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Sample records for decreases lactate signal

  1. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

    Science.gov (United States)

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

    2016-04-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure. © 2016 John Wiley & Sons Australia, Ltd.

  2. Lactate transport and signaling in the brain

    DEFF Research Database (Denmark)

    Bergersen, Linda Hildegard

    2015-01-01

    AMP. 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......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...

  3. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

    KAUST Repository

    Jourdain, P.

    2016-02-19

    Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

  4. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

    KAUST Repository

    Jourdain, P.; Allaman, I.; Rothenfusser, K.; Fiumelli, Hubert; Marquet, P.; Magistretti, Pierre J.

    2016-01-01

    Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

  5. Lactate in the brain: from metabolic end-product to signalling molecule

    KAUST Repository

    Magistretti, Pierre J.

    2018-03-08

    Lactate in the brain has long been associated with ischaemia; however, more recent evidence shows that it can be found there under physiological conditions. In the brain, lactate is formed predominantly in astrocytes from glucose or glycogen in response to neuronal activity signals. Thus, neurons and astrocytes show tight metabolic coupling. Lactate is transferred from astrocytes to neurons to match the neuronal energetic needs, and to provide signals that modulate neuronal functions, including excitability, plasticity and memory consolidation. In addition, lactate affects several homeostatic functions. Overall, lactate ensures adequate energy supply, modulates neuronal excitability levels and regulates adaptive functions in order to set the \\'homeostatic tone\\' of the nervous system.

  6. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

    KAUST Repository

    Yang, Jiangyan

    2014-07-28

    L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.

  7. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons

    KAUST Repository

    Yang, Jiangyan; Ruchti, Evelyne; Petit, Jean Marie; Jourdain, Pascal; Grenningloh, Gabriele; Allaman, Igor; Magistretti, Pierre J.

    2014-01-01

    L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.

  8. Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy.

    Science.gov (United States)

    Oishi, Yoshimi; Tsukamoto, Hayato; Yokokawa, Takumi; Hirotsu, Keisuke; Shimazu, Mariko; Uchida, Kenji; Tomi, Hironori; Higashida, Kazuhiko; Iwanaka, Nobumasa; Hashimoto, Takeshi

    2015-03-15

    We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals. Copyright © 2015 the American Physiological Society.

  9. MR spectroscopy detection of lactate and lipid signals in the brains of healthy elderly people

    Energy Technology Data Exchange (ETDEWEB)

    Sijens, P.E.; Heijboer, R.J.J.; Oudkerk, M. [Dept. of Radiology, Univ. Hospital Groningen (Netherlands); Heijer, T. den; Leeuw, F.E. de; Groot, J.C. de; Hofman, A.; Breteler, M.M.B. [Dept. of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam (Netherlands); Achten, E. [Dept. of Magnetic Resonance, Gent University Hospital (Belgium)

    2001-08-01

    Magnetic resonance spectroscopy was used to assess the presence of brain lactate and lipid signals, frequently associated with the presence of pathology, in healthy persons of 60-90 years old (n=540). Lactate and lipid signals were observed in, respectively, 25 and 6% of women, and 18 and 2% of men. Upon adjustment for age, and for MRI-detected cerebral atrophy and white matter lesions, the gender differences in lactate and lipid remained the same (p=0.05 and p=0.03, respectively). Brain lactate and lipid signals appear to be intrinsic to aging. However, the presence of these metabolites in very focal areas only, rather than in any distributed fashion within the brain (the latter generally the case with cerebral atrophy and white matter lesions), strongly suggests the existence of asymptomatic focal pathology not shown on MRI. (orig.)

  10. Lactation Biology Symposium: Lactocrine signaling and developmental programming

    Science.gov (United States)

    Lactocrine signaling is defined as transmission of bioactive factors from mother to offspring as a consequence of nursing. Lactocrine transmission of signaling molecules may be an evolutionarily conserved process through which bioactive factors necessary for support of neonatal development are deliv...

  11. Effect of decreasing dietary phosphorus supply on net recycling of inorganic phosphate in lactating dairy cows.

    Science.gov (United States)

    Puggaard, L; Kristensen, N B; Sehested, J

    2011-03-01

    Five ruminally cannulated lactating Holstein cows, fitted with permanent indwelling catheters in the mesenteric vein, hepatic vein, portal vein, and an artery were used to study intestinal absorption and net recycling of inorganic phosphate (P(i)) to the gastrointestinal tract. Treatments were low P (LP; 2.4 g of P/kg of DM) and high P (HP; 3.4 g of P/kg of DM). The dietary total P (tP) concentrations were obtained by replacing 0.50% calcium carbonate in the LP diet with 0.50% monocalcium phosphate in the HP diet. Diets were fed for 14 d and cows were sampled on d 14 in each period. Cows were fed restrictively, resulting in equal dry matter intakes as well as milk, fat, and protein yields between treatments. Net P(i) recycling (primarily salivary) was estimated as the difference between net portal plasma flux (net absorption of P(i)) and apparently digested tP (feed - fecal tP difference). Phosphorus intake, apparently digested tP, and fecal tP excretion decreased with LP. An effect of decreased tP intake on net portal plasma flux of P(i) could not be detected. However, despite numerically minute net fluxes across the liver, the net splanchnic flux of P(i) was less in LP compared with that in HP. Though arterial plasma P(i) concentration decreased, net P(i) recycling was not decreased when tP intake was decreased, and recycling of P(i) was maintained at the expense of deposition of P(i) in bones. Data are not consistent with salivary P(i) secretion being the primary regulator of P(i) homeostasis at low tP intakes. On the contrary, maintaining salivary P(i) recycling at low tP intakes indicates that rumen function was prioritized at the expense of bone P reserves. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Crude glycerin decreases nonesterified fatty acid concentration in ewes during late gestation and early lactation.

    Science.gov (United States)

    Polizel, D M; Susin, I; Gentil, R S; Ferreira, E M; de Souza, R A; Freire, A P A; Pires, A V; Ferraz, M V C; Rodrigues, P H M; Eastridge, M L

    2017-02-01

    Crude glycerin is a gluconeogenic substrate in ruminants and may help to decrease the occurrence of pregnancy toxemia. The objective in this trial was to determine the effects of feeding a diet containing crude glycerin on DMI, milk yield, milk composition, and blood metabolites in periparturient ewes and lamb performance. One hundred eighteen 90 (±1.1)-d pregnant Santa Inês ewes were used. After lambing, 32 ewes (62.8 ± 1.3 kg BW) were allotted in a randomized complete block design defined by prelambing diet, BW, BCS, lambing date, type of birth (single or twin), and sex of offspring. Diets were isonitrogenous (13.0 ± 0.3% CP, DM basis), composed of concentrate and raw sugarcane bagasse (70:30 ratio, DM basis), and fed ad libitum daily. Crude glycerin (83.6% glycerol) levels were 0 or 10% (DM basis), corresponding to the experimental diets G0 and G10, respectively. From 8 until 56 d of lactation, DMI was determined. In the same period, once a week at 1000 h, the ewes were separated from the lambs and mechanically milked after intravenous administration of 10 IU of synthetic oxytocin. Three hours after the first milking, ewes were milked again and milk yield and composition were determined. Glucose, NEFA, and β-hydroxybutyrate (BHBA) were determined at -14, -7, 0, 7, 14, 28, and 56 d relative to lambing and insulin was determined at -14, -7, 0, and 7 d. Crude glycerin did not affect DMI (2.2 kg/d for G0 vs. 2.2 kg/d for G10; = 0.93) or milk production (171 g/3 h for G0 vs. 164 g/3 h for G10; = 0.66). However, there was a decrease ( = 0.01) in milk fat percentage (8.1% for G0 vs. 7.0% for G10) for ewes fed glycerin. Ewes fed the G10 diet had decreased ( ewes fed the G10 diet (0.46 mmol/L for G0 vs. 0.61 mmol/L for G10). There was no effect of diets fed to ewes on lamb growth from birth to weaning. Crude glycerin improved energy balance of periparturient ewes, suggesting a reduced risk of developing clinical metabolic-related disorders. Crude glycerin can be

  13. Task-related signal decrease on functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Hara, Yoshie; Nakamura, Mitsugu; Tamaki, Norihiko; Tamura, Shogo; Kitamura, Junji

    2001-01-01

    An atypical pattern of signal change was identified on functional magnetic resonance (fMR) imaging in pathologic patients. Three normal volunteers and 34 patients with pathologic lesions near the primary motor cortex underwent fMR imaging with echo-planar imaging while performing a hand motor task. Signal intensities were evaluated with the z-score method, and the time course and changes of the signal intensity were calculated. Nine of the 34 patients with pathologic lesions displayed a significant task-related signal reduction in motor-related areas. They also presented a conventional task-related signal increase in other motor-related areas. The time courses of the increase and decrease were the inverse of each other. There was no significant difference between rates of signal increase and decrease. Our findings suggest that this atypical signal decrease is clinically significant, and that impaired vascular reactivity and altered oxygen metabolism could contribute to the task-related signal reduction. Brain areas showing such task-related signal decrease should be preserved at surgery. (author)

  14. In utero heat stress decreases calf survival and performance through the first lactation.

    Science.gov (United States)

    Monteiro, A P A; Tao, S; Thompson, I M T; Dahl, G E

    2016-10-01

    Calves born to cows exposed to heat stress during late gestation (i.e., the dry period) have lower birth weight and weaning weight and compromised passive immune transfer compared with those born to dams that are cooled. However, it is unknown if heat stress in utero has carryover effects after weaning. The objective was to evaluate the effect of heat stress (HT) or cooling (CL) in late gestation dairy cows on the survival, growth, fertility, and milk production in the first lactation of their calves. Data of animals obtained from previous experiments conducted during 5 consecutive summers in Florida were pooled and analyzed. Cows were dried off 46d before expected calving and randomly assigned to 1 of 2 treatments, HT or CL. Cooled cows were housed with sprinklers, fans, and shade, whereas only shade was provided to HT cows. Within 4h of birth, 3.8 L of colostrum was fed to calves from both groups of cows. All calves were managed in the same manner and weaned at 49d of age. Birth weight and survival of 146 calves (HT=74; CL=72) were analyzed. Additionally, body weight, growth rate, fertility, and milk production in the first lactation from 72 heifers (HT=34; CL=38) were analyzed. As expected, HT calves were lighter (means ± SEM; 39.1±0.7 vs. 44.8±0.7kg) at birth than CL calves. Cooled heifers were heavier up to 1yr of age, but had similar total weight gain (means ± SEM; 305.8±6.3 vs. 299.1±6.3kg, respectively) compared with HT heifers. No effect of treatment was observed on age at first insemination (AI) and age at first parturition. Compared with CL heifers, HT heifers had a greater number of services per pregnancy confirmed at d 30 after AI, but no treatment effect was observed on number of services per pregnancy confirmed at d 50 after AI. A greater percentage of CL heifers reached first lactation compared with HT heifers (85.4 vs. 65.9%). Moreover, HT heifers produced less milk up to 35wk of the first lactation compared with CL heifers (means ± SEM; 26

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

    Science.gov (United States)

    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.

  16. Inhibition of metastin (kisspeptin-54)-GPR54 signaling in the arcuate nucleus-median eminence region during lactation in rats.

    Science.gov (United States)

    Yamada, S; Uenoyama, Y; Kinoshita, M; Iwata, K; Takase, K; Matsui, H; Adachi, S; Inoue, K; Maeda, K-I; Tsukamura, H

    2007-05-01

    Follicular development and ovulation are suppressed during lactation in various mammalian species, mainly due to the suppression of pulsatile GnRH/LH secretion. Metastin (kisspeptin-54), a KiSS-1 gene product, is an endogenous ligand for GPR54, a G-protein-coupled receptor, and suggested to play a critical role in regulating the gonadal axis. The present study therefore aims to determine whether metastin (kisspeptin-54)-GPR54 signaling in discrete brain areas is inhibited by the suckling stimulus that causes suppression of LH secretion in lactating rats. Quantitative RT-PCR revealed that the KiSS-1 mRNA level was significantly lower in the arcuate nucleus (ARC)-median eminence region in lactating ovariectomized (OVX) and estrogen-treated OVX rats than in nonlactating controls. KiSS-1 mRNA in the anteroventral periventricular nucleus was kept at a low level in both lactating and nonlactating rats despite estrogen treatment. GPR54 mRNA levels were significantly lower in lactating than nonlactating rats in the anteroventral periventricular nucleus, but the levels in lactating mothers of the preoptic area and ARC-median eminence were comparable with nonlactating controls. Although KiSS-1 mRNA-expressing cells or metastin (kisspeptin-54) immunoreactivities were densely located in the ARC of nonlactating controls, few were found in the ARC of lactating OVX animals. Various doses of metastin (kisspeptin-54) (0.02, 0.2, and 2 nmol) injected into the third ventricle caused a significant increase in LH secretion in both lactating and nonlactating OVX rats, suggesting that lactating rats are responsive to metastin (kisspeptin-54) stimulus. Thus, the present study demonstrated that KiSS-1 mRNA/metastin (kisspeptin-54) expression is inhibited in the ARC by the suckling stimulus, suggesting that the inhibition is most probably involved in suppressing LH secretion in lactating rats.

  17. Stop signals decrease choices for palatable foods through decreased food evaluation

    Science.gov (United States)

    Veling, Harm; Aarts, Henk; Stroebe, Wolfgang

    2013-01-01

    The present study explores whether presenting specific palatable foods in close temporal proximity of stop signals in a go/no-go task decreases subsequent evaluations of such foods among participants with a relatively high appetite. Furthermore, we tested whether any decreased evaluations could mediate subsequent food choice. Participants first received a go/no-go task in which palatable foods were consistently linked to go cues or no-go cues within participants. Next, evaluation of the palatable foods was measured as well as food choice. Replicating previous work, results show that among participants with a relatively high appetite palatable foods associated with no-go cues are less often chosen as snacks compared to when these foods are associated with go cues, whereas this manipulation did not affect participants with a relatively low appetite. Moreover, this effect was completely mediated by decreased evaluation of the palatable foods that had been associated with the no-go cues, whereas evaluation of the foods associated with go cues did not mediate this effect. Results further showed that the devaluation effect of foods associated with no-go cues was independent of the amount of pairings (4 vs. 12 vs. 24) with the no-go cues. The current findings suggest that decreased food evaluation is a mechanism that explains effects of stop signals on food choice. PMID:24324451

  18. Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization.

    Science.gov (United States)

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Browne, Veron; Mendez-Garcia, Claudia; Yablonski, Elizabeth; Pontiggia, Laura; D'Mello, Anil P

    2015-04-01

    We have previously demonstrated that protein restriction throughout gestation and lactation reduces liver triglyceride content in adult rat offspring. However, the mechanisms mediating the decrease in liver triglyceride content are not understood. The aim of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty-acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and killed on day 65. Liver triglyceride content was reduced in male, but not female, low-protein offspring, both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity, suggesting increased fatty-acid transport into the mitochondrial matrix. However, medium-chain acyl coenzyme A dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of β-hydroxybutyrate were similar between low protein and control offspring, indicating a lack of change in fatty-acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein, were similar between low protein and control offspring. Because enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low-protein offspring is likely due to alterations in liver fatty-acid transport or triglyceride biosynthesis. © 2015 Wiley Publishing Asia Pty Ltd.

  19. The relationship between blood potassium, blood lactate, and electromyography signals related to fatigue in a progressive cycling exercise test.

    Science.gov (United States)

    Tenan, Matthew S; McMurray, Robert G; Blackburn, B Troy; McGrath, Melanie; Leppert, Kyle

    2011-02-01

    Local muscle fatigue may be related to potassium efflux from the muscle cell and/or lactate accumulation within the muscle. Local fatigue causes a decrease in median frequency (MPF) of the electromyogram's power spectrum during isometric contractions but its relationship to changes in potassium and lactate during dynamic exercise is equivocal. Thus, this investigation evaluated relationships between changes in the MPF from the vastus lateralis and blood levels of lactate and potassium during an incremental cycling test and recovery. Trained cyclists (n=8) completed a discontinuous, graded cycle test to exhaustion under normal and glycogen-reduced conditions. The glycogen reduced condition promoted an environment of lower lactate production while permitting a consistent potassium response. Blood samples and maximal isometric EMG data were collected at the end of each stage and during recovery. Maximal lactate levels were ∼ 60% lower in the glycogen reduced condition; potassium was similar between trials. MPF did not change significantly at volitional fatigue. Further, MPF was not significantly related to lactate (p>0.27) or potassium (p>0.16) in either condition. Though both lactate and potassium have been implicated as factors relating to local muscle fatigue, neither is significantly related to changes in MPF during or after progressive exercise on a cycle ergometer. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Lactate in the brain: from metabolic end-product to signalling molecule

    KAUST Repository

    Magistretti, Pierre J.; Allaman, Igor

    2018-01-01

    Lactate in the brain has long been associated with ischaemia; however, more recent evidence shows that it can be found there under physiological conditions. In the brain, lactate is formed predominantly in astrocytes from glucose or glycogen

  1. Plasma lactate and stress hormones in common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) during stepwise decreasing oxygen levels

    NARCIS (Netherlands)

    Vianen, GJ; Van den Thillart, GEEJM; Van Kampen, M; Van Heel, TI; Steffens, AB

    By measuring the lactate response it is possible to determine whether a teleost is able to adapt to a certain oxygen level. It is hypothesized that recovery will occur at oxygen levels above the critical oxygen level (PO2)(crit) reflected by a transient lactate increase. In contrast, continuous

  2. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Lena Willkomm

    Full Text Available Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs. Lactate (La-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3 known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD vs. high intensity RE (HIT. Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  3. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Science.gov (United States)

    Willkomm, Lena; Gehlert, Sebastian; Jacko, Daniel; Schiffer, Thorsten; Bloch, Wilhelm

    2017-01-01

    Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs). Lactate (La)-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK) which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3) known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM) and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC) leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE) associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD) vs. high intensity RE (HIT). Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  4. Metabolic and production profiles of dairy cows in response to decreased nutrient density to increase physiological imbalance at different stages of lactation

    DEFF Research Database (Denmark)

    Bjerre-Harpøth, Vibeke; Friggens, N C; Thorup, Vivi Mørkøre

    2012-01-01

    . Blood was collected daily and analyzed for metabolites: nonesterified fatty acids (NEFA), BHBA, glucose, plasma urea nitrogen, and insulin. The revised quantitative insulin sensitivity check index (RQUICKI) was calculated for each cow. Liver biopsies collected before and during restriction were analyzed...... for triglycerides, glycogen, phospholipids, glucose, and total lipid content. A generalized linear mixed model was used to determine the effect of stage of lactation on responses during restriction. Regression analyses were used to examine the effect of pre-restriction levels on changes during restriction. Similar...... decreases in milk yield among groups indicate that the capacity of individual responses is dependent on milk yield but the coping strategies used are dependent on stage of lactation. Milk yield was a better predictor of feed intake than DIM. Plasma glucose decreased for all cows, and cows in early lactation...

  5. Co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins in the lactation-induced mitochondrial hypotrophy of rat brown fat.

    Science.gov (United States)

    Martin, I; Giralt, M; Viñas, O; Iglesias, R; Mampel, T; Villarroya, F

    1995-01-01

    The relative abundance of the mitochondrial-encoded mRNAs for cytochrome c oxidase subunit II and NADH dehydrogenase subunit I was lower in brown adipose tissue (BAT) from lactating rats than in virgin controls. This decrease was in parallel with a significant decrease in mitochondrial 16 S rRNA levels and in the relative content of mitochondrial DNA in the tissue. BAT from lactating rats showed lowered mRNA expression of the nuclear-encoded genes for the mitochondrial uncoupling protein, subunit IV of cytochrome c oxidase and the adenine nucleotide translocase isoforms ANT1 and ANT2, whereas mRNA levels for the ATP synthase beta-subunit were unchanged. However, the relative content of this last protein was lower in BAT mitochondria from lactating rats than in virgin controls. It is concluded that lactation-induced mitochondrial hypotrophy in BAT is associated with a co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins. This decrease is caused by regulatory events acting at different levels, including pre- and post-transcriptional regulation. BAT appears to be a useful model with which to investigate the molecular mechanisms involved in the co-ordination of the expression of the mitochondrial and nuclear genomes during mitochondrial biogenesis. Images Figure 1 Figure 2 PMID:8948428

  6. Metabolic and production profiles of dairy cows in response to decreased nutrient density to increase physiological imbalance at different stages of lactation.

    Science.gov (United States)

    Bjerre-Harpøth, V; Friggens, N C; Thorup, V M; Larsen, T; Damgaard, B M; Ingvartsen, K L; Moyes, K M

    2012-05-01

    Physiological imbalance (PI) is a situation in which physiological parameters deviate from the normal, and cows consequently have an increased risk of developing production diseases and reduced production or reproduction. Our objectives were to (1) determine the effect of stage of lactation and milk yield on metabolic and production responses of cows during a nutrient restriction period to experimentally increase PI; (2) identify major metabolites that relate to degree of PI; and (3) identify potential biomarkers in milk for on-farm detection of PI throughout lactation. Forty-seven Holstein cows in early [n=14; 49±22 d in milk (DIM); parity=1.6±0.5], mid (n=15; 159±39 DIM; parity=1.5±0.5), and late (n=18; 273±3 DIM; parity=1.3±0.5) lactation were used. Prior to restriction, all cows were fed the same total mixed ration ad libitum. All cows were then nutrient restricted for 4 d by supplementing the ration with 60% wheat straw to induce PI. After restriction, cows returned to full feed. Daily milk yield was recorded and composite milk samples were analyzed for fat, protein, lactose, citrate, somatic cells, uric acid, alkaline phosphatase, β-hydroxybutyrate (BHBA), and milk urea nitrogen. Blood was collected daily and analyzed for metabolites: nonesterified fatty acids (NEFA), BHBA, glucose, plasma urea nitrogen, and insulin. The revised quantitative insulin sensitivity check index (RQUICKI) was calculated for each cow. Liver biopsies collected before and during restriction were analyzed for triglycerides, glycogen, phospholipids, glucose, and total lipid content. A generalized linear mixed model was used to determine the effect of stage of lactation on responses during restriction. Regression analyses were used to examine the effect of pre-restriction levels on changes during restriction. Similar decreases in milk yield among groups indicate that the capacity of individual responses is dependent on milk yield but the coping strategies used are dependent on

  7. Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

    Science.gov (United States)

    Salais-López, Hugo; Lanuza, Enrique; Agustín-Pavón, Carmen; Martínez-García, Fernando

    2017-03-01

    Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.

  8. Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but not lactate correlates positively with Ca2+ signalling in cultured mouse glutamatergic neurons.

    Science.gov (United States)

    Bak, Lasse K; Obel, Linea F; Walls, Anne B; Schousboe, Arne; Faek, Sevan A A; Jajo, Farah S; Waagepetersen, Helle S

    2012-04-05

    We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate-aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca2+ signalling.

  9. Lactate shuttles in nature.

    Science.gov (United States)

    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

  10. Skeletal muscle and hepatic insulin signaling is maintained in heat-stressed lactating Holstein cows.

    Science.gov (United States)

    Xie, G; Cole, L C; Zhao, L D; Skrzypek, M V; Sanders, S R; Rhoads, M L; Baumgard, L H; Rhoads, R P

    2016-05-01

    period, but the phosphorylation ratio (abundance of phosphorylated protein:abundance of total protein) of AKT was decreased in P2 for TNPF animals, but not during WFHS. These results indicate that mild systemic insulin resistance during HS may be related to reduced nutrient intake but skeletal muscle and liver insulin signaling remains unchanged. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Effects of decreasing metabolizable protein and rumen-undegradable protein on milk production and composition and blood metabolites of Holstein dairy cows in early lactation.

    Science.gov (United States)

    Bahrami-Yekdangi, H; Khorvash, M; Ghorbani, G R; Alikhani, M; Jahanian, R; Kamalian, E

    2014-01-01

    This study was conducted to evaluate the effects of decreasing dietary protein and rumen-undegradable protein (RUP) on production performance, nitrogen retention, and nutrient digestibility in high-producing Holstein cows in early lactation. Twelve multiparous Holstein lactating cows (2 lactations; 50 ± 7 d in milk; 47 kg/d of milk production) were used in a Latin square design with 4 treatments and 3 replicates (cows). Treatments 1 to 4 consisted of diets containing 18, 17.2, 16.4, and 15.6% crude protein (CP), respectively, with the 18% CP diet considered the control group. Rumen-degradable protein levels were constant across the treatments (approximately 10.9% on a dry matter basis), whereas RUP was gradually decreased. All diets were calculated to supply a postruminal Lys:Met ratio of about 3:1. Dietary CP had no significant effects on milk production or milk composition. In fact, 16.4% dietary CP compared with 18% dietary CP led to higher milk production; however, this effect was not significant. Feed intake was higher for 16.4% CP than for 18% CP (25.7 vs. 24.3 kg/d). Control cows had greater CP and RUP intakes, which resulted in higher concentrations of plasma urea nitrogen and milk urea nitrogen; cows receiving 16.4 and 15.6% CP, respectively, exhibited lower concentrations of milk urea nitrogen (15.2 and 15.1 vs. 17.3 mg/dL). The control diet had a significant effect on predicted urinary N. Higher CP digestibility was recorded for 18% CP compared with the other diets. Decreasing CP and RUP to 15.6 and 4.6% of dietary dry matter, respectively, had no negative effects on milk production or composition when the amounts of Lys and Met and the Lys:Met ratio were balanced. Furthermore, decreasing CP and RUP to 16.4 and 5.4%, respectively, increased dry matter intake. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Lactate promotes specific differentiation in bovine granulosa cells depending on lactate uptake thus mimicking an early post-LH stage

    Directory of Open Access Journals (Sweden)

    Anja Baufeld

    2018-02-01

    Full Text Available Abstract Background The LH-induced folliculo-luteal transformation is connected with alterations of the gene expression profile in cells of the granulosa layer. It has been described that hypoxic conditions occur during luteinization, thus favoring the formation of L-lactate within the follicle. Despite being a product of anaerobic respiration, L-lactate has been shown to act as a signaling molecule affecting gene expression in neuronal cells. During the present study, we tested the hypothesis that L-lactate may influence differentiation of follicular granulosa cells (GC. Methods In a bovine granulosa cell culture model effects of L- and D-lactate, of increased glucose concentrations and of the lactate transport inhibitor UK5099 were analyzed. Steroid hormone production was analyzed by RIA and the abundance of key transcripts was determined by quantitative real-time RT-PCR. Results L-lactate decreased the production of estradiol and significantly affected selected genes of the folliculo-luteal transition as well as genes of the lactate metabolism. CYP19A1, FSHR, LHCGR were down-regulated, whereas RGS2, VNN2, PTX3, LDHA and lactate transporters were up-regulated. These effects could be partly or completely reversed by pre-treatment of the cells with UK5099. The non-metabolized enantiomer D-lactate had even more pronounced effects on gene expression, whereas increased glucose concentrations did not affect transcript abundance. Conclusions In summary, our data suggest that L-lactate specifically alters physiological and molecular characteristics of GC. These effects critically depend on L-lactate uptake, but are not triggered by increased energy supply. Further, we could show that L-lactate has a positive feedback on the lactate metabolism. Therefore, we hypothesize that L-lactate acts as a signaling molecule in bovine and possibly other monovular species supporting differentiation during the folliculo-luteal transformation.

  13. Effect of hyperthyroidism on circulating prolactin and hypothalamic expression of tyrosine hydroxylase, prolactin signaling cascade members and estrogen and progesterone receptors during late pregnancy and lactation in the rat.

    Science.gov (United States)

    Pennacchio, Gisela E; Neira, Flavia J; Soaje, Marta; Jahn, Graciela A; Valdez, Susana R

    2017-02-15

    Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19). PRs mRNAs and protein decreased on G19 but afterwards PRA mRNA (G20), PRB mRNA (G21) and PRA mRNA and protein (L2) increased. ERα protein increased on G19 and decreased on G20. Thus, the altered hypothalamic PRLR, STAT5, PR and ERα expression in hyperthyroid rats may induce elevated TH expression and activation, that consequently, elevate dopaminergic tone during lactation, blunting suckling-induced PRL release and litter growth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Decreased T2 signal in the thalami may be a sign of lysosomal storage disease

    International Nuclear Information System (INIS)

    Autti, Taina; Joensuu, Raimo; Aaberg, Laura

    2007-01-01

    Lysosomal disorders are rare and are caused by genetically transmitted lysosomal enzyme deficiencies. A decreased T2 signal in the thalamus has occasionally been reported. Because the finding of bilateral abnormal signal intensity of the thalamus on T2-weighted images has not been systematically reviewed, and its value as a diagnostic tool critically evaluated, we carried out a systematic review of the literature. Articles in English with 30 trios of keywords were collected from PubMed. Exclusion criteria were lack of conventional T2-weighted images in the protocol and not being a human study. Finally, 111 articles were included. The thalamus was considered affected only if mentioned in the text or in the figure legends. Some 117 patients with various lysosomal diseases and five patients with ceruloplasmin deficiency were reported to have a bilateral decrease in T2 signal intensity. At least one article reported a bilateral decrease in signal intensity of the thalami on T2-weighted images in association with GM1 and GM2 gangliosidosis and with Krabbe's disease, aspartylglucosaminuria, mannosidosis, fucosidosis, and mucolipidosis IV. Furthermore, thalamic alteration was a consistent finding in several types of neuronal ceroid lipofuscinosis (NCL) including CLN1 (infantile NCL), CLN2 (classic late infantile NCL), CLN3 (juvenile NCL), CLN5 (Finnish variant late infantile NCL), and CLN7 (Turkish variant late infantile NCL). A decrease in T2 signal intensity in the thalami seems to be a sign of lysosomal disease. (orig.)

  15. Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis.

    Science.gov (United States)

    Ebrahimzadeh Bideskan, Alireza; Mohammadipour, Abbas; Fazel, Alireza; Haghir, Hossein; Rafatpanah, Houshang; Hosseini, Mahmoud; Rajabzadeh, Aliakbar

    2017-07-05

    The usage of Titanium dioxide nanoparticles (TiO 2 -NPs) covers a vast area in different fields ranging from cosmetics and food to the production of drugs. Maternal exposure to TiO 2 -NPs during developmental period has been associated with hippocampal injury and with a decrease in learning and memory status of the offspring. However, little is known about its injury mechanism. This paper describes the in vivo neurotoxic effects of TiO 2 -NPs on rat offspring hippocampus during developmental period. Pregnant and lactating Wistar rats received intragastric TiO 2 -NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21 and postnatal day (PD) 2 to (PD) 21 respectively. Animals in the control groups received an equal volume of distilled water via gavage. At the end of the treatment process, offspring were deeply anesthetized and sacrificed. Then brains of each group were collected and sections of the rat offspring's brains were stained using TUNEL staining (for detection of apoptotic cells) and immunostaining (for neurogenesis). Moreover, the right hippocampus (n=6 per each group) were removed from the right hemisphere for evaluating the expression of Bax and Bcl-2 level. Results of histopatological examination by TUNEL staining showed that maternal exposure to TiO 2 -NPs during pregnancy and lactation periods increased apoptotic cells significantly (P<0.01) in the offspring hippocampus. The immunolabeling of double cortin (DCX) protein as neurogenesis marker also showed that TiO 2 -NPs reduced neurogenesis in the hippocampus of the offspring (P<0.05). Moreover, in comparison with the control group, the mRNA levels of Bax and Bcl-2 in the TiO 2 -NPs group significantly increased and decreased, respectively (P<0.01). These findings provide strong evidence that maternal exposure to TiO 2 -NPs significantly impact hippocampal neurogenesis and apoptosis in the offspring. The potential impact of nanoparticle exposure for millions of pregnant mothers and

  16. Decreased hematocrit-to-viscosity ratio and increased lactate dehydrogenase level in patients with sickle cell anemia and recurrent leg ulcers.

    Directory of Open Access Journals (Sweden)

    Philippe Connes

    Full Text Available Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC- and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+--with no leg ulcers at the time of the study--were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties. The hematocrit-to-viscosity ratio (HVR, which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio may play a role.

  17. Bilateral Pulvinar Signal Intensity Decrease on T2-Weighted Images in Patients with Aspartylglucosaminuria

    International Nuclear Information System (INIS)

    Autti, T.; Loennqvist, T.; Joensuu, R.

    2008-01-01

    Background: Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal disease caused by deficiency of aspartylglucosaminidase. A thalamic T2 signal intensity decrease is associated with lysosomal diseases. Purpose: To investigate thalamic signal intensity in AGU by performing a retrospective review of brain magnetic resonance (MR) imaging studies of AGU patients. Material and Methods: A total of 25 MR examinations were available for 11 patients aged between 3 and 32 years (four patients underwent bone marrow transplantation). Of these, 13 examinations were performed after bone marrow transplantation. Five patients had from two to six examinations, and six patients had one examination each. In every patient, the diagnosis of AGU was confirmed by blood and urine tests. Eighteen examinations were performed with a 1.0T imager including dual spin-echo T2 and proton density (PD) axial and coronal images, and 10 examinations also included T1-weighted images. Seven examinations were performed with a 1.5T imager including turbo spin-echo axial and coronal T2-weighted images and axial fluid-attenuated inversion recovery (FLAIR) images; three examinations included T1-weighted three-dimensional magnetization-prepared rapid acquisition gradient-echo (3D MPRAGE) images. The signal intensity of the thalamus and pulvinar in every sequence was compared to that of the putamina. Results: In AGU, thalamic alterations were first detectable on T2-weighted images (25 examinations in 11 patients) from the age of 3 years 6 months, showing decreased signal intensity in 21 of 24 examinations. T1-weighted images (13 examinations) showed slightly increased thalamic signal intensity in five out of seven examinations from the age of 7 years, and PD images (19 examinations) showed decreased signal intensity from the age of 16 years (three examinations). The pulvinar showed decreased signal intensity on spin-echo T2-weighted images for 14 of 18 examinations or on FLAIR sequences for seven

  18. Once-daily milking during a feed deficit decreases milk production but improves energy status in early lactating grazing dairy cows.

    Science.gov (United States)

    Kay, J K; Phyn, C V C; Rius, A G; Morgan, S R; Grala, T M; Roche, J R

    2013-10-01

    The objective of this study was to investigate the effect of milking frequency (MF) at 2 feeding levels (FL) on milk production, body condition score, and metabolic indicators of energy status in grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n=120) grazed pasture and were milked twice daily (2×) from calving until 34 ± 6 d in milk (mean ± standard deviation). Cows were then allocated to 1 of 4 treatments in a 2 × 2 factorial arrangement. Treatments consisted of 2 FL: adequately fed [AF; 14.3 kg dry matter intake (DMI)/cow per d] or underfed (UF; 8.3 kg of DMI/cow per d) and 2 MF: 2× or once daily (1×). Treatments were imposed for 3 wk. After the treatment period, all cows were offered a generous pasture allowance (grazing residuals >1,600 kg of dry matter/ha) and milked 2×. During the 3-wk treatment period, we observed an interaction between FL and MF for energy-corrected milk (ECM), such that the decrease due to 1× milking was greater in AF than in UF cows (20 and 14% decrease, respectively). No interactions were found posttreatment. Cows previously UF produced 7% less ECM than AF cows during wk 4 to 12; however, no subsequent effect was observed of the previous underfeeding. Cows previously milked 1× produced 5% less ECM during wk 4 to 12, and differences remained during wk 13 to 23. During the 3-wk treatment period, UF cows lost 0.2 body condition score units (1-10 scale) and this was not affected by 1× milking. During the treatment period, UF cows had lower plasma glucose, insulin, and insulin-like growth factor I, and greater nonesterified fatty acids and β-hydroxybutyrate concentrations than AF cows. Cows milked 1× had greater plasma glucose, insulin, and insulin-like growth factor I, and lower nonesterified fatty acids and β-hydroxybutyrate concentrations compared with cows milked 2×. In conclusion, energy status was improved by 1× milking; however, when UF cows were milked 1

  19. Cholinergic Basal Forebrain Lesion Decreases Neurotrophin Signaling without Affecting Tau Hyperphosphorylation in Genetically Susceptible Mice.

    Science.gov (United States)

    Turnbull, Marion T; Coulson, Elizabeth J

    2017-01-01

    Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Our results reveal that the loss of BFCNs in pre-symptomatic pR5 (P301L) tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals' performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.

  20. Correlated cone noise decreases rod signal contributions to the post-receptoral pathways.

    Science.gov (United States)

    Hathibelagal, Amithavikram R; Feigl, Beatrix; Zele, Andrew J

    2018-04-01

    This study investigated how invisible extrinsic temporal white noise that correlates with the activity of one of the three [magnocellular (MC), parvocellular (PC), or koniocellular (KC)] post-receptoral pathways alters mesopic rod signaling. A four-primary photostimulator provided independent control of the rod and three cone photoreceptor excitations. The rod contributions to the three post-receptoral pathways were estimated by perceptually matching a 20% contrast rod pulse by independently varying the LMS (MC pathway), +L-M (PC pathway), and S-cone (KC pathway) excitations. We show that extrinsic cone noise caused a predominant decrease in the overall magnitude and ratio of the rod contributions to each pathway. Thus, the relative cone activity in the post-receptoral pathways determines the relative mesopic rod inputs to each pathway.

  1. Volume Replacement Therapy during Hip Arthroplasty using Hydroxyethyl Starch (130/0.4 Compared to Lactated Ringer Decreases Allogeneic Blood Transfusion and Postoperative Infection

    Directory of Open Access Journals (Sweden)

    Adilson Hamaji

    2013-01-01

    Full Text Available Background and objectives: Hydroxyethyl starch (HES 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. Methods: In this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15 mL.kg-1 of HES 130/0.4 and 24 patients received a preload of 30 mL.kg-1 lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications. Results: Red blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p = .029. Postoperative infections were more frequently observed in the Ringer group (17% compared to the HES group (0, p = .037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection. Conclusions: During hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated

  2. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

    Bensel, Tobias; Stotz, Martin; Borneff-Lipp, Marianne

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated...... and 25 stable CF patients via spectrophotometry and gaschromatography. Lung function was assessed via spirometry. Seven patients with chronic obstructive pulmonary disease (COPD) and three patients with acute lung inflammation served as control groups. Neutrophil and bacterial lactate production...

  3. Lactate Test

    Science.gov (United States)

    ... Plasma Free Metanephrines Platelet Count Platelet Function Tests Pleural Fluid Analysis PML-RARA Porphyrin Tests Potassium Prealbumin ... ency/article/000391.htm . (2002 January, Updated). Lactate (Liquid) Reagent Set. Pointe Scientific, Inc. [On-line Reagent ...

  4. Lactate: link between glycolytic and oxidative metabolism.

    Science.gov (United States)

    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.

  5. Normal lactate concentration range in the neonatal brain.

    Science.gov (United States)

    Tomiyasu, Moyoko; Aida, Noriko; Shibasaki, Jun; Tachibana, Yasuhiko; Endo, Mamiko; Nozawa, Kumiko; Shimizu, Eiji; Tsuji, Hiroshi; Obata, Takayuki

    2016-11-01

    Lactate peaks are occasionally observed during in vivo magnetic resonance spectroscopy (MRS) scans of the neonatal brain, even in healthy patients. The purpose of this study was to investigate the normal range of neonatal brain lactate concentration, as a definitive normal range would be clinically valuable. Using a clinical 3T scanner (echo/repetition times, 30/5000ms), single-voxel MRS data were obtained from the basal ganglia (BG) and centrum semiovale (CS) in 48 healthy neonates (postconceptional age (PCA), 30-43weeks), nine infants (age, 1-12months old), and 20 children (age, 4-15years). Lactate concentrations were calculated using an MRS signal quantification program, LCModel. Correlations between regional lactate concentration and PCA (neonates), or age (all subjects) were investigated. Absolute lactate concentrations of the BG and CS were as follows: neonates, 0.77mM (0-2.02) [median (range)] and 0.77 (0-1.42), respectively; infants, 0.38 (0-0.79) and 0.49 (0.17-1.17); and children, 0.17 (0-0.76) and 0.22 (0-0.80). Overall, subjects' lactate concentrations decreased significantly with age (Spearman: BG, n=61, ρ=-0.38, p=0.003; CS, n=68, ρ=-0.57, p<0.001). However, during the neonatal period no correlations were detected between lactate concentration in either region and PCA. We determined normal ranges of neonatal lactate concentration, which may prove useful for diagnostic purposes. Further studies regarding changes in brain lactate concentration during development would help clarify the reasons for higher concentrations observed during the neonatal period, and contribute to improvements in diagnoses. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Leptin Intake at Physiological Doses Throughout Lactation in Male Wistar Rats Normalizes the Decreased Density of Tyrosine Hydroxylase-Immunoreactive Fibers in the Stomach Caused by Mild Gestational Calorie Restriction

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    Nara Szostaczuk

    2018-03-01

    Full Text Available Introduction: Gestational under nutrition in rats has been shown to decrease expression of sympathetic innervation markers in peripheral tissues of offspring, including the stomach. This has been linked to lower gastric secretion and decreased circulating levels of ghrelin. Considering the critical role of leptin intake during lactation in preventing obesity and reversing adverse developmental programming effects, we aimed to find out whether leptin supplementation may reverse the above mentioned alterations caused by mild gestational calorie restriction.Methods: Three groups of male rats were studied at a juvenile age (25 days old and during adulthood (3 and 6 months old: the offspring of ad libitum fed dams (controls, the offspring of dams that were diet restricted (20% from days 1 to 12 of gestation (CR, and CR rats supplemented with a daily oral dose of leptin (equivalent to 5 times the average amount they could receive each day from maternal milk throughout lactation (CR-Leptin. The density of TyrOH-immunoreactive (TyrOH+ fibers and the levels of Tyrosine hydroxylase (TyrOH—used as potential markers of functional sympathetic innervation—were measured in stomach. Plasma leptin and ghrelin levels were also determined.Results: Twenty five-day-old CR rats, but not CR-Leptin rats, displayed lower density of TyrOH+ fibers (−46% and TyrOH levels (−47% in stomach compared to controls. Alterations in CR animals were mitigated at 6 months of age, and differences were not significant. Adult CR-Leptin animals showed higher plasma ghrelin levels than CR animals, particularly at 3 months (+16%, and a lower leptin/ghrelin ratio (−28 and −37% at 3 and 6 months, respectively.Conclusion: Leptin intake during lactation is able to reverse the alterations in the density of TyrOH+ fibers in the stomach and normalize the increased leptin/ghrelin ratio linked to a mild gestational calorie restriction in rats, supporting the relevance of leptin as an

  7. Chronic oral lactate supplementation does not affect lactate disappearance from blood after exercise

    DEFF Research Database (Denmark)

    Brouns, F; Fogelholm, M; Van Hall, Gerrit

    1995-01-01

    This study tested the hypothesis that a 3-week oral lactate supplementation affects postexercise blood lactate disappearance in untrained male subjects. Fifteen men were randomly assigned to either a lactate supplementation (n = 8) or a placebo (n = 7) treatment. During the treatment period...... they drank an oral lactate or a maltodextrin (placebo) supplement twice a day. The lactate drink contained 10 g of lactate as calcium, sodium, and potassium salts. Blood lactate concentrations were studied before, during, and immediately after three exercise tests, both pre- and posttreatment. Peak lactate...... values for placebo (PL) or lactate (L) treatment groups during different tests were as follows: Test 1 PL, 13.49 +/- 3.71; L, 13.70 +/- 1.90; Test 2 PL, 12.64 +/- 2.32; L, 12.00 +/- 2.23; Test 3 PL, 12.29 +/- 2.92; L, 11.35 +/- 1.38 and were reached 3 min postexercise. The decrease in blood lactate...

