolic and mitochondrial l-LDHs were found to differ from one another in their saturation kinetics. Having shown that l-lactate itself can enter Hep G2 cells, we found that Hep G2-M swell in ammonium l-lactate, but not in ammonium pyruvate solutions, in a manner inhibited by mersalyl, this showing the occurrence of a carrier-mediated l-lactate transport in these mitochondria. Occurrence of the l-lactate/pyruvate shuttle and the appearance outside mitochondria of oxaloacetate, malate and citrate arising from l-lactate uptake and metabolism together with the low oxygen consumption and membrane potential generation are in favor of an anaplerotic role for l-LAC in Hep G2-M. Copyright © 2012 Elsevier B.V. All rights reserved.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

PubMed

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

Effect of Substrate Conversion on Performance of Microbial Fuel Cells and Anodic Microbial Communities.

PubMed

Zhao, Yang-Guo; Zhang, Yi; She, Zonglian; Shi, Yue; Wang, Min; Gao, Mengchun; Guo, Liang

2017-09-01

Performance of microbial fuel cells (MFCs) was monitored during the influent nutrient change from lactate to glucose/acetate/propionate and then to lactate. Meanwhile, anodic microbial communities were characterized by culture-independent molecular biotechnologies. Results showed MFC performance recovered rapidly when the lactate was replaced by one of its metabolic intermediates acetate, while it needed a longer time to recover if lactate substrate was converted to glucose/propionate or acetate to lactate. Secondary lactate feed enhanced the enrichment of bacterial populations dominating in first lactate feed. Electricity-producing bacteria, Geobacter spp., and beneficial helpers, Anaeromusa spp. and Pseudomonas spp., revived from a low abundance as lactate secondary supply, but microbial communities were hard to achieve former profiles in structure and composition. Hence, microbial community profiles tended to recover when outside environmental condition were restored. Different substrates selected unique functional microbial populations.

Mechanisms driving the lactate switch in Chinese hamster ovary cells.

PubMed

Hartley, Fiona; Walker, Tracy; Chung, Vicky; Morten, Karl

2018-03-31

The metabolism of Chinese Hamster Ovary (CHO) cells in a production environment has been extensively investigated. However, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. Though commonly observed in CHO cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. Despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. This review aims to consolidate current theories surrounding the lactate switch. The influence of pH, NAD + /NADH, pyruvate availability and mitochondrial function on lactate consumption are explored. A hypothesis based on the cellular redox state is put forward to explain the onset of lactate consumption. Various techniques implemented to control the lactate switch, including manipulation of the culture environment, genetic engineering, and cell line selection are also discussed. © 2018 Wiley Periodicals, Inc.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

PubMed Central

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

Determinants of nutrient adequacy for lactating and pregnant mothers in a rural area of Bangladesh.

PubMed

Chaudhury, R H

1984-12-01

This study used data from a rural area of Bangladesh to examine the nutrient adequacy of the diets of pregnant and lactating women. Of the 106 women 15-45 years of age in the survey population, 30 were lactating and 25 were pregnant. Average caloric requirements and safe levels of protein intake were estimated for each member of the households studied to determine whether a person cunsumed more, less, or equal to his or her average requirement. Women who were neither pregnant nor lactating were significantly more likely to be meeting their calorie and protein requirements than those who were pregnant or lactating. That is, pregnancy and/or lactation status exerts a depressing effect on the nutrient adequacy ratio of an adult woman. The nutrient adequacy ratios were lowest for pregnant or lactating women, followed by those for women who were both pregnant and lactating. In addition, the observed to expected consumption of calories and protein was significantly lower among lactating and/or pregnant women than among other women. Economic position, measured in terms of per capita expenditure on food/day, was the most important factor affecting the nutritional status of pregnant and lactating women. These findings have serious implications for child health in Bangladesh since the lactation performance of poorly nourished women is likely to be inadequate. There is a need for income-generating programs for the rural poor to enable them to increase their expenditures on food. Also needed are educational programs to raise the awareness of rural people concerning the higher nutrient needs of pregnant and lactating women.

Economic weights for genetic improvement of lactation persistency and milk yield.

PubMed

Togashi, K; Lin, C Y

2009-06-01

This study aimed to establish a criterion for measuring the relative weight of lactation persistency (the ratio of yield at 280 d in milk to peak yield) in restricted selection index for the improvement of net merit comprising 3-parity total yield and total lactation persistency. The restricted selection index was compared with selection based on first-lactation total milk yield (I(1)), the first-two-lactation total yield (I(2)), and first-three-lactation total yield (I(3)). Results show that genetic response in net merit due to selection on restricted selection index could be greater than, equal to, or less than that due to the unrestricted index depending upon the relative weight of lactation persistency and the restriction level imposed. When the relative weight of total lactation persistency is equal to the criterion, the restricted selection index is equal to the selection method compared (I(1), I(2), or I(3)). The restricted selection index yielded a greater response when the relative weight of total lactation persistency was above the criterion, but a lower response when it was below the criterion. The criterion varied depending upon the restriction level (c) imposed and the selection criteria compared. A curvilinear relationship (concave curve) exists between the criterion and the restricted level. The criterion increases as the restriction level deviates in either direction from 1.5. Without prior information of the economic weight of lactation persistency, the imposition of the restriction level of 1.5 on lactation persistency would maximize change in net merit. The procedure presented allows for simultaneous modification of multi-parity lactation curves.

Assessment of brain metabolite correlates of adeno-associated virus-mediated over-expression of human alpha-synuclein in cortical neurons by in vivo (1) H-MR spectroscopy at 9.4 T.