  8. Dinosaur lactation?

    Science.gov (United States)

    Else, Paul L

    2013-02-01

    Lactation is a process associated with mammals, yet a number of birds feed their newly hatched young on secretions analogous to the milk of mammals. These secretions are produced from various sections (crop organ, oesophageal lining and proventriculus) of the upper digestive tract and possess similar levels of fat and protein, as well as added carotenoids, antibodies and, in the case of pigeons and doves, epidermal growth factor. Parental care in avian species has been proposed to originate from dinosaurs. This study examines the possibility that some dinosaurs used secretory feeding to increase the rate of growth of their young, estimated to be similar to that of present day birds and mammals. Dinosaur 'lactation' could also have facilitated immune responses as well as extending parental protection as a result of feeding newly hatched young in nest environments. While the arguments for dinosaur lactation are somewhat generic, a case study for lactation in herbivorous site-nesting dinosaurs is presented. It is proposes that secretory feeding could have been used to bridge the gap between hatching and establishment of the normal diet in some dinosaurs.

  9. Lactate fuels the human brain during exercise

    DEFF Research Database (Denmark)

    Quistorff, Bjørn; Secher, Niels H; Van Lieshout, Johannes J

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up......)] from a resting value of 6 to exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined beta(1)- and beta(2)-adrenergic receptor...

  10. A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.

    Directory of Open Access Journals (Sweden)

    Iana Parvanova

    Full Text Available The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC(50 of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans.

  11. Feeding of Whitefly on Tobacco Decreases Aphid Performance via Increased Salicylate Signaling.

    Directory of Open Access Journals (Sweden)

    Haipeng Zhao

    Full Text Available The feeding of Bemisia tabaci nymphs trigger the SA pathway in some plant species. A previous study showed that B. tabaci nymphs induced defense against aphids (Myzus persicae in tobacco. However, the mechanism underlying this defense response is not well understood.Here, the effect of activating the SA signaling pathway in tobacco plants through B. tabaci nymph infestation on subsequent M. persicae colonization is investigated. Performance assays showed that B. tabaci nymphs pre-infestation significantly reduced M. persicae survival and fecundity systemically in wild-type (WT but not salicylate-deficient (NahG plants compared with respective control. However, pre-infestation had no obvious local effects on subsequent M. persicae in either WT or NahG tobacco. SA quantification results indicated that the highest accumulation of SA was induced by B. tabaci nymphs in WT plants after 15 days of infestation. These levels were 8.45- and 6.14-fold higher in the local and systemic leaves, respectively, than in controls. Meanwhile, no significant changes of SA levels were detected in NahG plants. Further, biochemical analysis of defense enzymes polyphenol oxidase (PPO, peroxidase (POD, β-1,3-glucanase, and chitinase demonstrated that B. tabaci nymph infestation increased these enzymes' activity locally and systemically in WT plants, and there was more chitinase and β-1, 3-glucanase activity systemically than locally, which was opposite to the changing trends of PPO. However, B. tabaci nymph infestation caused no obvious increase in enzyme activity in any NahG plants except POD.In conclusion, these results underscore the important role that induction of the SA signaling pathway by B. tabaci nymphs plays in defeating aphids. It also indicates that the activity of β-1, 3-glucanase and chitinase may be positively correlated with resistance to aphids.

  12. Decreased Expression of Semaphorin3A/Neuropilin-1 Signaling Axis in Apical Periodontitis

    Directory of Open Access Journals (Sweden)

    Ying Lin

    2017-01-01

    Full Text Available Apical periodontitis (AP is a chronic infection of endodontic origin accompanied with bone destruction around the apical region. Semaphorin3A (Sema3A and neuropilin-1 (Nrp1 are regarded as a pair of immune regulators in bone metabolism. In this study, we firstly investigated the expression pattern of Sema3A/Nrp1 in apical periodontitis and its correlation with bone destruction. Using rat animal model, we analysed the level of mandibular bone destruction and the expression of Sema3A/Nrp1 on days 0, 7, 14, 21, 28, and 35 after pulp exposure. In addition, clinical samples from apical periodontitis patients were obtained to analyse the expression of Sema3A/Nrp1. These results indicated that the bone destruction level expanded from days 7 to 35. The number of positive cells and level of mRNA expression of Sema3A/Nrp1 were significantly decreased from days 7 to 35, with a negative correlation with bone destruction. Moreover, expression of Sema3A/Nrp1 in the AP group was reduced compared to the control group of clinical samples. In conclusion, decreased expression of Sema3A/Nrp1 was observed in periapical lesions and is potentially involved in the bone resorption of the periapical area, suggesting that Sema3A/Nrp1 may contribute to the pathological development of apical periodontitis.

  13. Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

    Science.gov (United States)

    Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

    2013-03-01

    Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

  14. Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells

    Science.gov (United States)

    Rios, Carmen; D'Ippolito, Gianluca; Curtis, Kevin M.; Delcroix, Gaëtan J.-R.; Gomez, Lourdes A.; El Hokayem, Jimmy; Rieger, Megan; Parrondo, Ricardo; de las Pozas, Alicia; Perez-Stable, Carlos; Howard, Guy A.

    2016-01-01

    Human bone marrow multipotent mesenchymal stromal cell (hMSC) number decreases with aging. Subpopulations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues and participate in their repair. Maintaining throughout adult life such cell subpopulations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain, notch target genes, neuronal transcriptional repressor element 1 (RE1)-silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1α), and additionally, by decreasing the expression of (i) the proapoptotic proteins, apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity. Furthermore, low oxygen increases canonical Wnt pathway signaling coreceptor Lrp5 expression, and PI3K/Akt pathway activation. Lrp5 inhibition decreases self-renewal marker Sox2 mRNA, Oct4a nuclear accumulation, and cell numbers. Wortmannin-mediated PI3K/Akt pathway inhibition leads to increased osteoblastic differentiation at both low and high oxygen tension. We demonstrate that low oxygen stimulates a complex signaling network involving PI3K/Akt, Notch, and canonical Wnt pathways, which mediate the observed increase in nuclear Oct4a and REST, with simultaneous decrease in p53, AIF, and Bak. Collectively, these pathway activations contribute to increased self-renewal with concomitant decreased differentiation, cell cycle arrest, apoptosis, and/or senescence in MIAMI cells. Importantly, the PI3K/Akt pathway plays a central mechanistic role in the oxygen tension-regulated self-renewal versus osteoblastic differentiation of progenitor cells. PMID:27059084

  15. Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

    Science.gov (United States)

    Vendelbo, Mikkel Holm; Møller, Andreas Buch; Christensen, Britt; Nellemann, Birgitte; Clasen, Berthil Frederik Forrest; Nair, K. Sreekumaran; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

    2014-01-01

    Aim Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth. Methods Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days. Results Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation. Conclusions Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth. PMID:25020061

  16. Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling.

    Directory of Open Access Journals (Sweden)

    Mikkel Holm Vendelbo

    Full Text Available Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR, a key regulator of cell growth.Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days.Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation.Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth.

  17. Decreased SAP expression in T cells from patients with SLE contributes to early signaling abnormalities and reduced IL-2 production

    Science.gov (United States)

    Karampetsou, Maria P.; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C.; Tsokos, George C.

    2016-01-01

    T cells from patients with systemic lupus erythematosus (SLE) display a number of functions including increased early signaling events following engagement of the T cell receptor (TCR). Signaling lymphocytic activation molecule family (SLAMF) cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating immune response. Here we present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and 3 men with SLE independently of disease activity. In SLE T cells the SAP protein is also subject to increased degradation by a caspase-3. Forced expression of SAP in SLE T cells simultaneously heightened IL-2 production, calcium (Ca2+) responses and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR antibodies, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

  18. Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex.

    Science.gov (United States)

    Angamo, Eskedar Ayele; ul Haq, Rizwan; Rösner, Jörg; Gabriel, Siegrun; Gerevich, Zoltán; Heinemann, Uwe; Kovács, Richard

    2017-08-23

    Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed the contribution of lactate to the maintenance of transmembrane potassium gradients, synaptic signaling and pathological network activity in chronic epileptic human tissue. Stimulus induced and spontaneous field potentials and extracellular potassium concentration changes (∆[K⁺] O ) were recorded in parallel with tissue pO₂ and pH in slices from TLE patients while blocking MCTs by α-cyano-4-hydroxycinnamic acid (4-CIN) or d-lactate. Intrinsic lactate contributed to the oxidative energy metabolism in chronic epileptic tissue as revealed by the changes in pO₂ following blockade of lactate uptake. However, unlike the results in rat hippocampus, ∆[K⁺] O recovery kinetics and field potential amplitude did not depend on the presence of lactate. Remarkably, inhibition of lactate uptake exerted pH-independent anti-seizure effects both in healthy rat and chronic epileptic tissue and this effect was partly mediated via adenosine 1 receptor activation following decreased oxidative metabolism.

  19. Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

    KAUST Repository

    Boury-Jamot, B

    2015-10-27

    A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

  20. Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

    KAUST Repository

    Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, Pierre J.; Boutrel, B

    2015-01-01

    A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

  1. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring

    OpenAIRE

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D���mello, Anil P

    2016-01-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal prote...

  2. Cocaine-induced behavioral sensitization decreases the expression of endocannabinoid signaling-related proteins in the mouse hippocampus.

    Science.gov (United States)

    Blanco, Eduardo; Galeano, Pablo; Palomino, Ana; Pavón, Francisco J; Rivera, Patricia; Serrano, Antonia; Alen, Francisco; Rubio, Leticia; Vargas, Antonio; Castilla-Ortega, Estela; Decara, Juan; Bilbao, Ainhoa; de Fonseca, Fernando Rodríguez; Suárez, Juan

    2016-03-01

    In the reward mesocorticolimbic circuits, the glutamatergic and endocannabinoid systems are implicated in neurobiological mechanisms underlying cocaine addiction. However, the involvement of both systems in the hippocampus, a critical region to process relational information relevant for encoding drug-associated memories, in cocaine-related behaviors remains unknown. In the present work, we studied whether the hippocampal gene/protein expression of relevant glutamate signaling components, including glutamate-synthesizing enzymes and metabotropic and ionotropic receptors, and the hippocampal gene/protein expression of cannabinoid type 1 (CB1) receptor and endocannabinoid metabolic enzymes were altered following acute and/or repeated cocaine administration resulting in conditioned locomotion and locomotor sensitization. Results showed that acute cocaine administration induced an overall down-regulation of glutamate-related gene expression and, specifically, a low phosphorylation level of GluA1. In contrast, locomotor sensitization to cocaine produced an up-regulation of several glutamate receptor-related genes and, specifically, an increased protein expression of the GluN1 receptor subunit. Regarding the endocannabinoid system, acute and repeated cocaine administration were associated with an increased gene/protein expression of CB1 receptors and a decreased gene/protein expression of the endocannabinoid-synthesis enzymes N-acyl phosphatidylethanolamine D (NAPE-PLD) and diacylglycerol lipase alpha (DAGLα). These changes resulted in an overall decrease in endocannabinoid synthesis/degradation ratios, especially NAPE-PLD/fatty acid amide hydrolase and DAGLα/monoacylglycerol lipase, suggesting a reduced endocannabinoid production associated with a compensatory up-regulation of CB1 receptor. Overall, these findings suggest that repeated cocaine administration resulting in locomotor sensitization induces a down-regulation of the endocannabinoid signaling that could

  3. Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells.

    Science.gov (United States)

    Chitchumroonchokchai, Chureeporn; Bomser, Joshua A; Glamm, Jayme E; Failla, Mark L

    2004-12-01

    Epidemiological studies suggest that consumption of vegetables rich in the xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing age-related cataract, a leading cause of vision loss. Although LUT and ZEA are the only dietary carotenoids present in the lens, direct evidence for their photoprotective effect in this organ is not available. The present study examined the effects of xanthophylls and alpha-tocopherol (alpha-TC) on lipid peroxidation and the mitogen-activated stress signaling pathways in human lens epithelial (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with LUT, ZEA, astaxanthin (AST), and alpha-TC as methyl-beta-cyclodextrin complexes, HLE cells accumulated the lipophiles in a concentration- and time-dependent manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures with either 2 micromol/L xanthophyll or 10 micromol/L alpha-TC for 4 h before exposure to 300 J/m(2) UVB radiation decreased lipid peroxidation by 47-57% compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls and alpha-TC also inhibited UVB-induced activation of c-JUN NH(2)-terminal kinase (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition of UVB-induced JNK and p38 activation for cells containing xanthophylls/mg, respectively, whereas >2.3 nmol alpha-TC/mg protein was required to significantly decrease UVB-induced stress signaling. These data suggest that xanthophylls are more potent than alpha-TC for protecting human lens epithelial cells against UVB insult.

  4. 14-3-3γ Regulates Lipopolysaccharide-Induced Inflammatory Responses and Lactation in Dairy Cow Mammary Epithelial Cells by Inhibiting NF-κB and MAPKs and Up-Regulating mTOR Signaling

    Directory of Open Access Journals (Sweden)

    Lixin Liu

    2015-07-01

    Full Text Available As a protective factor for lipopolysaccharide (LPS-induced injury, 14-3-3γ has been the subject of recent research. Nevertheless, whether 14-3-3γ can regulate lactation in dairy cow mammary epithelial cells (DCMECs induced by LPS remains unknown. Here, the anti-inflammatory effect and lactation regulating ability of 14-3-3γ in LPS-induced DCMECs are investigated for the first time, and the molecular mechanisms responsible for their effects are explored. The results of qRT-PCR showed that 14-3-3γ overexpression significantly inhibited the mRNA expression of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS. Enzyme-linked immunosorbent assay (ELISA analysis revealed that 14-3-3γ overexpression also suppressed the production of TNF-α and IL-6 in cell culture supernatants. Meanwhile, CASY-TT Analyser System showed that 14-3-3γ overexpression clearly increased the viability and proliferation of cells. The results of kit methods and western blot analysis showed that 14-3-3γ overexpression promoted the secretion of triglycerides and lactose and the synthesis of β-casein. Furthermore, the expression of genes relevant to nuclear factor-κB (NF-κB and mitogen-activated protein kinase (MAPKs and lactation-associated proteins were assessed by western blot, and the results suggested that 14-3-3γ overexpression inactivated the NF-κB and MAPK signaling pathways by down-regulating extracellular signal regulated protein kinase (ERK, p38 mitogen-activated protein kinase (p38MAPK and inhibitor of NF-κB (IκB phosphorylation levels, as well as by inhibiting NF-κB translocation. Meanwhile, 14-3-3γ overexpression enhanced the expression levels of β-casein, mammalian target of rapamycin (mTOR, ribosomal protein S6 kinase 1 (S6K1, serine/threonine protein kinase Akt 1 (AKT1, sterol regulatory element binding protein 1 (SREBP1 and peroxisome proliferator-activated receptor gamma

  5. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

    Directory of Open Access Journals (Sweden)

    Marcondes Alves Barbosa Da Silva

    2015-10-01

    Full Text Available Type 2 diabetes (DM2 increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR with spironolactone decreases ROS-associated vascular dysfunction and improves vascular NO signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db] mice, a model of DM2, and their counterpart controls [LepRdb/LepR+, (db/+ mice] received spironolactone (50 mg/kg body weight/day or vehicle (ethanol 1% via oral per gavage for 6 weeks. Spironolactone treatment abolished the endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS phosphorylation (Ser1177, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 (SOD1 and catalase expression, improved sodium nitroprusside (SNP and BAY 41-2272-induced relaxation, as well as increased soluble guanylyl cyclase (sGC subunit β protein expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes-associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes.

  6. Extended lactation in dairy cows

    DEFF Research Database (Denmark)

    Sorensen, Annette; Muir, D. Donald; Knight, Christopher Harold

    2008-01-01

    of the lactation, protein and fat percentages increasing and lactose percentage decreasing, irrespective of treatment. The quality of the milk for processing into cheese, fermented products, heat-treated products and cream liqueurs was assessed by calculation of casein number (casein protein as a proportion...

  7. A neuronal lactate uptake inhibitor slows recovery of extracellular ion concentration changes in the hippocampal CA3 region by affecting energy metabolism.

    Science.gov (United States)

    Angamo, Eskedar Ayele; Rösner, Joerg; Liotta, Agustin; Kovács, Richard; Heinemann, Uwe

    2016-11-01

    Astrocyte-derived lactate supports pathologically enhanced neuronal metabolism, but its role under physiological conditions is still a matter of debate. Here, we determined the contribution of astrocytic neuronal lactate shuttle for maintenance of ion homeostasis and energy metabolism. We tested for the effects of α-cyano-4-hydroxycinnamic acid (4-CIN), which could interfere with energy metabolism by blocking monocarboxylate-transporter 2 (MCT2)-mediated neuronal lactate uptake, on evoked potentials, stimulus-induced changes in K + , Na + , Ca 2+ , and oxygen concentrations as well as on changes in flavin adenine dinucleotide (FAD) autofluorescence in the hippocampal area CA3. MCT2 blockade by 4-CIN reduced synaptically evoked but not antidromic population spikes. This effect was dependent on the activation of K ATP channels indicating reduced neuronal ATP synthesis. By contrast, lactate receptor activation by 3,5-dihydroxybenzoic acid (3,5-DHBA) resulted in increased antidromic and orthodromic population spikes suggesting that 4-CIN effects are not mediated by lactate accumulation and subsequent activation of lactate receptors. Recovery kinetics of all ion transients were prolonged and baseline K + concentration became elevated by blockade of lactate uptake. Lactate contributed to oxidative metabolism as both baseline respiration and stimulus-induced changes in Po 2 were decreased, while FAD fluorescence increased likely due to a reduced conversion of FAD into FADH 2 These data suggest that lactate shuttle contributes to regulation of ion homeostatsis and synaptic signaling even in the presence of ample glucose. Copyright © 2016 the American Physiological Society.

  8. Small molecule ErbB inhibitors decrease proliferative signaling and promote apoptosis in philadelphia chromosome-positive acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Mary E Irwin

    Full Text Available The presence of the Philadelphia chromosome in patients with acute lymphoblastic leukemia (Ph(+ALL is a negative prognostic indicator. Tyrosine kinase inhibitors (TKI that target BCR/ABL, such as imatinib, have improved treatment of Ph(+ALL and are generally incorporated into induction regimens. This approach has improved clinical responses, but molecular remissions are seen in less than 50% of patients leaving few treatment options in the event of relapse. Thus, identification of additional targets for therapeutic intervention has potential to improve outcomes for Ph+ALL. The human epidermal growth factor receptor 2 (ErbB2 is expressed in ~30% of B-ALLs, and numerous small molecule inhibitors are available to prevent its activation. We analyzed a cohort of 129 ALL patient samples using reverse phase protein array (RPPA with ErbB2 and phospho-ErbB2 antibodies and found that activity of ErbB2 was elevated in 56% of Ph(+ALL as compared to just 4.8% of Ph(-ALL. In two human Ph+ALL cell lines, inhibition of ErbB kinase activity with canertinib resulted in a dose-dependent decrease in the phosphorylation of an ErbB kinase signaling target p70S6-kinase T389 (by 60% in Z119 and 39% in Z181 cells at 3 µM. Downstream, phosphorylation of S6-kinase was also diminished in both cell lines in a dose-dependent manner (by 91% in both cell lines at 3 µM. Canertinib treatment increased expression of the pro-apoptotic protein Bim by as much as 144% in Z119 cells and 49% in Z181 cells, and further produced caspase-3 activation and consequent apoptotic cell death. Both canertinib and the FDA-approved ErbB1/2-directed TKI lapatinib abrogated proliferation and increased sensitivity to BCR/ABL-directed TKIs at clinically relevant doses. Our results suggest that ErbB signaling is an additional molecular target in Ph(+ALL and encourage the development of clinical strategies combining ErbB and BCR/ABL kinase inhibitors for this subset of ALL patients.

  9. Lactate Transport and Receptor Actions in Retina

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vosborg, Fia; Henriksen, Jens Ulrik Lütken

    2016-01-01

    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......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...

  10. Inhibition of lactation.

    Science.gov (United States)

    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.

  11. Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche.

    Directory of Open Access Journals (Sweden)

    Chen-Yuan Tseng

    2014-12-01

    Full Text Available Stem cells have an innate ability to occupy their stem cell niche, which in turn, is optimized to house stem cells. Organ aging is associated with reduced stem cell occupancy in the niche, but the mechanisms involved are poorly understood. Here, we report that Notch signaling is increased with age in Drosophila female germline stem cells (GSCs, and this results in their removal from the niche. Clonal analysis revealed that GSCs with low levels of Notch signaling exhibit increased adhesiveness to the niche, thereby out-competing their neighbors with higher levels of Notch; adhesiveness is altered through regulation of E-cadherin expression. Experimental enhancement of Notch signaling in GSCs hastens their age-dependent loss from the niche, and such loss is at least partially mediated by Sex lethal. However, disruption of Notch signaling in GSCs does not delay GSC loss during aging, and nor does it affect BMP signaling, which promotes self-renewal of GSCs. Finally, we show that in contrast to GSCs, Notch activation in the niche (which maintains niche integrity, and thus mediates GSC retention is reduced with age, indicating that Notch signaling regulates GSC niche occupancy both intrinsically and extrinsically. Our findings expose a novel role of Notch signaling in controlling GSC-niche adhesion in response to aging, and are also of relevance to metastatic cancer cells, in which Notch signaling suppresses cell adhesion.

  12. Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

    DEFF Research Database (Denmark)

    Schäfer, Katharina; Blankenburg, Felix; Kupers, Ron

    2012-01-01

    that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI......) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT......-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition....

  13. Suppressor of cytokine signaling 1 (SOCS1) limits NFkappaB signaling by decreasing p65 stability within the cell nucleus.

    Science.gov (United States)

    Strebovsky, Julia; Walker, Patrick; Lang, Roland; Dalpke, Alexander H

    2011-03-01

    Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytoplasmic Janus kinases (Jak) and signal transducer and activator of transcription (STAT) signaling pathways. Previously the authors surprisingly observed that SOCS1 translocated into the nucleus, which was because of the presence of a nuclear localization sequence. This report now hypothesizes that SOCS1 mediates specific functions within the nuclear compartment because it is instantly transported into the nucleus, as shown by photoactivation and live cell imaging in human HEK293 cells. The NFκB component p65 is identified as an interaction partner for SOCS1 but not for other members of the SOCS family. SOCS1 bound to p65 only within the nucleus. By means of its SOCS box domain, SOCS1 operated as a ubiquitin ligase, leading to polyubiquitination and proteasomal degradation of nuclear p65. Thus, SOCS1 limited prolonged p65 signaling and terminated expression of NFκB inducible genes. Using mutants that lack either nuclear translocation or a functional SOCS box, this report identifies genes that are regulated in a manner dependent on the nuclear availability of SOCS1. Data show that beyond its receptor-proximal function in Jak/STAT signaling, SOCS1 also regulates the duration of NFκB signaling within the cell nucleus, thus exerting a heretofore unrecognized function.

  14. Nutrition during lactation

    National Research Council Canada - National Science Library

    Committee on Nutritional Status During Pregnancy and Lactation, Institute of Medicine

    On the basis of a comprehensive literature review and analysis, Nutrition During Lactation points out specific directions for needed research in understanding the relationship between the nutrition...

  15. Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland.

    Directory of Open Access Journals (Sweden)

    Sumanta Chatterjee

    Full Text Available BACKGROUND: Insulin like growth factors (IGFs and their binding proteins (IGFBPs are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals. RESULTS: We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland. CONCLUSION: Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland.

  16. Lactic acid and lactates

    NARCIS (Netherlands)

    Schreurs, V.V.A.M.

    2010-01-01

    This review aims to integrate the present state of knowledge on lactate metabolism in human and mammalian physiology as far as it could be subject to nutritional interventions. An integrated view on the nutritional, metabolic and physiological aspects of lactic acid and lactates might open a

  17. Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows.

    Science.gov (United States)

    Sadri, H; Bruckmaier, R M; Rahmani, H R; Ghorbani, G R; Morel, I; van Dorland, H A

    2010-10-01

    Gene expression of adipose factors, which may be part of the mechanisms that underlie insulin sensitivity, were studied in dairy cows around parturition. Subcutaneous fat biopsies and blood samples were taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.) and in week 5 p.p. In the adipose tissue samples, mRNA was quantified by real-time reverse transcription polymerase chain reaction for tumour necrosis factor alpha (TNFα), insulin-independent glucose transporter (GLUT1), insulin-responsive glucose transporter (GLUT4), insulin receptor, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), regulatory subunit of phosphatidylinositol-3 kinase (p85) and catalytic subunit of phosphatidylinositol-3 kinase. Blood plasma was assayed for concentrations of glucose, β-hydroxybutyric acid, non-esterified fatty acids (NEFA) and insulin. Plasma parameters followed a pattern typically observed in dairy cows. Gene expression changes were observed, but there were no changes in TNFα concentrations, which may indicate its local involvement in catabolic adaptation of adipose tissue. Changes in GLUT4 and GLUT1 mRNA abundance may reflect their involvement in reduced insulin sensitivity and in sparing glucose for milk synthesis in early lactation. Unchanged gene expression of IRS1, IRS2 and p85 over time may imply a lack of their involvement in terms of insulin sensitivity dynamics. Alternatively, it may indicate that post-transcriptional modifications of these factors came into play and may have concealed an involvement. © 2010 Blackwell Verlag GmbH.

  18. Bioactivity-guided identification and cell signaling technology to delineate the lactate dehydrogenase A inhibition effects of Spatholobus suberectus on breast cancer.

    Directory of Open Access Journals (Sweden)

    Zhiyu Wang

    Full Text Available Aerobic glycolysis is an important feature of cancer cells. In recent years, lactate dehydrogenase A (LDH-A is emerging as a novel therapeutic target for cancer treatment. Seeking LDH-A inhibitors from natural resources has been paid much attention for drug discovery. Spatholobus suberectus (SS is a common herbal medicine used in China for treating blood-stasis related diseases such as cancer. This study aims to explore the potential medicinal application of SS for LDH-A inhibition on breast cancer and to determine its bioactive compounds. We found that SS manifested apoptosis-inducing, cell cycle arresting and anti-LDH-A activities in both estrogen-dependent human MCF-7 cells and estrogen-independent MDA-MB-231 cell. Oral herbal extracts (1 g/kg/d administration attenuated tumor growth and LDH-A expression in both breast cancer xenografts. Bioactivity-guided fractionation finally identified epigallocatechin as a key compound in SS inhibiting LDH-A activity. Further studies revealed that LDH-A plays a critical role in mediating the apoptosis-induction effects of epigallocatechin. The inhibited LDH-A activities by epigallocatechin is attributed to disassociation of Hsp90 from HIF-1α and subsequent accelerated HIF-1α proteasome degradation. In vivo study also demonstrated that epigallocatechin could significantly inhibit breast cancer growth, HIF-1α/LDH-A expression and trigger apoptosis without bringing toxic effects. The preclinical study thus suggests that the potential medicinal application of SS for inhibiting cancer LDH-A activity and the possibility to consider epigallocatechin as a lead compound to develop LDH-A inhibitors. Future studies of SS for chemoprevention or chemosensitization against breast cancer are thus warranted.

  19. Lactate produced by glycogenolysis in astrocytes regulates memory processing.

    Science.gov (United States)

    Newman, Lori A; Korol, Donna L; Gold, Paul E

    2011-01-01

    When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocytes, which provide lactate to neurons as an energy substrate. Sensitive bioprobes were used to measure brain glucose and lactate levels in 1-sec samples. Extracellular glucose decreased and lactate increased while rats performed a spatial working memory task. Intrahippocampal infusions of lactate enhanced memory in this task. In addition, pharmacological inhibition of astrocytic glycogenolysis impaired memory and this impairment was reversed by administration of lactate or glucose, both of which can provide lactate to neurons in the absence of glycogenolysis. Pharmacological block of the monocarboxylate transporter responsible for lactate uptake into neurons also impaired memory and this impairment was not reversed by either glucose or lactate. These findings support the view that astrocytes regulate memory formation by controlling the provision of lactate to support neuronal functions.

  20. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Voss, Kelsey; Amaya, Moushimi [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Mueller, Claudius [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Roberts, Brian [Leidos Health Life Sciences, 5202 Presidents Court, Suite 110, Frederick, MD (United States); Kehn-Hall, Kylene; Bailey, Charles [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Petricoin, Emanuel [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Narayanan, Aarthi, E-mail: anaraya1@gmu.edu [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States)

    2014-11-15

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.

  1. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    International Nuclear Information System (INIS)

    Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius; Roberts, Brian; Kehn-Hall, Kylene; Bailey, Charles; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells

  2. Cerebral Lactate Concentration in Neonatal Hypoxic-Ischemic Encephalopathy: In Relation to Time, Characteristic of Injury, and Serum Lactate Concentration

    Directory of Open Access Journals (Sweden)

    Tai-Wei Wu

    2018-05-01

    Full Text Available BackgroundCerebral lactate concentration can remain detectable in neonatal hypoxic-ischemic encephalopathy (HIE after hemodynamic stability. The temporal resolution of regional cerebral lactate concentration in relation to the severity or area of injury is unclear. Furthermore, the interplay between serum and cerebral lactate in neonatal HIE has not been well defined. The study aims to describe cerebral lactate concentration in neonatal HIE in relation to time, injury, and serum lactate.Design/methodsFifty-two newborns with HIE undergoing therapeutic hypothermia (TH were enrolled. Magnetic resonance imaging and spectroscopy (MRI + MR spectroscopy were performed during and after TH at 54.6 ± 15.0 and 156 ± 57.6 h of life, respectively. Severity and predominant pattern of injury was scored radiographically. Single-voxel 1H MR spectra were acquired using short-echo (35 ms PRESS sequence localized to the basal ganglia (BG, thalamus (Thal, gray matter (GM, and white matter. Cerebral lactate concentration was quantified by LCModel software. Serum and cerebral lactate concentrations were plotted based on age at time of measurement. Multiple comparisons of regional cerebral lactate concentration based on severity and predominant pattern of injury were performed. Spearman’s Rho was computed to determine correlation between serum lactate and cerebral lactate concentration at the respective regions of interest.ResultsOverall, serum lactate concentration decreased over time. Cerebral lactate concentration remained low for less severe injury and decreased over time for more severe injury. Cerebral lactate remained detectable even after TH. During TH, there was a significant higher concentration of cerebral lactate at the areas of injury and also when injury was more severe. However, these differences were no longer observed after TH. There was a weak correlation between serum lactate and cerebral lactate concentration at the BG (rs

  3. Interpretation of the auto-mutual information rate of decrease in the context of biomedical signal analysis. Application to electroencephalogram recordings

    International Nuclear Information System (INIS)

    Escudero, Javier; Hornero, Roberto; Abásolo, Daniel

    2009-01-01

    The mutual information (MI) is a measure of both linear and nonlinear dependences. It can be applied to a time series and a time-delayed version of the same sequence to compute the auto-mutual information function (AMIF). Moreover, the AMIF rate of decrease (AMIFRD) with increasing time delay in a signal is correlated with its entropy and has been used to characterize biomedical data. In this paper, we aimed at gaining insight into the dependence of the AMIFRD on several signal processing concepts and at illustrating its application to biomedical time series analysis. Thus, we have analysed a set of synthetic sequences with the AMIFRD. The results show that the AMIF decreases more quickly as bandwidth increases and that the AMIFRD becomes more negative as there is more white noise contaminating the time series. Additionally, this metric detected changes in the nonlinear dynamics of a signal. Finally, in order to illustrate the analysis of real biomedical signals with the AMIFRD, this metric was applied to electroencephalogram (EEG) signals acquired with eyes open and closed and to ictal and non-ictal intracranial EEG recordings

  4. Interpretation of the auto-mutual information rate of decrease in the context of biomedical signal analysis. Application to electroencephalogram recordings.

    Science.gov (United States)

    Escudero, Javier; Hornero, Roberto; Abásolo, Daniel

    2009-02-01

    The mutual information (MI) is a measure of both linear and nonlinear dependences. It can be applied to a time series and a time-delayed version of the same sequence to compute the auto-mutual information function (AMIF). Moreover, the AMIF rate of decrease (AMIFRD) with increasing time delay in a signal is correlated with its entropy and has been used to characterize biomedical data. In this paper, we aimed at gaining insight into the dependence of the AMIFRD on several signal processing concepts and at illustrating its application to biomedical time series analysis. Thus, we have analysed a set of synthetic sequences with the AMIFRD. The results show that the AMIF decreases more quickly as bandwidth increases and that the AMIFRD becomes more negative as there is more white noise contaminating the time series. Additionally, this metric detected changes in the nonlinear dynamics of a signal. Finally, in order to illustrate the analysis of real biomedical signals with the AMIFRD, this metric was applied to electroencephalogram (EEG) signals acquired with eyes open and closed and to ictal and non-ictal intracranial EEG recordings.

  5. Thirty Minutes of Running Exercise Decreases T2 Signal Intensity but Not Thickness of the Knee Joint Cartilage: A 3.0-T Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Karanfil, Yiğitcan; Babayeva, Naila; Dönmez, Gürhan; Diren, H Barış; Eryılmaz, Muzaffer; Doral, Mahmut Nedim; Korkusuz, Feza

    2018-04-01

    Objective Recent studies showed a potential of magnetic resonance imaging (MRI), which can be used as an additional tool for diagnosing cartilage degeneration in the early stage. We designed a cross-sectional study in order to evaluate knee joint cartilage adaptation to running, using 3.0-T MRI equipped with the 3-dimensional turbo spin echo (VISTA = Volume ISotropic Turbo spin echo Acquisition) software. By this thickness (mm) and signal intensity (mean pixel value) can be quantified, which could be closely related to the fluid content of the knee joint cartilage, before and after running. Methods A total of 22 males, aged 18 to 35 years, dominant (right) and nondominant (left) knees were assessed before and after 30 minutes of running. Cartilage thickness and signal intensity of surfaces of the patella, medial and lateral femoral and tibial condyles were measured. Results Cartilage thickness of the lateral condyle decreased at the dominant knee, while it increased at the medial tibial plateau. Signal intensity decreased at all locations, except the lateral patella in both knees. The most obvious decrease in signal intensity (10.6%) was at the medial tibial plateau from 949.8 to 849.0 of the dominant knee. Conclusion There was an increase in thickness measurements and decrease in signal intensity in medial tibial plateau of the dominant knee after 30 minutes of running. This outcome could be related to fluid outflow from the tissue. Greater reductions in the medial tibial plateau cartilage indicate greater load sharing by these areas of the joint during a 30-minute running.

  6. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lingling, E-mail: liulingling2012@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Luo, Qing, E-mail: qing.luo@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Sun, Jinghui, E-mail: sunjhemail@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Wang, Aoli, E-mail: leaf13332@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Shi, Yisong, E-mail: shiyis@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Ju, Yang, E-mail: ju@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Morita, Yasuyuki, E-mail: morita@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2017-06-15

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

  7. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

    International Nuclear Information System (INIS)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2017-01-01

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

  8. Assessing the transport rate of hyperpolarized pyruvate and lactate from the intra- to the extracellular space.

    Science.gov (United States)

    Reineri, Francesca; Daniele, Valeria; Cavallari, Eleonora; Aime, Silvio

    2016-08-01

    The use of [1-(13) C]pyruvate hyperpolarized by means of dynamic nuclear polarization provides a direct way to track the metabolic transformations of this metabolite in vivo and in cell cultures. The identification of the intra- and extracellular contributions to the (13) C NMR resonances is not straightforward. In order to obtain information about the rate of pyruvate and lactate transport through the cellular membrane, we set up a method that relies on the sudden 'quenching' of the extracellular metabolites' signal. The paramagnetic Gd-tetraazacyclododecane triacetic acid (Gd-DO3A) complex was used to dramatically decrease the longitudinal relaxation time constants of the (13) C-carboxylate resonances of both pyruvate and lactate. When Gd-DO3A was added to an MCF-7 cellular culture, which had previously received a dose of hyperpolarized [1-(13) C]pyruvate, the contributions of the extracellular pyruvate and lactate signals were deleted. From the analysis of the decay curves of the (13) C-carboxylate resonances of pyruvate and lactate it was possible to extract information about the exchange rate of the two metabolites across the cellular membrane. In particular, it was found that, in the reported experimental conditions, the lactate transport from the intra- to the extracellular space is not much lower than the rate of lactate formation. The method reported herein is non-destructive and it could be translated to in vivo studies. It opens a route for the use of hyperpolarized pyruvate to assess altered activity of carboxylate transporter proteins that may occur in pathological conditions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Lactate induces osteoblast differentiation by stabilization of HIF1α.

    Science.gov (United States)

    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.

  10. Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

    Science.gov (United States)

    Biesdorf, C; Wang, A-L; Topic, B; Petri, D; Milani, H; Huston, J P; de Souza Silva, M A

    2015-09-01

    Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. (a) These results confirm the importance of DA release in the NAc for

  11. Lactational Infertility- A Review

    Directory of Open Access Journals (Sweden)

    Ramachandran Prema

    1987-01-01

    Full Text Available Studies undertaken by the National Institute of Nutrition during the last 10 years indicate that prolonged breast-feeding is still the rule among rural and urban low income group population in Hyderabad. Lactation induced hyperprolactinaemia prolongs postpartum amenorrhea and inter pregnancy interval by about 6 months. Duration of lactational amenorrhea infants results in a fall of plasma prolactin levels and rapid return of menstruation and fertility. Lactational amenorrhea lasts longer in undernourished women with low body weight and low fat fold rural women, duration of lactational amenorrhea is longer as compared to urban women. This might be partly attributable to the delay in introduction of supplements to the rural infants and partly to the lower body weight and fat fold thickness of rural women.

  12. Inhibition of human melanoma cell growth by dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels

    Science.gov (United States)

    Syed, Deeba N.; Afaq, Farrukh; Maddodi, Nityanand; Johnson, Jeremy J.; Sarfaraz, Sami; Ahmad, Adeel; Setaluri, Vijayasaradhi; Mukhtar, Hasan

    2011-01-01

    The prognosis of advanced melanoma remains poor in spite of treatment advances, emphasizing the importance of additional preventive measures. Flavonoids, natural components of our diet are being investigated for their chemopreventive/therapeutic properties. Microphthalmia-associated transcription factor (Mitf), downstream of Wnt/β-catenin pathway has become an important prognostic marker of melanoma. Here, we show that treatment of 451Lu melanoma cells with the dietary flavonoid fisetin resulted in decreased cell viability with G1-phase arrest and disruption of Wnt/β-catenin signaling. This was accompanied with a decrease in expression of Wnt protein and its co-receptors and a parallel increase in the expression of endogenous Wnt inhibitors. Fisetin-treated cells showed increased cytosolic levels of Axin and β-TrCP and decreased phosphorylation of GSK3-β assocaited with decreased β-catenin stabilization. Fisetin-mediated interference with the functional cooperation between β-catenin and LEF/TCF-2 resulted in downregulation of positively regulated TCF targets such as c-myc, Brn-2 and Mitf. Flowcytometric analysis of Mitf overexpressing cells showed that fisetin repressed Mitf-induced cell proliferation. Finally, administration of fisetin to 451Lu xenografted nude mice resulted in inhibition of tumor development and decreased Mitf expression. Our data suggest that fisetin can be developed as an effective agent against melanoma due to its potential inhibitory effect on β-catenin/Mitf signaling. PMID:21346776

  13. Dietary intake of Croatian lactating women

    Directory of Open Access Journals (Sweden)

    Greta Krešić

    2012-01-01

    Full Text Available Nutritional inadequacies during lactation may affect the well-being of both the mother and the infant. For this reason, breast-feeding women usually pay attention to their dietary practice during the breast-feeding period. The aim of this study was to examine changes in dietary intake of Croatian lactating women during six months postpartum. The study sample consisted of 83 lactating women whose diet records were collected at three measurements rounds: at 1 ± 0.25, 3 ± 0.25 and 6 ± 0.25 months postpartum. The mothers´ diets were investigated using two consecutive 24-hour dietary recalls. Energy and nutrient intakes were estimated using a nutritional database. The obtained results have shown that the diet of Croatian lactating women is hypocaloric (65.73 – 79.52 % DRI, p < 0.001 and deficient in magnesium, zinc, vitamins A, B1, B6, D and folate. Also evident was a moderate imbalance in the distribution of energy percentages from macronutrients. During six months postpartum, lactating women continuously decreased food intake resulting in a gradual decrease in energy intake (p < 0.001 and in the intake of all micronutrients. However, during six months postpartum, lactating women increased the share of total fat in energy intake (p = 0.006 and the share of saturated fatty acids (p = 0.048, while the share of monounsaturated fatty acids in total energy intake decreased (p = 0.004. It could be concluded that it is worthwhile to further study the nutritional status of Croatian lactating women during this vulnerable period especially regarding their micronutrients intake in order to achieve the recommended dietary requirements.

  14. Decreased exploratory activity in a mouse model of 15q duplication syndrome; implications for disturbance of serotonin signaling.

    Directory of Open Access Journals (Sweden)

    Kota Tamada

    Full Text Available Autism spectrum disorders (ASDs have garnered significant attention as an important grouping of developmental brain disorders. Recent genomic studies have revealed that inherited or de novo copy number variations (CNVs are significantly involved in the pathophysiology of ASDs. In a previous report from our laboratory, we generated mice with CNVs as a model of ASDs, with a duplicated mouse chromosome 7C that is orthologous to human chromosome 15q11-13. Behavioral analyses revealed paternally duplicated (patDp/+ mice displayed abnormal behaviors resembling the symptoms of ASDs. In the present study, we extended these findings by performing various behavioral tests with C57BL/6J patDp/+ mice, and comprehensively measuring brain monoamine levels with ex vivo high performance liquid chromatography. Compared with wild-type controls, patDp/+ mice exhibited decreased locomotor and exploratory activities in the open field test, Y-maze test, and fear-conditioning test. Furthermore, their decreased activity levels overcame increased appetite induced by 24 hours of food deprivation in the novelty suppressed feeding test. Serotonin levels in several brain regions of adult patDp/+ mice were lower than those of wild-type control, with no concurrent changes in brain levels of dopamine or norepinephrine. Moreover, analysis of monoamines in postnatal developmental stages demonstrated reduced brain levels of serotonin in young patDp/+ mice. These findings suggest that a disrupted brain serotonergic system, especially during postnatal development, may generate the phenotypes of patDp/+ mice.

  15. CSF LACTATE IN MENINGITIS

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    Anjampakuthikal Aboobekar Haris

    2017-05-01

    Full Text Available BACKGROUND Meningitis is an infection within the subarachnoid space characterised by a CNS inflammatory reaction. It is a serious condition requiring immediate diagnosis and appropriate treatment to be started at the earliest to prevent mortality as well as irreversible neurological deficits. CSF lactate has been found useful in differentiating bacterial meningitis from viral meningitis in many studies in the western population, but studies in Indian population are limited. The aim of the study is to study whether CSF lactate can be used to distinguish bacterial from viral meningitis and to study the levels of CSF lactate in tuberculosis meningitis. MATERIALS AND METHODS This was a descriptive study conducted in a tertiary care hospital. In this study, 78 cases of meningitis were selected. Cases are patients with bacterial, viral or tuberculosis meningitis admitted to the hospital under the Department of Medicine and Neurology. Cases are grouped into bacterial, viral and tuberculosis meningitis based on clinical picture, CSF analysis and imaging characteristics. CSF lactate estimation was done by dry chemistry method. Using appropriate statistical methods and SPSS software, CSF lactate levels were compared among these groups and analysed for any association with the final outcome. RESULTS The levels of CSF lactate in bacterial meningitis were higher than viral meningitis with a statistical significance of p 35 mg/dL for bacterial meningitis in this study was 95% and 100% respectively and the positive predictive value was 100% and the negative predictive value was 96%. The mean CSF lactate values in bacterial, viral and tuberculosis meningitis were 124.40 ± 35.85 mg/dL, 24.34 ± 6.05 mg/dL and 50.13 ± 9.89 mg/dL, respectively. CONCLUSION CSF lactate level was significantly elevated in bacterial meningitis than tuberculosis or viral meningitis and can be used as a marker for differentiating bacterial from viral meningitis.

  16. Inhibition of endogenous lactate turnover with lactate infusion in humans

    International Nuclear Information System (INIS)

    Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C.

    1989-01-01

    The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U- 14 C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production

  17. Rikkunshito, a Japanese Kampo Medicine, Ameliorates Decreased Feeding Behavior via Ghrelin and Serotonin 2B Receptor Signaling in a Novelty Stress Murine Model

    Directory of Open Access Journals (Sweden)

    Chihiro Yamada

    2013-01-01

    Full Text Available We investigated the effects of rikkunshito (RKT, a ghrelin signal enhancer, on the decrease in food intake after exposure to novelty stress in mice. RKT administration (500 mg/kg, per os improved the decrease in 6 h cumulative food intake. In control mice, the plasma acylated ghrelin levels significantly increased by 24 h fasting. In contrast, the acylated ghrelin levels did not increase by fasting in mice exposed to the novelty stress. RKT administration to the novelty stress mice showed a significant increase in the acylated ghrelin levels compared with that in the distilled-water-treated control mice. Food intake after administering serotonin 2B (5-HT2B receptor antagonists was evaluated to clarify the role of 5-HT2B receptor activation in the decrease in feeding behavior after novelty stress. SB215505 and SB204741, 5-HT2B receptor antagonists, significantly improved the decrease in food intake after exposure to novelty stress. A component of RKT, isoliquiritigenin, prevented the decrease in 6 h cumulative food intake. Isoliquiritigenin showed 5-HT2B receptor antagonistic activity in vitro. In conclusion, the results suggested that RKT improves the decrease in food intake after novelty stress probably via 5-HT2B receptor antagonism of isoliquiritigenin contained in RKT.

  18. Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease.

    Science.gov (United States)

    Alkadhi, Karim A; Tran, Trinh T

    2015-08-01

    An important factor that may affect the severity and time of onset of Alzheimer's disease (AD) is chronic stress. Epidemiological studies report that chronically stressed individuals are at an increased risk for developing AD. The purpose of this study was to reveal whether chronic psychosocial stress could hasten the appearance of AD symptoms including changes in basal levels of cognition-related signaling molecules in subjects who are at risk for the disease. We investigated the effect of chronic psychosocial stress on basal levels of memory-related signaling molecules in area CA1 of subclinical rat model of AD. The subclinical symptomless rat model of AD was induced by osmotic pump continuous intracerebroventricular (ICV) infusion of 160 pmol/day Aβ1-42 for 14 days. Rats were chronically stressed using the psychosocial stress intruder model. Western blot analysis of basal protein levels of important signaling molecules in hippocampal area CA1 showed no significant difference between the subclinical AD rat model and control rat. Following six weeks of psychosocial stress, molecular analysis showed that subclinical animals subjected to stress have significantly reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as decreased basal levels of p-CREB, total CREB, and BDNF. The present results suggest that these changes in basal levels of signaling molecules may be responsible for impaired learning, memory, and LTP in this rat model, which support the proposition that chronic stress may accelerate the emergence of AD in susceptible individuals.

  19. Non-nutritional factors affecting lactation persistency in dairy ewes: a review

    Directory of Open Access Journals (Sweden)

    Antonello Cannas

    2010-01-01

    Full Text Available Milk production is largely related to the shape of the lactation curve. Key elements of the lactation pattern are peak yield, which is the maximum daily yield reached during lactation, and lactation persistency, which is the medium rate of milk yield decrease after the lactation peak. The ideal lactation curve should have a reasonably high peak and a flat trend afterwards. A more persistent lactation is desirable because it is related to better animal health and reduction of feeding costs. Effective strategies to improve lactation persistency require a deep understanding of the main factors that affect this trait, including genetics, hormonal status and administration, udder morphology, seasonal changes, management, animal health (e.g. mastitis, stress and nutrition. This review covers the effects of non-nutritional factors on lactation persistency in dairy sheep.

  20. HEMATOLOGICAL PARAMETERS IN THE ALPINE GOATS DURING LACTATION

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    Zvonko Antunović

    2013-06-01

    Full Text Available The aim of this paper is to present haematological parameters in the Alpine goats during lactation. The study included 15 goats average age of 5 years in the 4th lactation. The blood sampling of goats was conducted on the 30th, 60th, 90th and 120th days of lactation. In the blood of goats, significant decrease in the number of red blood cells was determined, as lactation progressed, and their growth in the latter measure, but with no significant difference. Also, a significant decrease was found in the number of leukocytes as lactation progressed, whereas the 120th day of lactation showed their increase compared to the 90th day. A similar trend was found out for the content of hemoglobin and hematocrit. The mean volume of red blood cells and a significant proportion of monocytes were declining as lactation advance, while the mean concentration of hemoglobin significantly increased, and in the end of the study significantly decreased, compared to the measurement of 90th day. The above mentioned changes in hematological parameters indicate the quality of recovery and adjustment of goats in lactation.

  1. Eficácia da dose reduzida de gonadorelina e diferentes prostaglandinas no protocolo ovsynch em vacas holandesas Efficacy of decreasing dose of gonadorelin and comparison between different prostaglandins on ovsynch protocol in lactating Holstein cows

    Directory of Open Access Journals (Sweden)

    R.M. Santos

    2008-12-01

    Full Text Available Avaliou-se a eficácia da dose de 0,10 ou de 0,25mg de gonadorelina nas taxas de ovulação e de sincronização no protocolo Ovsynch e de 150mcg de D-cloprostenol ou 0,530mg de cloprostenol sódico na regressão do corpo lúteo (CL de sete dias e de todos os CL. Foram utilizadas 136 vacas lactantes da raça Holandesa, com média de produção de leite de 23,75,8kg/dia, com 138,4±72,0 dias em lactação. As vacas foram distribuídas aleatoriamente em quatro grupos, de acordo com a dose de gonadorelina e o tipo da prostaglandina. As taxas de ovulação e de sincronização foram de 52,9% e 80,9% para 0,10mg de gonadorelina e de 57,4% e 80,9% para 0,25mg de gonadorelina, respectivamente. A taxa de regressão do CL de sete dias foi de 97,1% para o D-cloprostenol e de 97,5% para o cloprostenol sódico. A taxa de prenhez não foi influenciada pelos tratamentos, mas foi influenciada pela taxa de ovulação à primeira aplicação de gonadorelina, 16,0% vs. 6,6% para as vacas que ovularam e não ovularam, respectivamente. Conclui-se que 0,10mg de gonadorelina foi eficiente e ambas prostaglandinas podem ser usadas em protocolos de sincronização da ovulação.The efficacy of 150mcg D-cloprostenol or 0.530mg cloprostenol sodium on the 7- day corpus luteum (CL regression rate, and of two doses of gonadorelin, 0.10mg vs. 0.25mg, on the ovulation and synchronization rates during the Ovsynch protocol were evaluated. Lactating Holstein cows (n=136, producing 23.75.8kg milk/d and 138.4±72.0 days in milk were randomly assigned to four groups, according to dose of gonadorelin and prostaglandin type. No effect of the products and doses tested on conception rate were observed. The ovulation and synchronization rates using 0.10mg or 0.25mg of gonadorelin were 52.9% and 80.9% vs. 57.4% and 80.9%, respectively. The CL regression rates in cows ovulating after the first GnRH using D-cloprostenol or cloprostenol sodium were 97.1% and 97.5%, respectively. The

  2. [Bone loss in lactating women and post-pregnancy osteoporosis].

    Science.gov (United States)

    Hirata, Go; Chaki, Osamu

    2011-09-01

    Measurement of the bone mineral density have shown that lactating women had 1 to 3% decrease in bone mineral density. Post pregnancy osteoporosis is rare condition that causes fragile fracture mostly in vertebrae. The bone loss in lactating women is caused by calcium loss, decrease in estrogen level, and increase in PTHrP (parathyroid hormone related protein) level. Some data have shown that extended lactation and amenorrhea had an association with the degree of bone loss. Mostly, the bone loss of the lactating women recovers to the baseline level, soon after the weaning, and there is no long term effect. Post pregnancy osteoporosis should be concerned, when we see a lactating woman with fragile fracture of the vertebrae.

  3. Lactation history, serum concentrations of persistent organic pollutants, and maternal risk of diabetes

    DEFF Research Database (Denmark)

    Zong, Geng; Grandjean, Philippe; Wang, Xiaobin

    2016-01-01

    OBJECTIVE: Lactation may help curb diabetes risk and is also known as an excretion route for some environmental pollutants. We evaluated associations of lifetime lactation history with serum concentrations of persistent organic pollutants (POPs) in the National Health and Nutrition Examination....... Prospective studies are needed to clarify how lactation could complement diabetes prevention through decreasing the POP body burdens....

  4. Flexible graphene bio-nanosensor for lactate.

    Science.gov (United States)

    Labroo, Pratima; Cui, Yue

    2013-03-15

    The development of a flexible nanosensor for detecting lactate could expand opportunities for using graphene, both in fundamental studies for a variety of device platforms and in practical applications. Graphene is a delicate single-layer, two-dimensional network of carbon atoms with ultrasensitive sensing capabilities. Lactic acid is important for clinical analysis, sports medicine, and the food industry. Recently, wearable and flexible bioelectronics on plastics have attracted great interest for healthcare, sports and defense applications due to their advantages of being light-weight, bendable, or stretchable. Here, we demonstrate for the first time the development of a flexible graphene-based bio-nanosensor to detect lactate. Our results show that flexible lactate biosensors can be fabricated on a variety of plastic substrates. The sensor can detect lactate sensitively from 0.08 μM to 20 μM with a fast steady-state measuring time of 2s. The sensor can also detect lactate under different mechanical bending conditions, the sensor response decreased as the bending angle and number of bending repetitions increased. We anticipate that these results could open exciting opportunities for fundamental studies of flexible graphene bioelectronics by using other bioreceptors, as well as a variety of wearable, implantable, real-time, or on-site applications in fields ranging from clinical analysis to defense. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

    Science.gov (United States)

    Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C

    2016-06-15

    T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. Ion-neutral gas reactions in a collision/reaction cell in inductively coupled plasma mass spectrometry: Correlation of ion signal decrease to kinetic rate constants

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Patrick J. [Trace Element Research Laboratory, School of Earth Sciences, The Ohio State University, 125 S. Oval Mall, Columbus, OH 43210 (United States); Department of Chemistry, The Ohio State University, 120 18th Avenue, Columbus, OH 43210 (United States); Olesik, John W., E-mail: olesik.2@osu.edu [Trace Element Research Laboratory, School of Earth Sciences, The Ohio State University, 125 S. Oval Mall, Columbus, OH 43210 (United States)

    2015-03-01

    Reaction gas flow rate dependent Ar{sub 2}{sup +} and Ar{sup +} signals are correlated to fundamental kinetic rate coefficients. A simple calculation, assuming that gas exits the reaction cell due only to effusion, is described to estimate the gas pressure in the reaction cell. The value of the product of the kinetic rate constant and the ion residence time in the reaction cell can be determined from experimental measurement of the decrease in an ion signal as a function of reaction gas flow rate. New kinetic rate constants are determined for the reaction of CH{sub 3}F with Ar{sup +} and Ar{sub 2}{sup +}. - Highlights: • How to determine pressure and the product of the kinetic rate constant times the ion residence time in reaction cell • Relate measured ICP-DRC-MS signals versus gas flow rate to kinetic rate constants measured previously using SIFT-MS • Describe how to determine previously unmeasured kinetic rate constants using ICP-DRC-MS.

  7. Combination of fat saturation and variable bandwidth imaging to increase signal-to-noise ratio and decrease motion artifacts for body MR imaging at high field

    International Nuclear Information System (INIS)

    Chew, W.M.

    1989-01-01

    The signal-to-noise ratio (SNR) of the MR imaging examination is a critical component of the quality of the image. Standard methods to increase SNR include signal averaging with multiple excitations, at the expense of imaging time (which on T2-weighted images could be quite significant), or increasing pixel volume by manipulation of field of view, matrix size, and/or section thickness, all at the expense of resolution. Another available method to increase SNR is to reduce the bandwidth of the receiver, which increases SNR by the square root of the amount of the reduction. The penalty imposed on high-field-strength MR examinations of the body is an unacceptable increase in chemical shift artifact. However, presaturating the fat resonance eliminates the chemical shift artifact. Thus, a combination of imaging techniques, fat suppression, and decreased bandwidth imaging can produce images free of chemical shift artifact with increased SNR and no penalty in resolution or imaging time. Early studies also show a reduction in motion artifact when fat saturation is used. This paper reports MR imaging performed with a 1.5-T Signa imager. With this technique, T2-weighted images (2,500/20/80 [repetition time msec/echo time msec/inversion time msec]) illustrating the increase in SNR and T1-weighted images (600/20) demonstrating a decrease in motion artifact are shown

  8. TGF-β1 downregulates StAR expression and decreases progesterone production through Smad3 and ERK1/2 signaling pathways in human granulosa cells.

    Science.gov (United States)

    Fang, Lanlan; Chang, Hsun-Ming; Cheng, Jung-Chien; Leung, Peter C K; Sun, Ying-Pu

    2014-11-01

    Regulation of progesterone production in granulosa cells is important for normal reproductive functions. Steroidogenic acute regulatory protein (StAR) is recognized as the key regulatory protein involved in the rate-limiting step of steroidogenesis. TGF-β1 protein is detected in human follicular fluid, and TGF-β1 and its receptors are expressed in human granulosa cells. However, the functional role of TGF-β1 in the regulation of StAR expression and progesterone production in human granulosa cells remains unknown. Our objective was to investigate the effects of TGF-β1 on StAR expression and progesterone production in human granulosa cells. SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with SV40 large T antigen. SVOG cells were used to investigate the effects of TGF-β1 on StAR expression and progesterone production at an academic research center. Levels of mRNA and protein were examined by RT-qPCR and western blotting, respectively. The accumulation levels of progesterone were measured by enzyme-linked immunosorbent assay (ELISA). TGF-β1 treatment downregulated StAR expression and decreased progesterone production. The suppressive effects of TGF-β1 on StAR expression and progesterone production were abolished by the inhibition of TGF-β type I receptor. In addition, treatment with TGF-β1 activated the Smad2/3 and ERK1/2 signaling pathways. The inhibition of the Smad3 and ERK1/2 signaling pathways attenuated the TGF-β1-induced downregulation of StAR expression and progesterone production. TGF-β1 downregulated StAR expression and decreased progesterone production by activating the Smad3 and ERK1/2 signaling pathways in human granulosa cells.

  9. Supplementation of lactating Dorper and Merino ewes on Themeda ...

    African Journals Online (AJOL)

    In summer, herbage intake of lactating Dorper ewes was not increased by supglementary CP (1983), but decreased by .... collection of samples on three successive days at three- ..... it was calculated that a feed intake of 250, 500 and 750 g.

  10. Lactate Biosensor Based on Cellulose Acetate Membrane Bound Lactate Oxidase

    Directory of Open Access Journals (Sweden)

    Suman

    2007-05-01

    Full Text Available Lactate biosensor was fabricated by immobilizing lactate oxidase in cellulose acetate membrane and by mounting over the sensing part of Pt electrode (working and connected to Ag/AgCl electrode (reference along with auxillary electrode through potentiostat. The enzyme electrode was anodically polarized at +400 mV to generate electrons from H2O2, which was formed from oxidation of serum lactate by immobilized lactate oxidase. The minimum detection limit of the electrode was 0.1mmoles/L and sensitivity of the sensor was 0.008 mA/mM/L lactate. Assay coefficients of variation were < 2% .A good correlation (r=0.99 was found between lactate values obtained by colorimetric method and lactate biosensor. The self-life of the biosensor was 18 days at 4ºC and enzyme electrode can be re-used 150 times without any significant loss in enzyme activity.

  11. Lactate up-regulates the expression of lactate oxidation complex-related genes in left ventricular cardiac tissue of rats.

    Directory of Open Access Journals (Sweden)

    Daniele Gabriel-Costa

    Full Text Available Besides its role as a fuel source in intermediary metabolism, lactate has been considered a signaling molecule modulating lactate-sensitive genes involved in the regulation of skeletal muscle metabolism. Even though the flux of lactate is significantly high in the heart, its role on regulation of cardiac genes regulating lactate oxidation has not been clarified yet. We tested the hypothesis that lactate would increase cardiac levels of reactive oxygen species and up-regulate the expression of genes related to lactate oxidation complex.Isolated hearts from male adult Wistar rats were perfused with control, lactate or acetate (20mM added Krebs-Henseleit solution during 120 min in modified Langendorff apparatus. Reactive oxygen species (O2●-/H2O2 levels, and NADH and NADPH oxidase activities (in enriched microsomal or plasmatic membranes, respectively were evaluated by fluorimetry while SOD and catalase activities were evaluated by spectrophotometry. mRNA levels of lactate oxidation complex and energetic enzymes MCT1, MCT4, HK, LDH, PDH, CS, PGC1α and COXIV were quantified by real time RT-PCR. Mitochondrial DNA levels were also evaluated. Hemodynamic parameters were acquired during the experiment. The key findings of this work were that lactate elevated cardiac NADH oxidase activity but not NADPH activity. This response was associated with increased cardiac O2●-/H2O2 levels and up-regulation of MCT1, MCT4, LDH and PGC1α with no changes in HK, PDH, CS, COXIV mRNA levels and mitochondrial DNA levels. Lactate increased NRF-2 nuclear expression and SOD activity probably as counter-regulatory responses to increased O2●-/H2O2.Our results provide evidence for lactate-induced up-regulation of lactate oxidation complex associated with increased NADH oxidase activity and cardiac O2●-/H2O2 driving to an anti-oxidant response. These results unveil lactate as an important signaling molecule regulating components of the lactate oxidation complex in

  12. Deletion of the innate immune NLRP3 receptor abolishes cardiac ischemic preconditioning and is associated with decreased Il-6/STAT3 signaling.

    Directory of Open Access Journals (Sweden)

    Coert J Zuurbier

    Full Text Available Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also by endogenous danger signals released during ischemia and necrosis. As triggers for the innate immune NLRP3 inflammasome protein complex appear to overlap with those for cardiac ischemia-reperfusion (I/R and ischemic preconditioning (IPC, we explored the possibility that the NLRP3 inflammasome is involved in IPC and acute I/R injury of the heart.Baseline cardiac performance and acute I/R injury were investigated in isolated, Langendorff-perfused hearts from wild-type (WT, ASC(-/- and NLRP3(-/- mice. Deletion of NLRP3 inflammasome components ASC(-/- or NLRP3(-/- did not affect baseline performance. The deletions exacerbated I/R-induced mechanical dysfunction, but were without effect on I/R-induced cell death. When subjected to IPC, WT and ASC(-/- hearts were protected against I/R injury (improved function and less cell death. However, IPC did not protect NLRP3(-/- hearts against I/R injury. NLRP3(-/- hearts had significantly decreased cardiac IL-6 levels with a trend towards lower IL-1β levels at end reperfusion, suggesting abrogation of IPC through diminished IL-6 and/or IL-1β signaling. Subsequent experiments showed that neutralising IL-6 using an antibody against IL-6 abrogated IPC in WT hearts. However, inhibition of the IL-1r receptor with the IL-1 receptor inhibitor Anakinra (100 mg/L did not abrogate IPC in WT hearts. Analysis of survival kinases after IPC demonstrated decreased STAT3 expression in NLRP3(-/- hearts when compared to WT hearts.The data suggest that the innate immune NLRP3 protein, in an NLRP3-inflammasome-independent fashion, is an integral component of IPC in the isolated heart, possibly through an IL-6/STAT3 dependent mechanism.

  13. Activation of α7 nicotinic acetylcholine receptor decreases on-site mortality in crush syndrome through insulin signaling-Na/K-ATPase pathway

    Directory of Open Access Journals (Sweden)

    Bo-Shi eFan

    2016-03-01

    Full Text Available On-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine is widely used in China for treatment of shock, and activation of α7 nicotinic acetylcholine receptor (α7nAChR mediates such antishock effect. The present work was designed to test whether activation of α7nAChR with anisodamine decreased mortality in crush syndrome shortly after decompression. Sprague-Dawley rats and C57BL/6 mice with crush syndrome were injected with anisodamine (20 mg/kg and 28 mg/kg respectively, i.p. 30 min before decompression. Survival time, serum potassium, insulin, and glucose levels were observed shortly after decompression. Involvement of α7nAChR was verified with methyllycaconitine (selective α7nAChR antagonist and PNU282987 (selective α7nAChR agonist, or in α7nAChR knockout mice. Effect of anisodamine was also appraised in C2C12 myotubes. Anisodamine reduced mortality and serum potassium and enhanced insulin sensitivity shortly after decompression in animals with crush syndrome, and PNU282987 exerted similar effects. Such effects were counteracted by methyllycaconitine or in α7nAChR knockout mice. Mortality and serum potassium in rats with hyperkalemia were also reduced by anisodamine. Phosphorylation of Na/K-ATPase was enhanced by anisodamine in C2C12 myotubes. Inhibition of tyrosine kinase on insulin receptor, phosphoinositide 3-kinase, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Na/K-ATPase counteracted the effect of anisodamine on extracellular potassium. These findings demonstrated that activation of α7nAChR could decrease on-site mortality in crush syndrome, at least in part based on the decline of serum potassium through insulin signaling-Na/K-ATPase pathway.

  14. Hyperoxia exposure induced hormesis decreases mitochondrial superoxide radical levels via Ins/IGF-1 signaling pathway in a long-lived age-1 mutant of Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Yanase, Sumino; Ishii, Naoaki

    2008-01-01

    The hormetic effect, which extends the lifespan by various stressors, has been confirmed in Caenorhabditis elegans (C. elegans). We have previously reported that oxidative stress resistance in a long-lived mutant age-1 is associated with the hormesis. In the age-1 allele, which activates an insulin/insulin-like growth factor-1 (Ins/IGF-1) signaling pathway, the superoxide dismutase (SOD) and catalase activities increased during normal aging. We now demonstrate changes in the mitochondrial superoxide radical (O 2 - ) levels of the hormetic conditioned age-related strains. The O 2 - levels in age-1 strain significantly decreased after intermittent hyperoxia exposure. On the other hand, this phenomenon was not observed in a daf-16 null mutant. This hormesis-dependent reduction of the O 2 - levels was observed even if the mitochondrial Mn-SOD was experimentally reduced. Therefore, it is indicated that the hormesis is mediated by events that suppress the mitochondrial O 2 - production. Moreover, some SOD gene expressions in the hormetic conditioned age-1 mutant were induced over steady state messenger ribonucleic acid (mRNA) levels. These data suggest that oxidative stress-inducible hormesis is associated with a reduction of the mitochondrial O 2 - production by activation of the antioxidant system via the Ins/IGF-1 signaling pathway. (author)

  15. Characterization of Lactate Sensors Based on Lactate Oxidase and Palladium Benzoporphyrin Immobilized in Hydrogels

    Directory of Open Access Journals (Sweden)

    Liam P. Andrus

    2015-07-01

    Full Text Available An optical biosensor for lactate detection is described. By encapsulating enzyme-phosphor sensing molecules within permeable hydrogel materials, lactate-sensitive emission lifetimes were achieved. The relative amount of monomer was varied to compare three homo- and co-polymer materials: poly(2-hydroxyethyl methacrylate (pHEMA and two copolymers of pHEMA and poly(acrylamide (pAam. Diffusion analysis demonstrated the ability to control lactate transport by varying the hydrogel composition, while having a minimal effect on oxygen diffusion. Sensors displayed the desired dose-variable response to lactate challenges, highlighting the tunable, diffusion-controlled nature of the sensing platform. Short-term repeated exposure tests revealed enhanced stability for sensors comprising hydrogels with acrylamide additives; after an initial “break-in” period, signal retention was 100% for 15 repeated cycles. Finally, because this study describes the modification of a previously developed glucose sensor for lactate analysis, it demonstrates the potential for mix-and-match enzyme-phosphor-hydrogel sensing for use in future multi-analyte sensors.

  16. Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior.

    Science.gov (United States)

    Mendes, Natalia Ferreira; Castro, Gisele; Guadagnini, Dioze; Tobar, Natalia; Cognuck, Susana Quiros; Elias, Lucila Leico Kagohara; Boer, Patricia Aline; Prada, Patricia Oliveira

    2017-05-01

    Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent. Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration.

    Science.gov (United States)

    Pyakurel, Aswin; Balmer, Delphine; Saba-El-Leil, Marc K; Kizilyaprak, Caroline; Daraspe, Jean; Humbel, Bruno M; Voisin, Laure; Le, Yun Z; von Lintig, Johannes; Meloche, Sylvain; Roduit, Raphaël

    2017-12-15

    Recent work suggested that the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) is increased in the retinal pigment epithelium (RPE) of age-related macular degeneration (ARMD) patients and therefore could be an attractive therapeutic target. Notably, ERK1/2 pathway inhibitors are used in cancer therapy, with severe and noncharacterized ocular side effects. To decipher the role of ERK1/2 in RPE cells, we conditionally disrupted the Erk1 and Erk2 genes in mouse RPE. The loss of ERK1/2 activity resulted in a significant decrease in the level of RPE65 expression, a decrease in ocular retinoid levels concomitant with low visual function, and a rapid disorganization of RPE cells, ultimately leading to retinal degeneration. Our results identify the ERK1/2 pathway as a direct regulator of the visual cycle and a critical component of the viability of RPE and photoreceptor cells. Moreover, our results caution about the need for a very fine adjustment of kinase inhibition in cancer or ARMD treatment in order to avoid ocular side effects. Copyright © 2017 Pyakurel et al.

  18. Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.

    Directory of Open Access Journals (Sweden)

    Bai-Wei Gu

    from human patients have so far not shown defects in pseudouridylation or ribosomal RNA processing. None of the mutant iPS cells presented here show decreased pseudouridine levels in rRNA or defective rRNA processing suggesting telomere maintenance defects account for most of the phenotype of X-linked DC. Finally gene expression analysis of the iPS cells shows that WNT signaling is significantly decreased in all mutant cells, raising the possibility that defective WNT signaling may contribute to disease pathogenesis.

  19. Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.

    Science.gov (United States)

    Gu, Bai-Wei; Apicella, Marisa; Mills, Jason; Fan, Jian-Meng; Reeves, Dara A; French, Deborah; Podsakoff, Gregory M; Bessler, Monica; Mason, Philip J

    2015-01-01

    patients have so far not shown defects in pseudouridylation or ribosomal RNA processing. None of the mutant iPS cells presented here show decreased pseudouridine levels in rRNA or defective rRNA processing suggesting telomere maintenance defects account for most of the phenotype of X-linked DC. Finally gene expression analysis of the iPS cells shows that WNT signaling is significantly decreased in all mutant cells, raising the possibility that defective WNT signaling may contribute to disease pathogenesis.

  20. p53 inactivation decreases dependence on estrogen/ERK signalling for proliferation but promotes EMT and susceptility to 3-bromopyruvate in ERα+ breast cancer MCF-7 cells.

    Science.gov (United States)

    Rieber, Manuel; Strasberg-Rieber, Mary

    2014-03-15

    Most breast cancers express the estrogen receptor alpha (ERα(+)), harbor wt TP53, depend on estrogen/ERK signalling for proliferation, and respond to anti-estrogens. However, concomittant activation of the epidermal growth factor receptor (EGFR)/MEK pathway promotes resistance by decreasing estrogen dependence. Previously, we showed that retroviral transduction of mutant p53 R175H into wt TP53 ERα(+) MCF-7 cells induces epidermal growth factor (EGF)-independent proliferation, activation of the EGF receptor (p-EGFR) and some characteristics of epithelial-mesenchymal transition (EMT). To investigate whether p53 inactivation augments ERα(+) cell proliferation in response to restrictive estradiol, chemical MEK inhibition or metabolic inhibitors. Introduction of mutant p53 R175H lowered expression of p53-dependent PUMA and p21WAF1, decreased E-cadherin and cytokeratin 18 associated with EMT, but increased the % of proliferating ERα(+)/Ki67 cells, diminishing estrogen dependence. These cells also exhibited higher proliferation in the presence of MEK-inhibitor UO126, reciprocally correlating with preferential susceptibility to the pyruvate analog 3-bromopyruvate (3-BrPA) without a comparable response to 2-deoxyglucose. p53 siRNA silencing by electroporation in wt TP53 MCF-7 cells also decreased estrogen dependence and response to MEK inhibition, while also conferring susceptibility to 3-BrPA. (a) ERα(+) breast cancer cells dysfunctional for TP53 which proliferate irrespective of low estrogen and chemical MEK inhibition are likely to increase metabolic consumption becoming increasingly susceptible to 3-BrPA; (b) targeting the pyruvate pathway may improve response to endocrine therapy in ERα(+) breast cancer with p53 dysfunction. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  2. Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

    Science.gov (United States)

    Patet, Camille; Quintard, Hervé; Suys, Tamarah; Bloch, Jocelyne; Daniel, Roy T; Pellerin, Luc; Magistretti, Pierre J; Oddo, Mauro

    2015-10-15

    Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r = 0.56; p 25. The correlation between blood and brain glucose also decreased from r = 0.62 to r = 0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

  3. Lactate in Bitches with Pyometra

    OpenAIRE

    Volpato, R. [UNESP; Rodello, L. [UNESP; Abibe, R. B. [UNESP; Lopes, Maria Denise [UNESP

    2012-01-01

    Lactate is a compound produced by the anaerobic metabolism of glucose, and hyperlactataemia occurs when the rate of production of lactate exceeds the rate of elimination. This occurs in situations of hypoxia and tissue hypoperfusion. Lactate has been considered a useful prognostic indicator in critically ill patients. Pyometra is a disease of adult female dogs characterized by inflammation of the uterus with an accumulation of exudate, which occurs during the luteal phase. It is one of the mo...

  4. Lactate in bitches with pyometra.

    Science.gov (United States)

    Volpato, R; Rodello, L; Abibe, R B; Lopes, M D

    2012-12-01

    Lactate is a compound produced by the anaerobic metabolism of glucose, and hyperlactataemia occurs when the rate of production of lactate exceeds the rate of elimination. This occurs in situations of hypoxia and tissue hypoperfusion. Lactate has been considered a useful prognostic indicator in critically ill patients. Pyometra is a disease of adult female dogs characterized by inflammation of the uterus with an accumulation of exudate, which occurs during the luteal phase. It is one of the most common diseases that occur in the genital tract of female dogs. A total of 31 dogs were diagnosed with pyometra. The diagnosis was confirmed at ultrasonography. Of the 31 dogs, 25 females had open cervix pyometra and six had closed cervix pyometra. Plasma lactate concentrations were determined by an enzymatic colorimetric method. The average concentration (±SD) of plasma lactate in all 31 bitches with pyometra was 3.55 ± 0.46 mm. Healthy dogs had plasma lactate concentrations between 0.3 and 2.5 mm (mean ± SD). Concentrations ranged from 0.8 to 2.9 mm when plasma lactate was measured with a portable device and 0.4-2.6 mm with the blood gas analyser. Even though plasma lactate values vary between several studies and equipment used to measure concentrations, our results for dogs with pyometra are higher indicating hyperlactataemia (Thorneloe et al. , Can Vet J 48, 283-288). Plasma lactate in dogs with closed cervix pyometra was mean ± SD and in dogs with open cervix pyometra, it was mean ± SD. The plasma lactate concentration in dogs with pyometra was higher than in healthy bitches, and there was no influence of patency of the cervix on the concentration of plasma lactate concentrations. Plasma lactate concentrations were similar for animals with open and closed pyometra (3.54 ± 0.52 to 3.64 ± 1.03 mm). © 2012 Blackwell Verlag GmbH.

  5. Peripheral administration of lactate produces antidepressant-like effects

    KAUST Repository

    Carrard, A; Elsayed, M; Margineanu, Michael B.; Boury-Jamot, B; Fragniè re, L; Meylan, E M; Petit, J-M; Fiumelli, Hubert; Magistretti, Pierre J.; Martin, J-L

    2016-01-01

    In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

  6. Peripheral administration of lactate produces antidepressant-like effects

    KAUST Repository

    Carrard, A

    2016-10-18

    In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

  7. Functional interaction between bicarbonate transporters and carbonic anhydrase modulates lactate uptake into mouse cardiomyocytes.

    Science.gov (United States)

    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.

  8. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

    Directory of Open Access Journals (Sweden)

    Imre Farkas

    Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

  9. In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

    KAUST Repository

    Mä chler, Philipp; Wyss, Matthias  T.; Elsayed, Maha; Stobart, Jillian; Gutierrez, Robin; von  Faber-Castell, Alexandra; Kaelin, Vincens; Zuend, Marc; San  Martí n, Alejandro; Romero-Gó mez, Ignacio; Baeza-Lehnert, Felipe; Lengacher, Sylvain; Schneider, Bernard  L.; Aebischer, Patrick; Magistretti, Pierre J.; Barros, L.  Felipe; Weber, Bruno

    2015-01-01

    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. © 2016 Elsevier Inc.

  10. In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

    KAUST Repository

    Mächler, Philipp

    2015-11-19

    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. © 2016 Elsevier Inc.

  11. Safety assessment of lactate esters

    NARCIS (Netherlands)

    Clary, J.J.; Feron, V.J.; Velthuijsen, J.A. van

    1998-01-01

    Lactate eaters have an oral LD50 greater than 2000 mg/kg and the inhalation LC50 is generally above 5000 mg/m3 and they may be potential eye and skin irritants, but not skin sensitizers. No evidence of teratogenicity or maternal toxicity was observed in an inhalation (2-ethylhexyl-L-lactate) or

  12. Elevated lactate during psychogenic hyperventilation

    NARCIS (Netherlands)

    ter Avest, E.; Patist, F. M.; ter Maaten, J. C.; Nijsten, M. W. N.

    Study objective Elevated arterial lactate levels are closely related to morbidity and mortality in various patient categories. In the present retrospective study, the relation between arterial lactate, partial pressure of carbon dioxide (Pco(2)) and pH was systematically investigated in patients who

  13. Comparison and evaluation of mathematical lactation curve ...

    African Journals Online (AJOL)

    p2492989

    A mathematical model of the lactation curve provides summary information about culling and milking strategies ..... Table 2 Statistics of the edited data for first lactation Holstein cows ..... Application of different models to the lactation curves of.

  14. Azathioprine treatment during lactation

    DEFF Research Database (Denmark)

    Christensen, L.A.; Dahlerup, J.F.; Nielsen, M.J.

    2008-01-01

    BACKGROUND: Thiopurines are widely used to maintain remission in inflammatory bowel disease. Treatment during pregnancy is generally recommended to improve the chance of a normal birth outcome, but advice concerning breastfeeding is conflicting. Aim To estimate the exposure of breastfed infants...... to 6-mercaptopurine, as a metabolite of azathioprine, from maternal milk. METHODS: Eight lactating women with inflammatory bowel disease receiving maintenance therapy with azathioprine 75-200 mg daily were studied. Milk and plasma samples were obtained 30 and 60 min after drug administration and hourly...... for the following 5 h. RESULTS: The variation in the bioavailability of the drug was reflected in a wide range of peak plasma values of 6-mercaptopurine within the first 3 h. A similar curve, but with an hour's delay and at significantly lower concentrations varying from 2-50 microg/L, was seen in maternal milk...

  15. Blood flow changes in Alzheimer's disease induced by lactate

    International Nuclear Information System (INIS)

    Pavics, L.; Sera, T.; Kalman, J.; Janka, Z.; Csernay, L.