PubMed

Cuellar-Baena, Sandra; Landeck, Natalie; Sonnay, Sarah; Buck, Kerstin; Mlynarik, Vladimir; In 't Zandt, René; Kirik, Deniz

2016-06-01

In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild-type alpha-synuclein (α-syn) over-expression. Our goal was to find out if the increased α-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human α-syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). Next, we assessed the effect of age and found increased levels of GABA, Tau, and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lac levels (p = 0.005) were specifically lower in the α-syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector-injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose-lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N-acetylaspartate) consistent with the fact that α-syn over-expression in cortical neurons did not result in neurodegeneration in this model. We acquired the neurochemical profile longitudinally in a rat model of human wild-type alpha-synuclein (α-syn) over-expression in cortical neurons. We found that Lactate levels were reduced in the α-syn group compared to the control groups and Ascorbate levels were increased in the vector-injected groups. No changes were found in markers of neuronal integrity consistent with the fact that α-syn over-expression did not result in frank neurodegeneration. © 2016 International Society for Neurochemistry.

ED presentations of acute renal infarction.

PubMed

Huang, Chien-Cheng; Lo, Hong-Chang; Huang, Hsien-Hao; Kao, Wei-Fong; Yen, David Hung-Tsang; Wang, Lee-Min; Huang, Chun-I; Lee, Chen-Hsen

2007-02-01

The objective of the study was to investigate initial clinical characteristics that can suggest an early diagnosis of patients with acute renal infarction presenting with flank and/or abdominal pain in the emergency department (ED). From January 1, 1996, through December 31, 2005, 20 adult patients with renal infarction diagnosed by contrast-enhanced computed tomography in the ED were enrolled. Medical records, including demographic data, risk factors for thromboembolism, initial clinical presentations, laboratory data, treatment programs and outcomes, were retrospectively reviewed and analyzed. Mean patient age was 60.3 years (range, 21-80). The estimated incidence of renal infarction was 0.004% (20 of 481,540) among the ED census. The median time of onset of symptoms before the ED visit was 31 hours (range, 1-285). Eighteen patients (90%) had a history of more than 1 risk factor for thromboembolic events. In clinical presentations, all the patients had either abdominal or flank pain and tenderness. Nineteen patients (95%) had an elevated serum lactate dehydrogenase level with a mean +/- SD of 812.1 +/- 569.4 U/L. Sixteen patients (80%) presented with the triad--persisting flank or abdominal pain/tenderness, elevated serum lactate dehydrogenase level, and proteinuria. Among all 20 patients, 10 patients (50%) were diagnosed as having renal infarction at the initial ED visit. No specific clinical characteristics could be identified to distinguish those patients diagnosed early and those with delayed diagnosis. All 20 patients received medical treatment with coumadin, which was given in combination with heparin treatment in 11, peripheral intravenous and/or local intra-arterial thrombolytics with urokinase in 5, and mitral valve replacement in 1. No patient died. Although 4 patients had a mildly elevated serum creatinine level (>1.5 mg/dL) during hospitalization, none of them needs dialysis after more than 1 year of follow-up. In this study, we delineated specifically clinical features for emergency physicians to raise their suspicion index for an early diagnosis of patients with renal infarction, a disease which is uncommon and is usually delayed or missed at initial ED presentation.

Prolactin regulation of oxytocin neurone activity in pregnancy and lactation.

PubMed

Augustine, Rachael A; Ladyman, Sharon R; Bouwer, Gregory T; Alyousif, Yousif; Sapsford, Tony J; Scott, Victoria; Kokay, Ilona C; Grattan, David R; Brown, Colin H

2017-06-01

During lactation, prolactin promotes milk synthesis and oxytocin stimulates milk ejection. In virgin rats, prolactin inhibits the activity of oxytocin-secreting neurones. We found that prolactin inhibition of oxytocin neurone activity is lost in lactation, and that some oxytocin neurones were excited by prolactin in lactating rats. The change in prolactin regulation of oxytocin neurone activity was not associated with a change in activation of intracellular signalling pathways known to couple to prolactin receptors. The change in prolactin regulation of oxytocin neurone activity in lactation might allow coordinated activation of both populations of neurones when required for successful lactation. Secretion of prolactin for milk synthesis and oxytocin for milk secretion is required for successful lactation. In virgin rats, prolactin inhibits oxytocin neurones but this effect would be counterproductive during lactation when secretion of both hormones is required for synthesis and delivery of milk to the newborn. Hence, we determined the effects of intracerebroventricular (i.c.v.) prolactin on oxytocin neurones in urethane-anaesthetised virgin, pregnant and lactating rats. Prolactin (2 μg) consistently inhibited oxytocin neurones in virgin and pregnant rats (by 1.9 ± 0.4 and 1.8 ± 0.5 spikes s -1 , respectively), but not in lactating rats; indeed, prolactin excited six of 27 oxytocin neurones by >1 spike s -1 in lactating rats but excited none in virgin or pregnant rats (χ 2 2  = 7.2, P = 0.03). Vasopressin neurones were unaffected by prolactin (2 μg) in virgin rats but were inhibited by 1.1 ± 0.2 spikes s -1 in lactating rats. Immunohistochemistry showed that i.c.v. prolactin increased oxytocin expression in virgin and lactating rats and increased signal transducer and activator of transcription 5 phosphorylation to a similar extent in oxytocin neurones of virgin and lactating rats. Western blotting showed that i.c.v. prolactin did not affect phosphorylation of extracellular regulated kinase 1 or 2, or of Akt in the supraoptic or paraventricular nuclei of virgin or lactating rats. Hence, prolactin inhibition of oxytocin neurones is lost in lactation, which might allow concurrent elevation of prolactin secretion from the pituitary gland and activation of oxytocin neurones for synthesis and delivery of milk to the newborn. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer

PubMed Central

Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi

2018-01-01

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle. PMID:29856804

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

PubMed

Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi; Esumi, Hiroyasu

2018-01-01

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers—Applications of the Warburg Effect

PubMed Central

Goldberg, Joel S.

2011-01-01

It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA. PMID:21487535

Lactate as an insidious metabolite due to the Warburg effect.