    2002-01-01

    Full text: Lactate, as metabolite of the glycolysis is a source of energy of the nerves. In vitro and in vivo experiments showed the neuroprotective effect of lactate and improvement of brain function after ischaemic injury. Intravenous infusion of lactate increases the global cerebral blood flow (CBF). In Alzheimer disease (AD) characteristic regional blood flow abnormalities and in the cerebrospinal fluid abnormal lactate levels were detected. Since disturbed CBF and vasoregulation was found in AD the effect of intravenous Na-lactate on CBF and related metabolic parameters was examined in order to assess the CBF response in the AD brain. In twenty (14 woman, 6 man, age ± SD.: 74 ± 7 years) patients with Alzheimer's disease (DSM IV, MMT.:13 ± 6) self-control study was performed. rCBF SPECT (99mTc-HMPAO) investigations were fulfilled during 5 mg/kg body weight 0.5 M Na-lactate infusion and in control state (0.9 % saline infusion) one week apart. The rCBF changes visually and by statistical parametric mapping were analyzed. ECG, blood pressure, heart rate, venous blood pH, pCO 2 , bicarbonate, serum lactate and cortisol level were measured before and after the SPECT investigation. Acute panic inventory and anxiety rating scales were used to access the psychiatric effect of lactate. The serum lactate levels increased in average from 0.8 mmol/L to 4.6 mmol/L, and 6.1 mmol/L 10 and 20 minutes after lactate infusion respectively. Compensatory changes were found in the venous blood pH, pCO 2 and bicarbonate levels. Significant psychiatric symptoms and blood pressure and heart rate increase were not observed. The serum cortisol level remained unchanged. At the baseline investigation all of the patients have bilateral temporal or parietal hypoperfused areas in 8 patients with other additional localization of abnormalities. In 12 patients the global cerebral blood flow increased, in 8 decreased rCBF was detected by visual evaluation. According to the SPM analysis the

  16. Central thermoregulatory effects of lactate in the toad Bufo paracnemis.

    Science.gov (United States)

    Branco, L G; Steiner, A A

    1999-04-01

    Hypoxia induces a regulated decrease in body temperature (Tb; anapyrexia) in organisms ranging from protozoans to mammals, but very little is known about the mechanisms involved. Several candidates have been suggested to mediate hypoxia-induced anapyrexia, among them lactate, which is a classical compansion of hypoxic stress in vertebrates. The present study was designed to assess the central thermoregulatory effects of lactate in Bujo paracnemis. Toads equipped with a temperature probe were tested over a thermal gradient (10-40 degrees C). Lactate injected systemically (4.0 mmol kg-1) caused a significant reduction of Tb from 24.6 +/- 2.1 to 17.4 +/- 3.9 degrees C. To assess the role of central thermoregulatory mechanisms, a lower dose (0.4 mmol kg-1) of lactate was injected into the fourth cerebral ventricle or systemically. Intracerebroventricular injection of lactate caused a similar decrease in Tb, whereas systemic injection caused no change. The data indicate that lactate may play a role in hypoxia-induced anapyrexia in central rather than peripheral sites.

  17. Significance of Tl-201 redistribution on infarcted region assessed by coronary sinus flow and lactate metabolism

    International Nuclear Information System (INIS)

    Mori, Takao; Yamabe, Hiroshi; Suda, Kenichirou; Ohnishi, Masataka; Shiotani, Hideyuki; Kurimoto, Yasuyuki; Kobayashi, Katsuya; Maeda, Kazumi; Fukuzaki, Hisashi

    1987-01-01

    To clarify the significance of Tl-201 redistribution on infarcted regions, coronary sinus and great cardiac vein flow response and lactate metabolism assessed by Webster catheter on 14 infarcted regions after dipyridamole administration were compared with Tl-201 redistribution phenomenon. The regional coronary flow response and lactate extraction ratio in 11 regions with Tl-201 redistribution were lower than those in 3 regions without Tl-201 redistribution. Only 5 regions in 11 with Tl-201 redistribution showed lactate production. The coronary flow response in 5 regions with lactate production was not different from those in 6 without lactate production (1.16 ± 0.89 vs. 1.47 ± 0.67; n.s.). The degree of Tl-201 redistribution assessed by relative activity was not different between regions with and without lactate production. The left ventricular end-diastolic pressure elevated in 5 regions with lactate production (17.8 ± 5.4 mmHg to 29.6 ± 4.9 mmHg; p < 0.05), but didn't in 6 regions without lactate production. Five regions with lactate production contained 4 hypokinetic regions, on the other hand 6 regions without lactate production contained only 3 hypokinetic regions. In conclusion, Tl-201 redistribution on infarcted region revealed not only ischemia but also decreased coronary flow response without lactate production and/or left ventricular dysfunction. (author)

  18. Lactate is oxidized outside of the mitochondrial matrix in rodent brain.

    Science.gov (United States)

    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.

  19. Is lactate a volume transmitter of metabolic states of the brain?

    DEFF Research Database (Denmark)

    Bergersen, Linda H; Gjedde, Albert

    2012-01-01

    We present the perspective that lactate is a volume transmitter of cellular signals in brain that acutely and chronically regulate the energy metabolism of large neuronal ensembles. From this perspective, we interpret recent evidence to mean that lactate transmission serves the maintenance...... of network metabolism by two different mechanisms, one by regulating the formation of cAMP via the lactate receptor GPR81, the other by adjusting the NADH/NAD(+) redox ratios, both linked to the maintenance of brain energy turnover and possibly cerebral blood flow. The role of lactate as mediator...

  20. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    Directory of Open Access Journals (Sweden)

    Jungsuwadee Paiboon

    2011-02-01

    Full Text Available Abstract Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In addition, decreased levels of mRNA associated with T-cell signaling were found in the jejunum and ileum. Several members of the Solute Carrier (SLC and Adenosine Triphosphate Binding Cassette (ABC superfamilies of membrane transporters were found to be differentially expressed; these genes may play a role in differences in nutrient and xenobiotic absorption and disposition. mRNA expression of SLC39a4_predicted, a zinc transporter, was increased in all tissues, suggesting that it is involved in increased zinc uptake during lactation. Microarray data are available through GEO under GSE19175. Conclusions We detected differential expression of mRNA from several pathways in lactating dams, including upregulation of the cholesterol biosynthetic pathway in liver and intestine, consistent with Srebp activation. Differential T-Cell signaling in the two most distal regions of the small intestine (ileum and

  1. CD147 required for corneal endothelial lactate transport.

    Science.gov (United States)

    Li, Shimin; Nguyen, Tracy T; Bonanno, Joseph A

    2014-06-26

    CD147/basigin is a chaperone for lactate:H(+) cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  2. High postnatal susceptibility of hippocampal cytoskeleton in response to ethanol exposure during pregnancy and lactation.

    Science.gov (United States)

    Reis, Karina Pires; Heimfarth, Luana; Pierozan, Paula; Ferreira, Fernanda; Loureiro, Samanta Oliveira; Fernandes, Carolina Gonçalves; Carvalho, Rônan Vivian; Pessoa-Pureur, Regina

    2015-11-01

    Ethanol exposure to offspring during pregnancy and lactation leads to developmental disorders, including central nervous system dysfunction. In the present work, we have studied the effect of chronic ethanol exposure during pregnancy and lactation on the phosphorylating system associated with the astrocytic and neuronal intermediate filament (IF) proteins: glial fibrillary acidic protein (GFAP), and neurofilament (NF) subunits of low, medium, and high molecular weight (NFL, NFM, and NFH, respectively) in 9- and 21-day-old pups. Female rats were fed with 20% ethanol in their drinking water during pregnancy and lactation. The homeostasis of the IF phosphorylation was not altered in the cerebral cortex, cerebellum, or hippocampus of 9-day-old pups. However, GFAP, NFL, and NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. PKA had been activated in the hippocampus, and Ser55 in the N-terminal region of NFL was hyperphosphorylated. In addition, JNK/MAPK was activated and KSP repeats in the C-terminal region of NFM were hyperphosphorylated in the hippocampus of 21-day-old pups. Decreased NFH immunocontent but an unaltered total NFH/phosphoNFH ratio suggested altered stoichiometry of NFs in the hippocampus of ethanol-exposed 21-day-old pups. In contrast to the high susceptibility of hippocampal cytoskeleton in developing rats, the homeostasis of the cytoskeleton of ethanol-fed adult females was not altered. Disruption of the cytoskeletal homeostasis in neural cells supports the view that regions of the brain are differentially vulnerable to alcohol insult during pregnancy and lactation, suggesting that modulation of JNK/MAPK and PKA signaling cascades target the hippocampal cytoskeleton in a window of vulnerability in 21-day-old pups. Our findings are relevant, since disruption of the cytoskeleton in immature hippocampus could contribute to later hippocampal damage associated with ethanol toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Continuous lactation in dairy cows

    DEFF Research Database (Denmark)

    Madsen, Torben Gosvig; Nielsen, Mette Benedicte Olaf; Andersen, Jens Bech

    2008-01-01

    Reports over the past decade have indicated that normal lactational performance can be achieved in genetically superior and high-producing dairy cows, even when the dry period between 2 lactations is omitted. The hypothesis tested in this experiment was that normal lactogenesis I and metabolic...... function may be achievable in continuously milked high-yielding dairy cows as a result of the genetic selection for lactation performance and hence longevity of mammary epithelial cells. The milk production and mammary nutrient uptake in response to omission of the dry period for cows with an expected peak...... milk yield higher than 45 kg/d were studied in 28 Holstein dairy cows managed without bovine somatotropin. Performance and metabolic parameters were followed in late gestation and in the following early lactation. Fourteen cows were milked continuously throughout late gestation, and another 14 dairy...

  4. Elevated blood lactate is associated with increased motor cortex excitability.

    Science.gov (United States)

    Coco, Marinella; Alagona, Giovanna; Rapisarda, Giuseppe; Costanzo, Erminio; Calogero, Roberto Antonio; Perciavalle, Valentina; Perciavalle, Vincenzo

    2010-01-01

    No information has yet been provided about the influence of blood lactate levels on the excitability of the cerebral cortex, in particular, of the motor cortex. The aim of the present study was to examine the effects of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, on motor cortex excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, whereas 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the motor cortex was evaluated by using the transcranial magnetic stimulation. In both of these experimental conditions, it was observed that an increase of blood lactate is associated with a decrease of motor threshold, that is, an enhancement of motor cortex excitability. We conclude by hypothesizing that in the motor cortex the lactate could have a protective role against fatigue.

  5. Quantitative studies of skeletal muscle lactate metabolism

    International Nuclear Information System (INIS)

    Pagliassotti, M.J.

    1988-01-01

    In Situ, single-pass perfusions were employed on three isolated rabbit skeletal muscle preparations of differing fiber type and oxidative capacity to investigate the influence of fiber type and oxidative capacity per se on net carbon, 14 C-lactate, and 3 H-glucose fluxes. Preparations were exposed to six lactate concentrations ranging from 1-11mM. At basal lactate concentrations all preparations displayed net lactate release, 14 C-lactate removal and 14 CO 2 release, all were linearly correlated with lactate concentration. By 4mM all preparations switched to net lactate uptake and 14 C-lactate removal always exceeded net lactate uptake. To quantify the fate of net carbon, 14 C-lactate, and 3 H-glucose removal preparations were perfused at either basal or elevated lactate. Under basal conditions net carbon influx from glucose and glycogen was removed primarily via net lactate release in the glycolytic and mixed preparations and oxidation and net lactate release in the oxidative preparation. At elevated lactate, net carbon influx from lactate, pyruvate and glucose was removed primarily by net glycogen synthesis in the glycolytic preparation and both alanine release and oxidation in the mixed and oxidative preparations

  6. Deletion of the innate immune NLRP3 receptor abolishes cardiac ischemic preconditioning and is associated with decreased Il-6/STAT3 signaling

    NARCIS (Netherlands)

    Zuurbier, C.J.; Jong, W.M.; Eerbeek, O.; Koeman, A.; Pulskens, W.P.C.; Butter, L.M.; Leemans, J.C.; Hollmann, M.W.

    2012-01-01

    OBJECTIVE: Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also by endogenous danger signals released during ischemia and necrosis. As triggers for the innate immune NLRP3 inflammasome protein complex appear to overlap with those

  7. Glucose metabolism in lactating reindeer

    Energy Technology Data Exchange (ETDEWEB)

    White, R G; Luick, J R

    1976-01-01

    Changes in glucose synthesis during the lactation cycle were estimated in pen-fed and grazing reindeer. The pool size, space, transfer rate, and irreversible loss of glucose were determined using simultaneous injections of (2-/sup 3/H)glucose and primed infusions of (U-/sup 14/C)glucose in reindeer lactating for 1-2, 4-5, 8-9, and 12-16 weeks. Glucose transfer rate and irreversible loss were higher during early to midlactation than at other times of the year; maximum estimates were at 8-9 week postpartum (July), and a decline was noted at 12-16 weeks (August). During the first 1-2 weeks in pen-fed and 4-5 weeks in grazing reindeer, glucose transfer rate and irreversible loss were almost twice the values reported for reindeer at maintenance. No difference in the irreversible loss of glucose was noted between lactating and non-lactating reindeer at 18-20 weeks postpartum (September), and there is evidence that this may occur as early as 12-16 weeks postpartum. No significant trend was noted in the glucose space throughout lactation; however, a significant increase in plasma glucose concentration and pool size was noted when glucose synthesis was highest (8-9 weeks postpartum). Glucose turnover time was consistently faster (78-88 min) in lactating than in non-lactating reindeer (107-140 min). Reindeer used a smaller proportion of plasma glucose-C for lactose synthesis than did other domestic species. This probably results from the low lactose content of reindeer milk and the relatively low rate of milk secretion. (auth)

  8. Accuracy of Handheld Point-of-Care Fingertip Lactate Measurement in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Gaieski, David G

    2013-02-01

    Full Text Available Introduction: Early recognition of elevated lactate levels in sepsis may hasten the detection of those patients eligible for aggressive resuscitation. Point-of-care (POC testing is now increasingly available for use in the emergency department (ED. We examined the accuracy and time-saving effect of a handheld POC device for the measurement of fingertip and whole blood lactate as compared with reference laboratory testing in critically ill ED patients.Methods: A convenience sample of adult ED patients receiving serum lactate testing was prospectively enrolled at an urban, tertiary care US hospital. Consenting patients underwent fingertip POC lactate measurement with a portable device and simultaneous whole blood sampling for analysis by both the POC device and standard laboratory analyzer (‘‘reference method’’. Lactate measurements were compared by intraclass correlation (ICC and Bland and Altman plots. Differences in time to test result were compared by paired t test.Results: Twenty-four patients, 19 (79% with sepsis and 21 (88% with lactate levels below 4 mmol/L, were included from April 2005 to May 2005. Fingertip POC and whole blood POC lactate measurements each correlated tightly with the reference method (ICC ¼ 0.90 and ICC ¼ 0.92, respectively. Mean time between obtaining fingertip lactate samples and whole blood reference lactate samples was 8 6 13 minutes. Mean time between obtaining POC and reference laboratory lactate results was 65 minutes (95% confidence interval, 30–103.Conclusion: Fingertip POC lactate measurement is an accurate method to determine lactate levels in infected ED patients with normal or modestly elevated lactate values and significantly decreases time to test results. These findings should be verified in a larger, more critically ill, ED population. [West J Emerg Med. 2013;14(1:58-62.

  9. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  10. A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice

    Czech Academy of Sciences Publication Activity Database

    Waaler, J.; Machoň, Ondřej; Tůmová, Lucie; Dinh, H.; Kořínek, Vladimír; Wilson, S.R.; Paulsen, J.E.; Pedersen, N.M.; Eide, T.J.; Machoňová, Olga; Gradl, D.; Voronkov, A.; von Kries, J.P.; Krauss, S.

    2012-01-01

    Roč. 72, č. 11 (2012), s. 2822-2832 ISSN 0008-5472 R&D Projects: GA ČR GAP305/12/2042; GA MŠk 2B06077 Institutional research plan: CEZ:AV0Z50520514 Keywords : beta-catenin * canonical Wnt signaling * tankyrase * inhibition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.650, year: 2012

  11. A Review of Worksite Lactation Accommodations.

    Science.gov (United States)

    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.

  12. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  13. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    International Nuclear Information System (INIS)

    Lunsing, Roelineke J.; Strating, Kim; Koning, Tom J. de; Sijens, Paul E.

    2017-01-01

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  14. Appetite - decreased

    Science.gov (United States)

    Loss of appetite; Decreased appetite; Anorexia ... Any illness can reduce appetite. If the illness is treatable, the appetite should return when the condition is cured. Loss of appetite can cause weight ...

  15. Luteolin decreases invasiveness, deactivates STAT3 signaling, and reverses interleukin-6 induced epithelial–mesenchymal transition and matrix metalloproteinase secretion of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Huang XC

    2015-10-01

    Full Text Available Xince Huang,1 Shengjie Dai,1 Juji Dai,1 Yuwu Xiao,1 Yongyu Bai,1 Bicheng Chen,1,2 Mengtao Zhou1 1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China Abstract: Luteolin, a flavone, has been shown to exhibit anticancer properties. Here, we investigated whether luteolin affects epithelial–mesenchymal transition (EMT and invasiveness of pancreatic cancer cell lines and their underlying mechanism. Pancreatic cancer cell lines PANC-1 and SW1990 were used in our study, and their EMT characters, matrix metalloproteinase (MMP expression level, invasiveness, and signal transducer and activator of transcription 3 (STAT3 activity were determined after luteolin treatment. We also treated pancreatic cancer cells with interleukin-6 (IL-6 to see whether IL-6-induced activation of STAT3, EMT, and MMP secretion was affected by luteolin. We found that luteolin inhibits EMT and MMP2, MMP7, and MMP9 expression in a dose-dependent manner, similar to STAT3 signaling. Through Transwell assay, we found that invasiveness of pancreatic cancer cells was inhibited by luteolin. EMT characters and MMP secretion increase with STAT3 activity after IL-6 treatment and these effects, caused by IL-6, were inhibited by luteolin. We concluded that luteolin inhibits invasiveness of pancreatic cancer cells, and we speculated that luteolin inhibits EMT and MMP secretion likely through deactivation of STAT3 signaling. Luteolin has potential antitumor effects and merits further investigation. Keywords: epithelial–mesenchymal transition, matrix metalloproteinase, luteolin, STAT3

  16. Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.

    Science.gov (United States)

    Egbert, Jeremy R; Yee, Siu-Pok; Jaffe, Laurinda A

    2018-03-01

    Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Aspalathin Reverts Doxorubicin-Induced Cardiotoxicity through Increased Autophagy and Decreased Expression of p53/mTOR/p62 Signaling

    Directory of Open Access Journals (Sweden)

    Rabia Johnson

    2017-09-01

    Full Text Available Doxorubicin (Dox is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53, adenosine monophosphate-activated protein kinase (AMPK, nucleoporin p62 (p62, and the mammalian target of rapamycin (mTOR are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco’s Modified Eagle’s medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2 µM Dox were co-treated with either 20 µM Dexrazozane (Dexra or 0.2 µM aspalathin (ASP daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity.

  18. Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats

    DEFF Research Database (Denmark)

    Brandt, Nina; De Bock, Katrien; Richter, Erik

    2010-01-01

    Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned...... to 12-wk intervention groups: chow-fed controls (CON), cafeteria diet (CAF), and cafeteria diet plus swimming exercise during the last 4 wk (CAF(TR)). CAF feeding led to increased body weight (16%, P ...) among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK...

  19. Energy Consumption of Lactating Mothers: Current Situation and Problems

    Directory of Open Access Journals (Sweden)

    Sandra Fikawati

    2014-08-01

    Full Text Available Recommendations on the adequacy of nutrient intake indicate that lactating mothers have higher nutritional needs than do pregnant mothers. High nutrient intake is necessary to help mothers recover after childbirth, produce milk, and maintain the quantity and quality of breast milk. It also prevents maternal malnutrition. Research has shown, however, that the dietary energy consumption of mothers during lactation was significantly lower than that during pregnancy. The current study explored the factors associated with decreased nutritional intake during maternal lactation. The study was conducted in March–April 2013, and the subjects were mothers with infants aged >6 months. Results revealed that the factors causing low dietary energy consumption among breastfeeding mothers were poor nutritional knowledge and attitude toward high energy intake requirements during lactation, lack of time to cook and eat because of infant care, reduced consumption of milk and supplements, dietary restrictions and prohibitions, and suboptimal advice from midwives/health personnel. Beginning from the antenatal care visit, health personnel should conduct effective counseling on the importance of nutrient intake during lactation. Advice should be provided not only to mothers, but also to their families to enable them to thoroughly support the mothers as they breastfeed their infants.

  20. Inducing Lactation: Breastfeeding for Adoptive Moms

    Science.gov (United States)

    ... Dynamics > Adoption & Foster Care > Inducing Lactation: Breastfeeding for Adoptive Moms Family Life Listen Español Text Size Email Print Share Inducing Lactation: Breastfeeding for Adoptive Moms Page Content Article Body A growing number ...

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

    Science.gov (United States)

    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

  2. TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Serotonin and the regulation of calcium transport in dairy cows.

    Science.gov (United States)

    Hernandez, L L

    2017-12-01

    The mammary gland regulates maternal metabolism during lactation. Numerous factors within the tissue send signals to shift nutrients to the mammary gland for milk synthesis. Serotonin is a monoamine that has been well documented to regulate several aspects of lactation among species. Maintenance of maternal calcium homeostasis during lactation is a highly evolved process that is elegantly regulated by the interaction of the mammary gland with the bone, gut, and kidney tissues. It is well documented that dietary calcium is insufficient to maintain maternal calcium concentrations during lactation, and mammals must rely on bone resorption to maintain normocalcemia. Our recent work focused on the ability of the mammary gland to function as an accessory parathyroid gland during lactation. It was demonstrated that serotonin acts to stimulate parathyroid hormone-related protein (PTHrP) in the mammary gland during lactation. The main role of mammary-derived PTHrP during mammalian lactation is to stimulate bone resorption to maintain maternal calcium homeostasis during lactation. In addition to regulating PTHrP, it was shown that serotonin appears to directly affect calcium transporters and pumps in the mammary gland. Our current working hypothesis regarding the control of calcium during lactation is as follows: serotonin directly stimulates PTHrP production in the mammary gland through interaction with the sonic hedgehog signaling pathway. Simultaneously, serotonin directly increases calcium movement into the mammary gland and, subsequently, milk. These 2 direct actions of serotonin combine to induce a transient maternal hypocalcemia required to further stimulate PTHrP production and calcium mobilization from bone. Through these 2 routes, serotonin is able to improve maternal calcium concentrations. Furthermore, we have shown that Holstein and Jersey cows appear to regulate calcium in different manners and also respond differently to serotonergic stimulation of the calcium

  3. 21 CFR 582.1207 - Calcium lactate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium lactate. 582.1207 Section 582.1207 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is...

  4. Changes in cisternal compartment based on stage of lactation and time since milk ejection in the udder of dairy cows

    DEFF Research Database (Denmark)

    Caja, G; Ayadi, M; Knight, Christopher Harold

    2004-01-01

    (by cannula) and cisternal area (by ultrasonography) in the front quarters. Cisternal milk and cisternal area were correlated (r = 0.74 to 0.82) for all stages of lactation. As lactation advanced, volumes of alveolar and cisternal milk and cisternal area decreased. Proportion of cisternal milk varied...... compartment. We termed this 'cisternal recoil.' In conclusion, ultrasonography was a useful method to evaluate dynamic changes in cisternal milk throughout lactation and after udder stimulation in dairy cows. Evidence exists that udder cisterns decrease when lactation advances and milk returns to the alveolar...

  5. 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).

    Science.gov (United States)

    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 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.

  6. [Effect of pregnancy and lactation on the nutritional status of essential fatty acids in rat].

    Science.gov (United States)

    Araya, J; Barriga, C

    1996-08-01

    Pregnancy and lactation could be high risk situations for the development of essential fatty acid deficiencies. To study the effect of pregnancy and lactation on red blood cell phospholipids percentual fatty acid composition of virgin, pregnant and lactating rats. Twenty four pregnant rats of 50 +/- 1 days of age were supplement with soy and 24 with fish oil during 21 days. Twelve rats of each group were sacrificed after 18 days of lactation, twenty four non pregnant rats received soy oil and acted as controls of pregnant and lactating rats. Red blood cell phospholipid fatty acid composition was analyzed by gas chromatography. The percentage of total omega-6 fatty acids of red blood cell phospholipid was 37.8 +/- 5.9, 32.6 +/- 0.6 and 38.3 +/- 3.5% in non pregnant, pregnant and lactating rats respectively (p oil reverted the decrease in omega-6 and omega-3 fatty acid percentage of pregnant and lactating rats. Pregnancy and lactation decrease the capacity to transform precursors of essential fatty acids in long chain polyunsaturated fatty acids.

  7. Association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002-2008).

    Science.gov (United States)

    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 dogs with a high initial lactate (HIL) 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 dogs with a final 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.

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

    Science.gov (United States)

    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

  9. TLR2−/− Mice Display Decreased Severity of Giardiasis via Enhanced Proinflammatory Cytokines Production Dependent on AKT Signal Pathway

    Directory of Open Access Journals (Sweden)

    Xin Li

    2017-09-01

    Full Text Available Giardia infection is one of the most common causes of waterborne diarrheal disease in a wide array of mammalian hosts, including humans globally. Although numerous studies have indicated that adaptive immune responses are important for Giardia defense, however, whether the host innate immune system such as TLRs recognizes Giardia remains poorly understood. TLR2 plays a crucial role in pathogen recognition, innate immunity activation, and the eventual pathogen elimination. In this study, we investigated the role of TLR2 as a non-protective inflammatory response on controlling the severity of giardiasis. RT-PCR analysis suggested that TLR2 expression was increased in vitro. We demonstrated that Giardia lamblia-induced cytokines expression by the activation of p38 and ERK pathways via TLR2. Interestingly, the expression of IL-12 p40, TNF-α, and IL-6, but not IFN-γ, was enhanced in TLR2-blocked and TLR2−/− mouse macrophages exposed to G. lamblia trophozoites compared with wild-type (WT mouse macrophages. Further analysis demonstrated that G. lamblia trophozoites reduced cytokines secretion by activating AKT pathway in WT mouse macrophages. Immunohistochemical staining in G. lamblia cysts infected TLR2−/− and WT mice showed that TLR2 was highly expressed in duodenum in infected WT mice. Also, infected TLR2−/− and AKT-blocked mice showed an increased production of IL-12 p40 and IFN-γ compared with infected WT mice at the early stage during infection. Interestingly, infected TLR2−/− and AKT-blocked mice displayed a decreased parasite burden, an increased weight gain rate, and short parasite persistence. Histological morphometry showed shortened villus length, hyperplastic crypt and decreased ratio of villus height/crypt depth in infected WT mice compared with in infected TLR2−/− and AKT-blocked mice. Together, our results suggested that TLR2 deficiency leads to alleviation of giardiasis and reduction of parasite burden through

  10. Fatigue and gene expression in human leukocytes: Increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue

    Science.gov (United States)

    Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Arevalo, Jesusa M.G.; Cole, Steve W.

    2013-01-01

    Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n = 11) and non-fatigued controls (n = 10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p < .05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors. PMID:20854893

  11. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B

    2013-01-01

    of four separate and specific substrate titration protocols, the respirometric analysis revealed that mitochondria were capable of oxidizing lactate in the absence of exogenous LDH. The titration of lactate and NAD(+) into the respiration medium stimulated respiration (P = 0.003). The addition...... of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within...

  12. Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling

    International Nuclear Information System (INIS)

    Oh, Somi; You, Eunae; Ko, Panseon; Jeong, Jangho; Keum, Seula; Rhee, Sangmyung

    2017-01-01

    Microtubules are required for diverse cellular processes, and abnormal regulation of microtubule dynamics is closely associated with severe diseases including malignant tumors. In this study, we report that α-tubulin N-acetyltransferase (αTAT1), a regulator of α-tubulin acetylation, is required for colon cancer proliferation and invasion via regulation of Wnt1 and its downstream genes expression. Public transcriptome analysis showed that expression of ATAT1 is specifically upregulated in colon cancer tissue. A knockout (KO) of ATAT1 in the HCT116 colon cancer cell line, using the CRISPR/Cas9 system showed profound inhibition of proliferative and invasive activities of these cancer cells. Overexpression of αTAT1 or the acetyl-mimic K40Q α-tubulin mutant in αTAT1 KO cells restored the invasiveness, indicating that microtubule acetylation induced by αTAT1 is critical for HCT116 cell invasion. Analysis of colon cancer-related gene expression in αTAT1 KO cells revealed that the loss of αTAT1 decreased the expression of WNT1. Mechanistically, abrogation of tubulin acetylation by αTAT1 knockout inhibited localization of β-catenin to the plasma membrane and nucleus, thereby resulting in the downregulation of Wnt1 and of its downstream genes including CCND1, MMP-2, and MMP-9. These results suggest that αTAT1-mediated Wnt1 expression via microtubule acetylation is important for colon cancer progression. - Highlights: • Ablation of αTAT1 inhibits HCT116 colon cancer cell invasion. • αTAT1/acetylated microtubules regulate expression of Wnt1/β-catenin target genes. • Acetylated microtubules regulate cellular localization of β-catenin. • Loss of αTAT1 prevents Wnt1 from inducing β-catenin-dependent and -independent pathways.

  13. Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals.

    Science.gov (United States)

    Challet, E; Turek, F W; Laute, M; Van Reeth, O

    2001-08-03

    The circadian pacemaker in the suprachiasmatic nuclei is primarily synchronized to the daily light-dark cycle. The phase-shifting and synchronizing effects of light can be modulated by non-photic factors, such as behavioral, metabolic or serotonergic cues. The present experiments examine the effects of sleep deprivation on the response of the circadian pacemaker to light and test the possible involvement of serotonergic and/or metabolic cues in mediating the effects of sleep deprivation. Photic phase-shifting of the locomotor activity rhythm was analyzed in mice transferred from a light-dark cycle to constant darkness, and sleep-deprived for 8 h from Zeitgeber Time 6 to Zeitgeber Time 14. Phase-delays in response to a 10-min light pulse at Zeitgeber Time 14 were reduced by 30% in sleep-deprived mice compared to control mice, while sleep deprivation without light exposure induced no significant phase-shifts. Stimulation of serotonin neurotransmission by fluoxetine (10 mg/kg), a serotonin reuptake inhibitor that decreases light-induced phase-delays in non-deprived mice, did not further reduce light-induced phase-delays in sleep-deprived mice. Impairment of serotonin neurotransmission with p-chloroamphetamine (three injections of 10 mg/kg), which did not increase light-induced phase-delays in non-deprived mice significantly, partially normalized light-induced phase-delays in sleep-deprived mice. Injections of glucose increased light-induced phase-delays in control and sleep-deprived mice. Chemical damage of the ventromedial hypothalamus by gold-thioglucose (600 mg/kg) prevented the reduction of light-induced phase-delays in sleep-deprived mice, without altering phase-delays in control mice. Taken together, the present results indicate that sleep deprivation can reduce the light-induced phase-shifts of the mouse suprachiasmatic pacemaker, due to serotonergic and metabolic changes associated with the loss of sleep.

  14. Buddleja globosa (matico) prevents collagen-induced platelet activation by decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation signaling.

    Science.gov (United States)

    Fuentes, Manuel; Sepúlveda, Cesar; Alarcón, Marcelo; Palomo, Iván; Fuentes, Eduardo

    2018-01-01

    Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal plants could be one of the most important factors that influence risks for platelet activation. Buddleja globosa (known as "matico") is a medicinal plant with many biological activities. The high content of polyphenols suggest that matico could have antiplatelet activity. The present study was aimed at evaluating mechanisms of antiplatelet action of an extract of matico. We demonstrated that matico extract at low concentrations and in a concentration dependent manner (0.05-1 mg/mL) was a potent inhibitor of platelet aggregation in response to collagen, convulsion and ADP (IC 50 values was 61 μg/mL, 72 μg/mL and 290 μg/mL, respectively). In this sense matico extract exerted the greatest antiaggregant activity induced by collagen. Similarly, matico showed a decrease in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 32 ± 2%, 29 ± 2 (p < 0.05), 19 ± 1 (p < 0.01), 15 ± 2 (p < 0.01), 10 ± 1% (p < 0.01) and 7 ± 2% (p < 0.01), respectively) and PAC-1 binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 ± 1, 58 ± 3 (n.s), 55 ± 2 (p < 0.05), 50 ± 2 (p < 0.01), 38 ± 1 (p < 0.01), 36 ± 2 (p < 0.01). The cellular mechanism for the antiplatelet activity of matico might be mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C phosphorylation. This beneficial property of matico may be of importance in thrombosis, in which platelet activation and aggregation are important determinants of thrombus initiation and development, and may contribute to the beneficial effects of matico intake in the prevention of cardiovascular diseases.

  15. Buddleja globosa (matico prevents collagen-induced platelet activation by decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation signaling

    Directory of Open Access Journals (Sweden)

    Manuel Fuentes

    2018-01-01

    Full Text Available Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal plants could be one of the most important factors that influence risks for platelet activation. Buddleja globosa (known as “matico” is a medicinal plant with many biological activities. The high content of polyphenols suggest that matico could have antiplatelet activity. The present study was aimed at evaluating mechanisms of antiplatelet action of an extract of matico. We demonstrated that matico extract at low concentrations and in a concentration dependent manner (0.05–1 mg/mL was a potent inhibitor of platelet aggregation in response to collagen, convulsion and ADP (IC50 values was 61 μg/mL, 72 μg/mL and 290 μg/mL, respectively. In this sense matico extract exerted the greatest antiaggregant activity induced by collagen. Similarly, matico showed a decrease in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 32 ± 2%, 29 ± 2 (p < 0.05, 19 ± 1 (p < 0.01, 15 ± 2 (p < 0.01, 10 ± 1% (p < 0.01 and 7 ± 2% (p < 0.01, respectively and PAC-1 binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 ± 1, 58 ± 3 (n.s, 55 ± 2 (p < 0.05, 50 ± 2 (p < 0.01, 38 ± 1 (p < 0.01, 36 ± 2 (p < 0.01. The cellular mechanism for the antiplatelet activity of matico might be mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C phosphorylation. This beneficial property of matico may be of importance in thrombosis, in which platelet activation and aggregation are important determinants of thrombus initiation and development, and may contribute to the beneficial effects of matico intake in the prevention of cardiovascular diseases.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  18. Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain

    DEFF Research Database (Denmark)

    Overgaard, Morten; Rasmussen, Peter; Bohm, Aske M

    2012-01-01

    Lactate is shuttled between organs, as demonstrated in the Cori cycle. Although the brain releases lactate at rest, during physical exercise there is a cerebral uptake of lactate. Here, we evaluated the cerebral lactate uptake and release in hypoxia, during exercise and when the two interventions...... were combined. We measured cerebral lactate turnover via a tracer dilution method ([1-(13)C]lactate), using arterial to right internal jugular venous differences in 9 healthy individuals (5 males and 4 females), at rest and during 30 min of submaximal exercise in normoxia and hypoxia (F(i)o(2) 10...

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

    Science.gov (United States)

    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

  20. Peripheral blood and milk leukocytes subsets of lactating Sarda ewes

    Directory of Open Access Journals (Sweden)

    Piero Bonelli

    2013-05-01

    Full Text Available Leukocytes subpopulations in blood and milk of lactating Sarda ewes were investigated. Animals characterized by a SSC level <500×103cells/mL and a negative bacteriological examination were sampled in early, mid and late lactation. Milk differential cell count evidenced that macrophage represented the main population (42.8%±3.5 followed by lymphocytes (40.2%±3.4 and neutrophils (8,6%±2.1. Flow cytometry analysis showed that lymphocytes subsets in milk were quite different from blood. High CD8+ and low CD4+ lymphocytes percentages determined a CD4/CD8 ratio inversion in milk compared to blood (0.3%±0.03 vs 1.8%±0.08. CD8+ decreased while, conversely, CD4+ increased in late lactation. γδ T cells were more represented in milk (12.6%±1.3 than in blood (6.8%±0.3 and their proportions appeared similar throughout lactation in both compartments. IL-2 receptor was mainly expressed in milk on T cytotoxic lymphocytes. Data obtained in uninfected mammary glands could allow an early discrimination between physiological and pathological changes occurring in ewe milk. Further phenotypical and functional studies on milk leukocytes subsets might help to understand defense mechanisms of the ovine mammary gland against IMI.

  1. Maternal Zinc Intakes and Homeostatic Adjustments during Pregnancy and Lactation

    Science.gov (United States)

    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

  2. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    Directory of Open Access Journals (Sweden)

    Jimena Laporta

    Full Text Available 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.

  3. Lactate quantification by proton magnetic resonance spectroscopy using a clinical MRI machine: a basic study

    International Nuclear Information System (INIS)

    Isobe, T.; Muraishi, H.; Matsumura, A.; Kawamura, H.; Shibata, Y.; Anno, I.; Minami, M.

    2007-01-01

    The purpose of this study was to establish quantification method of lactate concentration by proton magnetic resonance spectroscopy (MRS) carried out using a conventional 1.5-T MRI machine. We used a lactate phantom with known concentrations (1, 1.5, 3, 6, 12 and 14 mmol/L). As a clinical example, a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was evaluated. Proton MRS was carried out using a clinical 1.5-T super-conducting magnetic resonance whole-body system. Data were acquired by point resolved spectroscopy. A coupling constant of J = 7.35 Hz (2/7 = 272 ms) and two long in-phase echo time of 272 ms and 544 ms were used to calculate the T2 relaxation time. The tissue water signal was used as an internal standard to quantify lactate. The correlation coefficient R between the calculated lactate concentrations and the known concentration of lactate was 0.99 with a constant factor of 0.32 (1/3.14). In patients with MELAS, the lactate concentration measured by MRS was 6.2 mmol/kg wet weight, which is similar to the value obtained in previous studies. In the present study, we have established a reliable method for lactate quantification in a phantom study and have shown a sample of clinical case of MELAS

  4. 21 CFR 184.1207 - Calcium lactate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium lactate. 184.1207 Section 184.1207 Food and... Substances Affirmed as GRAS § 184.1207 Calcium lactate. (a) Calcium lactate (C6H10CaO6.xH2O, where x is any... calcium carbonate or calcium hydroxide. (b) The ingredient meets the specifications of the Food Chemicals...

  5. Maternal Zinc Intakes and Homeostatic Adjustments during Pregnancy and Lactation

    OpenAIRE

    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 e...

  6. Quercetin inhibits epithelial–mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial–mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Yu D

    2017-09-01

    Full Text Available Dinglai Yu,1 Tingting Ye,1 Yukai Xiang,1 Zhehao Shi,1 Jie Zhang,1 Bin Lou,1 Fan Zhang,1 Bicheng Chen,1,2 Mengtao Zhou1 1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China Abstract: Quercetin, a flavone, is multifaceted, having anti-oxidative, anti-inflammatory, and anticancer properties. In the present study, we explored the effects of quercetin on the epithelial–mesenchymal transition (EMT and invasion of pancreatic cancer cells and the underlying mechanisms. We noted that quercetin exerted pronounced inhibitory effects in PANC-1 and PATU-8988 cells. Moreover, quercetin inhibited EMT and decreased the secretion of matrix metalloproteinase (MMP. Meanwhile, we determined the activity of STAT3 after quercetin treatment. STAT3 phosphorylation decreased following treatment with quercetin. We also used activating agent of STAT3, IL-6, to induce an increase in cell malignancy and to observe the effects of treatment with quercetin. As expected, the EMT and MMP secretion increased with activation of the STAT3 signaling pathway, and quercetin reversed IL-6-induced EMT, invasion, and migration. Therefore, our results demonstrate that quercetin triggers inhibition of EMT, invasion, and metastasis by blocking the STAT3 signaling pathway, and thus, quercetin merits further investigation. Keywords: quercetin, EMT, MMPs, STAT3, pancreatic cancer

  7. Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2014-09-01

    Full Text Available Lactate is a versatile metabolite with important roles in modulation of brain glucose utilization rate (CMRglc, diagnosis of brain-injured patients, redox- and receptor-mediated signaling, memory, and alteration of gene transcription. Neurons and astrocytes release and accumulate lactate using equilibrative monocarboxylate transporters that carry out net transmembrane transport of lactate only until intra- and extracellular levels reach equilibrium. Astrocytes have much faster lactate uptake than neurons and shuttle more lactate among gap junction-coupled astrocytes than to nearby neurons. Lactate diffusion within syncytia can provide precursors for oxidative metabolism and glutamate synthesis and facilitate its release from endfeet to perivascular space to stimulate blood flow. Lactate efflux from brain during activation underlies the large underestimation of CMRglc with labeled glucose and fall in CMRO2/CMRglc ratio. Receptor-mediated effects of lactate on locus coeruleus neurons include noradrenaline release in cerebral cortex and c-AMP-mediated stimulation of astrocytic gap junctional coupling, thereby enhancing its dispersal and release from brain. Lactate transport is essential for its multifunctional roles.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  10. Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex

    OpenAIRE

    Angamo, Eskedar Ayele; ul Haq, Rizwan; Roesner, Joerg; Gabriel, Siegrun; Gerevich, Zoltan; Heinemann, Uwe; Kovacs, Richard

    2017-01-01

    Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed th...

  11. Decrease of miR-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin.

    Directory of Open Access Journals (Sweden)

    Maarten Hulsmans

    Full Text Available BACKGROUND: Low adiponectin, a well-recognized antidiabetic adipokine, has been associated with obesity-related inflammation, oxidative stress and insulin resistance. Globular adiponectin is an important regulator of the interleukin-1 receptor-associated kinase (IRAK/NFκB pathway in monocytes of obese subjects. It protects against inflammation and oxidative stress by inducing IRAK3. microRNA (miR-146b-5p inhibits NFκB-mediated inflammation by targeted repression of IRAK1 and TNF receptor-associated factor-6 (TRAF6. Therefore, we measured the expression of miR-146b-5p in monocytes of obese subjects. Because it was low we determined the involvement of this miR in the anti-inflammatory, antioxidative and insulin signaling action of globular adiponectin. METHODS: miR-146b-5p expression in monocytes of obese subjects was determined by qRT-PCR. The effect of miR-146b-5p silencing on molecular markers of inflammation, oxidative stress and insulin signaling and the association with globular adiponectin was assessed in human THP-1 monocytes. RESULTS: miR-146b-5p was downregulated in monocytes of obese persons. Low globular adiponectin decreased miR-146b-5p and IRAK3 in THP-1 monocytes, associated with increased mitochondrial reactive oxygen species (ROS. Intracellular ROS and insulin receptor substrate-1 (IRS1 protein were unchanged. Silencing of miR-146b-5p with an antisense inhibitor resulted in increased expression of IRAK1 and TRAF6 leading to more NFκB p65 DNA binding activity and TNFα. As a response IRAK3 and IRS1 protein increased. Mitochondrial and intracellular ROS production did not increase despite more inflammation. In addition, exposure of miR-146b-5p-depleted THP-1 monocytes to high levels of globular adiponectin resulted in an increased production of TNFα and intracellular ROS. Still, they did not lose their potential to increase IRAK3 and IRS1 protein and to decrease mitochondrial ROS. CONCLUSION: miR-146b-5p, decreased in monocytes

  12. Histological features in the mammary glands of female dogs throughout lactation.

    Science.gov (United States)

    Orfanou, D C; Pourlis, A; Ververidis, H N; Mavrogianni, V S; Taitzoglou, I A; Boscos, C M; Fthenakis, G C

    2010-10-01

    The objective of this study was to describe the histology of the mammary glands of female dogs throughout lactation. Twelve lactating female dogs were operated 4, 7, 10, 14, 21, 28, 35, 42, 56, 70 and 84 days post-partum; four mammary glands of each animal were excised for histological, ultrastructural and morphometric examination. During early lactation and mid-lactation, all lobes and lobules within the same gland had similar features; alveoli were well developed and distended and had a spherical to slightly ovoid structure, with muscular fibres grasping them around; inflammatory cells were seen in the inter- and intra-alveolar space; mammary lobules were separated with a scant amount of connective tissue. In late lactation, connective tissue was abundant and dense, with large numbers of inflammatory cells; alveoli appeared to be irregularly shaped and collapsing, shrunken or fully collapsed. Number of alveoli per lobule and number of epithelial cells per alveolus, as well as diameter of alveoli and height of epithelial cells decreased as lactation progressed. The third mammary glands (from caudal to cranial) had a significantly smaller number of alveoli, but not of epithelial cells per alveolus, than each of the two mammary glands caudally to that. The results suggest that progressive involution of the normal mammary gland starts around the end of the 2nd month of lactation and continues until the end of the 3rd month. © 2010 Blackwell Verlag GmbH.

  13. Plasma lactate concentrations in free-ranging moose (Alces alces) immobilized with etorphine.

    Science.gov (United States)

    Haga, Henning A; Wenger, Sandra; Hvarnes, Silje; Os, Oystein; Rolandsen, Christer M; Solberg, Erling J

    2009-11-01

    To investigate plasma lactate concentrations of etorphine-immobilized moose in relation to environmental, temporal and physiological parameters. Prospective clinical study. Fourteen female and five male moose (Alces alces), estimated age range 1-7 years. The moose were darted from a helicopter with 7.5 mg etorphine per animal using projectile syringes and a dart gun. Once immobilized, the moose were approached, a venous blood sample was obtained and vital signs including pulse oximetry were recorded. Diprenorphine was administered to reverse the effects of etorphine. Timing of events, ambient temperature and snow depth were recorded. Blood samples were cooled and centrifuged before plasma was harvested and frozen. The plasma was thawed later and lactate analysed. Data were analysed using descriptive statistics and regression analysis. All animals recovered uneventfully and were alive 12 weeks after immobilization. Mean +/- SD plasma lactate was found to be 9.2 +/- 2.1 mmol L(-1). Plasma lactate concentrations were related positively to snow depth and negatively to time from induction of immobilization to blood sampling. The model that best described the variability in plasma lactate concentrations used induction time (time from firing the dart to the moose being immobilized). The second best model included induction time and snow depth. Plasma lactate concentrations in these etorphine-immobilized moose were in the range reported for other immobilized wild ruminants. Decreasing induction time, which may be related to a more profound etorphine effect, and increasing snow depth possibly may increase plasma lactate concentrations in etorphine-immobilized moose.

  14. Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

    Science.gov (United States)

    Won, Seok Joon; Jang, Bong Geom; Yoo, Byung Hoon; Sohn, Min; Lee, Min Woo; Choi, Bo Young; Kim, Jin Hee; Song, Hong Ki; Suh, Sang Won

    2012-06-01

    Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ∼80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels.

  15. Analysis of glucose and lactate in hippocampal dialysates of rats during the operant conditioned reflex using microdialysis.

    Science.gov (United States)

    Dong, Yu; Wang, Lei; Shangguan, Dihua; Yu, Xiao; Zhao, Rui; Han, Huiwan; Liu, Guoquan

    2003-07-01

    Changes of extracellular glucose and lactate in hippocampus for freely moving rats during the operant conditioned reflex were examined simultaneously. Samples of the dialysate were assayed for both glucose and lactate using in vivo microdialysis and a microbore flow injection analysis-immobilized enzyme reactor-electrochemical detection (FIA-IMER-ECD) system. Microdialysis samplings were conducted in a Skinner box where lights were delivered as conditioned stimuli (CS) paired with foot shocks as unconditioned stimuli (US). In the treatment group the concentration of glucose and lactate showed no fluctuations during the whole process. However, in the control group in which the rats were exposed to many foot shocks, lactate levels decreased by 19% below baseline during the behavioral session and glucose showed a delayed decrease (by 18%). Compared with glucose, lactate can immediately indicate the dynamic changes in brain.

  16. Lactate as a fuel for mitochondrial respiration

    DEFF Research Database (Denmark)

    Van Hall, Gerrit

    2000-01-01

    Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during muscle contraction is a subject of debate. Historically, skeletal muscle was seen mainly as the site of lactate production during contraction...

  17. Lactate biosensors: current status and outlook

    NARCIS (Netherlands)

    Rassaei, Liza; Olthuis, Wouter; Tsujimura, Seiya; Sudhölter, Ernst J.R.; Sudholter, Ernst; van den Berg, Albert

    2013-01-01

    Many research efforts over the last few decades have been devoted to sensing lactate as an important analytical target in clinical care, sport medicine, and food processing. Therefore, research in designing lactate sensors is no longer in its infancy and now is more directed toward viable sensors

  18. Relationships between milking frequency, lactation persistency and milk yield in Sweish Red heifers and cows milked in a voluntary attendance automatic milking system

    DEFF Research Database (Denmark)

    Pettersson, Gunnar; Svvenersten-Sjaunja, Kerstin; Knight, Christopher Harold

    2011-01-01

    A large dataset comprising output from an automatic milking (AM) system between 1999 and 2006 was examined and a total of 172 cow lactation curves and 68 heifer lactation curves were identified for further analysis. Relationships between milking frequency at different stages of lactation...... and lactation persistency and total lactation yield were determined. Cows had higher peak and total milk yields than heifers, but heifers had higher persistency (defined as the rate of decline in milk yield between days 100 and 300 post calving). Milking frequency did not differ significantly between cows...... and heifers in early lactation, but thereafter decreased significantly more in cows than in heifers. The effect of milking frequency on yield characteristics was analysed by comparing the highest and lowest quartiles for milking frequency. High milking frequency in early lactation was consistently associated...

  19. Treatment of mastitis during lactation.

    Science.gov (United States)

    Pyörälä, S

    2009-04-01

    Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials.

  20. Treatment of mastitis during lactation

    Directory of Open Access Journals (Sweden)

    Pyörälä S

    2009-04-01

    Full Text Available Abstract Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials.

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

    Science.gov (United States)

    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

  2. Choline and Choline Metabolite Patterns and Associations in Blood and Milk during Lactation in Dairy Cows

    Science.gov (United States)

    Artegoitia, Virginia M.; Middleton, Jesse L.; Harte, Federico M.; Campagna, Shawn R.; de Veth, Michael J.

    2014-01-01

    Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in early, mid and late lactation and analyzed for acetylcholine, free choline, betaine, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine and sphingomyelin using hydrophilic interaction liquid chromatography-tandem mass spectrometry, and quantified using stable isotope-labeled internal standards. Total choline concentration in plasma, which was almost entirely phosphatidylcholine, increased 10-times from early to late lactation (1305 to 13,535 µmol/L). In milk, phosphocholine was the main metabolite in early lactation (492 µmol/L), which is a similar concentration to that found in human milk, however, phosphocholine concentration decreased exponentially through lactation to 43 µmol/L in late lactation. In contrast, phosphatidylcholine was the main metabolite in mid and late lactation (188 µmol/L and 659 µmol/L, respectively), with the increase through lactation positively correlated with phosphatidylcholine in plasma (R 2 = 0.78). Unlike previously reported with human milk we found no correlation between plasma free choline concentration and milk choline metabolites. The changes in pattern of phosphocholine and phosphatidylcholine in milk through lactation observed in the bovine suggests that it is possible to manufacture infant formula that more closely matches these metabolites profile in human milk. PMID:25157578

  3. Choline and choline metabolite patterns and associations in blood and milk during lactation in dairy cows.

    Directory of Open Access Journals (Sweden)

    Virginia M Artegoitia

    Full Text Available Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in early, mid and late lactation and analyzed for acetylcholine, free choline, betaine, glycerophosphocholine, lysophosphatidylcholine, phosphatidylcholine, phosphocholine and sphingomyelin using hydrophilic interaction liquid chromatography-tandem mass spectrometry, and quantified using stable isotope-labeled internal standards. Total choline concentration in plasma, which was almost entirely phosphatidylcholine, increased 10-times from early to late lactation (1305 to 13,535 µmol/L. In milk, phosphocholine was the main metabolite in early lactation (492 µmol/L, which is a similar concentration to that found in human milk, however, phosphocholine concentration decreased exponentially through lactation to 43 µmol/L in late lactation. In contrast, phosphatidylcholine was the main metabolite in mid and late lactation (188 µmol/L and 659 µmol/L, respectively, with the increase through lactation positively correlated with phosphatidylcholine in plasma (R2 = 0.78. Unlike previously reported with human milk we found no correlation between plasma free choline concentration and milk choline metabolites. The changes in pattern of phosphocholine and phosphatidylcholine in milk through lactation observed in the bovine suggests that it is possible to manufacture infant formula that more closely matches these metabolites profile in human milk.

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

    Science.gov (United States)

    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.

  5. Comparative 2D-DIGE proteomic analysis of bovine mammary epithelial cells during lactation reveals protein signatures for lactation persistency and milk yield.

    Directory of Open Access Journals (Sweden)

    Jagadeesh Janjanam

    Full Text Available Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling.

  6. Colostrum and milk production in multiparous sows fed supplementary arginine during gestation and lactation

    DEFF Research Database (Denmark)

    Larsen, Uffe Krogh; Oksbjerg, Niels; Purup, Stig

    2016-01-01

    ) or isonitrogenous amounts of alanine (CON; n = 10) from d 30 of gestation until weaning on d 28 of lactation (in 2 blocks). Piglets were weighed 0, 12, 24, and 36 h after birth of the first piglet and on d 2, 7, 14, 21, and 28 in lactation for estimation of colostrum and milk intake. Colostrum samples obtained at 0......, 12, 24, and 36 h after parturition and milk from sows on d 3, 10, 17, and 24 of lactation were analyzed for macrochemical composition. Also, the content of IGF-I was determined in colostrum. Arginine supplementation decreased lactose and increased DM content of colostrum (P ... on colostrum or milk yield, piglet weight, piglet ADG, or fat content of colostrum and milk was observed (P > 0.10). Concentration of protein and IGF-I tended to be increased in ARG-fed sows. In conclusion, arginine supplementation of sows during gestation and lactation affected macrochemical composition...

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

    Science.gov (United States)

    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

  8. Lactate Clearance sebagai Prediktor Mortalitas pada Pasien Sepsis Berat dan Syok Septik di Intesive Care Unit Rumah Sakit Dr. Hasan Sadikin Bandung

    Directory of Open Access Journals (Sweden)

    Muhammad Budi Kurniawan

    2017-04-01

    Full Text Available Mortality incidence predictor used for sepsis and shock septic in Intensive Care Unit (ICU were measured using Acute Physiology and Chronic Health Evaluation (APACHE II score, which needs many complex examinations. The purpose of this study was to examine lactate clearance as an alternative mortality predictor. Decreased percentage of lactate clearance is related to poor perfusion in microcirculation which leads to the possibility that lactate clearance can be used to predict mortality incidence in severe sepsis and shock septic patients in the ICU of Dr. Hasan Sadikin General Hospital Bandung. This was a prospective observational cohort study involving 51 patients who met sepsis and shock septic criteria during the period of September to November 2015. Lactate was examined continuously in all patients at first hour (H0 and H24 and then the lactate clearance value was measured using the following formula: lactate initial–lactate delayed/lactate initial x100%. Subjects were divided into two groups according to the low lactate clearance(40%. The Mann Whitney test was used for numeric data and exact Fisher test was used for categorical data. Results showed that the lactate clearance had a sensitivity of 100%, specificity of 88.4%, positive predictive value of 89.2%, negative predictive value of 100%, likelihood ratio positive of 86.6%, likelihood ratio negative of 0% and accuracy of 94.11%. Thus, lactate clearance can be used to predict mortality incidence in severe sepsis and shock septic patients.

  9. Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity.

    Science.gov (United States)

    Matsui, Takashi; Omuro, Hideki; Liu, Yu-Fan; Soya, Mariko; Shima, Takeru; McEwen, Bruce S; Soya, Hideaki

    2017-06-13

    Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry-based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.

  10. Investigating the molecular pathway through which L-Lactate interacts with synaptic NMDAR to modulate neuronal plasticity

    KAUST Repository

    Ibrahim, Engy

    2016-12-01

    In the brain, glycogen, the storage form of glucose, is exclusively localized in astrocytes (Magistretti and Allaman, 2015). Glycogenolysis leads to the production of L-lactate, which is shuttled to neurons for ATP production. Interestingly, L-lactate was recently shown to be not only a source of energy, but also a signaling molecule to neurons. This was demonstrated through the inhibition of L-lactate production or transport in an inhibitory avoidance paradigm, where the rodents developed amnesia. This inhibition of memory consolidation was rescued by L-lactate and not by equicaloric glucose emphasizing that L-lactate acts as a signaling molecule as well (Suzuki et al., 2011). A recent study in our laboratory suggests that the action of L-lactate takes place through a cascade of molecular events via the modulation of N-methyl-D-aspartate receptor (NMDAR) activity (Yang et al., 2014). Since NADH produced similar results to those seen with L-lactate, it was hypothesized that the action of the latter is based on altering the redox state of the cell, in particular in view of the fact that redox-sensitive sites are present on the NMDAR. However, the precise molecular mechanism underlying the apparent change in the NMDAR activity is not fully elucidated. The objective of this study is to explore those mechanisms.

  11. Lactate uptake against a concentration gradient

    DEFF Research Database (Denmark)

    Nordström, Carl-Henrik; Nielsen, Troels Halfeld; Nielsen, Hans Boye

    2014-01-01

    The recently published article by Jalloh et al (Jalloh I, Helmy A, Shannon RJ, Gallagher CN, Menon D, Carpenter K, Hutchinson P. Lactate uptake by the injured human brain - evidence from an arterio-venous gradient and cerebral microdialysis study. J Neurotrauma. 2013 Aug 22. [Epub ahead of print......]) concludes that lactate may be transported across the blood brain barrier into the brain against a concentration gradient. Unfortunately the authors have misinterpreted the concept of analytical imprecision and their conclusion is based on analytical artifact. As the topic of lactate transport into the brain...

  12. Managing antiepileptic drugs during pregnancy and lactation

    DEFF Research Database (Denmark)

    Sabers, Anne; Tomson, Torbjörn

    2009-01-01

    PURPOSE OF REVIEW: This review discusses data on the pharmacokinetics of antiepileptic drugs (AEDs) in pregnancy and lactation, and the clinical consequences thereof, thus providing a basis for a rational management of AEDs during pregnancy and lactation. RECENT FINDINGS: Studies have confirmed...... of AEDs in pregnancy and during lactation is important to enable optimal treatment. Gestation induced alterations in pharmacokinetics vary with the AED but also between patients and are difficult to predict. Therapeutic drug monitoring is, therefore, advisable during pregnancy and the use...... of the individual patient's optimal prepregnancy drug level is recommended as reference. Breastfeeding is in general safe but needs appropriate observation of the nursing infant....

  13. Lactate biosensors: current status and outlook.

    Science.gov (United States)

    Rassaei, Liza; Olthuis, Wouter; Tsujimura, Seiya; Sudhölter, Ernst J R; van den Berg, Albert

    2014-01-01

    Many research efforts over the last few decades have been devoted to sensing lactate as an important analytical target in clinical care, sport medicine, and food processing. Therefore, research in designing lactate sensors is no longer in its infancy and now is more directed toward viable sensors for direct applications. In this review, we provide an overview of the most immediate and relevant developments toward this end, and we discuss and assess common transduction approaches. Further, we critically describe the pros and cons of current commercial lactate sensors and envision how future sensing design may benefit from emerging new technologies.

  14. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    Science.gov (United States)

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  15. Hyperthyroidism affects lipid metabolism in lactating and suckling rats.

    Science.gov (United States)

    Varas, S M; Jahn, G A; Giménez, M S

    2001-08-01

    Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

  16. Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1-40/42 and Phospho-Tau May Abet Alzheimer Development.

    Science.gov (United States)

    Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret; Farese, Robert V

    2016-07-01

    Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1–40/42 and Phospho-Tau May Abet Alzheimer Development

    Science.gov (United States)

    Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret

    2016-01-01

    Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat–fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1–40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1–40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID:26895791

  18. A localized in vivo detection method for lactate using zero quantum coherence techniques

    NARCIS (Netherlands)

    van Dijk, J. E.; Bosman, D. K.; Chamuleau, R. A.; Bovee, W. M.

    1991-01-01

    A method is described to selectively measure lactate in vivo using proton zero quantum coherence techniques. The signal from lipids is eliminated. A surface coil and additionally slice selective localization are used. The resulting spectra demonstrate the good performance of the method

  19. Mapping quantitative trait loci (QTL in sheep. IV. Analysis of lactation persistency and extended lactation traits in sheep

    Directory of Open Access Journals (Sweden)

    Lam Mary K

    2011-06-01

    Full Text Available Abstract Background In sheep dairy production, total lactation performance, and length of lactation of lactation are of economic significance. A more persistent lactation has been associated with improved udder health. An extended lactation is defined by a longer period of milkability. This study is the first investigation to examine the presence of quantitative trait loci (QTL for extended lactation and lactation persistency in sheep. Methods An (Awassi × Merino × Merino single-sire backcross family with 172 ewes was used to map QTL for lactation persistency and extended lactation traits on a framework map of 189 loci across all autosomes. The Wood model was fitted to data from multiple lactations to estimate parameters of ovine lactation curves, and these estimates were used to derive measures of lactation persistency and extended lactation traits of milk, protein, fat, lactose, useful yield, and somatic cell score. These derived traits were subjected to QTL analyses using maximum likelihood estimation and regression analysis. Results Overall, one highly significant (LOD > 3.0, four significant (2.0 Conclusion This study identified ten novel QTL for lactation persistency and extended lactation in sheep, but results suggest that lactation persistency and extended lactation do not have a major gene in common. These results provide a basis for further validation in extended families and other breeds as well as targeting regions for genome-wide association mapping using high-density SNP arrays.

  20. On-farm evaluation of the effect of metabolic diseases on the shape of the lactation curve in dairy cows through the MilkBot lactation model.

    Science.gov (United States)

    Hostens, M; Ehrlich, J; Van Ranst, B; Opsomer, G

    2012-06-01

    equally with or without another MD. Overall, 305-d milk production was decreased in complicated metritis (10,603 ± 50 kg vs. 10,114 ± 172 kg). Although care should be taken in generalizing conclusions from a highly specialized transition management facility, the current study demonstrated that lactation curve analysis may contribute substantially to the evaluation of both short- and long-term effects of metabolic diseases on milk production by detecting changes in the distribution of production that are not apparent when only totals are analyzed. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. High-pressure phase behavior of propyl lactate and butyl lactate in supercritical carbon dioxide

    International Nuclear Information System (INIS)

    Cho, Dong Woo; Shin, Jungin; Shin, Moon Sam; Bae, Won; Kim, Hwayong

    2012-01-01

    Highlights: ► The phase behavior of propyl lactate and butyl lactate in scCO 2 was measured. ► Experimental data were correlated by the PR-EOS. ► The critical constants were estimated by the three group contribution methods. ► Acentric factor was estimated by the Lee–Kesler method. ► The Nannoolal–Rarey and Lee–Kesler method shows the best correlation results. - Abstract: Lactate esters synthesized with lactic acid and ester are used as solvents and reactants in various industries, including agricultural chemistry, pharmaceuticals, electronics, and fine chemicals. Among lactate esters, high purity propyl lactate and butyl lactate are used to produce fine chemicals and in the synthesis of chiral intermediates for use in pesticides and drugs. However, distillation for the removal of propyl lactate and butyl lactate alters or degenerates products due the high boiling points of these two lactate esters. This problem can be solved by supercritical fluid extraction (SCFE) at lower temperatures. SCFE process requires high-pressure phase behavior data on CO 2 and lactates for its design and operation. In this study, high-pressure phase behavior of propyl lactate and butyl lactate in CO 2 was measured from (323.2 to 363.2) K using a variable-volume view cell apparatus. Experimental data were well correlated by the Peng–Robinson equation of state using the van der Waals one-fluid mixing rules. The critical constants were estimated by the Joback method, the Constantinou–Gani method, and the Nannoolal–Rarey method. Acentric factor was estimated by the Lee–Kesler method.

  2. A Successful Induction of Lactation in Surrogate Pregnancy with Metoclopramide and Review of Lactation Induction

    OpenAIRE

    Elahe Mirzaaga; Arezoo Arabipoor; Mitra Frotan; Marzieh Shiva

    2010-01-01

    In surrogate pregnancies genetic parents have little opportunity for early bonding with their infants,either prenatally (in utero) or during the immediate postnatal period. Procedures commonlyused to induce lactation include both pharmacologic and nonpharmacologic methods, often incombination. Studies reporting induced lactation are sparse, due to the rarity of augmentedlactation. Here we report a case of lactation induction following a surrogate pregnancy. Othermethods that can be used to au...

  3. Bioassay Guided Chromatographic Isolation Of Lactation Inducing ...

    African Journals Online (AJOL)

    MBI

    2014-01-07

    Jan 7, 2014 ... The production of breast milk is controlled by an interplay of various hormones, with ... including estrogen, progesterone, insulin, growth hormone, cortisol ..... and Serum Prolactin on Cows Hormonally. Induced into Lactation.

  4. effect of hippocratea obtusifolia extracts on lactation

    African Journals Online (AJOL)

    DR. AMINU

    2014-06-01

    Jun 1, 2014 ... milk is controlled by interplay of various hormones, with prolactin being the ... insulin, growth hormone, cortisol, thyroxine and human placental lactogen ..... prolactin on cows hormonally induced into lactation. J. Dairy sci.

  5. Lactate metabolism in chronic liver disease

    DEFF Research Database (Denmark)

    Jeppesen, Johanne B; Mortensen, Christian; Bendtsen, Flemming

    2013-01-01

    Background. In the healthy liver there is a splanchnic net-uptake of lactate caused by gluconeogenesis. It has previously been shown that patients with acute liver failure in contrast have a splanchnic release of lactate caused by a combination of accelerated glycolysis in the splanchnic region...... and a reduction in hepatic gluconeogenesis. Aims. The aims of the present study were to investigate lactate metabolism and kinetics in patients with chronic liver disease compared with a control group with normal liver function. Methods. A total of 142 patients with chronic liver disease and 14 healthy controls...... underwent a liver vein catheterization. Blood samples from the femoral artery and the hepatic and renal veins were simultaneously collected before and after stimulation with galactose. Results. The fasting lactate levels, both in the hepatic vein and in the femoral artery, were higher in the patients than...

  6. The effect of stage of lactation on daily milk yield, and milk fat and protein content in Tsigai and Improved Valachian ewes

    Directory of Open Access Journals (Sweden)

    Marta Oravcová

    2015-02-01

    Full Text Available The objective of this study was to analyse the effect of stage of lactation on daily milk yield, and milk fat and protein content in Tsigai and Improved Valachian ewes. Breed lactation curves for daily milk yield, and milk fat and protein content were modelled as a sub-model of the three-trait animal model based on repeated test-day records that were collected by the Breeding Services of the Slovak Republic between 1995 and 2010. Data included 188403 (Tsigai and 352094 (Improved Valachian ewe’s performance records. Pedigree file included 35484 (Tsigai and 66994 (Improved Valachian animals with genetic ties to ewes with milk performance data. The fixed part of the model included parity, litter size and stage of lactation. The effect of days in milk (i.e. stage of lactation was fitted using Ali and Schaeffer lactation curve. The random part of the model included flock-test day effect, direct additive genetic effect, and permanent environmental effect of ewe nested within lactation. Due to limited number of test-day records in the first and the eighth month of lactation and related difficulties in modelling milk traits in these phases of lactation, the lactation curves were plotted between days 30 and 210. During lactation period the daily milk yield curves were decreasing, while milk fat and protein content were increasing. Because of higher changes at the beginning of lactation balanced with higher changes at the end of lactation in Tsigai and smaller changes at the beginning of lactation balanced with smaller changes at the end of lactation in Improved Valachian, 150d milk yield and average milk fat and protein content were almost the same in both breeds.

  7. A Successful Induction of Lactation in Surrogate Pregnancy with Metoclopramide and Review of Lactation Induction

    Directory of Open Access Journals (Sweden)

    Elahe Mirzaaga

    2010-01-01

    Full Text Available In surrogate pregnancies genetic parents have little opportunity for early bonding with their infants,either prenatally (in utero or during the immediate postnatal period. Procedures commonlyused to induce lactation include both pharmacologic and nonpharmacologic methods, often incombination. Studies reporting induced lactation are sparse, due to the rarity of augmentedlactation. Here we report a case of lactation induction following a surrogate pregnancy. Othermethods that can be used to augment lactation are described below. We used metoclopramide inthis case due to the success rates reported in previous studies and case reports. Additionally, itis a well tolerated and safe agent.

  8. Cerebral lactate production and blood flow in acute stroke

    DEFF Research Database (Denmark)

    Henriksen, O; Gideon, P; Sperling, B

    1992-01-01

    that follows reperfusion. The amount of lactate present in the acute phase reflects the severity of ischemia in the affected region. The lactate level was still above normal in the subacute phase with hyperemia, suggesting lactate production through aerobic glycolysis. Thus, the lactate level in the subacute...... phase probably does not reflect the degree of anaerobic glycolysis in hypoxic neuronal tissue....

  9. Variations in the milk yield and milk composition of dairy cows during lactation.

    Science.gov (United States)

    Bedö, S; Nikodémusz, E; Percsich, K; Bárdos, L

    1995-01-01

    Variations in the milk yield and milk composition of a dairy cow colony (n = 23) were analyzed during 11 months of lactation. Milk yield followed a characteristic decreasing pattern in negative correlations with solid components (milk protein, lactose, total solids, milk fat). Titrable acidity (degree SH) was significantly (p < 0.1) higher in the milk of fresh-milking cows and it correlated negatively with lactose and positively with milk protein, milk fat and total solids. The concentrations of Zn, Fe and Cu tended to decrease, while Mn showed insignificant variation during lactation. Milk vitamin A showed a significant positive whilst milk vitamin E had a negative correlation with milk fat.

  10. Posthemorrhage glycogen and lactate metabolism in the liver: an experimental study with postprandial rats

    International Nuclear Information System (INIS)

    Boija, P.O.; Nylander, G.; Suhaili, A.; Ware, J.

    1988-01-01

    Glycogen and lactate metabolism was studied in livers from three groups of postprandial rats sustaining 70 mm Hg hemorrhagic hypotension for variable periods, 60 min (60H group), 120 min (120H group), and nonbled controls. The donor livers were investigated after completed hemorrhage using an in vitro perfusion system with L-lactate as substrate, together with U- 14 C-lactate. The residual glycogen stores were determined after perfusions. The incorporation of labelled lactate to glucose was increased in the 120H group by 66.7% and 116.8% compared to the 60H group and controls (p less than 0.01), but glycogenolysis was still the main source of glucose released in the 120H group. Glycogen formation from labelled lactate was 46.6% higher in the 120H group compared to controls (p less than 0.05) and lactate oxidation was decreased by 67.5% (p less than 0.05). The data suggest that hepatocytes are capable of rapid change from glycolysis to gluconeogenesis during hemorrhagic hypovolemia. However, energy-sparing glycogen breakdown is given priority over gluconeogenesis as long as glycogen remains available

  11. Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation.

    Science.gov (United States)

    Dugoua, Jean-Jacques; Seely, Dugald; Perri, Daniel; Koren, Gideon; Mills, Edward

    2008-01-01

    There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbs used during pregnancy and lactation. This is one article in a series that systematically reviews the evidence for herbs commonly used during pregnancy and lactation. To systematically review the literature for evidence on the use, safety and pharmacology of chastetree, focusing on issues pertaining to pregnancy and lactation. We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS In pregnancy, there is poor evidence based on theoretical and expert opinion and in vitro studies that chastetree may have estrogenic and progesteronic activity, uterine stimulant activity, emmenagogue activity and prevent miscarriages. In lactation, theoretical and expert opinion conflict as to whether chastetree increases or decreases lactation. Given its relatively common use amongst women of childbearing age, it is likely that some women may consume chastetree while unknowingly pregnant. Complementary and alternative medicine, midwifery and medical practitioners should be aware of this fact when prescribing chastetree to women of childbearing age, particularly when the patient is planning a family. Key words: Chastetree, vitex agnus-castus, pregnancy, lactation, breastfeeding, systematic review.

  12. Limits to sustained energy intake. XV. Effects of wheel running on the energy budget during lactation.

    Science.gov (United States)

    Zhao, Zhi-Jun; Król, Elzbieta; Moille, Sophie; Gamo, Yuko; Speakman, John R

    2013-06-15

    The capacity of animals to dissipate heat may constrain sustained energy intake during lactation. We examined these constraints at peak lactation in MF1 mice that had ad libitum access to food, or that had to run a pre-set target on running wheels to obtain ad libitum access to food. The voluntary distance run decreased sharply during pregnancy and peak lactation. When lactating females were provided with 80% of their estimated food requirements, and had to run pre-set distances of 2, 4 or 6 km before given access to additional ad libitum food, most of them did not complete the running target during late lactation and the mice with the highest targets failed to reach their targets earlier in lactation. There were consequently significant group differences in asymptotic food intake (2 km, 16.97 ± 0.40 g day(-1); 4 km, 14.29 ± 0.72 g day(-1); and 6 km, 12.65 ± 0.45 g day(-1)) and weaned litter masses (2 km, 71.11 ± 2.39 g; 4 km, 54.63 ± 4.28 g and 6 km, 47.18 ± 2.46 g). When the females did run sufficiently to gain ad libitum food access, their intake did not differ between the different distance groups or from controls that were not required to run. Thus, despite being physically capable of running the distances, mice could not exercise sufficiently in lactation to gain regular ad libitum access to food, probably because of the risks of hyperthermia when combining heat production from exercise with thermogenesis from lactation.

  13. Lactate versus pH levels in fetal scalp blood during labor--using the Lactate Scout System

    DEFF Research Database (Denmark)

    Lundin, Ingeborg Christina Rørbye; Perslev, Anette; Nickelsen, Carsten Nahne Amtoft

    2016-01-01

    OBJECTIVE: To assess if lactate measured with the Scout Lactate System is a reliable alternative to pH in intrapartum monitoring of the fetus. METHODS: A prospective study analyzing (1) the correlation between scalp lactate measured by the Scout Lactate System and the Automatic Blood Laboratory (...

  14. Urinary excretion levels of water-soluble vitamins in pregnant and lactating women in Japan.

    Science.gov (United States)

    Shibata, Katsumi; Fukuwatari, Tsutomu; Sasaki, Satoshi; Sano, Mitsue; Suzuki, Kahoru; Hiratsuka, Chiaki; Aoki, Asami; Nagai, Chiharu

    2013-01-01

    Recent studies have shown that the urinary excretion levels of water-soluble vitamins can be used as biomarkers for the nutritional status of these vitamins. To determine changes in the urinary excretion levels of water-soluble vitamins during pregnant and lactating stages, we surveyed and compared levels of nine water-soluble vitamins in control (non-pregnant and non-lactating women), pregnant and lactating women. Control women (n=37), women in the 2nd (16-27 wk, n=24) and 3rd trimester of pregnancy (over 28 wk, n=32), and early- (0-5 mo, n=54) and late-stage lactating (6-11 mo, n=49) women took part in the survey. The mean age of subjects was ~30 y, and mean height was ~160 cm. A single 24-h urine sample was collected 1 d after the completion of a validated, self-administered comprehensive diet history questionnaire to measure water-soluble vitamins or metabolites. The average intake of each water-soluble vitamin was ≍ the estimated average requirement value and adequate intake for the Japanese Dietary Reference Intakes in all life stages, except for vitamin B6 and folate intakes during pregnancy. No change was observed in the urinary excretion levels of vitamin B2, vitamin B6, vitamin B12, biotin or vitamin C among stages. Urine nicotinamide and folate levels were higher in pregnant women than in control women. Urine excretion level of vitamin B1 decreased during lactation and that of pantothenic acid decreased during pregnancy and lactation. These results provide valuable information for setting the Dietary Reference Intakes of water-soluble vitamins for pregnant and lactating women.

  15. Invited review: Carryover effects of early lactation feeding on total lactation performance in dairy cows

    DEFF Research Database (Denmark)

    Jørgensen, Carina; Spörndly, R; Bertilsson, J

    2016-01-01

    In comparison with the intensive research on the direct effects of energy supply on dairy cow lactation performance, little attention has been paid to the effect of early lactation feeding on subsequent production. The present paper reviews 9 studies carried out with the aim of quantifying...... the immediate and subsequent responses in milk production and body weight to early lactation feeding. Most results showed that a more generous feeding in early lactation caused a positive carryover effect on subsequent production, whereas an inadequate level of feed in early lactation has been shown to reduce...... to be determined by several factors including duration of the treatment and post-treatment feeding level. The most important factor though appears to be the magnitude of over- or underfeeding (i.e., a strong relationship between the treatment period feeding level and the subsequent response in production)....

  16. Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.

    Science.gov (United States)

    Newcomb, Dawn C; Cephus, Jacqueline Yvonne; Boswell, Madison G; Fahrenholz, John M; Langley, Emily W; Feldman, Amy S; Zhou, Weisong; Dulek, Daniel E; Goleniewska, Kasia; Woodward, Kimberly B; Sevin, Carla M; Hamilton, Robert G; Kolls, Jay K; Peebles, R Stokes

    2015-10-01

    Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA. We sought to Determine the mechanism by which 17β-estradiol (E2) and progesterone (P4) increase IL-17A production. IL-17A production was determined by using flow cytometry in TH17 cells from women (n = 14) and men (n = 15) with severe asthma. Cytokine levels were measured by using ELISA, and IL-23R and let-7f expression was measured by using quantitative PCR in TH17-differentiated cells from healthy women (n = 13) and men (n = 14). In sham-operated or ovariectomized female mice, 17β-E2, P4, 17β-E2+P4, or vehicle pellets were administered for 3 weeks before ex vivo TH17 cell differentiation. Airway neutrophil infiltration and CXCL1 (KC) expression were also determined in ovalbumin (OVA)-challenged wild-type female recipient mice with an adoptive transfer of OVA-specific TH17 cells from female and male mice. In patients with severe asthma and healthy control subjects, IL-17A production was increased in TH17 cells from women compared with men. IL-23R expression was increased and let-7f expression was decreased in TH17-differentiated cells from women compared with men. In ovariectomized mice IL-17A and IL-23R expression was increased and Let-7f expression was decreased in TH17 cells from mice administered 17β-E2+P4 compared with those administered vehicle. Furthermore, transfer of female OVA-specific TH17 cells increased acute neutrophil infiltration in the lungs of OVA-challenged recipient mice compared with transfer of male OVA-specific TH17 cells. 17β-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells.

    Science.gov (United States)

    Liu, Xunxian; Allen, Jeffrey D; Arnold, Julia T; Blackman, Marc R

    2008-04-01

    Prostate stromal and epithelial cell communication is important in prostate functioning and cancer development. Primary human stromal cells from normal prostate stromal cells (PRSC) maintain a smooth muscle phenotype, whereas those from prostate cancer (6S) display reactive and fibroblastic characteristics. Dihydrotestosterone (DHT) stimulates insulin-like growth factor-I (IGF-I) production by 6S but not PSRC cells. Effects of reactive versus normal stroma on normal human prostate epithelial (NPE or PREC) cells are poorly understood. We co-cultured NPE plus 6S or PRSC cells to compare influences of different stromal cells on normal epithelium. Because NPE and PREC cells lose androgen receptor (AR) expression in culture, DHT effects must be modulated by associated stromal cells. When treated with camptothecin (CM), NPE cells, alone and in stromal co-cultures, displayed a dose-dependent increase in DNA fragmentation. NPE/6S co-cultures exhibited reduced CM-induced cell death with exposure to DHT, whereas NPE/PRSC co-cultures exhibited CM-induced cell death regardless of DHT treatment. DHT blocked CM-induced, IGF-I-mediated, NPE death in co-cultured NPE/6S cells without, but not with, added anti-IGF-I and anti-IGF-R antibodies. Lycopene consumption is inversely related to human prostate cancer risk and inhibits IGF-I and androgen signaling in rat prostate cancer. In this study, lycopene, in dietary concentrations, reversed DHT effects of 6S cells on NPE cell death, decreased 6S cell IGF-I production by reducing AR and beta-catenin nuclear localization and inhibited IGF-I-stimulated NPE and PREC growth, perhaps by attenuating IGF-I's effects on serine phosphorylation of Akt and GSK3beta and tyrosine phosphorylation of GSK3. This study expands the understanding of the preventive mechanisms of lycopene in prostate cancer.

  18. Management of hyperthyroidism during pregnancy and lactation.

    Science.gov (United States)

    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.

  19. Neuronal Progenitor Maintenance Requires Lactate Metabolism and PEPCK-M-Directed Cataplerosis.

    Science.gov (United States)

    Álvarez, Zaida; Hyroššová, Petra; Perales, José Carlos; Alcántara, Soledad

    2016-03-01

    This study investigated the metabolic requirements for neuronal progenitor maintenance in vitro and in vivo by examining the metabolic adaptations that support neuronal progenitors and neural stem cells (NSCs) in their undifferentiated state. We demonstrate that neuronal progenitors are strictly dependent on lactate metabolism, while glucose induces their neuronal differentiation. Lactate signaling is not by itself capable of maintaining the progenitor phenotype. The consequences of lactate metabolism include increased mitochondrial and oxidative metabolism, with a strict reliance on cataplerosis through the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) pathway to support anabolic functions, such as the production of extracellular matrix. In vivo, lactate maintains/induces populations of postnatal neuronal progenitors/NSCs in a PEPCK-M-dependent manner. Taken together, our data demonstrate that, lactate alone or together with other physical/biochemical cues maintain NSCs/progenitors with a metabolic signature that is classically found in tissues with high anabolic capacity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    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 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.

  1. Glycolysis and the significance of lactate in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Keri Linda Carpenter

    2015-04-01

    Full Text Available In traumatic brain injury (TBI patients, elevation of the brain extracellular lactate concentration and the lactate/pyruvate ratio are well recognised, and are associated statistically with unfavourable clinical outcome. Brain extracellular lactate was conventionally regarded as a waste product of glucose, when glucose is metabolised via glycolysis (Embden-Meyerhof-Parnas pathway to pyruvate, followed by conversion to lactate by the action of lactate dehydrogenase, and export of lactate into the extracellular fluid. In TBI, glycolytic lactate is ascribed to hypoxia or mitochondrial dysfunction, although the precise nature of the latter is incompletely understood. Seemingly in contrast to lactate’s association with unfavourable outcome is a growing body of evidence that lactate can be beneficial. The idea that the brain can utilise lactate by feeding into the tricarboxylic acid (TCA cycle of neurons, first published two decades ago, has become known as the astrocyte-neuron lactate shuttle hypothesis. Direct evidence of brain utilisation of lactate was first obtained 5 years ago in a cerebral microdialysis study in TBI patients, where administration of 13C-labelled lactate via the microdialysis catheter and simultaneous collection of the emerging microdialysates, with 13C NMR analysis, revealed 13C labelling in glutamine consistent with lactate utilisation via the TCA cycle. This suggests that where neurons are too damaged to utilise the lactate produced from glucose by astrocytes, i.e. uncoupling of neuronal and glial metabolism, high extracellular levels of lactate would accumulate, explaining association between high lactate and poor outcome. An intravenous exogenous lactate supplementation study in TBI patients showed evidence for a beneficial effect judged by surrogate endpoints. Here we review current knowledge about glycolysis and lactate in TBI, how it can be measured in patients, and whether it can be modulated to achieve better

  2. Early lactation production, health, and welfare characteristics of cows selected for extended lactation.

    Science.gov (United States)

    Lehmann, J O; Mogensen, L; Kristensen, T

    2017-02-01

    Some cows are able to achieve relatively high milk yields during extended lactations beyond 305 d in milk, and farmers may be able to use this potential by selecting the most suitable cows for an extended lactation. However, the decision to postpone insemination has to rely on information available in early lactation. The main objectives of this study were, therefore, to assess the association between the information available in early lactation and the relative milk production of cows on extended lactation, and to investigate if this information can be used to differentiate time of first insemination between cows. Data came from 4 Danish private herds practicing extended lactation in which some cows are selected to have a delayed time of planned first insemination. Average herd size varied from 93 to 157 cows, and milk yield varied from 7,842 to 12,315 kg of energy-corrected milk (ECM) per cow per year across herds. The analysis was based on 422 completed extended lactations (427 ± 87 d), and each lactation was assigned to 1 of 3 (low, medium, and high) milk performance groups (MPG) within parity group within herd based on a standardized lactation yield. For cows in the high MPG, peak ECM yield, and ECM yield at dry off were significantly greater, the relative reduction in milk yield between 60 and 305 d in milk was significantly smaller, and a smaller proportion had a body condition score (scale: 1-5) at dry off of 3.5 or greater compared with cows in low MPG. Previous lactation days in milk at peak ECM yield and ECM yield at dry off were higher, the relative reduction in milk yield between 60 and 305 d in milk was smaller, and the number of inseminations per conception was higher for multiparous cows in high MPG compared with low. Current lactation ECM yield at second and third milk recording were greater for cows in high MPG compared with low. A principal component analysis indicated that variables related to fertility, diseases, and milk yield explained most

  3. Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

    Science.gov (United States)

    Hasen, Nina S; Gammie, Stephen C

    2011-03-01

    The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  5. Dermatological treatment during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Lilianna Kulczycka

    2010-02-01

    Full Text Available Since wellbeing and health have become fashionable and widespread polypragmasia is popular, adverse drug reactions are a particularly important medical problem. Pregnant women as well as breast-feeding mothers need very particular care from the physician. Treatment during pregnancy or lactation is a more complicated issue not only because it concerns at least two persons, but also because of the many anatomical and functional differences between the adult and fetus or newborn organism. The safety aspects of dermatological treatment during pregnancy and lactation are presented. Both topical and systemic treatment, mainly for bacterial, viral, fungal, and parasitic dermatoses and acne, alopecia, psoriasis, and autoimmunological processes, are discussed. Moreover, the most recent methods of dermatological treatment are mentioned taking into consideration their safety during pregnancy and lactation. Furthermore, the traditional drug classification made by the United States Food and Drug Administration as well as the most modern division, which is under construction, are presented.