PubMed

Luc, Raymond; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

2015-04-01

Although oncogenetics remains a critical component of cancer biology and therapeutic research, recent interest has been taken towards the non-genetic features of tumour development and progression, such as cancer metabolism. Specifically, it has been observed that tumour cells are inclined to preferentially undergo glycolysis despite presence of adequate oxygen. First reported by Otto Warburg in the 1920s, and now termed the 'Warburg effect', this aberrant metabolism has become of particular interest due to the prevalence of the fermentation phenotype in a variety of cancers studied. Consequently, this phenotype has proven to play a pivotal role in cancer proliferation. As such Warburg's observations are now being integrated within the modern paradigms of cancer and in this review we explore the role of lactate as an insidious metabolite due to the Warburg effect.

Discrete expression of TRPV2 within the hypothalamo-neurohypophysial system: Implications for regulatory activity within the hypothalamic-pituitary-adrenal axis.

PubMed

Wainwright, Anna; Rutter, A Richard; Seabrook, Guy R; Reilly, Kathryn; Oliver, Kevin R

2004-06-14

Transient receptor potential channel proteins (TRPs) constitute a steadily growing family of ion channels with a range of purported functions. It has been demonstrated that TRPV2 is activated by moderate thermal stimuli and, in the rat, is expressed in medium to large diameter dorsal root ganglion neurons. In this study, antisera specific for the human TRPV2 homologue were raised and characterized for immunohistochemical use. Subsequently, thorough investigation was made of the localization of this cation channel in the macaque primate brain. TRPV2-immunoreactive material was highly restrictively localized to hypothalamic paraventricular, suprachiasmatic, and supraoptic nuclei. Confocal double- and triple-labeling studies demonstrated that TRPV2 immunoreactivity is preferentially localized to oxytocinergic and vasopressinergic neurons. Few, if any, cells in these regions expressed TRPV2 immunoreactivity in the absence of oxytocin immunoreactivity or vasopressin immunoreactivity. Expression in the paraventricular and supraoptic nuclei suggests that TRPV2 is likely to play a fundamental role in mediating cation transport in neurohypophysial neurons. TRPV2 has been shown to be translocated upon cell activation and neurons expressing TRPV2 immunoreactivity in vivo are among those known to engage in sporadic, intense activity. Taken together, these data suggest that this channel may play a vital role in mediating physiological activities associated with oxytocin and vasopressin release such as parturition, lactation, and diuresis. These data may also implicate the involvement of TRPV2 in disorders of the hypothalamic-pituitary-adrenal axis, including anxiety, depression, hypertension, and preterm labor. Copyright 2004 Wiley-Liss, Inc.

Mathematical modelling of cell layer growth in a hollow fibre bioreactor.

PubMed

Chapman, Lloyd A C; Whiteley, Jonathan P; Byrne, Helen M; Waters, Sarah L; Shipley, Rebecca J

2017-04-07

Generating autologous tissue grafts of a clinically useful volume requires efficient and controlled expansion of cell populations harvested from patients. Hollow fibre bioreactors show promise as cell expansion devices, owing to their potential for scale-up. However, further research is required to establish how to specify appropriate hollow fibre bioreactor operating conditions for expanding different cell types. In this study we develop a simple model for the growth of a cell layer seeded on the outer surface of a single fibre in a perfused hollow fibre bioreactor. Nutrient-rich culture medium is pumped through the fibre lumen and leaves the bioreactor via the lumen outlet or passes through the porous fibre walls and cell layer, and out via ports on the outer wall of the extra-capillary space. Stokes and Darcy equations for fluid flow in the fibre lumen, fibre wall, cell layer and extra-capillary space are coupled to reaction-advection-diffusion equations for oxygen and lactate transport through the bioreactor, and to a simple growth law for the evolution of the free boundary of the cell layer. Cells at the free boundary are assumed to proliferate at a rate that increases with the local oxygen concentration, and to die and detach from the layer if the local fluid shear stress or lactate concentration exceed critical thresholds. We use the model to predict operating conditions that maximise the cell layer growth for different cell types. In particular, we predict the optimal flow rate of culture medium into the fibre lumen and fluid pressure imposed at the lumen outlet for cell types with different oxygen demands and fluid shear stress tolerances, and compare the growth of the cell layer when the exit ports on the outside of the bioreactor are open with that when they are closed. Model simulations reveal that increasing the inlet flow rate and outlet fluid pressure increases oxygen delivery to the cell layer and, therefore, the growth rate of cells that are tolerant to high shear stresses, but may be detrimental for shear-sensitive cells. The cell layer growth rate is predicted to increase, and be less sensitive to the lactate tolerance of the cells, when the exit ports are opened, as the radial flow through the bioreactor is enhanced and the lactate produced by the cells cleared more rapidly from the cell layer. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings.

PubMed

Uluc, Kayihan; Baskan, Ozdil; Yildirim, Kadriye Agan; Ozsahin, Selda; Koseoglu, Mesrure; Isak, Baris; Scheper, G C; Gunal, Dilek Ince; van der Knaap, M S

2008-10-15

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive mode of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, have been found as the underlying defect. We report a 19-year-old male patient with cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging (MRI) and characteristic magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound-heterozygous for two mutations in DARS2. MRI showed selective involvement of cerebral and cerebellar white matter and superior and inferior cerebellar peduncles, without contrast enhancement. The U-fibers were spared. The sensory and the pyramidal tracts were affected over their entire length. Involvement of the intraparenchymal trajectories of the trigeminal nerves and mesencephalic trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS of the frontal and cerebellar white matter showed elevated lactate, reduced N-acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2.

Improving Safe and Effective Use of Drugs in Pregnancy and Lactation: Workshop Summary.