  6. GPR81, a Cell-Surface Receptor for Lactate, Regulates Intestinal Homeostasis and Protects Mice from Experimental Colitis.

    Science.gov (United States)

    Ranganathan, Punithavathi; Shanmugam, Arulkumaran; Swafford, Daniel; Suryawanshi, Amol; Bhattacharjee, Pushpak; Hussein, Mohamed S; Koni, Pandelakis A; Prasad, Puttur D; Kurago, Zoya B; Thangaraju, Muthusamy; Ganapathy, Vadivel; Manicassamy, Santhakumar

    2018-03-01

    At mucosal sites such as the intestine, the immune system launches robust immunity against invading pathogens while maintaining a state of tolerance to commensal flora and ingested food Ags. The molecular mechanisms underlying this phenomenon remain poorly understood. In this study, we report that signaling by GPR81, a receptor for lactate, in colonic dendritic cells and macrophages plays an important role in suppressing colonic inflammation and restoring colonic homeostasis. Genetic deletion of GPR81 in mice led to increased Th1/Th17 cell differentiation and reduced regulatory T cell differentiation, resulting in enhanced susceptibility to colonic inflammation. This was due to increased production of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and decreased expression of immune regulatory factors (IL-10, retinoic acid, and IDO) by intestinal APCs lacking GPR81. Consistent with these findings, pharmacological activation of GPR81 decreased inflammatory cytokine expression and ameliorated colonic inflammation. Taken together, these findings identify a new and important role for the GPR81 signaling pathway in regulating immune tolerance and colonic inflammation. Thus, manipulation of the GPR81 pathway could provide novel opportunities for enhancing regulatory responses and treating colonic inflammation. Copyright © 2018 by The American Association of Immunologists, Inc.

  7. The effect of selection during first lactation on the phenotypic and ...

    African Journals Online (AJOL)

    Comine Pienaar

    a marked improvement on the genetic merit of first lactation cows in the herd. ... With a higher milk yield per cow, productive efficiency increases and fixed costs such as maintenance needs decrease as a percentage of total costs (Muller, 2001). ... make the smallest contribution to the total milk production of a dairy herd.

  8. High energy electron beam inactivation of lactate dehydrogenase suspended in different aqueous media

    International Nuclear Information System (INIS)

    Hategan, A.; Oproiu, C.; Popescu, A.; Hategan, D.; Morariu, V.V.

    1998-01-01

    The direct and indirect effects of 5 MeV electron beam irradiation at various low temperatures, as well as the influence of the presence or absence of deuterium ions in the suspending medium of the enzyme, on the global enzymatic activity of lactate dehydrogenase have been studied. Frozen lactate dehydrogenase suspensions at 0 degC, -3 degC and -196 degC temperatures have been irradiated with the 5 MeV electron beam of a linear accelerator in the dose range 0-400 Gy. Liquid lactate dehydrogenase suspensions in D 2 O (99.98 %) and ultrapure water (17 ppm) at 0 degC have been irradiated in the dose range 0 -15 Gy. An exponential decrease was found in the enzymatic activity of irradiated lactate dehydrogenase, at all irradiation temperatures. The drastic decrease in the activity for the enzyme irradiated at 0 degC (total inhibition for a final dose of 100 Gy) indicate that at this temperature the indirect effects of radiation (due to the water radicals induced by radiation in the samples) are predominant. At -3 degC irradiation temperature the indirect effects of radiation are smaller but still present (a total decrease in the enzymatic activity for a dose of 250 Gy), while at -196 degC they are orders of magnitude reduced and the decrease in the enzymatic activity is due almost to the direct interaction of electrons with the macromolecules (70 % for a dose of 400 Gy)

  9. Galaktocele of Lactating Woman in Atypical Localisation

    International Nuclear Information System (INIS)

    Pavlendova, G.; Bartalosova, M.; Ondrkalova, M.

    2011-01-01

    Galactocele is a benign breast lesion mostly occurring in pregnant and lactating women. Due to its variable ultrasound appearance it may be difficult to differentiate it from other lesions, either benign or malignant, such as fibroadenoma, lactating adenoma, abscess, phyllodes tumor, papilloma or breast cancer and in these cases fine needle aspiration should be performed. Biochemical analysis of the aspirate shows variable proportions of proteins, fat and lactose. In rare cases where galactocele has only solid appearance, a core-cut biopsy could also be performed to rule out breast cancer. The authors present a case of a 34-years old patient with this diagnosis. (author)

  10. Whole-cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production.

    Science.gov (United States)

    Goers, Lisa; Ainsworth, Catherine; Goey, Cher Hui; Kontoravdi, Cleo; Freemont, Paul S; Polizzi, Karen M

    2017-06-01

    Many high-value added recombinant proteins, such as therapeutic glycoproteins, are produced using mammalian cell cultures. In order to optimize the productivity of these cultures it is important to monitor cellular metabolism, for example the utilization of nutrients and the accumulation of metabolic waste products. One metabolic waste product of interest is lactic acid (lactate), overaccumulation of which can decrease cellular growth and protein production. Current methods for the detection of lactate are limited in terms of cost, sensitivity, and robustness. Therefore, we developed a whole-cell Escherichia coli lactate biosensor based on the lldPRD operon and successfully used it to monitor lactate concentration in mammalian cell cultures. Using real samples and analytical validation we demonstrate that our biosensor can be used for absolute quantification of metabolites in complex samples with high accuracy, sensitivity, and robustness. Importantly, our whole-cell biosensor was able to detect lactate at concentrations more than two orders of magnitude lower than the industry standard method, making it useful for monitoring lactate concentrations in early phase culture. Given the importance of lactate in a variety of both industrial and clinical contexts we anticipate that our whole-cell biosensor can be used to address a range of interesting biological questions. It also serves as a blueprint for how to capitalize on the wealth of genetic operons for metabolite sensing available in nature for the development of other whole-cell biosensors. Biotechnol. Bioeng. 2017;114: 1290-1300. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

  11. Whole‐cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production

    Science.gov (United States)

    Goers, Lisa; Ainsworth, Catherine; Goey, Cher Hui; Kontoravdi, Cleo; Freemont, Paul S.

    2017-01-01

    ABSTRACT Many high‐value added recombinant proteins, such as therapeutic glycoproteins, are produced using mammalian cell cultures. In order to optimize the productivity of these cultures it is important to monitor cellular metabolism, for example the utilization of nutrients and the accumulation of metabolic waste products. One metabolic waste product of interest is lactic acid (lactate), overaccumulation of which can decrease cellular growth and protein production. Current methods for the detection of lactate are limited in terms of cost, sensitivity, and robustness. Therefore, we developed a whole‐cell Escherichia coli lactate biosensor based on the lldPRD operon and successfully used it to monitor lactate concentration in mammalian cell cultures. Using real samples and analytical validation we demonstrate that our biosensor can be used for absolute quantification of metabolites in complex samples with high accuracy, sensitivity, and robustness. Importantly, our whole‐cell biosensor was able to detect lactate at concentrations more than two orders of magnitude lower than the industry standard method, making it useful for monitoring lactate concentrations in early phase culture. Given the importance of lactate in a variety of both industrial and clinical contexts we anticipate that our whole‐cell biosensor can be used to address a range of interesting biological questions. It also serves as a blueprint for how to capitalize on the wealth of genetic operons for metabolite sensing available in nature for the development of other whole‐cell biosensors. Biotechnol. Bioeng. 2017;114: 1290–1300. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:28112405

  12. Effect of gestational and lactational exposure to heat stress on performance in rabbits

    Directory of Open Access Journals (Sweden)

    F. Marco-Jiménez

    2017-03-01

    Full Text Available Reproductive performance is greatly affected by environmental factors such as temperature. Heat stress (HS during pregnancy and lactation can influence not only foetal growth but also postnatal development of kits. The aim of this study was to test the effect of HS during gestation and lactation on postnatal growth till Spanish commercial liveweight. To investigate this, 32 primiparous non lactating rabbit does were exposed to 1 of 2 environmental treatments: high temperature (between 25 and 36°C, HS group; n=16 or thermoneutral conditions (between 14 and 20°C, TN group; n=16. Does were allowed to acclimate 30 d before the artificial insemination. At birth, kits were allocated into 4 groups: HS was only applied during gestation (G group; n=54; HS was applied during gestation and lactation period (GL group; n=85; HS was only applied during lactation period (L group; n=60; and TN was applied during gestation and lactation period (C group; n=77. All litters were kept under each experimental environment until weaning at day 30. Then, litters were moved to TN temperatures until slaughter at day 63. Compared with TN does, the HS does presented lower litter size (9.7 and 11.4; P<0.05, litter weight (503.0 vs. 630.5 g; P<0.05 and kit weight at birth (56.6 vs. 61.4 g; P<0.05, as well as a higher stillborn rate (25.4 vs. 9.9%; P<0.05. The kits from does subjected to HS during gestation (G group had similar postnatal growth compared to offspring from does gestated in TN conditions (C group, whereas kits from does that experienced HS during gestation and lactation (GL group and during their lactation (L group presented decreased postnatal growth. Together, these results demonstrate that kits from does that underwent HS during gestation did not alter postnatal growth until Spanish commercial liveweight, whereas HS during lactation resulted in decreased postnatal growth.

  13. Pattern of γ-glutamyl transferase activity in cow milk throughout lactation and relationships with metabolic conditions and milk composition.

    Science.gov (United States)

    Calamari, L; Gobbi, L; Russo, F; Cappelli, F Piccioli

    2015-08-01

    The main objective of this experiment was to study the γ-glutamyl transferase (GGT) activity in milk during lactation and its relationship with metabolic status of dairy cows, milk yield, milk composition, and cheesemaking properties. The study was performed in a tied stall barn and involved 20 lactations from 12 healthy multiparous Italian Friesian dairy cows. During lactation starting at d 10, milk samples were collected weekly and analyzed for composition, somatic cells count, titratable acidity, and milk coagulation properties. The GGT activity was measured in defatted samples. Blood samples were collected weekly to assess biochemical indicators related to energy, protein, and mineral metabolism, markers of inflammation and some enzyme activities. The lactations of each cow were retrospectively categorized into 2 groups according to their milk GGT activity value through lactation. A median value of GGT activity in the milk of all lactations was calculated (3,045 U/L), and 10 lactations with lower GGT activity were classified as low while 10 lactations with greater GGT activity were classified as high. The average value of milk GGT activity during lactation was 3,863 and 3,024 U/L for high and low, respectively. The GGT activity decreased in early lactation and reached minimum values in the second month (3,289 and 2,355 U/L for high and low, respectively). Thereafter GGT activity increased progressively, reaching values in late lactation of 4,511 and 3,540 U/L in high and low, respectively. On average, milk yield was 40.81 and 42.76 kg/d in high and low, respectively, and a negative partial correlation with milk GGT activity was observed. A greater milk protein concentration was observed in high (3.39%) compared with low (3.18%), and a positive partial correlation with milk GGT activity was observed. Greater titratable acidity in high than that in low (3.75 vs. 3.45 degrees Soxhlet-Henkel/50 mL, respectively) was also observed. Plasma glucose was greater in

  14. Evaluation of Serum Lactate Dehydrogenase Activity in a Virtual Environment

    Directory of Open Access Journals (Sweden)

    V.M.T. Trindade

    2013-05-01

    Full Text Available Introduction: Lactate dehydrogenase is a citosolic enzyme involved in reversible transformation of pyruvate to lactate. It participates in anaerobic glycolysis of skeletal muscle and red blood cells, in liver gluconeogenesis and in aerobic metabolism of heart muscle. The determination of its activity helps in the diagnosis of various diseases, because it is increased in serum of patients suffering from myocardial infarction, acute hepatitis, muscular dystrophy and cancer. This paper presents a learning object, mediated by computer, which contains the simulation of the laboratory determination serum lactate dehydrogenase activity measured by the spectrophotometric method, based in the decrease of absorbance at 340 nm. Materials and Methods: Initially, pictures and videos were obtained recording the procedure of the methodology. The most representative images were selected, edited and inserted into an animation developed with the aid of the tool Adobe ® Flash ® CS3. The validation of the object was performed by the students of Biochemistry I (Pharmacy-UFRGS from the second semester of 2009 and both of 2010. Results and Discussion: The analysis of students' answers revealed that 80% attributed the excellence of the navigation program, the display format and to aid in learning. Conclusion: Therefore, this software can be considered an adequate teaching resource as well as an innovative support in the construction of theoretical and practical knowledge of Biochemistry. Available at: http://www6.ufrgs.br/gcoeb/LDH

  15. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid.

    Science.gov (United States)

    Castro, Maite A; Beltrán, Felipe A; Brauchi, Sebastián; Concha, Ilona I

    2009-07-01

    In this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K(+)]. Neurons are cells well equipped to consume glucose because they express glucose transporters and glycolytic and tricarboxylic acid cycle enzymes. Moreover, neuronal cells express monocarboxylate transporters and lactate dehydrogenase isoenzyme 1, which is inhibited by pyruvate. As glycolysis produces an increase in pyruvate concentration and a decrease in NAD(+)/NADH, lactate and glucose consumption are not viable at the same time. In this context, we discuss ascorbic acid participation as a metabolic switch modulating neuronal metabolism between rest and activation periods. Ascorbic acid is highly concentrated in CNS. Glutamate stimulates ascorbic acid release from astrocytes. Ascorbic acid entry into neurons and within the cell can inhibit glucose consumption and stimulate lactate transport. For this switch to occur, an ascorbic acid flow is necessary between astrocytes and neurons, which is driven by neural activity and is part of vitamin C recycling. Here, we review the role of glucose and lactate as metabolic substrates and the modulation of neuronal metabolism by ascorbic acid.

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

    Science.gov (United States)

    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

  17. Effect of dry period length on milk production in subsequent lactation

    DEFF Research Database (Denmark)

    Sørensen, J.T.; Enevoldsen, Carsten

    1991-01-01

    , two treatments were compared within herd. Compared with a 7-wk planned dry period, a 3-wk decrease lowered the level of milk production by 2.8 kg of 4% FCM/d in the first 84 d of the subsequent lactation, whereas a 3-wk increase raised the level of milk production by .5 kg/d. In the first 168 d......The effect of planned dry period lengths of 4, 7, and 10 wk on subsequent lactational yield was estimated with 366 cows in an experiment in which dry period was manipulated independently of milk yield prior to drying off. In two herds, all three treatments were compared within herd; in six herds...... of the subsequent lactation, the difference between 4-wk and 7-wk planned dry periods was 2.7 kg/d, and the difference between 7- and 10-wk periods was .4 kg/d. There was no indication of interaction among planned dry period length and lactation number, days open in previous lactation, previous milk yield, breed...

  18. Changes in handgrip force and blood lactate as response to simulated climbing competition

    Directory of Open Access Journals (Sweden)

    J Gajewski

    2009-07-01

    Full Text Available The aim of the study was to estimate post-competition changes in handgrip strength and blood lactate in climbers and relationships of the studied variables with declared climbing ability of the tested athletes. Twenty one male climbers volunteered to take part in the experiment. Each subject took part in simulated lead climbing competition on the artificial wall – (difficulty 7a in French scale. The blood lactate concentration was measured pre-climbing and then 3 min and 30 min post-climbing. Grip force of both hands (dominant and non-dominant was measured twice – pre-climbing and 1 min post-climbing (semi-final. Maximum heart rate during climbing reached 181.4±7.7 beats per minute. Lactate concentration amounted to 6.35±1.50 mmol/l and 2.28±0.66 mmol/l 3 min and 30 min post-climbing, respectively. Handgrip force related to body mass (averaged for both hands decreased significantly from 7.39±1.30 N/kg pre-climbing to 6.57±1.05 N/kg 1 min post-climbing. Self reported climbing ability was correlated with lactate concentration and handgrip force, as well. It was demonstrated that athletes reporting higher climbing ability showed better lactate recovery.

  19. Channel-Mediated Lactate Release by K+-Stimulated Astrocytes

    KAUST Repository

    Sotelo-Hitschfeld, T.; Niemeyer, M. I.; Machler, P.; Ruminot, I.; Lerchundi, R.; Wyss, M. T.; Stobart, J.; Fernandez-Moncada, I.; Valdebenito, R.; Garrido-Gerter, P.; Contreras-Baeza, Y.; Schneider, B. L.; Aebischer, P.; Lengacher, S.; San Martin, A.; Le Douce, J.; Bonvento, G.; Magistretti, Pierre J.; Sepulveda, F. V.; Weber, B.; Barros, L. F.

    2015-01-01

    in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission.

  20. Application of isotopes to the study of lactate metabolism

    International Nuclear Information System (INIS)

    Katz, J.

    1986-01-01

    The use of 14 C as tracer to measure lactate turnover and oxidation and its role in gluconeogenesis are discussed. Lactate is formed as well as utilized in many cells, and most of it in the body is present within cells so that interpretation of 14 C data from labelled lactate is more complex and more difficult than that of compounds present largely extracellularly, such as glucose. Apparent uptake of [ 14 C]lactate may occur in the absence of net lactate utilization, and 14 CO 2 production does not provide a measure of true lactate oxidation. In vivo sites of tracer administration and sampling of blood are of critical significance for evaluation of lactate turnover, lactate space, its incorporation into glucose, and oxidation

  1. Lactate kinetics in human tissues at rest and during exercise

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2010-01-01

    lactate metabolism at rest and during exercise and suggestions are put forward to explain the simultaneous lactate uptake and release; and (2) lactate metabolism in the heart, liver, kidneys, brain, adipose tissue and lungs will be discussed and its potential importance in these tissues.......Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during exercise is much debated. In the early days skeletal muscle was mainly seen as the site of lactate production during contraction and lactate production...... associated with a lack of muscle oxygenation and fatigue. Later it was recognized that skeletal muscle not only played an important role in lactate production but also in lactate clearance and this led to a renewed interest, not the least from the Copenhagen School in the 1930s, in the metabolic role...

  2. Cumulative lactate and hospital mortality in ICU patients

    NARCIS (Netherlands)

    van Beest, Paul A.; Brander, Lukas; Jansen, Sebastiaan P. A.; Rommes, Johannes H.; Kuiper, Michael A.; Spronk, Peter E.

    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

  3. Clinical use of lactate monitoring in critically ill patients

    NARCIS (Netherlands)

    J. Bakker (Jan); M.W.N. Nijsten (Maarten); T.C. Jansen (Tim)

    2013-01-01

    textabstractIncreased blood lactate levels (hyperlactataemia) are common in critically ill patients. Although frequently used to diagnose inadequate tissue oxygenation, other processes not related to tissue oxygenation may increase lactate levels. Especially in critically ill patients, increased

  4. Lactation studies of anticonvulsants : A quality review

    NARCIS (Netherlands)

    van der Meer, Douwe H.; Wieringa, Andre; Wegner, Ilse; Wilffert, Bob; Ter Horst, Peter G.J.

    2015-01-01

    AIM: The aim of this review was to investigate the quality of the current literature on the transfer of anticonvulsants to breast milk to provide an overview of which anticonvulsants are in need of further research. METHODS: We reviewed the quality of the available lactation studies for 19

  5. Osteoporosis presenting in pregnancy, puerperium, and lactation.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Self-Powered Electrochemical Lactate Biosensing

    Directory of Open Access Journals (Sweden)

    Ankit Baingane

    2017-10-01

    Full Text Available This work presents the development and characterization of a self-powered electrochemical lactate biosensor for real-time monitoring of lactic acid. The bioanode and biocathode were modified with D-lactate dehydrogenase (D-LDH and bilirubin oxidase (BOD, respectively, to facilitate the oxidation and reduction of lactic acid and molecular oxygen. The bioelectrodes were arranged in a parallel configuration to construct the biofuel cell. This biofuel cell’s current–voltage characteristic was analyzed in the presence of various lactic acid concentrations over a range of 1–25 mM. An open circuit voltage of 395.3 mV and a short circuit current density of 418.8 µA/cm² were obtained when operating in 25 mM lactic acid. Additionally, a 10 pF capacitor was integrated via a charge pump circuit to the biofuel cell to realize the self-powered lactate biosensor with a footprint of 1.4 cm × 2 cm. The charge pump enabled the boosting of the biofuel cell voltage in bursts of 1.2–1.8 V via the capacitor. By observing the burst frequency of a 10 pF capacitor, the exact concentration of lactic acid was deduced. As a self-powered lactate sensor, a linear dynamic range of 1–100 mM lactic acid was observed under physiologic conditions (37 °C, pH 7.4 and the sensor exhibited an excellent sensitivity of 125.88 Hz/mM-cm2. This electrochemical lactate biosensor has the potential to be used for the real-time monitoring of lactic acid level in biological fluids.

  8. Free ferulic acid uptake in lactating cows.

    Science.gov (United States)

    Soberon, M A; Cherney, J H; Liu, R H; Ross, D A; Cherney, D J R

    2012-11-01

    Ferulic acid (FRA), a phenolic compound with antioxidant and anticancer activities, naturally occurs in plants as a lignin precursor. Many veins of research have been devoted to releasing FRA from the lignin complex to improve digestibility of ruminant feeds. Thus, the objective of this research was to investigate the transfer of a given dosage of the free form of FRA into the milk of dairy cattle. Six mid- to late-lactation Holstein cows at the Cornell Research Farm (Harford, NY) were given 14-d adaptation to diet and stall position. Ad libitum access to a total mixed ration based on haylage and maize silage (31.1% neutral detergent fiber containing 5.52 mg of FRA/g) was provided during the study. A crossover design was implemented so that each cow alternated weekly between FRA-dosed and control. On d 1, jugular cannulas and urine catheters were placed in all cows. On d 2, FRA-dosed cows received a single dosage of 150 g of pure FRA powder at 0830 h via their fistula (n=4) or a balling gun for nonfistulated cows (n=2). Plasma, urine, feces, feed, orts, milk, and rumen fluid were sampled intensively for the next 36 h and analyzed for FRA concentration. On d 8, the cows crossed over and the experiment was repeated. When compared with the control, FRA administration did not have an effect on dry matter intake, milk yield, milk fat yield, milk protein yield, somatic cell count, or neutral detergent fiber content of orts and feces. The concentration of FRA in the feces did not change as a result of FRA dosage. As expected, FRA concentration increased dramatically upon FRA dosage and decreased over time until returning to basal levels in rumen fluid (4 h after dosage), plasma (5.5 h after dosage), urine (10 h after dosage), and milk (14 h after dosage). Baseline values for FRA in urine and rumen fluid were variable among cows and had an effect on FRA concentration in FRA-dosed cows. From this study, it is observed that orally ingested FRA can be transported into the

  9. Cerebral H-1 MR spectroscopy revealing white matter NAA decreases in glutaric aciduria type I

    NARCIS (Netherlands)

    Sijens, P. E.; Smit, G. P. A.; Meiners, L. C.; Oudkerk, M.; van Spronsen, F. J.

    MR spectroscopy in two patients with glutaric aciduria type I revealed reductions in the white matter N-acetylaspartate signal, in the more severe case accompanied by a loss of glutamate and the appearance of lactate signals. (c) 2006 Elsevier Inc. All rights reserved.

  10. Characterization of the L-lactate dehydrogenase from Aggregatibacter actinomycetemcomitans.

    Directory of Open Access Journals (Sweden)

    Stacie A Brown

    Full Text Available Aggregatibacter actinomycetemcomitans is a Gram-negative opportunistic pathogen and the proposed causative agent of localized aggressive periodontitis. A. actinomycetemcomitans is found exclusively in the mammalian oral cavity in the space between the gums and the teeth known as the gingival crevice. Many bacterial species reside in this environment where competition for carbon is high. A. actinomycetemcomitans utilizes a unique carbon resource partitioning system whereby the presence of L-lactate inhibits uptake of glucose, thus allowing preferential catabolism of L-lactate. Although the mechanism for this process is not fully elucidated, we previously demonstrated that high levels of intracellular pyruvate are critical for L-lactate preference. As the first step in L-lactate catabolism is conversion of L-lactate to pyruvate by lactate dehydrogenase, we proposed a model in which the A. actinomycetemcomitans L-lactate dehydrogenase, unlike homologous enzymes, is not feedback inhibited by pyruvate. This lack of feedback inhibition allows intracellular pyruvate to rise to levels sufficient to inhibit glucose uptake in other bacteria. In the present study, the A. actinomycetemcomitans L-lactate dehydrogenase was purified and shown to convert L-lactate, but not D-lactate, to pyruvate with a K(m of approximately 150 microM. Inhibition studies reveal that pyruvate is a poor inhibitor of L-lactate dehydrogenase activity, providing mechanistic insight into L-lactate preference in A. actinomycetemcomitans.

  11. A neurokinin 3 receptor-selective agonist accelerates pulsatile luteinizing hormone secretion in lactating cattle.

    Science.gov (United States)

    Nakamura, Sho; Wakabayashi, Yoshihiro; Yamamura, Takashi; Ohkura, Satoshi; Matsuyama, Shuichi

    2017-07-01

    Pulsatile gonadotropin-releasing hormone (GnRH) secretion, which is indispensable for follicular development, is suppressed in lactating dairy and beef cattle. Neurokinin B (NKB) neurons in the arcuate nucleus of the hypothalamus are considered to play an essential role in generating the pulsatile mode of GnRH/luteinizing hormone (LH) secretion. The present study aimed to clarify the role of NKB-neurokinin 3 receptor (NK3R) signaling in the pulsatile pattern of GnRH/gonadotropin secretion in postpartum lactating cattle. We examined the effects of the administration of an NK3R-selective agonist, senktide, on gonadotropin secretion in lactating cattle. The lactating cattle, at approximately 7 days postpartum, were intravenously infused with senktide (30 or 300 nmol/min) or vehicle for 24 h. The administration of 30 or 300 nmol/min senktide significantly increased LH pulse frequency compared to in the control group during 0-4 or 20-24 h after infusion, respectively. Moreover, LH and follicle-stimulating hormone levels were gradually increased by 300 nmol/min administration of senktide during the 0-4-h sampling period. Ultrasonography of the ovaries was performed to identify the first postpartum ovulation in senktide-administered lactating cattle. The interval from calving to first postpartum ovulation was significantly shorter in the 300 nmol/min senktide-administered group than in the control group. Taken together, these findings suggest that senktide infusion elicits an increase in LH pulse frequency that may stimulate follicular development and, in turn, induce the first postpartum ovulation in lactating cattle. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Effects of feeding brown midrib corn silage with a high dietary concentration of alfalfa hay on lactational performance of Holstein dairy cows for the first 180 days of lactation.

    Science.gov (United States)

    Holt, M S; Eun, J-S; Thacker, C R; Young, A J; Dai, X; Nestor, K E

    2013-01-01

    This experiment was conducted to test a hypothesis that lactating dairy cows fed 35% brown midrib (BMR) corn silage and 25% alfalfa hay (dry matter (DM) basis) would consume more DM around peak lactation compared with those fed conventional corn silage (CS), resulting in longer peak milk production. Twenty-eight multiparous Holstein cows were used starting at the onset of lactation through 180 d in milk (DIM). Treatments were formulated to maintain a forage-to-concentrate ratio of 60:40, differing only in the CS hybrids used. Two dietary treatments were assessed in a completely randomized design: total mixed ration based on conventional CS (CCS) and total mixed ration based on BMR silage. Through peak lactation (1-60 DIM), DM intake was not different between dietary treatments, whereas DM intake post-peak lactation (61-180 DIM) tended to increase by feeding the BMR diet compared with the CCS diet (25.8 vs. 24.7 kg/d). Cows fed the BMR diet tended to lose less body weight through peak lactation compared with those fed the CCS diet (-0.22 vs. -0.52 kg/d). Although milk yield was not different between dietary treatments through peak lactation, milk yield post-peak lactation increased by feeding the BMR diet compared with the CCS diet (41.0 vs. 38.8 kg/d). Yield of 3.5% fat-corrected milk was similar between dietary treatments throughout the experiment (41.4 kg/d, on average), but milk fat concentration decreased by feeding the BMR diet compared with the CCS diet post-peak lactation (3.47 vs. 3.80%). Overall milk protein concentration was similar between dietary treatments throughout the experiment (2.96%, on average), whereas milk protein yield tended to be higher for the BMR diet post-peak lactation compared with the CCS diet (1.19 vs.1.13 kg/d). Feeding BMR silage with a high dietary concentration of alfalfa hay maintained more body weight, but did not affect milk production through peak lactation; however, cows fed the BMR diet post-peak lactation consumed more

  13. Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Rattigan, Yanique I.; Patel, Brijesh B. [Graduate School of Biomedical Sciences, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Ackerstaff, Ellen [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (United States); Sukenick, George [Molecular Pharmacology and Chemistry Research Program, Sloan-Kettering Institute, 415 E 68th Street, New York, NY 10065 (United States); Koutcher, Jason A. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (United States); Glod, John W. [Graduate School of Biomedical Sciences, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Department of Pediatric Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); and others

    2012-02-15

    Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells, which play a role in tumor progression. We have shown earlier that breast cancer cells secrete higher levels of interleukin-6 (IL-6) under hypoxia, leading to the recruitment of hMSCs towards hypoxic tumor cells. We found that (i) MDA-MB-231 cells secrete significantly higher levels of lactate (3-fold more) under hypoxia (1% O{sub 2}) than under 20% O{sub 2} and (ii) lactate recruits hMSCs towards tumor cells by activating signaling pathways to enhance migration. The mRNA and protein expression of functional MCT1 in hMSCs is increased in response to lactate exposure. Thus, we hypothesized that hMSCs and stromal carcinoma associated fibroblasts (CAFs) in the tumor microenvironment have the capacity to take up lactate expelled from tumor cells and use it as a source of energy. Our {sup 13}C NMR spectroscopic measurements indicate that {sup 13}C-lactate is converted to {sup 13}C-alpha ketoglutarate in hMSCs and CAFs supporting this hypothesis. To our knowledge this is the first in vitro model system demonstrating that hMSCs and CAFs can utilize lactate produced by tumor cells.

  14. Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment

    International Nuclear Information System (INIS)

    Rattigan, Yanique I.; Patel, Brijesh B.; Ackerstaff, Ellen; Sukenick, George; Koutcher, Jason A.; Glod, John W.

    2012-01-01

    Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells, which play a role in tumor progression. We have shown earlier that breast cancer cells secrete higher levels of interleukin-6 (IL-6) under hypoxia, leading to the recruitment of hMSCs towards hypoxic tumor cells. We found that (i) MDA-MB-231 cells secrete significantly higher levels of lactate (3-fold more) under hypoxia (1% O 2 ) than under 20% O 2 and (ii) lactate recruits hMSCs towards tumor cells by activating signaling pathways to enhance migration. The mRNA and protein expression of functional MCT1 in hMSCs is increased in response to lactate exposure. Thus, we hypothesized that hMSCs and stromal carcinoma associated fibroblasts (CAFs) in the tumor microenvironment have the capacity to take up lactate expelled from tumor cells and use it as a source of energy. Our 13 C NMR spectroscopic measurements indicate that 13 C-lactate is converted to 13 C-alpha ketoglutarate in hMSCs and CAFs supporting this hypothesis. To our knowledge this is the first in vitro model system demonstrating that hMSCs and CAFs can utilize lactate produced by tumor cells.

  15. An ultra­high field Magnetic Resonance Spectroscopy study of post exercise brain lactate, glutamate and glutamine change in the human brain.

    Directory of Open Access Journals (Sweden)

    Andrea eDennis

    2015-12-01

    Full Text Available During strenuous exercise there is a progressive increase in lactate uptake and metabolism into the brain as workload and plasma lactate levels increase. Although it is now widely accepted that the brain can metabolise lactate, few studies have directly measured brain lactate following vigorous exercise. Here, we used ultra-high field Magnetic Resonance Spectroscopy of the brain to obtain static measures of brain lactate, as well as brain glutamate and glutamine after vigorous exercise. The aims of our experiment were to (a track the changes in brain lactate following recovery from exercise and, (b to simultaneously measure the signals from brain glutamate and glutamine. The results of our experiment showed that vigorous exercise resulted in a significant increase in brain lactate. Furthermore, both glutamate and glutamine were successfully resolved, and as expected, although contrary to some previous reports, we did not observe any significant change in either amino acid after exercise. We did however observe a negative correlation between glutamate and a measure of fitness. These results support the hypothesis that peripherally-derived lactate is taken up by the brain when available. Our data additionally highlight the potential of ultra-high field magnetic resonance spectroscopy as a non-invasive way of measuring multiple brain metabolite changes with exercise.

  16. Lactate dehydrogenase has no control on lactate production but has a strong negative control on formate production in Lactococcus lactis

    DEFF Research Database (Denmark)

    Andersen, H.W.; Pedersen, M.B.; Hammer, Karin

    2001-01-01

    enhanced in the strain deleted for lactate dehydrogenase. What is more surprising is that the enzyme had a strong negative control (C- LDH(F1)J=-1.3) on the flux to formate at the wild-type level of lactate dehydrogenase. Furthermore, we showed that L. lactis has limited excess of capacity of lactate...

  17. Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue

    OpenAIRE

    Reverchon, Maxime; Ramé, Christelle; Cognié, Juliette; Briant, Eric; Elis, Sébastien; Guillaume, Daniel; Dupont, Joëlle

    2014-01-01

    Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigat...

  18. Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue

    Science.gov (United States)

    Reverchon, Maxime; Ramé, Christelle; Cognié, Juliette; Briant, Eric; Elis, Sébastien; Guillaume, Daniel; Dupont, Joëlle

    2014-01-01

    Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP) and at five months of gestation (5 MG). We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA) levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. PMID:24675707

  19. Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue.

    Directory of Open Access Journals (Sweden)

    Maxime Reverchon

    Full Text Available Resistin is an adipokine that has been implicated in energy metabolism regulation in rodents but has been little studied in dairy cows. We determined plasma resistin concentrations in early lactation in dairy cows and investigated the levels of resistin mRNA and protein in adipose tissue and the phosphorylation of several components of insulin signaling pathways one week post partum (1 WPP and at five months of gestation (5 MG. We detected resistin in mature bovine adipocytes and investigated the effect of recombinant bovine resistin on lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin concentration was low before calving, subsequently increasing and reaching a peak at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP. Plasma resistin concentration was significantly positively correlated with plasma non esterified fatty acid (NEFA levels and negatively with milk yield, dry matter intake and energy balance between WPP1 to WPP22. We showed, by quantitative RT-PCR and western blotting, that resistin mRNA and protein levels in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation of several early and downstream insulin signaling components (IRβ, IRS-1, IRS-2, Akt, MAPK ERK1/2, P70S6K and S6 in adipose tissue was also lower at 1 WPP than at 5 MG. Finally, we showed that recombinant bovine resistin increased the release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase and HSL (hormone-sensitive lipase in adipose tissue explants. Overall, resistin levels were high in the plasma and adipose tissue and were positively correlated with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro.

  20. Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells

    DEFF Research Database (Denmark)

    Larsen, Claus Morten; Døssing, M G; Papa, S

    2006-01-01

    IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen...

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

    Science.gov (United States)

    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.

  2. In Vivo1H Magnetic Resonance Spectroscopy of Lactate in Patients With Stage IV Head and Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Le, Quynh-Thu; Koong, Albert; Lieskovsky, Yee Yie; Narasimhan, Balasubramanian; Graves, Edward; Pinto, Harlan; Brown, J. Martin; Spielman, Daniel

    2008-01-01

    Purpose: To investigate in vivo 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 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 2 ) was obtained in the same lymph node before MRS. Patients 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 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 2 (mean, 0.46 ± 0.10 for hypoxic nodes [pO 2 ≤10 mm Hg, n = 15] vs. 0.36 ± 0.07 for nonhypoxic nodes [pO 2 >10 mm Hg, n = 21], p = 0.44). A significant correlation was found between the choline/creatine ratios and tumor pO 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 2 , treatment response, or locoregional control. Additional research is needed to refine this technique

  3. RNA sequencing of the human milk fat layer transcriptome reveals distinct gene expression profiles at three stages of lactation.

    Directory of Open Access Journals (Sweden)

    Danielle G Lemay

    Full Text Available 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 (10(5-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

  4. Monocarboxylate Transporters and Lactate Metabolism in Equine Athletes: A Review

    Directory of Open Access Journals (Sweden)

    Pösö AR

    2002-06-01

    Full Text Available Lactate is known as the end product of anaerobic glycolysis, a pathway that is of key importance during high intensity exercise. Instead of being a waste product lactate is now regarded as a valuable substrate that significantly contributes to the energy production of heart, noncontracting muscles and even brain. The recent cloning of monocarboxylate transporters, a conserved protein family that transports lactate through biological membranes, has given a new insight into the role of lactate in whole body metabolism. This paper reviews current literature on lactate and monocarboxylate transporters with special reference to horses.

  5. Lactation Curve Pattern and Prediction of Milk Production Performance in Crossbred Cows

    Directory of Open Access Journals (Sweden)

    Suresh Jingar

    2014-01-01

    Full Text Available Data pertaining to 11728 test-day daily milk yields of normal and mastitis Karan Fries cows were collected from the institute herd and divided as mastitis and nonmastitis and parity-wise. The data of lactation curves of the normal and mastitis crossbred cows was analyzed using gamma type function. FTDMY in normal and mastitis cows showed an increasing trend from TD-1 to TD-4 and a gradual decrease (P<0.01 thereafter until the end of lactation (TD-21 in different parities. The FTDMY was maximum (peak yield in the fourth parity. Parity-wise lactation curve revealed a decrease in persistency, steeper decline in descending slope (c, and steeper increase in ascending slope (b from 1st to 5th and above parity. The higher coefficient of determination (R2 and lower root mean square error (RMSE indicated goodness and accuracy of the model for the prediction of milk prediction performance under field conditions. Clinical mastitis resulted in a significantly higher loss of milk yield (P<0.05. The FTDMY was maximum (P<0.05 in the fourth parity in comparison to the rest of parity. It is demonstrated that gamma type function can give the best fit lactation curve in normal and mastitis infected crossbred cows.

  6. Impact of feeding reduced crude protein diets to lactating sows on nitrogen utilizatilon

    DEFF Research Database (Denmark)

    Huber, L; de Lange, C F M; Larsen, Uffe Krogh

    2015-01-01

    -fed; analyzed contents; HCP); 2) 15.7% CP (MHCP); 3) 14.3% CP (MLCP); 4) 13.2% CP (LCP); diet HCP was formulated using soybean meal and corn as the only Lys sources. The reduced CP diets contained CAA to meet requirements of the limiting AA. Sow and piglet BW were measured on d 1, 3, 7, 14, 18, and 21...... of lactation. Nitrogen retention was measured on sows between d 3 and 7 (early) and d 14 and 18 (peak) of lactation. Milk true protein output was calculated from estimated milk yield and analyzed true protein concentration. Sow BW change (overall mean: -4.2 ± 3.37 kg over the 21-d lactation period) and average...... daily DM intake (overall mean: 4.05 ± 0.18 and 6.12 ± 0.20 kg/d, early and peak lactation, respectively) did not differ between diets. Nitrogen intake decreased as dietary CP concentration decreased (114.3, 106.0, 107.4, and 99.0 ± 5.29 g/d and 169.5, 168.3, 161.2, and 145.1 ± 5.29 g/d for HCP, MHCP...

  7. Effect of decreasing dietary phosphorus supply on net recycling of inorganic phosphate in lactating dairy cows

    DEFF Research Database (Denmark)

    Puggaard, Liselotte; Kristensen, Niels Bastian; Sehested, Jens Jakob

    2011-01-01

    (LP; 2.4 g of P/kg of DM) and high P (HP; 3.4 g of P/kg of DM). The dietary total P (tP) concentrations were obtained by replacing 0.50% calcium carbonate in the LP diet with 0.50% monocalcium phosphate in the HP diet. Diets were fed for 14 d and cows were sampled on d 14 in each period. Cows were fed...... restrictively, resulting in equal dry matter intakes as well as milk, fat, and protein yields between treatments. Net Pi recycling (primarily salivary) was estimated as the difference between net portal plasma flux (net absorption of Pi) and apparently digested tP (feed – fecal tP difference). Phosphorus intake...