PubMed

Riley, Laura E; Cahill, Alison G; Beigi, Richard; Savich, Renate; Saade, George

2017-07-01

In February 2015, given high rates of use of medications by pregnant women and the relative lack of data on safety and efficacy of many drugs utilized in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the Society for Maternal-Fetal Medicine (SMFM), the American College of Obstetricians and Gynecologists (ACOG), and the American Academy of Pediatrics (AAP) convened a group of experts to review the "current" state of the clinical care and science regarding medication use during the perinatal period. The expert panel chose select medications to demonstrate what existing safety and efficacy data may be available for clinicians and patients when making decisions about use in pregnancy or lactation. Furthermore, these example medications also provided opportunities to highlight where data are lacking, thus forming a list of research gaps. Last, after reviewing the existing vaccine safety surveillance system as well as the legislative history surrounding the use of drugs for pediatric diseases, the expert panel made specific recommendations concerning policy efforts to stimulate more research and regulatory attention on drugs for pregnant and lactating women. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

NMR studies of preimplantation embryo metabolism in human assisted reproductive techniques: a new biomarker for assessment of embryo implantation potential.

PubMed

Pudakalakatti, Shivanand M; Uppangala, Shubhashree; D'Souza, Fiona; Kalthur, Guruprasad; Kumar, Pratap; Adiga, Satish Kumar; Atreya, Hanudatta S

2013-01-01

There has been growing interest in understanding energy metabolism in human embryos generated using assisted reproductive techniques (ART) for improving the overall success rate of the method. Using NMR spectroscopy as a noninvasive tool, we studied human embryo metabolism to identify specific biomarkers to assess the quality of embryos for their implantation potential. The study was based on estimation of pyruvate, lactate and alanine levels in the growth medium, ISM1, used in the culture of embryos. An NMR study involving 127 embryos from 48 couples revealed that embryos transferred on Day 3 (after 72 h in vitro culture) with successful implantation (pregnancy) exhibited significantly (p < 10(-5) ) lower pyruvate/alanine ratios compared to those that failed to implant. Lactate levels in media were similar for all embryos. This implies that in addition to lactate production, successfully implanted embryos use pyruvate to produce alanine and other cellular functions. While pyruvate and alanine individually have been used as biomarkers, the present study highlights the potential of combining them to provide a single parameter that correlates strongly with implantation potential. Copyright © 2012 John Wiley & Sons, Ltd.

Physiological pattern changes in response to a simulated competition in elite women artistic gymnasts.

PubMed

Isacco, Laurie; Ennequin, Gaël; Cassirame, Johan; Tordi, Nicolas

2017-08-04

The outstanding progress in women's artistic gymnastics in recent decades has led to increased technical and physiological demands. The aim of this study was to investigate i) the physiological demands of elite French gymnasts and ii) the impact of a competitive routine on physiological pattern changes. Fourteen French elite female gymnasts performed anthropometric measurements, physical fitness tests and a simulated four event competition. Heart rate (HR) was continuously recorded throughout the duration of the simulated competition. Blood lactate concentrations were assessed at rest, before the beginning and at 2, 4 and 10 min after completion of the routine on each apparatus. Isometric handgrip strength and anaerobic endurance and power were assessed during the simulated competition. The highest values of HR and blood lactate concentrations were reached during the floor and uneven bar exercises. Blood lactate concentrations and HR kinetics were apparatus dependent and values remained significantly increased at 10 min of recovery compared with resting data. Anaerobic endurance and power decreased significantly as the competition progressed (P <0.001). The present results show specifically cardiorespiratory and anaerobic apparatus- dependent responses throughout a simulated competition. Recovery approaches appear relevant to prevent and/or minimize fatigue and optimize performance in these athletes.

Hepatic lipidosis in anorectic, lactating holstein cattle: a retrospective study of serum biochemical abnormalities.

PubMed

Cebra, C K; Garry, F B; Getzy, D M; Fettman, M J

1997-01-01

The association between hepatic lipidosis (HL) and disease in 59 anorectic, ketotic, lactating Holstein heifers and cows was investigated. Severe HL, as determined by histologic evaluation of liver tissue, was present in 46 animals; only half of these animals required intensive treatment for ketosis, and only half had serum biochemical evidence of liver disease, as determined by the presence of a last value of 2-fold or greater than the upper limit of the reference ranges for at least 2 of the 4 serum tests: gamma-glutamyl transferase, aspartate aminotransferase, and sorbitol dehydrogenase activities and bile acid concentrations. Most cattle with biochemical evidence of liver disease and severe HL had been lactating for 14 or more days. Cows that required intensive treatment inconsistently had serum biochemical evidence of liver disease. Although cattle with severe HL had significantly higher serum bilirubin concentrations and aspartate aminotransferase and sorbitol dehydrogenase activities than cattle with less severe lipidosis, the specificity of abnormally high serum sorbitol dehydrogenase activity or bilirubin concentration for severe lipidosis was only 8%. Abnormally high serum aspartate aminotransferase activity was 83% sensitive and 62% specific for severe lipidosis. Serum glucose and total carbon dioxide concentrations were significantly lower in cattle with severe lipidosis than in those with mild or moderate lipidosis, and low serum glucose or total carbon dioxide concentrations were rare in cattle without severe lipidosis. From these data, we conclude that the use of a single biochemical or histopathologic criterion to define severity of disease or degree of liver compromise in anorectic, ketotic cows results in the misidentification of many animals.

Serum-free suspension cultivation of PER.C6(R) cells and recombinant adenovirus production under different pH conditions.

PubMed

Xie, Liangzhi; Pilbrough, Warren; Metallo, Christian; Zhong, Tanya; Pikus, Lana; Leung, John; Auniņs, John G; Zhou, Weichang

2002-12-05

PER.C6(R) cell growth, metabolism, and adenovirus production were studied in head-to-head comparisons in stirred bioreactors under different pH conditions. Cell growth rate was found to be similar in the pH range of 7.1-7.6, while a long lag phase and a slower growth rate were observed at pH 6.8. The specific consumption rates of glucose and glutamine decreased rapidly over time during batch cell growth, as did the specific lactate and ammonium production rates. Cell metabolism in both infected and uninfected cultures was very sensitive to culture pH, resulting in dramatic differences in glucose/glutamine consumption and lactate/ammonium production under different pH conditions. It appeared that glucose metabolism was suppressed at low pH but the efficiency of energy production from glucose was enhanced. Adenovirus infection resulted in profound changes in cell growth and metabolism. Cell growth was largely arrested under all pH conditions, while glucose consumption and lactate production were elevated post virus infection. Virus infection induced a reduction in glutamine consumption at low pH but an increase at high pH. The optimal pH for adenovirus production was found to be 7.3 under the experimental conditions used in the study. Deviations from this optimum resulted in significant reductions of virus productivity. The results indicate that culture pH is a very critical process parameter in PER.C6(R) cell culture and adenovirus production. Copyright 2002 Wiley Periodicals, Inc.

Dietary choline supplementation to dams during pregnancy and lactation mitigates the effects of in utero stress exposure on adult anxiety-related behaviors.

PubMed

Schulz, Kalynn M; Pearson, Jennifer N; Gasparrini, Mary E; Brooks, Kayla F; Drake-Frazier, Chakeer; Zajkowski, Megan E; Kreisler, Alison D; Adams, Catherine E; Leonard, Sherry; Stevens, Karen E

2014-07-15

Brain cholinergic dysfunction is associated with neuropsychiatric illnesses such as depression, anxiety, and schizophrenia. Maternal stress exposure is associated with these same illnesses in adult offspring, yet the relationship between prenatal stress and brain cholinergic function is largely unexplored. Thus, using a rodent model, the current study implemented an intervention aimed at buffering the potential effects of prenatal stress on the developing brain cholinergic system. Specifically, control and stressed dams were fed choline-supplemented or control chow during pregnancy and lactation, and the anxiety-related behaviors of adult offspring were assessed in the open field, elevated zero maze and social interaction tests. In the open field test, choline supplementation significantly increased center investigation in both stressed and nonstressed female offspring, suggesting that choline-supplementation decreases female anxiety-related behavior irrespective of prenatal stress exposure. In the elevated zero maze, prenatal stress increased anxiety-related behaviors of female offspring fed a control diet (normal choline levels). However, prenatal stress failed to increase anxiety-related behaviors in female offspring receiving supplemental choline during gestation and lactation, suggesting that dietary choline supplementation ameliorated the effects of prenatal stress on anxiety-related behaviors. For male rats, neither prenatal stress nor diet impacted anxiety-related behaviors in the open field or elevated zero maze. In contrast, perinatal choline supplementation mitigated prenatal stress-induced social behavioral deficits in males, whereas neither prenatal stress nor choline supplementation influenced female social behaviors. Taken together, these data suggest that perinatal choline supplementation ameliorates the sex-specific effects of prenatal stress. Published by Elsevier B.V.

Dietary choline supplementation to dams during pregnancy and lactation mitigates the effects of in utero stress exposure on adult anxiety-related behaviors

PubMed Central

Schulz, Kalynn M.; Pearson, Jennifer N.; Gasparrini, Mary E.; Brooks, Kayla F.; Drake-Frazier, Chakeer; Zajkowski, Megan E.; Kreisler, Alison D.; Adams, Catherine E.; Leonard, Sherry; Stevens, Karen E.

2014-01-01

Brain cholinergic dysfunction is associated with neuropsychiatric illnesses such as depression, anxiety, and schizophrenia. Maternal stress exposure is associated with these same illnesses in adult offspring, yet the relationship between prenatal stress and brain cholinergic function is largely unexplored. Thus, using a rodent model, the current study implemented an intervention aimed at buffering the potential effects of prenatal stress on the developing brain cholinergic system. Specifically, control and stressed dams were fed choline-supplemented or control chow during pregnancy and lactation, and the anxiety-related behaviors of adult offspring were assessed in the open field, elevated zero maze and social interaction tests. In the open field test, choline supplementation significantly increased center investigation in both stressed and nonstressed female offspring, suggesting that choline-supplementation decreases female anxiety-related behavior irrespective of prenatal stress exposure. In the elevated zero maze, prenatal stress increased anxiety-related behaviors of female offspring fed a control diet (normal choline levels). However, prenatal stress failed to increase anxiety-related behaviors in female offspring receiving supplemental choline during gestation and lactation, suggesting that dietary choline supplementation ameliorated the effects of prenatal stress on anxiety-related behaviors. For male rats, neither prenatal stress nor diet impacted anxiety-related behaviors in the open field or elevated zero maze. In contrast, perinatal choline supplementation mitigated prenatal stress-induced social behavioral deficits in males, whereas neither prenatal stress nor choline supplementation influenced female social behaviors. Taken together, these data suggest that perinatal choline supplementation ameliorates the sex-specific effects of prenatal stress. PMID:24675162

Increased densities of monocarboxylate transporter MCT1 after chronic hyperglycemia in rat brain.

PubMed

Canis, Martin; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

2009-02-27

The brain is capable of taking up monocarboxylates as energy substrates. Under physiological conditions, plasma levels of monocarboxylates are very low and glucose is the primary energy substrate in brain metabolism. However, given conditions such as hyperglycemia and ketosis, levels of circulating monocarboxylates such as lactate and pyruvate are elevated. Previous studies reported an increased expression of monocarboxylate transporter MCT1 in brain following ketotic diet. The major aim of the present study was to answer the question whether chronic hyperglycemia is likewise sufficient to change local densities of MCT1 in the brain. Moreover, chronic hyperglycemia increases local cerebral glucose utilization (LCGU) in particular brain areas. Glucose hereby enters the brain parenchyma via glucose transporters and is partially metabolised by astrocytes, which then release lactate to meet the energetic demands of surrounding neurons. Streptozotocin was given intravenously to induce chronic hyperglycemia and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. The density of monocarboxylate transporter MCT1 was significantly increased in 10 of 24 brain structures investigated (median increase 11.7+/-3.4 %). Immunocytochemical stainings of these substructures revealed an expression of MCT1 within endothelial cells and astrocytes. A comparison of MCT1 densities with LCGU measured in a previous study under normo- and hyperglycemic conditions revealed a partial correlation between both parameters and under both conditions. Four out of 10 brain areas, which showed a significant increase in MCT1 density due to hyperglycemia, also showed a significant increase in LCGU. In summary, our data show that chronic hyperglycemia induces a moderate increase of local and global density of MCT1 in several brain structures. However, in terms of brain topologies and substructures this phenomenon did only partially match with increased LCGU. It is concluded that MCT1 transporters were up-regulated during chronic hyperglycemia at the level of brain substructures and independently of LCGU.