  8. Channel-Mediated Lactate Release by K+-Stimulated Astrocytes

    KAUST Repository

    Sotelo-Hitschfeld, T.

    2015-03-11

    Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have shown that lactate modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled receptors specific for lactate, but little is known about the cellular and molecular mechanisms responsible for the increase in interstitial lactate. Using a panel of genetically encoded fluorescence nanosensors for energy metabolites, we show here that mouse astrocytes in culture, in cortical slices, and in vivo maintain a steady-state reservoir of lactate. The reservoir was released to the extracellular space immediately after exposure of astrocytes to a physiological rise in extracellular K+ or cell depolarization. Cell-attached patch-clamp analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel activated by cell depolarization. The channel was modulated by lactate itself, resulting in a positive feedback loop for lactate release. A rapid fall in intracellular lactate levels was also observed in cortical astrocytes of anesthetized mice in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission.

  9. Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

    Science.gov (United States)

    Bollmann, Marc-Daniel; Revelly, Jean-Pierre; Tappy, Luc; Berger, Mette M; Schaller, Marie-Denise; Cayeux, Marie-Christine; Martinez, Alexandre; Chioléro, René-Louis

    2004-06-01

    To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. Each patient received the two buffers in a randomized sequence over two consecutive days. The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

  10. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

    Science.gov (United States)

    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.

  11. Leg and arm lactate and substrate kinetics during exercise

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Jensen-Urstad, M; Rosdahl, H

    2003-01-01

    To study the role of muscle mass and muscle activity on lactate and energy kinetics during exercise, whole body and limb lactate, glucose, and fatty acid fluxes were determined in six elite cross-country skiers during roller-skiing for 40 min with the diagonal stride (Continuous Arm + Leg) followed...... kinetics changed multiple times when exercise mode was changed. Whole body glucose and glycerol turnover was unchanged during the different skiing modes; however, limb net glucose uptake changed severalfold. In conclusion, the arterial lactate concentration can be maintained at a relatively low level...... despite high lactate R(a) during exercise with a large muscle mass because of the large capacity of active skeletal muscle to take up lactate, which is tightly correlated with lactate delivery. The limb lactate uptake during exercise is oxidized at rates far above resting oxygen consumption, implying...

  12. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    Science.gov (United States)

    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

  13. Chronic pain management in pregnancy and lactation.

    Science.gov (United States)

    Coluzzi, F; Valensise, H; Sacco, M; Allegri, M

    2014-02-01

    During pregnancy most of women will experience some kind of pain, either as a result of a pre-existing condition (low back pain, headache, fibromyalgia, and rheumatoid arthritis) or as a direct consequence of pregnancy (weight gain, postural changes, pelvic floor dysfunction, hormonal factors). However, chronic pain management during pregnancy and lactation remains a challenge for clinicians and pregnant women are at risk of undertreatment for painful conditions, because of fear about use of drugs during pregnancy. Few analgesic drugs have been demonstrated to be absolutely contraindicated during pregnancy and breastfeeding, but studies in pregnant women are not available for most of pain medications. The aim of this paper is to review the safety profile in pregnancy or lactation of the commonly prescribed pain medications and non-pharmacological treatments. In addition to the conventional classifications from the Food and Drug Administration and the American Academy of Paediatrics, authors analyzed the currently available clinical data from literature.

  14. Splenic implant preservation after conservation in lactated Ringer´s solution

    Directory of Open Access Journals (Sweden)

    ARGOS SOARES DE MATOS FILHO

    2018-02-01

    Full Text Available ABSTRACT Objective: to evaluate the morphology and function of autogenous splenic tissue implanted in the greater omentum, 24 hours after storage in Ringer-lactate solution. Methods: we divided 35 male rats into seven groups (n=5: Group 1: no splenectomy; Group 2: total splenectomy without implant; Group 3: total splenectomy and immediate autogenous implant; Group 4: total splenectomy, preservation of the spleen in Ringer-lactate at room temperature, then sliced and implanted; Group 5: total splenectomy, spleen sliced and preserved in Ringer-lactate at room temperature before implantation; Group 6: total splenectomy with preservation of the spleen in Ringer-lactate at 4°C and then sliced and implanted; Group 7: total splenectomy and the spleen sliced for preservation in Ringer-lactate at 4°C before implantation. After 90 days, we performed scintigraphic studies with Tc99m-colloidal tin (liver, lung, spleen or implant and clot, haematological exams (erythrogram, leucometry, platelets, biochemical dosages (protein electrophoresis and anatomopathological studies. Results: regeneration of autogenous splenic implants occurred in the animals of the groups with preservation of the spleen at 4ºC. The uptake of colloidal tin was higher in groups 1, 3, 6 and 7 compared with the others. There was no difference in hematimetric values in the seven groups. Protein electrophoresis showed a decrease in the gamma fraction in the group of splenectomized animals in relation to the operated groups. Conclusion: the splenic tissue preserved in Ringer-lactate solution at 4ºC maintains its morphological structure and allows functional recovery after being implanted on the greater omentum.

  15. Splenic implant preservation after conservation in lactated Ringer´s solution.

    Science.gov (United States)

    Matos Filho, Argos Soares DE; Petroianu, Andy; Cardoso, Valbert Nascimento; Vidigal, Paula Vieira Teixeira

    2018-01-01

    to evaluate the morphology and function of autogenous splenic tissue implanted in the greater omentum, 24 hours after storage in Ringer-lactate solution. we divided 35 male rats into seven groups (n=5): Group 1: no splenectomy; Group 2: total splenectomy without implant; Group 3: total splenectomy and immediate autogenous implant; Group 4: total splenectomy, preservation of the spleen in Ringer-lactate at room temperature, then sliced ​​and implanted; Group 5: total splenectomy, ​​spleen sliced and preserved in Ringer-lactate at room temperature before implantation; Group 6: total splenectomy with preservation of the spleen in Ringer-lactate at 4°C and then sliced ​​and implanted; Group 7: total splenectomy and the spleen sliced for preservation in Ringer-lactate at 4°C before implantation. After 90 days, we performed scintigraphic studies with Tc99m-colloidal tin (liver, lung, spleen or implant and clot), haematological exams (erythrogram, leucometry, platelets), biochemical dosages (protein electrophoresis) and anatomopathological studies. regeneration of autogenous splenic implants occurred in the animals of the groups with preservation of the spleen at 4ºC. The uptake of colloidal tin was higher in groups 1, 3, 6 and 7 compared with the others. There was no difference in hematimetric values ​​in the seven groups. Protein electrophoresis showed a decrease in the gamma fraction in the group of splenectomized animals in relation to the operated groups. the splenic tissue preserved in Ringer-lactate solution at 4ºC maintains its morphological structure and allows functional recovery after being implanted on the greater omentum.

  16. Weter consumption during pregnancy and lactation

    OpenAIRE

    Figueroa Damián Ricardo; Beltrán Montoya Jorge; Espino y Sosa Salvador

    2014-01-01

    During pregnancy, water is retained partially owing to an increase in vasopressin production. Ingested water is used to produce amniotic fluid. Climate conditions and physical activity, gestational nausea and vomit, and a higher caloric intake, increases water needs; during lactation, more water is needed to produce milk. Dehydration during pregnancy is especially dangerous; it must be avoided. Physiological changes during pregnancy modify water metabolism: blood volume and glomerular filtrat...

  17. Is Lactate an undervalued functional component of lactic acid bacteria-fermented food products?

    Directory of Open Access Journals (Sweden)

    Graciela eGarrote

    2015-06-01

    Full Text Available Although it has been traditionally regarded as an intermediate of carbon metabolism and major component of fermented dairy products contributing to organoleptic and antimicrobial properties of food, there is evidence gathered in recent years that lactate has bioactive properties that may be responsible of broader properties of functional foods. Lactate can regulate critical functions of several key players of the immune system such as macrophages and dendritic cells, being able to modulate inflammatory activation of epithelial cells as well. Intraluminal levels of lactate derived from fermentative metabolism of lactobacilli have been shown to modulate inflammatory environment in intestinal mucosa. The molecular mechanisms responsible to these functions, including histone deacetylase dependent-modulation of gene expression and signalling through G-protein coupled receptors have started to be described. Since lactate is a major fermentation product of several bacterial families with probiotic properties, we here propose that it may contribute to some of the properties attributed to these microorganisms and in a larger view, to the properties of food products fermented by lactic acid bacteria.

  18. Weter consumption during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Figueroa Damián Ricardo

    2014-07-01

    Full Text Available During pregnancy, water is retained partially owing to an increase in vasopressin production. Ingested water is used to produce amniotic fluid. Climate conditions and physical activity, gestational nausea and vomit, and a higher caloric intake, increases water needs; during lactation, more water is needed to produce milk. Dehydration during pregnancy is especially dangerous; it must be avoided. Physiological changes during pregnancy modify water metabolism: blood volume and glomerular filtration rate increase; more water is lost trhough sweating and respiration. Placenta con- tains up to 500 mL of water, and there are between 500-1,200 mL of amniotic fluid. Different studies recommend a total water intake of 2,700-4,800 mL/day during pregnancy, of which 1,470-2,370 should be beverages and water. For the Mexican population, the recommendation is 3,000 mL/day. Based on energy intake and the rule of 1-1.5 mL of water per kcal, water intake must increase in at least 300 mL/day at the beginning of the third pregnancy trimester. During lactation the recommended intake is of 3-3.6 L/ day, depending on age. Obesity and overweight during pregnancy are a major health problem, to which sugary beverages contribute. Water must be considered the best choice for hydration during pregnancy and lactation.

  19. Lactation studies of anticonvulsants: a quality review.

    Science.gov (United States)

    van der Meer, Douwe H; Wieringa, Andre; Wegner, Ilse; Wilffert, Bob; Ter Horst, Peter G J

    2015-04-01

    The aim of this review was to investigate the quality of the current literature on the transfer of anticonvulsants to breast milk to provide an overview of which anticonvulsants are in need of further research. We reviewed the quality of the available lactation studies for 19 anticonvulsants against the guidelines of the Food and Drug Administration (FDA) and the International Lactation Consultant Association (ILCA). Except for one study on lamotrigine and one case report on gabapentin, no study on anticonvulsants had both the absolute infant dose (AID) and milk to plasma ratio (M : P) correctly assessed. Only one study on carbamazepine, phenytoin and vigabatrin was found that correctly assessed the AID. The main cause for this low number is the lack of essential details in published studies, since 25 of 62 studies were case reports, letters or abstracts. Other major shortcomings were the lack of information on sampling methods, the number of samples in a particular dose interval as well as the low number of study participants. The quality of the current literature on the transfer of anticonvulsants to breast milk is low, except for lamotrigine, which makes it hard to draw conclusions about the safety of the use of anticonvulsants during the lactation period. Therefore, further research is needed. © 2014 The British Pharmacological Society.

  20. A novel continuous subcutaneous lactate monitoring system.

    Science.gov (United States)

    Poscia, A; Messeri, D; Moscone, D; Ricci, F; Valgimigli, F

    2005-05-15

    A novel continuous lactate monitoring system has been developed modifying the GlucoDay portable medical device (A. Menarini Diagnostics), already present in the European market, and used to continuously measure glucose levels. Lactate oxidase based biosensors have been developed immobilising the enzyme on nylon net and placing it on a Pt electrode. The biosensor was connected to the portable device provided with a micro-pump and coupled to a microdialysis system. It is capable to record subcutaneous lactate every 3 min. In vitro analytical results confirmed that the sensors respond linearly in the interval of concentration between 0.1 and 10 mmol/L, covering the whole physiological range. During prolonged monitoring periods, the response of the biosensors remained stable, showing a limited drift of 8%, within 60 h. Stability tests are still on route. However, preliminary results have shown a shelf life of about 10 months. In vivo experiments performed on healthy rabbits have demonstrated the good accuracy and reproducibility of the system. A correlation coefficient equal to 0.9547 (N=80) was found, which represents a good correlation between the GlucoDay and the laboratory reference analyser. A 16 h in vivo monitoring on a healthy volunteer has been also performed.

  1. Microbial Community Dynamics of Lactate Enriched Hanford Groundwaters

    International Nuclear Information System (INIS)

    Mosher, Jennifer J.; Drake, Meghan M.; Carroll, Susan L.; Yang, Zamin K.; Schadt, Christopher W.; Brown, Stephen D.; Podar, Mircea; Hazen, Terry C.; Arkin, Adam P.; Phelps, Tommy J.; Palumbo, Anthony V.; Faybishenko, Boris A.; Elias, Dwayne A.

    2010-01-01

    The Department of Energy site at Hanford, WA, has been historically impacted by U and Cr from the nuclear weapons industry. In an attempt to stimulate microbial remediation of these metals, in-situ lactate enrichment experiments are ongoing. In order to bridge the gap from the laboratory to the field, we inoculated triplicate anaerobic, continuous-flow glass reactors with groundwater collected from well Hanford 100-H in order to obtain a stable, enriched community while selecting for metal-reducing bacteria. Each reactor was fed from a single carboy containing defined media with 30 mM lactate at a rate of 0.223 ml/min under continuous nitrogen flow at 9 ml/min. Cell counts, organic acids, gDNA (for qPCR and pyrosequencing) and gases were sampled during the experiment. Cell counts remained low (less than 1x107 cells/ml) during the first two weeks of the experiment, but by day 20, had reached a density greater than 1x108 cells/ml. Metabolite analysis showed a decrease in the lactate concentrations over time. Pyruvate concentrations ranged from 20-40 uM the first week of the experiment then was undetectable after day 10. Likewise, formate appeared in the reactors during the first week with concentrations of 1.48-1.65 mM at day 7 then the concentrations decreased to 0.69-0.95 on day 10 and were undetectable on day 15. Acetate was present in low amounts on day 3 (0.15-0.33 mM) and steadily increased to 3.35-5.22 mM over time. Similarly, carbon dioxide was present in low concentrations early on and increased to 0.28-0.35 mM as the experiment progressed. We also were able to detect low amounts of methane (10-20 uM) during the first week of the experiment, but by day 10 the methane was undetectable. From these results and pyrosequencing analysis, we conclude that a shift in the microbial community dynamics occurred over time to eventually form a stable and enriched microbial community. Comprehensive investigations such as these allow for the examination of not only which

  2. Food intake and weight of lactating rats maintained on different protein-calorie diets, and pup growth

    Directory of Open Access Journals (Sweden)

    R.P.B. Cambraia

    1997-08-01

    Full Text Available Studies on rats maintained on low-protein-calorie diets during the lactation period show that food intake decreases. This process results in weight loss and a delay in litter development. The purpose of the present study was to determine the alterations in food intake, maternal weight and litter growth during lactation when dams were exposed to diets with different levels of protein and carbohydrate. Female Wistar rats receiving one of 4 different diets, A (N = 14, B (N = 14, C (N = 9 and D (N = 9, were used. Diet A contained 16% protein and 66% carbohydrate; diet B, 6% protein and 77% carbohydrate; diet C, 6% protein and 66% carbohydrate; diet D, 16% protein and 56% carbohydrate. Thus, C and D diets were hypocaloric, while A and B were isocaloric. The intake of a low-protein diet in groups B and C affected the weight of dams and litters during the last two weeks of lactation, while the low-calorie diets limited the growth of D litters at 21 days compared with A litters, but had no effect on the weight of D dams. Group B showed an increase in intake during the first five days of lactation, resulting in a behavioral calorie compensation due to the increase in carbohydrate content, but the intake decreased during the last part of lactation. Food intake regulation predominantly involves the recruitment of a variety of peripheral satiety systems that attempt to decrease the central feeding command system.

  3. Structurally Integrated Photoluminescence-Based Lactate Sensor Using Organic Light Emitting Devices (OLEDs) as the Light Source

    International Nuclear Information System (INIS)

    Chengliang Qian

    2006-01-01

    Multianalyte bio(chemical) sensors are extensively researched for monitoring analytes in complex systems, such as blood serum. As a step towards developing such multianalyte sensors, we studied a novel, structurally integrated, organic light emitting device (OLED)-based sensing platform for detection of lactate. Lactate biosensors have attracted numerous research efforts, due to their wide applications in clinical diagnosis, athletic training and food industry. The OLED-based sensor is based on monitoring the oxidation reaction of lactate, which is catalyzed by the lactate oxidase (LOX) enzyme. The sensing component is based on an oxygen-sensitive dye, Platinum octaethyl porphyrin (PtOEP), whose photoluminescence (PL) lifetime τ decreases as the oxygen level increases. The PtOEP dye was embedded in a thin film polystyrene (PS) matrix; the LOX was dissolved in solution or immobilized in a sol-gel matrix. τ was measured as a function of the lactate concentration; as the lactate concentration increases, τ increases due to increased oxygen consumption. The sensors performance is discussed in terms of the detection sensitivity, dynamic range, and response time. A response time of ∼32 sec was achieved when the LOX was dissolved in solution and kept in a closed cell. Steps towards development of a multianalyte sensor array using an array of individually addressable OLED pixels were also presented

  4. High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

    Science.gov (United States)

    Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

    2013-01-01

    The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

  5. Structurally Integrated Photoluminescence-Based Lactate Sensor Using Organic Light Emitting Devices (OLEDs) as the Light Source

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Chengliang [Iowa State Univ., Ames, IA (United States)

    2006-01-01

    Multianalyte bio(chemical) sensors are extensively researched for monitoring analytes in complex systems, such as blood serum. As a step towards developing such multianalyte sensors, we studied a novel, structurally integrated, organic light emitting device (OLED)-based sensing platform for detection of lactate. Lactate biosensors have attracted numerous research efforts, due to their wide applications in clinical diagnosis, athletic training and food industry. The OLED-based sensor is based on monitoring the oxidation reaction of lactate, which is catalyzed by the lactate oxidase (LOX) enzyme. The sensing component is based on an oxygen-sensitive dye, Platinum octaethyl porphyrin (PtOEP), whose photoluminescence (PL) lifetime τ decreases as the oxygen level increases. The PtOEP dye was embedded in a thin film polystyrene (PS) matrix; the LOX was dissolved in solution or immobilized in a sol-gel matrix. τ was measured as a function of the lactate concentration; as the lactate concentration increases, τ increases due to increased oxygen consumption. The sensors performance is discussed in terms of the detection sensitivity, dynamic range, and response time. A response time of ~32 sec was achieved when the LOX was dissolved in solution and kept in a closed cell. Steps towards development of a multianalyte sensor array using an array of individually addressable OLED pixels were also presented.

  6. Effect of sodium lactate /sodium diacetate in combination with sodium nitrite on physiochemical, microbial properties and sensory evaluation of cow sausage

    Directory of Open Access Journals (Sweden)

    Habib Sedghi

    2014-11-01

    Full Text Available Sodium nitrite has been always considered as one of the common additives due to its antibacterial effects on Clostridium botulinum and meat products' color, however it produces cancer creating nitrosamine. Recently, organic acids and their salts such as lactates have been employed as antimicrobial compounds. Lactates also improve organileptic properties including color, texture and taste and antioxidant properties. Sodium lactate causes to more reduction of anaerobic spore former bacteria than nitrite, inhibits botulin produced by Clostridium botulinum. Sodium lactate produces a permanent reddish pink color through reduction of deoxymygloboline and producing deoxymyoglobuline. In this study, the decrease of sodium nitrite amount from 120ppm to 15ppm by adding sodium lactate / sodium diacetate led to achieve an acceptable product. The best results revealed through adding 3.0625% of sodium lactate / sodium diacetate in combination with 30ppm sodium nitrite. Results also exhibited more reduction of pathogens' growth than nitrite, enhanced flavor slightly, but unable to produce reddish pink color as produced by nitrite. Results also exhibited that sodium lactate / diacetate cause to retard in microbial growth, reducing chemical change, enhance sensory properties, partially improvement in taste and texture. Although inappropriate color demonstrated sodium lactate / diacetate's inability in red pink color production in 4th sample (contains 15 ppm nitrite, its synergy effect in combination with sodium nitrite on nitroso myoglobuline production has been proven, led to sodium nitrite reduction in sausages.

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

    Science.gov (United States)

    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.

  8. Response of primiparous and multiparous buffaloes to yeast culture supplementation during early and mid-lactation

    Directory of Open Access Journals (Sweden)

    Hanne H. Hansen

    2017-12-01

    Full Text Available Strains of live Saccharomyces cerevisiae yeast have exhibited probiotic effects in ruminants. This study investigated the effects of the dietary yeast supplement, S. cerevisiae (Yea-Sacc1026, on primiparous (PP and multiparous (MP Egyptian buffaloes in early to mid-lactation. Lactating buffaloes were fed either a basal total mixed ration (TMR, control; 4 PP and 8 MP or the basal TMR plus 10 g Yea-Sacc1026 per buffalo cow per day (yeast; 4 PP and 8 MP. The feeds were given from 15 days prepartum to 180 days postpartum. Feed intake, body weight, and milk yields (MY were recorded, and milk and blood samples were collected for analyses. Feces were collected from days 45 to 47 during early lactation and from days 90 to 92 during mid-lactation to determine apparent digestibility of dry matter (DM, organic matter (OM, crude protein (CP and crude fiber (CF. Energy corrected milk yield (ECM, feed conversion, and energy and nitrogen conversion efficiency were calculated. Yeast treated MP buffaloes consumed more DM (P ≤ 0.041 and CP than the untreated control group. Apparent digestibility of DM and OM were significantly greater at mid-lactation for treated versus control group (P = 0.001. Crude fiber digestibility was greater in MP than in PP buffaloes (P = 0.049, and yeast supplemented MP cows had a greater CF digestibility than control MP buffaloes at mid-lactation (P = 0.010. Total blood lipids decreased after yeast supplementation (P = 0.029. Milk yields, ECM, fat and protein yields increased for yeast treated MP buffaloes (P ≤ 0.039. The study concluded that the response to yeast supplementation in buffalo cows is parity dependent. Multiparous buffaloes respond to yeast supplementation with an increased DM intake and CF digestibility without significant weight gains, allowing a greater ECM yield with less fat mobilization. Supplementing buffaloes with yeast culture may increase milk production in early lactation and results in a

  9. Importance of measuring lactate levels in children with sepsis.

    Science.gov (United States)

    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.

  10. Computed exercise plasma lactate concentrations: A conversion formula

    Directory of Open Access Journals (Sweden)

    Lia Bally

    2016-04-01

    Full Text Available Objectives: Blood lactate measurements are common as a marker of skeletal muscle metabolism in sport medicine. Due to the close equilibrium between the extracellular and intramyocellular space, plasma lactate is a more accurate estimate of muscle lactate. However, whole blood-based lactate measurements are more convenient in field use. The purpose of this investigation was therefore (1 to establish a plasma-converting lactate formula for field use, and (2 to validate the computed plasma lactate levels by comparison to a laboratory standard method. Design and methods: A total of 91 venous samples were taken from 6 individuals with type 1 diabetes during resting and exercise conditions and assessed for whole blood and plasma lactate using the YSI 2300 analyzer. A linear model was applied to establish a formula for converting whole blood lactate to plasma lactate. The validity of computed plasma lactate values was assessed by comparison to a laboratory standard method. Results: Whole blood YSI lactate could be converted to plasma YSI values (slope 1.66, intercept 0.12 for samples with normal hematocrit. Computed plasma levels compared to values determined by the laboratory standard method using Passing-Bablok regression yielded a slope of 1.03 (95%CI:0.99:1.08 with an intercept of -0.11 (95%CI:-0.18:-0.06. Conclusions: Whole blood YSI lactate values can be reliably converted into plasma values which are in line with laboratory determined plasma measurements. Keywords: Lactate, Plasma vs whole-blood, Hematocrit, Enzyme electrodes, Sample treatment

  11. Fatigue and changes of ATP, creatine phosphate, and lactate during the 400-m sprint.

    Science.gov (United States)

    Hirvonen, J; Nummela, A; Rusko, H; Rehunen, S; Härkönen, M

    1992-06-01

    Fatigue during the 400-m sprint was studied by measuring muscle ATP, creatine phosphate (CP), lactate (M-La), and blood lactate (B-La) in six male runners before and after four experimental sprints (100, 200, 300, and 400 m). During the first 100 m, muscle CP decreased from 15.8 +/- 1.7 to 8.3 +/- 0.3 mmol/kg while M-La increased to 3.6 +/- 0.4 mmol/kg. After 200 m the CP had decreased to 6.5 +/- 0.5 mmol/kg and M-La had increased to 8.3 +/- 1.1 mmol/kg. At the end of the 400 meters, ATP and CP concentrations had decreased by 27% and 89%, respectively, and M-La had increased to 17.3 +/- 0.9 mmol/kg. It was concluded that after 200 m the speed of running decreased, although CP was not depleted and lactate concentration was not at maximum level. Complete fatigue occurred when CP stores were depleted and B-La and M-La attained an individual maximum.

  12. Astrocytes take the stage in a tale of signaling-metabolism coupling

    DEFF Research Database (Denmark)

    Bak, Lasse K

    2017-01-01

    Astrocytes are crucial cells in the brain that are intimately coupled with neuronal metabolism. A new paper from San Martín et al. provides evidence that physiological levels of the gaseous signal molecule NO can rapidly and reversibly increase astrocyte metabolism of glucose and production...... of lactate. A proposed neurological coupling-from the potential source of NO, endothelial cells, to the potential beneficiary from the lactate, neurons-prompts new questions regarding the controversial role of lactate in the brain....

  13. Effects of two months training on blood lactate levels in adolescent swimmers

    Directory of Open Access Journals (Sweden)

    T Atan

    2010-06-01

    Full Text Available The aim of this study is to examine the effects of two months swimming training on aerobic and anaerobic capacities with blood lactate. A total of 17 adolescent male swimmers (15.17±0.81 years were included in the study. The first measurement was conducted 1.5 months after the beginning of the season and this was followed by a second measurement conducted two months after the first measurement. A test protocol of 8x100 m crawl style was applied in the measurements and the subjects swam from slow to fast at five different swimming workloads. Between each training run, blood samples were provided from the earlobes of the subjects in order to measure the amount of blood lactate. Heart rate was measured after five swims. Furthermore, swimming styles and duration were recorded in order to calculate the swimming speed of each subject at each swimming workload. The comparison of blood lactate and speed values of all subjects before and after the training season revealed that lactate acid values had not changed significantly (p>0.05 at the lowest swimming workload (75% and that the speed had significantly increased (p<0.01. As for the rest of the swimming workloads, both lactate acid and speed increased significantly (p<0.05 and p<0.01. Our two month training programme dwelt heavily upon anaerobic training and accordingly aerobic capacity decreased and anaerobic capacity increased at higher speeds. On the other hand, in our study, we found out that anaerobic capacity had not increased only at the 75% workload and that it had decreased at the rest of the workloads.

  14. Augmented β-Cell Function and Mass in Glucocorticoid-Treated Rodents Are Associated with Increased Islet Ir-β/AKT/mTOR and Decreased AMPK/ACC and AS160 Signaling

    Directory of Open Access Journals (Sweden)

    André O. P. Protzek

    2014-01-01

    Full Text Available Glucocorticoid (GC therapies may adversely cause insulin resistance (IR that lead to a compensatory hyperinsulinemia due to insulin hypersecretion. The increased β-cell function is associated with increased insulin signaling that has the protein kinase B (AKT substrate with 160 kDa (AS160 as an important downstream AKT effector. In muscle, both insulin and AMP-activated protein kinase (AMPK signaling phosphorylate and inactivate AS160, which favors the glucose transporter (GLUT-4 translocation to plasma membrane. Whether AS160 phosphorylation is modulated in islets from GC-treated subjects is unknown. For this, two animal models, Swiss mice and Wistar rats, were treated with dexamethasone (DEX (1 mg/kg body weight for 5 consecutive days. DEX treatment induced IR, hyperinsulinemia, and dyslipidemia in both species, but glucose intolerance and hyperglycemia only in rats. DEX treatment caused increased insulin secretion in response to glucose and augmented β-cell mass in both species that were associated with increased islet content and increased phosphorylation of the AS160 protein. Protein AKT phosphorylation, but not AMPK phosphorylation, was found significantly enhanced in islets from DEX-treated animals. We conclude that the augmented β-cell function developed in response to the GC-induced IR involves inhibition of the islet AS160 protein activity.

  15. Effect of ambient temperature and sodium bicarbonate supplementation on water and electrolyte balances in dry and lactating Holstein cows.

    Science.gov (United States)

    Khelil-Arfa, H; Faverdin, P; Boudon, A

    2014-01-01

    The aim of this study was to quantify the effect of the interaction between 2 constant ambient temperatures [thermoneutrality (TN; 15°C) and high temperature (HT; 28°C)] and 2 levels of Na bicarbonate supplementation [calculated to provide diet Na contents of 0.20%DM (Na-) and 0.50%DM (Na+)] on water partitioning in dairy cows. Treatments were compared on 4 dry and 4mid-lactation Holstein cows according to 2 Latin squares (1 for each physiological stage) over the course of 4 periods of 15d. Diets consisted of a total mixed ration based on maize silage. Dry cows were restricted to their protein and energy requirements, whereas lactating cows were fed ad libitum. The daily average temperature-humidity index was 59.4 for TN and 73.2 for HT. Lactating and dry cows had higher vaginal temperatures at HT than at TN, but the increase was more pronounced in lactating cows (+1.05 vs. +0.12°C for vaginal temperature, respectively). Dry matter intake (DMI) of lactating cows decreased by 2.3kg/d at HT. Free water intake (FWI) and estimated volume of water lost to evaporation increased at HT in both lactating and dry cows; no interactions were observed between temperature and physiological stage. When expressed as a proportion of DMI, the increase in evaporation that occurred with increasing temperature was completely compensated for by an increase in FWI for both physiological stages. The urinary water excretion increased slightly at HT in lactating cows but not in dry cows, which may be related to the low chloride content of the offered diet. High Na supplementation increased DMI slightly in lactating cows, but milk yield was not affected. Sodium supplementation did not limit the decrease in DMI observed in lactating cows at HT; this observation is likely due to the high diet electrolyte balance of the offered diets. Sodium supplementation increased FWI in lactating cows and urinary flow in both physiological states. The interaction between ambient temperature and Na

  16. Oxytocin and prolactin suppress cortisol responses to acute stress in both lactating and non-lactating sheep.

    Science.gov (United States)

    Cook, C J

    1997-08-01

    Cortisol response to stress appears to differ between lactating and non-lactating animals. Lactating (14 d post partum) and non-lactating sheep were fitted with probes so that drugs and hormones could be infused directly into the posterior pituitary and paraventricular nucleus of the hypothalamus. The animals were also fitted with instruments to allow monitoring of heart rate, body temperature and blood cortisol levels. Their reactions to a source of acute stress (a barking dog) were then followed, with or without drug and hormone manipulation. Results in both lactating and non-lactating animals indicated shortcomings in the use of cortisol as a stress indicator. Infusing prolactin and oxytocin into either the posterior pituitary or the paraventricular nucleus of the hypothalamus suppressed cortisol responsiveness to stress in both lactating and non-lactating animals (the latter to a greater extent). In the absence of drugs, lactating animals had a slightly higher basal level of cortisol and a lower cortisol response to stress than their non-lactating counterparts. Despite suppression of cortisol responses, with or without drugs, other indicators of stress still changed with the presence of a barking dog, suggesting the complexity of control involved in stress responses.

  17. 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects.

    Science.gov (United States)

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Chung, S P; Diem, T H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-02-01

    Oxidative stress-energy depletion therapy using oxidative stress induced by D-amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner.

  18. Daidzein enhances immune function in late lactation cows under heat stress.

    Science.gov (United States)

    Liu, De-Yi; He, Shao-Jun; Liu, Shi-Qing; Tang, Yi-Guo; Jin, Er-Hui; Chen, Hui-Liang; Li, Sheng-He; Zhong, Liang-Ting

    2014-01-01

    Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress. © 2013 Japanese Society of Animal Science.

  19. The hypothalamic paraventricular nucleus has a pivotal role in regulation of prolactin release in lactating rats.

    Science.gov (United States)

    Kiss, J Z; Kanyicska, B; Nagy, G Y

    1986-08-01

    The affect of paraventricular nucleus (PVN) lesions on PRL secretory response to suckling was studied in adult female rats. Basal levels of PRL were similar in the control and lesioned groups. Substantial decreases in PRL levels occurred after separation of pups from their mothers in the control as well as lesioned animals. When mothers and pups were reunited, the circulating PRL concentrations of the control groups rose immediately from basal values of 50-100 micrograms/liter to reach peaks of 450-550 micrograms/liter. PVN lesions significantly decreased the suckling-induced rise of PRL levels. Furthermore, PVN lesions abolished the high amplitude, episodic pattern of PRL release in continuously lactating rats. These findings are consistent with the view that PVN neurons produce PRL releasing factor(s), which is (are) required for normal secretory patterns of PRL in lactating rats.

  20. Effects of accelerated electrons and microwaves on frozen enzyme lactate dehydrogenase

    International Nuclear Information System (INIS)

    Hategan, A.; Martin, D.; Popescu, L.M.; Butan, C.

    2000-01-01

    Results on the influence of 6 MeV electron beam irradiation and 2.45 GHz 565 W microwaves as well as the effects of the combined electron and microwave irradiation, at - 21 deg. C, on enzyme lactate dehydrogenase are presented. The microwave irradiated macromolecules exhibited a non-linear behaviour (successive activation and inactivation of the enzyme molecules) suggesting the major influence of the nonthermal component of microwave radiation. The combined electron and microwave irradiation lead to a similar decrease of the activity as the electron beam irradiation, the microwave influence being apparently insignificant in the dose, power and time ranges used. Radiation target analysis of the enzymatic decrease due to electron irradiation indicated very large aggregation of the enzyme molecules. Our data suggest that radiation target analysis is not suitable to measure the molecular mass of lactate dehydrogenase, when irradiating frozen enzyme suspensions. (authors)

  1. Simultaneous detection of lactate and glucose by integrated printed circuit board based array sensing chip

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xuelian [Institute for Clean Energy and Advanced Materials, Southwest University, Chongqing 400715 (China); School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Zang, Jianfeng [Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708 (United States); Liu, Yingshuai; Lu, Zhisong [Institute for Clean Energy and Advanced Materials, Southwest University, Chongqing 400715 (China); Li, Qing, E-mail: Qli@swu.edu.cn [School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Li, Chang Ming, E-mail: ecmli@swu.edu.cn [Institute for Clean Energy and Advanced Materials, Southwest University, Chongqing 400715 (China)

    2013-04-10

    Highlights: ► An integrated printed circuit board (PCB) based array sensing chip was developed. ► Simultaneous detection of lactate and glucose in serum has been demonstrated. ► The array electronic biochip has high signal to noise ratio and high sensitivity. ► Additional electrodes were designed on the chip to correct interferences. -- Abstract: An integrated printed circuit board (PCB) based array sensing chip was developed to simultaneously detect lactate and glucose in mouse serum. The novelty of the chip relies on a concept demonstration of inexpensive high-throughput electronic biochip, a chip design for high signal to noise ratio and high sensitivity by construction of positively charged chitosan/redox polymer Polyvinylimidazole-Os (PVI-Os)/carbon nanotube (CNT) composite sensing platform, in which the positively charged chitosan/PVI-Os is mediator and electrostatically immobilizes the negatively charged enzyme, while CNTs function as an essential cross-linker to network PVI-Os and chitosan due to its negative charged nature. Additional electrodes on the chip with the same sensing layer but without enzymes were prepared to correct the interferences for high specificity. Low detection limits of 0.6 μM and 5 μM were achieved for lactate and glucose, respectively. This work could be extended to inexpensive array sensing chips with high sensitivity, good specificity and high reproducibility for various sensor applications.

  2. Lactate metabolism during exercise in patients with mitochondrial myopathy

    DEFF Research Database (Denmark)

    Jeppesen, Tina Dysgaard; Ørngreen, Mette Cathrine; van Hall, Gerrit

    2013-01-01

    Patients with mitochondrial DNA mutations often have elevated plasma lactate at rest and during exercise, but it is unknown whether the high lactate levels are caused by a high production, an impaired oxidation or a combination. We studied lactate kinetics in 10 patients with mtDNA mutations and 10...... matched healthy control subjects at rest and during cycle exercise with a combination of femoral arterio-venous differences of lactate, and lactate tracer dilution methodology. During exercise, lactate concentration and production rates were several-fold higher in patients, but despite mitochondrial...... is not solely an indicator of impaired oxidative capacity, but an important fuel for oxidative metabolism, even in muscle with severely impaired mitochondrial function....

  3. The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep.

    Science.gov (United States)

    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

  4. Maternal lactation for preterm newborn infants.

    Science.gov (United States)

    Aguayo, J

    2001-11-01

    In recent decades, neonatologists have made considerable progress in life support techniques, especially in the treatment and prevention of respiratory disorders, which has led to a higher neonatal survival rate. Research into neonatal nutrition has also produced great benefits. It has been found that one of the key points regarding the improved survival rate of infants is the necessity for nutrition that is both adequate and as natural as possible. In this respect, it is necessary to achieve a better understanding of the process, protection, support and maintenance of maternal lactation in neonatal units. Humanization of perinatal attention during delivery, respect for the rights of parents and their children, protection of the mother and child bonding process, early skin contact with the mother and greater attention to individualized care are all key factors in the reinforcement of maternal lactation and are issues that must be addressed within the field of neonatology. Research activities need to concern themselves with: (1) acquiring greater knowledge concerning the common problems and difficulties that arise with mothers and their preterm babies; (2) training healthcare professionals in these aspects, for example in the extraction and storage of milk and in improving techniques of emotional and communicational skills; (3) by means of specific programmes such as the setting up of support groups, so that the effort made to encourage the initiation of breastfeeding is justified by its continuation for as long as possible. Thus, we hope to establish standards of care based on starting, encouraging and prolonging maternal lactation, in sufficient quantity and quality, always remembering that the fundamental goal of our research is the well-being of the child and its family.

  5. Lactation and changes in maternal metabolic risk factors.

    Science.gov (United States)

    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; Pdecrements 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 (Pdecrement 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.

  6. Brain lactate metabolism in humans with subarachnoid hemorrhage.

    Science.gov (United States)

    Oddo, Mauro; Levine, Joshua M; Frangos, Suzanne; Maloney-Wilensky, Eileen; Carrera, Emmanuel; Daniel, Roy T; Levivier, Marc; Magistretti, Pierre J; LeRoux, Peter D

    2012-05-01

    Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) 119 μmol/L) versus nonhyperglycolytic. Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

  7. Brain Lactate Metabolism in Humans With Subarachnoid Hemorrhage

    OpenAIRE

    Oddo M; Levine JM; Frangos S; Maloney-Wilensky E; Carrera E; Daniel RT; Levivier M; Magistretti PJ; LeRoux PD

    2012-01-01

    Abstract BACKGROUND AND PURPOSE: Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. METHODS: Thirty one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxi...

  8. Effect of pretreatment female lactating rats with albendazole on preventing developmental and neurobehavioral toxicity of enrofloxacin in suckling pups

    Directory of Open Access Journals (Sweden)

    M. K. Shindala

    2012-01-01

    Full Text Available The aim of the present study was to evaluated the effect of treated female lactating rats with enrofloxacin alone and itsinteraction with albendazole on the occurrence of developmental and neurobehavioral toxicity in suckling pups by usingpercentage of survival of pups to weaning as well as neurobehavioral test (surface righting reflex. The exposure of sucklingpups to enrofloxacin alone through the milk caused sever toxic effects manifested by significant decrease in percentage ofsurvival in pups to weaning to (0% as result from death all pups from dams were treated with enrofloxacin at high dose (480mg/kg, i.m. during the first 5 days of lactation. Whereas, treated lactating female rats with albendazole at (300 mg/kg, orally,1 hour before enrofloxacin (480 mg/kg, i.m. during the first 5 days of lactation protected suckling pups from developmentaltoxic effects of enrofloxacin which mainly appeared as a significant increase in percentage of survival of pups to 100% asresult from survival all suckling pups to weaning, accompanied by preventing the neurobehavioral toxicity of enrofloxacin insuckling pups manifested by highly significant decreased response time to surface righting reflex to (2.64 ± 0.57 minuets inthe postnatal day 3 in compared with pups from dams that treated with enrofloxacin alone which reached to (15.82 ± 0.27minuets. In conclusion, our results suggest that pretreatment of female lactating rats with albendazole protecte suckling pupsfrom developme-ntal and neurobehavioral toxicity of enrofloxacin.

  9. Role of lactate in ischemic acidosis

    International Nuclear Information System (INIS)

    Nagai, Y.; Naruse, S.; Vink, R.; Weiner, M.W.

    1987-01-01

    Brain ischemia produces cerebral acidosis that is associated with a rise in lactic acid levels. It is generally thought that the acidosis is due to lactic acid. To investigate this, rats were made hypoglycemic with insulin and the cerebral ischemia was produced. P-31 MR imaging and H-1 MR spectroscopy were used to measure pH and lactate. Hypoclygemia inhibited the rise in lactic acid levels but did not affect pH. Therefore, the fall in pH produced by cerebral ischemia cannot be due to lactic acidosis

  10. A Rare Cause of Postpartum Low Back Pain: Pregnancy- and Lactation-Associated Osteoporosis

    OpenAIRE

    Terzi, Rabia; Terzi, Hasan; Özer, Tülay; Kale, Ahmet

    2014-01-01

    Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis. It results in severe low back pain in the last trimester of pregnancy and in the postpartum period, decreases in height, and fragility fractures, particularly in the vertebra. The current case report presents a 32-year-old patient who presented with back and low back pain that began in the last trimester of the pregnancy and worsened at two months postpartum and who was diagnosed with pregnancy- and lactati...