Growth and Development Symposium: Inflammation: Role in the etiology and pathophysiology of clinical mastitis in dairy cows.

PubMed

Ballou, M A

2012-05-01

Genetic selection for increased milk production in dairy cattle was not associated with an attenuated inflammatory response. The systemic and local inflammatory responses contribute to altered metabolism, reduced production performance, and increased cull rate of lactating dairy cows with clinical mastitis. More aggressive inflammatory responses were observed during the peripartum period when compared with cows in late lactation after an intramammary challenge with purified lipopolysaccharide. The epidemiology of clinical mastitis indicates that the greatest incidence is observed during the peripartum period; therefore, an enhanced inflammatory response with concomitant suppression in other immune responses may be involved in the etiology and severity of the clinical mastitis observed in peripartum cows. Milk production losses and compositional changes are observed among all mammary quarters from a cow with clinical mastitis, but the responses are more severe and sustained among infected quarters. The infected mammary quarters reflect both the systemic and local reactions, whereas uninfected quarters represent only the systemic response. The systemic effects of the inflammatory response include reduced DMI, hyperthermia, and changes in whole-body nutrient partitioning affecting mammary epithelial substrate availability, whereas local inflammatory effects include energetic requirements of the increased inflammatory leukocyte pool, decreased synthetic capacity of mammary epithelium independent of substrate availability, and paracellular leakage of milk components from the alveolar lumen into the extracellular fluid. Research has focused on improving host immunological defenses, attenuating the inflammatory response, or improving the resolution of the disease state to limit the deleterious effects during clinical mastitis. This paper highlights the role inflammation plays in the etiology and pathophysiology of clinical mastitis as well as potential management strategies to reduce or prevent those losses.

Does living near a Superfund site contribute to higher polychlorinated biphenyl (PCB) exposure?

PubMed

Choi, Anna L; Levy, Jonathan I; Dockery, Douglas W; Ryan, Louise M; Tolbert, Paige E; Altshul, Larisa M; Korrick, Susan A

2006-07-01

We assessed determinants of cord serum polychlorinated biphenyl (PCB) levels among 720 infants born between 1993 and 1998 to mothers living near a PCB-contaminated Superfund site in Massachusetts, measuring the sum of 51 PCB congeners (capital sigmaPCB) and ascertaining maternal address, diet, sociodemographics, and exposure risk factors. Addresses were geocoded to obtain distance to the Superfund site and neighborhood characteristics. We modeled log10(capital sigmaPCB) as a function of potential individual and neighborhood risk factors, mapping model residuals to assess spatial correlates of PCB exposure. Similar analyses were performed for light (mono-tetra) and heavy (penta-deca) PCBs to assess potential differences in exposure pathways as a function of relative volatility. PCB-118 (relatively prevalent in site sediments and cord serum) was assessed separately. The geometric mean of capital sigmaPCB levels was 0.40 (range, 0.068-18.14) ng/g serum. Maternal age and birthplace were the strongest predictors of capital sigmaPCB levels. Maternal consumption of organ meat and local dairy products was associated with higher and smoking and previous lactation with lower capital sigmaPCB levels. Infants born later in the study had lower capital sigmaPCB levels, likely due to temporal declines in exposure and site remediation in 1994-1995. No association was found between capital sigmaPCB levels and residential distance from the Superfund site. Similar results were found with light and heavy PCBs and PCB-118. Previously reported demographic (age) and other (lactation, smoking, diet) correlates of PCB exposure, as well as local factors (consumption of local dairy products and Superfund site dredging) but not residential proximity to the site, were important determinants of cord serum PCB levels in the study community.

Change in Lactate Levels After Hemodialysis in Patients With End-Stage Renal Disease.

PubMed

Hourmozdi, Justin J; Gill, Jasreen; Miller, Joseph B; Markin, Abraham; Adams, Beth; Soi, Vivek; Jaehne, Anja K; Taylor, Andrew R; Langberg, Sam; Rodriguez, Lauren; Fox, Carynne; Uduman, Junior; Yessayan, Lenar T; Rivers, Emanuel P

2018-06-01

Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels. This was a prospective observational cohort study performed at an outpatient dialysis facility at an urban tertiary care hospital. The study consisted of 226 patients with end-stage renal disease who were receiving long-term hemodialysis and were enrolled during a 2-day period at the beginning of December 2015. Blood drawn for lactate levels was immediately analyzed before and after hemodialysis sessions. All patients completed their hemodialysis sessions. The prevalence of an abnormal lactate level (greater than 1.8 mmol/L) before hemodialysis was 17.7% (n=40). Overall, lactate levels decreased by 27% (SD 35%) after hemodialysis, with a decrease of 37% (SD 31%) for subgroups with a lactate level of 1.9 to 2.4 mmol/L, and 62% (SD 14%) with a lactate of 2.5 to 3.9 mmol/L. The data presented help providers understand the prevalence of abnormal lactate values in an outpatient end-stage renal disease population. After hemodialysis, lactate levels decreased significantly. This information may help medical providers interpret lactate values when patients with end-stage renal disease present to the ED. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Genetics of heat tolerance for milk yield and quality in Holsteins.

PubMed

Santana, M L; Bignardi, A B; Pereira, R J; Stefani, G; El Faro, L

2017-01-01

Tropical and sub-tropical climates are characterized by high temperature and humidity, during at least part of the year. Consequently, heat stress is common in Holstein cattle and productive and reproductive losses are frequent. Our objectives were as follows: (1) to quantify losses in production and quality of milk due to heat stress; (2) to estimate genetic correlations within and between milk yield (MY) and milk quality traits; and (3) to evaluate the trends of genetic components of tolerance to heat stress in multiple lactations of Brazilian Holstein cows. Thus, nine analyses using two-trait random regression animal models were carried out to estimate variance components and genetic parameters over temperature-humidity index (THI) values for MY and milk quality traits (three lactations: MY×fat percentage (F%), MY×protein percentage (P%) and MY×somatic cell score (SCS)) of Brazilian Holstein cattle. It was demonstrated that the effects of heat stress can be harmful for traits related to milk production and milk quality of Holstein cattle even though most herds were maintained in a modified environment, for example, with fans and sprinklers. For MY, the effect of heat stress was more detrimental in advanced lactations (-0.22 to -0.52 kg/day per increase of 1 THI unit). In general, the mean heritability estimates were higher for lower THI values and longer days in milk for all traits. In contrast, the heritability estimates for SCS increased with increasing THI values in the second and third lactation. For each trait studied, lower genetic correlations (different from unity) were observed between opposite extremes of THI (THI 47 v. THI 80) and in advanced lactations. The genetic correlations between MY and milk quality trait varied across the THI scale and lactations. The genotype×environment interaction due to heat stress was more important for MY and SCS, particularly in advanced lactations, and can affect the genetic relationship between MY and milk quality traits. Selection for higher MY, F% or P% may result in a poor response of the animals to heat stress, as a genetic antagonism was observed between the general production level and specific ability to respond to heat stress for these traits. Genetic trends confirm the adverse responses in the genetic components of heat stress over the years for milk production and quality. Consequently, the selection of Holstein cattle raised in modified environments in both tropical and sub-tropical regions should take into consideration the genetic variation in heat stress.

Dietary selenium and nutritional plane alter specific aspects of maternal endocrine status during pregnancy and lactation.

PubMed

Lemley, C O; Meyer, A M; Neville, T L; Hallford, D M; Camacho, L E; Maddock-Carlin, K R; Wilmoth, T A; Wilson, M E; Perry, G A; Redmer, D A; Reynolds, L P; Caton, J S; Vonnahme, K A

2014-01-01

Objectives were to examine effects of selenium (Se) supply and maternal nutritional plane during gestation on placental size at term and maternal endocrine profiles throughout gestation and early lactation. Ewe lambs (n = 84) were allocated to treatments that included Se supply of adequate Se (ASe; 11.5 μg/kg BW) or high Se (HSe; 77 μg/kg BW) initiated at breeding and nutritional plane of 60% (RES), 100% (CON), or 140% (EXC) of requirements beginning on day 40 of gestation. At parturition, lambs were removed from their dams, and ewes were transitioned to a common diet that met requirements of lactation. Blood samples were taken from a subset of ewes (n = 42) throughout gestation, during parturition, and throughout lactation to determine hormone concentrations. Cotyledon number was reduced (P = 0.03) in RES and EXC ewes compared with CON ewes. Placental delivery time tended (P = 0.08) to be shorter in HSe ewes than in ASe ewes, whereas placental delivery time was longer (P = 0.02) in RES ewes than in CON and EXC ewes. During gestation, maternal progesterone, estradiol-17β, and GH were increased (P < 0.05) in RES ewes and decreased (P < 0.05) in EXC ewes compared with CON ewes. In contrast, maternal cortisol, IGF-I, prolactin, triiodothyronine, and thyroxine were decreased in RES ewes and increased in EXC ewes compared with CON ewes during gestation. Selenium supply did not alter maternal hormone profiles during gestation. During parturition and lactation, maternal hormone concentrations were influenced by both Se and maternal nutritional plane. During the parturient process, HSe ewes tended to have greater (P = 0.06) concentrations of estradiol-17β than ASe ewes. Three hours after parturition a surge of GH was observed in ASe-RES ewes that was muted in HSe-RES ewes and not apparent in other ewes. Growth hormone area under the curve during the parturient process was increased (P < 0.05) in ASe-RES vs HSe-RES ewes. Ewes that were overfed during gestation had reduced (P < 0.05) estradiol-17β but greater IGF-I, triiodothyronine, and thyroxine (P < 0.05) compared with RES ewes. Even though ewes were transitioned to a common diet after parturition, endocrine status continued to be affected into lactation. Moreover, it appears that gestational diet may partially affect lactational performance through altered endocrine status. Copyright © 2014 Elsevier Inc. All rights reserved.

Human Milk Cells and Lipids Conserve Numerous Known and Novel miRNAs, Some of Which Are Differentially Expressed during Lactation

PubMed Central

Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

2016-01-01

Human milk (HM) is rich in miRNAs, which are thought to contribute to infant protection and development. We used deep sequencing to profile miRNAs in the cell and lipid fractions of HM obtained post-feeding from 10 lactating women in months 2, 4, and 6 postpartum. In both HM fractions, 1,195 mature known miRNAs were identified, which were positively associated with the cell (p = 0.048) and lipid (p = 0.010) content of HM. An additional 5,167 novel miRNA species were predicted, of which 235 were high-confidence miRNAs. HM cells contained more known miRNAs than HM lipids (1,136 and 835 respectively, p<0.001). Although the profile of the novel miRNAs was very different between cells and lipids, with the majority conserved in the cell fraction and being mother-specific, 2/3 of the known miRNAs common between cells and lipids were similarly expressed (p>0.05). Great similarities between the two HM fractions were also found in the profile of the top 20 known miRNAs. These were largely similar also between the three lactation stages examined, as were the total miRNA concentration, and the number and expression of the known miRNAs common between cells and lipids (p>0.05). Yet, approximately a third of all known miRNAs were differentially expressed during the first 6 months of lactation (p<0.05), with more pronounced miRNA upregulation seen in month 4. These findings indicate that although the total miRNA concentration of HM cells and lipids provided to the infant does not change in first 6 months of lactation, the miRNA composition is altered, particularly in month 4 compared to months 2 and 6. This may reflect the remodeling of the gland in response to infant feeding patterns, which usually change after exclusive breastfeeding, suggesting adaptation to the infant’s needs. PMID:27074017

Community pharmacists’ services for women during pregnancy and breast feeding in Kuwait: a cross-sectional study

PubMed Central

Albassam, Abdullah

2018-01-01

Objectives This study was designed to identify the services provided by community pharmacists in Kuwait and their views regarding self-care in pregnancy and lactation. In addition, it determined the pharmacists’ recommendations for treatment of pregnancy-related and breast feeding-related ailments. Design Cross-sectional questionnaire-based survey. Setting Community pharmacies in Kuwait. Participants 207 pharmacies were randomly selected from the Ministry of Health database. One registered pharmacist was approached from each pharmacy. One hundred and ninety-two (92.8%) pharmacists agreed to participate and completed a self-administered questionnaire. Outcomes The proportions of pharmacists offering particular advice for health conditions in pregnancy and lactation, pharmacists’ recommendations for common and specific ailments during pregnancy and breast feeding, and pharmacists’ views about self-care in pregnancy and breast feeding. Results The top services provided to pregnant and lactating women were recommending vitamins and food supplements (89.8%) and contraception advice (83.4%), respectively. More than half of participants indicated that they would recommend medications for headache, constipation, cough, runny nose, sore throat, nausea/vomiting, indigestion, sore or cracked nipple and insufficient milk. Diarrhoea, haemorrhoids, insomnia, varicose vein, swelling of the feet and legs, vaginal itching, back pain, fever, mastitis and engorgement were frequently referred to the physician. Recommendations on medication use were occasionally inappropriate in terms of unneeded drug therapy, off-label use and safety. In relation to offering advice and solving medication and health problems of pregnant and lactating women, more than half of pharmacists indicated that they have sufficient knowledge (61.5%; 50.5%) and confidence (58.3%; 53.1%), respectively. Most of the respondents (88.5%) agreed that a continuing education programme on this topic would be of value for their practice. Conclusion The present findings show that respondents had different recommendations for treatment of pregnancy-related and lactation-related ailments; and also highlight the need for interventions, including continuing professional development and revision of the undergraduate pharmacy curriculum. PMID:29306891

Characterization of the major dehydrogenase related to d-lactic acid synthesis in Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293.

PubMed

Li, Ling; Eom, Hyun-Ju; Park, Jung-Mi; Seo, Eunyoung; Ahn, Ji Eun; Kim, Tae-Jip; Kim, Jeong Hwan; Han, Nam Soo

2012-10-10

Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 is a lactic acid bacterium that converts pyruvate mainly to d-(-)-lactic acid by using d-(-)-lactate dehydrogenase (ldhD). The aim of this study was to identify the gene responsible for d-lactic acid formation in this organism and to characterize the enzyme to facilitate the production of optically pure d-lactic acid. A genomic analysis of L. mesenteroides ATCC 8293 revealed that 7 genes encode lactate-related dehydrogenase. According to transcriptomic, proteomic, and phylogenetic analyses, LEUM_1756 was the major gene responsible for the production of d-lactic acid. The LEUM_1756 gene, of 996bp and encoding 332 amino acids (36.5kDa), was cloned and overexpressed in Escherichia coli BL21(DE3) Star from an inducible pET-21a(+) vector. The enzyme was purified by Ni-NTA column chromatography and showed a specific activity of 4450U/mg, significantly higher than those of other previously reported ldhDs. The gel permeation chromatography analysis showed that the purified enzyme exists as tetramers in solution and this was the first report among lactic acid bacteria. The pH and temperature optima were pH 8.0 and 30°C, respectively, for the pyruvate reduction reaction, and pH 11.0 and 20°C, respectively, for the lactate oxidation reaction. The K(m) kinetic parameters for pyruvate and lactate were 0.58mM and 260mM, respectively. In addition, the k(cat) values for pyruvate and lactate were 2900s(-1) and 2280s(-1), respectively. The enzyme was not inhibited by Ca(2+), Co(2+), Cu(2+), Mg(2+), Mn(2+), Na(+), or urea, but was inhibited by 1mM Zn(2+) and 1mM SDS. Copyright © 2012 Elsevier Inc. All rights reserved.

Metabolic fuel kinetics in fish: swimming, hypoxia and muscle membranes.

PubMed

Weber, Jean-Michel; Choi, Kevin; Gonzalez, Alex; Omlin, Teye

2016-01-01

Muscle performance depends on the supply of metabolic fuels and disposal of end-products. Using circulating metabolite concentrations to infer changes in fluxes is highly unreliable because the relationship between these parameters varies greatly with physiological state. Quantifying fuel kinetics directly is therefore crucial to the understanding of muscle metabolism. This review focuses on how carbohydrates, lipids and amino acids are provided to fish muscles during hypoxia and swimming. Both stresses force white muscle to produce lactate at higher rates than it can be processed by aerobic tissues. However, lactate accumulation is minimized because disposal is also strongly stimulated. Exogenous supply shows that trout have a much higher capacity to metabolize lactate than observed during hypoxia or intense swimming. The low density of monocarboxylate transporters and their lack of upregulation with exercise explain the phenomenon of white muscle lactate retention. This tissue operates as a quasi-closed system, where glycogen stores act as an 'energy spring' that alternates between explosive power release during swimming and slow recoil from lactate in situ during recovery. To cope with exogenous glucose, trout can completely suppress hepatic production and boost glucose disposal. Without these responses, glycemia would increase four times faster and reach dangerous levels. The capacity of salmonids for glucoregulation is therefore much better than presently described in the literature. Instead of albumin-bound fatty acids, fish use lipoproteins to shuttle energy from adipose tissue to working muscles during prolonged exercise. Proteins may play an important role in fueling muscle work in fish, but their exact contribution is yet to be established. The membrane pacemaker theory of metabolism accurately predicts general properties of muscle membranes such as unsaturation, but it does not explain allometric patterns of specific fatty acids. Investigations of metabolic fuel kinetics carried out in fish to date have demonstrated that these ectotherms use several unique strategies to orchestrate energy supply to working muscles and to survive hypoxia. © 2016. Published by The Company of Biologists Ltd.