  11. Combat Stress Decreases Memory of Warfighters in Action.

    Science.gov (United States)

    Delgado-Moreno, Rosa; Robles-Pérez, José Juan; Clemente-Suárez, Vicente Javier

    2017-08-01

    The present research aimed to analyze the effect of combat stress in the psychophysiological response and attention and memory of warfighters in a simulated combat situation. Variables of blood oxygen saturation, heart rate, blood glucose, blood lactate, body temperature, lower body muscular strength manifestation, cortical arousal, autonomic modulation, state anxiety and memory and attention through a postmission questionnaire were analyzed before and after a combat simulation in 20 male professional Spanish Army warfighters. The combat simulation produces a significant increase (p body temperature post, HF post/correct sound, body temperature post/glucose post, CFFTpre/lactate post, CFFT post/wrong sound, glucose post/AC pre, AC post/wrong fusil, AS post/SC post and SC post/wrong olfactory; and negative correlations: LF post/correct sound, body temperature post/lactate post and glucose post/lactate post. This data suggest that combat stress actives fight-flight system of soldiers. As conclusion, Combat stress produces an increased psychophysiological response that cause a selective decrease of memory, depending on the nature, dangerous or harmless of the objects.

  12. Continuous lactation effects on mammary remodeling during late gestation and lactation in dairy goats

    DEFF Research Database (Denmark)

    Safayi, Sina; Theil, Peter Kappel; Hou, Lei

    2010-01-01

    The present study aimed to 1) elucidate whether continuous milking during late gestation in dairy goats negatively affects mammary remodeling and hence milk production in the subsequent lactation, and 2) identify the regulatory factors responsible for changes in cell turnover and angiogenesis in ...

  13. Lactate and lactate dehydrogenase in predicting the severity of transient tachypnea of the newborn.

    Science.gov (United States)

    Ozkiraz, Servet; Gokmen, Zeynel; Boke, Saltuk Bugra; Kilicdag, Hasan; Ozel, Deniz; Sert, Ahmet

    2013-08-01

    Low Apgar score is strongly associated with the incidence of transient tachypnea of the newborn (TTN) and other respiratory diseases of the newborn. We aimed to investigate the relationship between hypoxia determinants and the prolonged oxygen and respiratory support requirement even if the Apgar scores were normal. Retrospective case-controlled study. Infants born after 35 weeks of gestational age with clinical signs, chest X-ray findings and clinical course consistent with TTN were included. Receiver operating characteristic curves were used to assess the predictive values of determinants in predicting the risk for prolonged oxygen requirement and mechanical ventilatory support. We showed a positive correlation between the duration of oxygen with lactate and lactate dehydrogenase (LDH) levels. LDH offered the best predictive value for prolonged oxygen requirement with a positive predictive value (PPV) of 88.9%. The predictive value of lactate exceeds the predictive value of LDH, aspartate aminotransferase, and percentage of normoblasts to predict the requirement of respiratory support with a PPV of 88.5%. Lactate and LDH might be useful for clinicians at first level hospitals for decision making to refer the TTN patient to the secondary or tertiary level neonatal intensive care unit before the clinical situation is worsened.

  14. Trends of fresh green food for lactating roe deer females

    Science.gov (United States)

    Menzel, Annette; Stahl, Benjamin; Laube, Julia

    2017-04-01

    Increasing temperatures, changed precipitation patterns as well as more intense and frequent extreme events will alter the phenology of both flora and fauna and shift species distributions. Moreover, farmers respond to climate change by adapting land use and management, and thus the cultural landscape is changing. Therefore, the health and fitness of wild animals will be largely affected by factors directly and indirectly linked to climate change. Familiar examples of mismatch due to loss of temporal synchrony in food webs are known from birds (timing of migration or egg laying in relation to food resources) and insect pollination (timing of first flights in relation to plant flowering). However, also large herbivory mammals may suffer from climate change induced phenological mismatch if they are not able to "surf on the green wave" any more. Taking roe deer (Capreolus capreolus L.) as key example, we studied changes in the spring phenology of potential food plants during the last four decades in southern Germany. Our analysis is based on the phenological observations of the German Meteorological Service as well as on the comprehensive multi-species dataset of a dedicated citizen scientist. Roe deer is sensitive to slight phenological changes of food plants, since only the first fresh green contains maximal protein contents which are needed by the females to suckle their fawns born mid of May till mid of June. We find indications for an increasing number of food plant species available in the lactation period, however probably with a decreasing food quality over the decades. Since females have delayed implantation it may be difficult to well synchronise the postnatal period to the vegetation development. A unique dataset of marked fawns suggests that also the timing of birth has slightly advanced in recent decades. We discuss these changes in the match-mismatch of lactation period of roe deer and spring leaf phenology and their driving factors in detail.

  15. Mesquite pod meal in diets for lactating goats

    Directory of Open Access Journals (Sweden)

    Taiala Cristina de Jesus Pereira

    2013-02-01

    Full Text Available The objective of this study was to evaluate the effects inclusion of 0%, 33.3%, 66.7% and 100% natural matter (NM of mesquite pod meal (MPM, in substitution of corn, on the intake, digestibility and feeding behavior of lactating Saanen goats. The forage:concentrate ratio in the diet was 40:60, using elephant grass silage as a forage source. Eight adult lactating goats with about 60 days in milk and weighting 50 kg were divided into two 4 × 4 latin squares and four 17-day experimental periods. Dry matter (DM, crude protein (CP and total digestible nutrient (TDN intakes were not influenced by MPM levels. Ether extract (0.51; 0.34; 0.36; 0.20 kg/day and non-fiber carbohydrate (NFC (0.54; 0.53; 0.49; 0.36 kg/day intakes showed a linear effect with increased MPM. Organic matter (OM and NDF intakes presented a quadratic behavior. The maximum OM intake was estimated with the replacement of 40.5%. The maximum estimated intakes for NDF were 0.665 kg/day and 14.8 g/kg body weight, with a replacement close to 60%. Nutrient digestibility coefficients and TDN levels (655.0 g/kg were not affected, except for NFC. The time spent eating, ruminating and idle was not influenced by the addition of MPM. The feeding rate of DM had a linear decrease which reflected the intake restriction. Corn replacement with MPM should not exceed 40.5%, although its total replacement does not interfere with the intake of DM, CP and TDN on the apparent digestibility of nutrients and most ingestive behavior parameters.

  16. Renal lactate elimination is maintained during moderate exercise in humans

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Dawson, Ellen A; Dalsgaard, Mads

    2012-01-01

    (2) (CaO(2)-CvO(2)) and lactate concentration differences were 0.8 ± 0.2 and 0.02 ± 0.02 mmol x L(-1), respectively. During exercise, arterial lactate and CaO(2)-CvO(2) increased to 7.1 ± 1.1 and 2.6 ± 0.8 mmol x L(-1), respectively (P renal blood flow...... with no significant change in the renal venous erythropoietin concentration (0.8 ± 1.4 U x L(-1)). The a-v lactate concentration difference increased to 0.5 ± 0.8 mmol x L(-1), indicating similar lactate elimination as at rest. In conclusion, a -70% reduction in renal blood flow does not provoke critical renal......Reduced hepatic lactate elimination initiates blood lactate accumulation during incremental exercise. In this study, we wished to determine whether renal lactate elimination contributes to the initiation of blood lactate accumulation. The renal arterial-to-venous (a-v) lactate difference...

  17. Lactate storm marks cerebral metabolism following brain trauma.

    Science.gov (United States)

    Lama, Sanju; Auer, Roland N; Tyson, Randy; Gallagher, Clare N; Tomanek, Boguslaw; Sutherland, Garnette R

    2014-07-18

    Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Lactation and Reactivity to Physical and Psychological Stress

    National Research Council Canada - National Science Library

    Carter, C

    1997-01-01

    .... Findings to date include lack of changes in attention and memory functions during pregnancy and lactation, lack of difference in hormonal and anxiety responses to psychological stress, enhanced...

  19. Calcium and bone metabolism disorders during pregnancy and lactation.

    Science.gov (United States)

    Kovacs, Christopher S

    2011-12-01

    Pregnancy and lactation cause a substantial increase in demand for calcium that is met by different maternal adaptations within each period. Intestinal calcium absorption more than doubles during pregnancy, whereas the maternal skeleton resorbs to provide most of the calcium content of breast milk during lactation. These maternal adaptations also affect the presentation, diagnosis, and management of disorders of calcium and bone metabolism. Although some women may experience fragility fractures as a consequence of pregnancy or lactation, for most women, parity and lactation do not affect the long-term risks of low bone density, osteoporosis, or fracture. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Lactation and Reactivity to Physical and Psychological Stress

    National Research Council Canada - National Science Library

    Carter, C

    1998-01-01

    .... Studies of basal cortisol levels, cognitive performance and reactivity to stressors were conducted in human subjects during late pregnancy and immediately postpartum in women that were lactating...

  1. Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May Disturb Innate and Adaptive Immune Responses

    Directory of Open Access Journals (Sweden)

    Alexandre Morrot

    2018-03-01

    Full Text Available The tumor microenvironment (TME is composed by cellular and non-cellular components. Examples include the following: (i bone marrow-derived inflammatory cells, (ii fibroblasts, (iii blood vessels, (iv immune cells, and (v extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago. One of the main products of this reprogrammed cell metabolism is lactate. “Lactagenic” or lactate-producing cancer cells are characterized by their immunomodulatory properties, since lactate, the end product of the aerobic glycolysis, besides acting as an inducer of cellular signaling phenomena to influence cellular fate, might also play a role as an immunosuppressive metabolite. Over the last 10 years, it has been well accepted that in the TME, the lactate secreted by transformed cells is able to compromise the function and/or assembly of an effective immune response against tumors. Herein, we will discuss recent advances regarding the deleterious effect of high concentrations of lactate on the tumor-infiltrating immune cells, which might characterize an innovative way of understanding the tumor-immune privilege.

  2. Relationship between season, lactation number and incidence of clinical mastitis in different stages of lactation in a Holstein dairy farm

    Directory of Open Access Journals (Sweden)

    Maede Moosavi

    2013-12-01

    Full Text Available 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.

  3. ROLE OF LACTATION IN FAMILY PLANNING

    Directory of Open Access Journals (Sweden)

    Surekha Kishore

    2010-06-01

    Full Text Available Objectives: 1. To evaluate the role of Lactational Amenorrhea Method (LAM as a spacing method. 2. To assess knowledge attitude and practices regarding breastfeeding. 3. To bring awareness regarding importance of breastfeeding on child health and as a method of family planning so that exclusive breast feeding is promoted. Study Design: Cross sectional study. Setting: In rural village of district Wardha. Study Universe : All the lactating mothers who had2 children (one of which was less than 3 years. Study Variables: Duration of Breast Feeding, LAM, Importance of Breast Feeding. Knowledge of Colostrum, Awareness of Breast Feeding, etc. Statistical analysis used: Percentages and proportions. Result: A total 42 families were included in the survey of which 26 (61.9% belongs to nuclear families with majority of the women 19(45.2% in the age group of 20-25 yrs, 20 (47.6% were illiterate and 18(42.8% families were of lower Socio Economic Status. A directly proportional relationship was found between duration of Breastfeeding & LAM and period of LAM & age of youngest child when the mother delivered again. Only 31% knew about the importance of breastfeeding. 16.6% of woman initiated Breast Feeding within 1/2 hr.

  4. Galactography in non-lactating nipple discharge

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Myung Ok; Lee, Joo Mi; Moon, Jang Ho; Kang, Ik Won; Chung, Soo Young; Bae, Sang Hoon; Park, Soo Sung [Hallym University College of Medicine, Seoul (Korea, Republic of)

    1988-08-15

    Nipple discharge in non-lactating breast is classified as 2 groups. The first group is stagnation discharge which is determined by an apocrino-like exfoliation and stagnation within the ductal system. The second group is hyperplastic or neoplastic group. The secretory breast disease combined with nipple discharge can not be diagnosed by simple X-ray mammography of ultrasonography. For differential diagnosis of secretory breast disease and for localization of lesions, the galactography is necessary. We analysed 49 cases of galactography is non-lactating breat and obtained following results. 1. The most common cause of discharge was duct ectasis (39%) in stagnation discharge group and papilloma (23%) in hyperplastic discharge group. 2. Hyperplastic discharge group occurred most frequently in 5th decade of age and was discovered more frequently in fatty parenchymal pattern on simple mammography. 3. The most frequent type of nipple discharge was cloudy-milky type in stagnation group and bloody nature in hyperplastic group. 4. The most common cause of bloody discharge was papilloma (58%). 5. The bloody nipple discharge among 56 cases of breast cancer during 4 years occurred only in 5 cases (9%)

  5. Influence of lactation on motor activity and elevated plus maze behavior

    Directory of Open Access Journals (Sweden)

    Silva M.R.P.

    1997-01-01

    Full Text Available Lactating rats show less noise-induced freezing and fewer inhibitory responses on the 6th day post-delivery when submitted to water and food deprivation in a classical conflict paradigm. Lactating mice go more often to the illuminated chamber in a light-dark cage and stay longer in it than virgin females. The present study was designed to assess the influence of this physiological state, i.e. lactation, on the elevated plus maze (EPM and open-field behavior in adult female rats. Total (TL and central (CL locomotion and rearing (RF frequencies were measured in an open-field. Number of entries into the open and closed arms as well as the time spent in each of these arms were measured in the EPM. Percent time spent and number of entries into the open arms were calculated and compared. In the open-field, TL was significantly decreased (115 ± 10.6 vs 150 ± 11.6 while CL and RF did not differ from those presented by virgin rats. In the EPM, lactating rats displayed a significant reduction in percent time spent (10.9 ± 1.5 vs 17.4 ± 2.3 in the open arms as well as a tendency to a reduction in percent entries into the open arms (35.7 ± 4.7 vs 45.7 ± 4.3. These results show that the physiological state of lactation modulates the open-field and EPM behaviors in rats

  6. Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Michael K G Stewart

    Full Text Available Pannexin1 (Panx1 subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer.

  7. Is lactate production related to muscular fatigue? A pedagogical proposition using empirical facts.

    Science.gov (United States)

    Macedo, Denise Vaz; Lazarim, Fernanda Lorenzi; Catanho da Silva, Fernando Oliveira; Tessuti, Lucas Samuel; Hohl, Rodrigo

    2009-12-01

    The cause-effect relationship between lactic acid, acidosis, and muscle fatigue has been established in the literature. However, current experiments contradict this premise. Here, we describe an experiment developed by first-year university students planned to answer the following questions: 1) Which metabolic pathways of energy metabolism are responsible for meeting the high ATP demand during high-intensity intermittent exercise? 2) Which metabolic pathways are active during the pause, and how do they influence phosphocreatine synthesis? and 3) Is lactate production related to muscular fatigue? Along with these questions, students received a list of materials available for the experiment. In the classroom, they proposed two protocols of eight 30-m sprints at maximum speed, one protocol with pauses of 120 s and the other protocol with pauses of 20 s between sprints. Their performances were analyzed through the velocity registered by photocells. Blood lactate was analyzed before the first sprint and after the eighth sprint. Blood uric acid was analyzed before exercise and 15 and 60 min after exercises. When discussing the data, students concluded that phosphocreatine restoration is time dependent, and this fact influenced the steady level of performance in the protocol with pauses of 120 s compared with the performance decrease noted in the protocol with pauses of 20 s. As the blood lactate levels showed similar absolute increases after both exercises, the students concluded that lactate production is not related to the performance decrement. This activity allows students to integrate the understanding of muscular energy pathways and to reconsider a controversial concept with facts that challenge the universality of the hypothesis relating lactate production to muscular fatigue.

  8. Influence of hexavalent chromium on lactate-enriched Hanford groundwater microbial communities.

    Energy Technology Data Exchange (ETDEWEB)

    Somenahally, Anil C [ORNL; Mosher, Jennifer J [ORNL; Yuan, Tong [University of Oklahoma; Podar, Mircea [ORNL; Phelps, Tommy Joe [ORNL; Brown, Steven D [ORNL; Yang, Zamin Koo [ORNL; Hazen, Terry C [ORNL; Arkin, Adam [Lawrence Berkeley National Laboratory (LBNL); Palumbo, Anthony Vito [ORNL; Zhou, Jizhong [University of Oklahoma; Elias, Dwayne A [ORNL

    2013-01-01

    Microbial reduction and immobilization of chromate (Cr(VI)) is a plausible bioremediation strategy. However, higher Cr(VI) concentrations may impose stress on native Cr-reducing communities. We sought to determine if Cr(VI) would influence the lactate enriched native microbial community structure and function in groundwater from the Cr contaminated site at Hanford, WA. Steady state continuous flow bioreactors were amended with lactate and Cr(VI) (0.0, 0.1 and 3.0 mg/L). Microbial growth, metabolites, Cr(VI) concentrations, 16S rRNA gene sequences and GeoChip based functional gene composition in bioreactors were monitored for 15 weeks. Temporal trends and some differences in growth, metabolite profiles, and community composition were observed, largely between Low-Cr and High-Cr bioreactors. In both High-Cr and Low-Cr bioreactors, Cr(VI) was reduced in the bioreactors. With lactate enrichment, the native communities did not significantly differ between Cr concentrations. Native bacterial communities were diverse, whereas after lactate enrichment, Pelosinus spp., and Sporotalea spp., were the most predominant groups in all bioreactors. Similarly, the Archaea diversity significantly decreased from Methanosaeta (35%), Methanosarcina (17%), Halobacteriales (12%), Methanoregula (8%) and others, to mostly Methanosarcina spp. (95%) after lactate enrichment. Composition of several key functional genes was distinct in Low-Cr bioreactors compared to High-Cr. Among the Cr resistant probes (chrA), Burkholderia vietnamiensis, Comamonas testosterone and Ralstonia pickettii proliferated in Cr amended bioreactors. In-situ fermentative conditions facilitated Cr(VI) reduction, and as a result the 3.0 mg/L Cr(VI) did not appear to give chromate reducing strains a competitive advantage for proliferation or for increasing Cr-reduction.

  9. EVALUATION OF SERUM LACTATE LEVELS AS A PROGNOSTIC INDICATOR IN VARIOUS TYPES OF SHOCK

    Directory of Open Access Journals (Sweden)

    Siddaraj Wali

    2017-08-01

    predict impending complications or grave outcome in patients of shock. Interventions that decrease lactate values to normal may improve chances of survival and can be considered effective therapy.

  10. Use of erythropoietin and its effects on blood lactate and 2, 3-diphosphoglycerate in premature neonates.

    Science.gov (United States)

    Soubasi, V; Kremenopoulos, G; Tsantali, C; Savopoulou, P; Mussafiris, C; Dimitriou, M

    2000-11-01

    The aim of this study was to investigate the effect of recombinant human erythropoietin (rHu-EPO) on oxygen affinity and adequate oxygen delivery to the tissues of stable premature infants. 36 very-low-birth-weight infants were randomly assigned to either receive rHu-EPO (200 units/kg every other day) or not, and both groups were supplemented with iron, folic acid and vitamin E. Arterial blood gases, oxygen saturation, complete blood counts, fetal haemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and blood lactate were analysed weekly, from the 1st week till discharge. Patients in the two groups were comparable. There was a trend in increasing lactate values towards the 4th to 5th weeks of life, which did not reach statistical significance. There was no correlation between lactate values and the studied variables (pH, BE, oxygen saturation). In 35 transfusions, pre- and 24 h post-transfusion blood lactate status was studied. In 23 of them, a decrease in post-transfusion lactate was noticed, whilst an increased post-transfusion level was shown in 10 cases and no change in 2 cases. The mean pre-transfusion lactate value was significantly higher than the post-transfusion one (24.04 +/- 11.9 mg/dl before and 16.27 +/- 8.5 mg/dl after transfusion; p = 0.0025). In both groups there was a steady rise in 2,3-DPG concentration over the period of study, and the 2,3-DPG values at the end of our study were significantly increased in the rHu-EPO group (rHu-EPO 5.98 +/- 0.9, control 4.84 +/- 0.7; p = 0.04). In conclusion, the use of rHu-EPO did not affect blood lactate levels compared to the control group. Regarding oxygen affinity, it seems that rHu-EPO causes a shift of the oxy-haemoglobin dissociation curve to the right. This is a previously unreported effect of rHu-EPO and its clinical use may, thus, confer to preterm babies an added advantage.

  11. High fat diet alters lactation outcomes: possible involvement of inflammatory and serotonergic pathways.

    Directory of Open Access Journals (Sweden)

    Laura L Hernandez

    Full Text Available Delay in the onset of lactogenesis has been shown to occur in women who are obese, however the mechanism altered within the mammary gland causing the delay remains unknown. Consumption of high fat diets (HFD has been previously determined to result decreased litters and litter numbers in rodent models due to a decrease in fertility. We examined the effects of feeding a HFD (60% kcal from fat diet versus a low-fat diet (LFD; 10% kcal from fat to female Wistar rats on lactation outcomes. Feeding of HFD diet resulted in increased pup weights compared to pups from LFD fed animals for 4 d post-partum. Lactation was delayed in mothers on HFD but they began to produce copious milk volumes beginning 2 d post-partum, and milk yield was similar to LFD by day 3. Mammary glands collected from lactating animals on HFD diet, displayed a disrupted morphologies, with very few and small alveoli. Consistently, there was a significant decrease in the mRNA expression of milk protein genes, glucose transporter 1 (GLUT1 and keratin 5 (K5, a luminobasal cell marker in the mammary glands of HFD lactating animals. Expression of tryptophan hydroxylase 1 (TPH1, the rate-limiting enzyme in serotonin (5-HT biosynthesis, and the 5-HT(7 receptor (HTR7, which regulates mammary gland involution, were significantly increased in mammary glands of HFD animals. Additionally, we saw elevation of the inflammatory markers interleukin-6 (IL-6 and tumor necrosis factor-α (TNF- α. These results indicate that consumption of HFD impairs mammary parenchymal tissue and impedes its ability to synthesize and secrete milk, possibly through an increase in 5-HT production within the mammary gland leading to an inflammatory process.

  12. Effects of mineral salt supplement on enteric methane emissions, ruminal fermentation and methanogen community of lactating cows.

    Science.gov (United States)

    Li, Xiaohua; Liu, Chong; Chen, Yongxing; Shi, Rongguang; Cheng, Zhenhua; Dong, Hongmin

    2017-08-01

    We evaluated the effects of mineral salt supplement on enteric methane emissions, ruminal fermentation and methanogen community of dairy cows over a whole lactation period. Ten Holstein cows fed a total mixed ration (TMR) diet were randomly allocated into two groups, one supplied with mineral salts as the treatment group and the other as the control group. The methane measurement showed that the ingestion of mineral salts lowered enteric methane emissions significantly (P methane emissions by mineral salt intake could be attributed to decreased density of methanogenic archaea and that fluctuations in methane emission over the lactation period might be related to Methanobrevibacter diversity. © 2016 Japanese Society of Animal Science.

  13. The influence of lactate and dipyridamole on myocardial fatty acid metabolism in man, traced with 123I-17-iodoheptadecanoic acid

    International Nuclear Information System (INIS)

    Duwel, C.M.B.; Visser, F.C.; Eenige, M.J. van; Roos, J.P.; Westera, G.

    1990-01-01

    Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123 I-17-iodoheptadecanoic acid ( 123 I-17-HDA). In patients (paired, n=7) lactate loading decreased the uptake of 123 I-17-HDA significantly from 27 (control:22-36) to 20 counts/min/pixel (16-31; p 123 I-17-HDA scintigraphy of the heart. (orig.) [de

  14. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

    OpenAIRE

    Haricharan, S; Li, Y

    2013-01-01

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, prog...

  15. Using an incomplete gamma function to quantify the effect of dystocia on the lactation performance of Holstein dairy cows in Iran.

    Science.gov (United States)

    Atashi, H; Abdolmohammadi, A R; Asaadi, A; Akhlaghi, A; Dadpasand, M; Ahangari, Y Jafari

    2012-05-01

    The aim of the present study was to estimate the effect of dystocia on lactation performance, using an incomplete gamma function. Data from March 2000 to April 2009 comprising 100,628 lactations of 65,421 cows in 204 dairy herds collected by the Animal Breeding Center of Iran were used. Of 100,628 births, 91.8% required no assistance, whereas 8.2% required assistance of some sort. Factors associated with the presence of dystocia were calving season, calving year, herd, calf sex, parity, and age of dam. Peak yield for primiparous cows with dystocia at calving occurred on d 87.2 [standard error (SE) 0.47], and for primiparous cows with easy calving, the peak of lactation was on d 83.3 (0.25). Peak yield was lowered by 0.39 (SE 0.07), 2.20 (SE 0.15), 2.22 (SE 0.21), and 2.54 (SE 0.32) kg for cows with incidence of dystocia compared with normal cows in parity 1 to 4, respectively. Dystocia was associated with decreased 305-d lactation performance in all parities, mostly in early lactation. Although more difficult births occurred in heifer calvings, loss in lactation performance was greater in second or later lactations following a difficult birth. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Regional differences in adipocyte lactate production from glucose

    International Nuclear Information System (INIS)

    Newby, F.D.; Sykes, M.N.; DiGirolamo, M.

    1988-01-01

    Having shown that lactate is an important product of glucose metabolism by rat epididymal adipocytes, the authors investigated possible regional differences in adipocyte lactate production and the role of the animals' nutritional state and stage of development. [U- 14 C]glucose metabolism, lactate production, and response to insulin were measured in fat cells isolated from four adipose regions from young lean and older fatter rats, killed either in the fed state or after fasting for 48 h. In the absence of insulin, mesenteric fat cells from either age group metabolized significantly more glucose per cell and converted more glucose to lactate than cells from other depots, regardless of nutritional state. Adipocytes from fasted lean rats showed a significant increase in the relative glucose conversion to lactate in all depots when compared with cells from fed lean rats. Fasting of older fatter rats, however, had limited effects on the relative adipocyte glucose conversion to lactate since lactate production was already high. Mesenteric fat cells had the lowest relative response to insulin, possibly due to the high basal rate of glucose metabolism. These findings indicate that differences exist among adipose regions in the rates of glucose metabolism, lactate production and response to insulin. The anatomical location of the mesenteric adipose depot, coupled with a high metabolic rate and blood perfusion, suggests that mesenteric adipocytes may provide a unique and more direct contribution of metabolic substrates for hepatic metabolism than adipocytes from other depots

  17. Genetic relationship between lactation curve traits of dairy cattle in ...

    African Journals Online (AJOL)

    Wasike Chrislukovian

    2014-08-23

    Aug 23, 2014 ... Lactation milk yield is an important trait in selection of dairy cattle all ... affect functional traits such as fertility, somatic cell count and mastitis, ... explain physiological issues reported in Kenyan herds and guide future selection decisions. The correlation between milk yield and lactation curve traits has not ...

  18. 1981 EFFECT OF STAGE OF LACTATION ON THE PHYSICAL AND ...

    African Journals Online (AJOL)

    IBNELBACHYR

    The results of the present investigation show that Drâa goat milk is rich with desirable components like fat and protein for dairy product manufacturers, and that the late lactation stage seems to be the best period to ensure an optimum technological valorization. Key words: Goat, Morocco, milk, physicochemical, lactation ...

  19. Fluorometric determination of d-lactate in biological fluids

    DEFF Research Database (Denmark)

    Larsen, Torben

    2017-01-01

    in the body may lead to D-lactate acidosis and neurotoxicity; consequently, the possibility of diagnosis of this condition is important. Several analytical procedures for D-lactate have been introduced, but it is absolutely mandatory to distinguish this metabolite from the much more abundant and naturally......-up in the laboratory....

  20. New enzymatic assay, parasite lactate dehydrogenase in diagnosis ...

    African Journals Online (AJOL)

    Background: The unique ability of plasmodial lactate dehydrogenase p(LDH) to utilise 3-acetyl pyridine dinucleotide (APAD) in lieu of NAD as a coenzyme in the conversion of pyruvate to lactate, led to the development of a biochemical assay for the detection of plasmodial parasitaemia. Researchers have reported that ...

  1. Complete lactational failure in four consecutive deliveries: a case ...

    African Journals Online (AJOL)

    Although the ever-breastfeeding rate in Nigeria is over 98%, there are some women who may not be able to lactate despite the desire and motivation to do so. Some of the reasons for this failure include lack of skilled support and inherent failure to lactate. We report .the case of a 29-year old graduate, who, despite ...

  2. Vulvar lactating adenoma associated to a fibroadenoma: common ...

    African Journals Online (AJOL)

    Ectopic breast tissue is defined as glands located outside of the breast. Ectopic breast tissue should be excised because it may develop benign (fibroadenoma) or malignant pathologic processes. Less than forty cases of fibroadenomas have been reported in the literature. Although lactation changes can occur, lactating ...

  3. Induction of lactational estrus in organic piglet production

    DEFF Research Database (Denmark)

    Kongsted, Anne Grete; Hermansen, John Erik

    2009-01-01

    , if lactational estrus is to be beneficial under practical husbandry conditions, it is crucial that the majority of sows are successfully mated within a few days to make batch farrowing procedures possible. The objective of this study was to investigate the occurrence and timing of lactational estrus...

  4. Malnutrition and iron deficiency anaemia in lactating women in ...

    African Journals Online (AJOL)

    Objective: To determine the status of iron deficiency anaemia (IDA) and malnutrition in lactating women. Design: A cross-sectional study. Setting: Six urban slum communities in Teklehaimanot district, Addis Ababa. Subjects: One thousand and seventeen lactating women were enrolled and assessed for their haemoglobin ...

  5. Glycogen synthesis from lactate in a chronically active muscle

    International Nuclear Information System (INIS)

    Talmadge, R.J.; Scheide, J.I.; Silverman, H.

    1989-01-01

    In response to neural overactivity (pseudomyotonia), gastrocnemius muscle fibers from C57Bl/6Jdy2J/dy2J mice have different metabolic profiles compared with normal mice. A population of fibers in the fast-twitch superficial region of the dy2J gastrocnemius stores unusually high amounts of glycogen, leading to an increased glycogen storage in the whole muscle. The dy2J muscle also contains twice as much lactate as normal muscle. A [ 14 C]lactate intraperitoneal injection leads to preferential 14 C incorporation into glycogen in the dy2J muscle compared with normal muscle. To determine whether skeletal muscles were incorporating lactate into glycogen without body organ (liver, kidney) input, gastrocnemius muscles were bathed in 10 mM [ 14 C]lactate with intact neural and arterial supply but with impeded venous return. The contralateral gastrocnemius serves as a control for body organ input. By using this in situ procedure, we demonstrate that under conditions of high lactate both normal and dy2J muscle can directly synthesize glycogen from lactate. In this case, normal whole muscle incorporates [14C] lactate into glycogen at a higher rate than dy2J whole muscle. Autoradiography, however, suggests that the high-glycogen-containing muscle fibers in the dy2J muscle incorporate lactate into glycogen at nearly four times the rate of normal or surrounding muscle fibers

  6. Lactic acid and Lactates in Health and wellness

    NARCIS (Netherlands)

    Gertjan Schaafsma; Victor Schreurs

    2010-01-01

    This review aims to integrate the present state of knowledge on lactate metabolism in human and mammalian physiology as far as it could be subject to nutritional interventions. An integrated view on the nutritional, metabolic and physiological aspects of lactic acid and lactates might open a

  7. Renal Development and Blood Pressure in Offspring from Dams Submitted to High-Sodium Intake during Pregnancy and Lactation

    Directory of Open Access Journals (Sweden)

    Terezila M. Coimbra

    2012-01-01

    Full Text Available Exposure to an adverse environment in utero appears to programme physiology and metabolism permanently, with long-term consequences for health of the fetus or offspring. It was observed that the offspring from dams submitted to high-sodium intake during pregnancy present disturbances in renal development and in blood pressure. These alterations were associated with lower plasma levels of angiotensin II (AII and changes in renal AII receptor I (AT1 and mitogen-activated protein kinase (MAPK expressions during post natal kidney development. Clinical and experimental evidence show that the renin-angiotensin system (RAS participates in renal development. Many effects of AII are mediated through MAPK pathways. Extracellular signal-regulated protein kinases (ERKs play a pivotal role in cellular proliferation and differentiation. In conclusion, high-sodium intake during pregnancy and lactation can provoke disturbances in renal development in offspring leading to functional and structural alterations that persist in adult life. These changes can be related at least in part with the decrease in RAS activity considering that this system has an important role in renal development.

  8. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky......We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...

  9. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  10. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...... rule was provided by Moulin and Shenker (J Econ Theory 64:178-201, 1994). This paper gives an axiomatic characterization of the decreasing serial rule....

  11. LACTATE PROFILE DURING GRECO-ROMAN WRESTLING MATCH

    Directory of Open Access Journals (Sweden)

    Ognjen Uljevic

    2009-11-01

    Full Text Available The objective of this study was to determine and compare lactate profile of two groups of Greco-Roman wrestlers with different competences and training experience. Study was conducted on 10 wrestles that were members of Croatian national team and 10 wrestlers that were members of Wrestling club Split. Lactate samples were collected at four intervals during control fights that were held according to international wrestling rules of World wrestling federation FILA. Values of lactate increased as competition progressed, and they were highest at the end of the match for both groups of wrestlers. According to this study there were no significant differences in lactate between two groups at the end of the match, while significant differences were noted during the match. The information about lactate profile presented in this study can be used by coaches and wrestlers to develop condition programs

  12. Lactate/H+ transport kinetics in rat skeletal muscle related to fibre type and changes in transport capacity

    DEFF Research Database (Denmark)

    Juel; Pilegaard

    1998-01-01

    muscles, muscles of old rats and rats that had been subjected to high-intensity training, endurance training, repeated exposure to hypoxia, and hypothyroid or hyperthyroid treatments. The lactate/H+ transport capacity of red muscles was greater than that of white muscles, and this difference...... and hypothyroidism was due to a decrease in Vmax. The denervation-induced decline in lactate/H+ transport capacity resulted from both an increased Km and a reduced Vmax. The present data show that muscle type differences and most changes in the lactate/H+ transport capacity are mediated by modifications in Vmax......, which is expected to represent the number of membrane transporter molecules. Km is unaffected by most treatments and appears to be independent of fibre type....

  13. Effect of gamma radiation on the concentration of pyruvate and lactate in erythrocytes of healthy men after submaximal physical exercise

    International Nuclear Information System (INIS)

    Zagorski, T.; Dudek, I.; Berkan, L.; Chmielewski, H.; Kedziora, J.

    1993-01-01

    The aim of this work was to study the effect of gamma radiation and submaximal physical exercise on the concentration of final products of anaerobic glycolytic pathway in erythrocytes of healthy men. Twenty one men aged 20-22 were examined. They underwent physical exercise at doses of 2 w/kg body weight for 15 min. Erythrocytes were taken in the rest and after physical exercise and were exposed to gamma radiation (500 Gy doses) from 60 Co source. The concentration of pyruvate was estimated by Fermognost tests and the concentration of lactate by Boehringer Mannheim tests. The submaximal physical exercise was found to cause a significantly increased concentration of pyruvate and lactate in the non-radiated and irradiated erythrocytes. Gamma radiation at 500 Gy dose was found to increase concentration of pyruvate in erythrocytes (in the rest and after physical exercise) with simultaneous decrease of lactate concentration. (author). 17 refs, 1 tab

  14. MCT1 and MCT4 expression and lactate flux activity increase during white and brown adipogenesis and impact adipocyte metabolism

    DEFF Research Database (Denmark)

    Petersen, Charlotte; Nielsen, Mette D.; Andersen, Elise S.

    2017-01-01

    RNA and protein levels of the lactate-H+ transporter MCT1 and the Na+,HCO3 - cotransporter NBCe1 were upregulated in mouse interscapular brown and inguinal white adipose tissue upon cold induction of thermogenesis and browning. MCT1, MCT4, and NBCe1 were furthermore strongly upregulated at the mRNA and protein...... level upon differentiation of cultured pre-adipocytes. Adipocyte differentiation was accompanied by increased plasma membrane lactate flux capacity, which was reduced by MCT inhibition and by MCT1 knockdown. Finally, in differentiated brown adipocytes, glycolysis (assessed as ECAR), and after...... noradrenergic stimulation also oxidative metabolism (OCR), was decreased by MCT inhibition. We suggest that upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated HCO3 -/pH homeostasis are important for the physiological function of mature adipocytes....

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

    Science.gov (United States)

    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.

  16. Effect of incorporation of calcium lactate on physico-chemical, textural, and sensory properties of restructured buffalo meat loaves.

    Science.gov (United States)

    Irshad, A; Sharma, B D; Ahmed, S R; Talukder, S; Malav, O P; Kumar, Ashish

    2016-02-01

    The present study was conducted to develop a functional meat product by fortifying calcium (in the form of calcium lactate) with restructured buffalo meat loaf (RBML). Deboned buffalo meat obtained from the carcass of adult female buffalo within 5-6 h of slaughter and stored under frozen condition. Calcium fortified RBML were prepared by replacing the lean buffalo meat with calcium lactate powder at 0%, 1%, 1.25%, and 1.5% level through the pre-standardized procedure. The developed products were evaluated for physico-chemical properties, proximate composition, calcium concentration (mg/100 g), water activity (aw), Lovibond(®) tintometer color units, texture profile analysis (TPA), and sensory qualities as per-standard procedures. Of the various product quality parameters evaluated, cooking yield (%), product pH, moisture (%), protein (%), fat (%), and water activity (aw) decreases significantly with increasing level of calcium lactate. Calcium content of fortified functional RBMLs was 135.02, 165.73, and 203.85 mg/100 g as compared to 6.48 mg/100 g in control. Most of the sensory scores at 1% and 1.25% levels of calcium lactate in treatment products remained comparable among themselves and control product, with a gradual decline. The present study concluded that 1.25% calcium lactate was the optimum level for the fortification of calcium in RBML without affecting the textural and sensory properties which could meet out 15% of recommended dietary allowance for calcium.

  17. Effect of incorporation of calcium lactate on physico-chemical, textural, and sensory properties of restructured buffalo meat loaves

    Directory of Open Access Journals (Sweden)

    A. Irshad

    2016-02-01

    Full Text Available Aim: The present study was conducted to develop a functional meat product by fortifying calcium (in the form of calcium lactate with restructured buffalo meat loaf (RBML. Materials and Methods: Deboned buffalo meat obtained from the carcass of adult female buffalo within 5-6 h of slaughter and stored under frozen condition. Calcium fortified RBML were prepared by replacing the lean buffalo meat with calcium lactate powder at 0%, 1%, 1.25%, and 1.5% level through the pre-standardized procedure. The developed products were evaluated for physico-chemical properties, proximate composition, calcium concentration (mg/100 g, water activity (aw, Lovibond® tintometer color units, texture profile analysis (TPA, and sensory qualities as per-standard procedures. Results: Of the various product quality parameters evaluated, cooking yield (%, product pH, moisture (%, protein (%, fat (%, and water activity (aw decreases significantly with increasing level of calcium lactate. Calcium content of fortified functional RBMLs was 135.02, 165.73, and 203.85 mg/100 g as compared to 6.48 mg/100 g in control. Most of the sensory scores at 1% and 1.25% levels of calcium lactate in treatment products remained comparable among themselves and control product, with a gradual decline. Conclusions: The present study concluded that 1.25% calcium lactate was the optimum level for the fortification of calcium in RBML without affecting the textural and sensory properties which could meet out 15% of recommended dietary allowance for calcium.

  18. Effect of Fenugreek Supplementation on Physiological Functions and Milk Traits o f Heat Stressed Lactating Baladi Goats

    International Nuclear Information System (INIS)

    El-Tarabany, A.A.; Teama, F.E.I.; Atta, M.A.A.

    2017-01-01

    This experiment was conducted to study the importance of supplementary fenugreek to the diet of lactating local goats in Egypt for ameliorative their some blood biochemical components, milk production and some milk components. Forty two lactating goats were used in the present study which lasted 5 months. The animals were divided randomly into three equal groups, the 1st group was fed basic ration without supplement (control), while the 2nd and the 3rd groups of animals were fed on the same basic ration with supplemented fenugreek at the rate of 50 and 100 g/head/day. Blood samples were withdrawn at the end of experiment to assess blood concentrations. Also, milk yield and some milk components were determined. The results showed that the addition of fenugreek at the rate of 100 g/ head/ day to the diet of lactating goats significantly increased the concentrations of total proteins, albumin, globulin , T4 hormone, total antioxidants and hemoglobin (Hb), red blood cells (RBC) and led to a significant decrease in the levels of total cholesterol, triglyceride, wight blood cells (WBC) and T3 hormone in blood, while significantly increased milk yield and some milk components. It can be concluded that the addition of fenugreek at the rat of (100 g/ h/day) to heat stressed lactating Baladi goats led to modification of all blood components studied here in and led to amending the setraits, milk production and some milk components. Therefore, the use of the fenugreek in lactating stages can be recommended

  19. Cyolane residues in milk of lactating goats

    International Nuclear Information System (INIS)

    Zayed, S.M.A.D.; Osman, A.; Fakhr, I.M.I.

    1981-01-01

    Consecutive feeding of lactating goats with 14 C-alkyl labelled cyolane for 5 days at dietary levels 8 and 16 ppm resulted in the appearance of measurable insecticide residues in milk (0.02-0.04 mg/kg). The residue levels were markedly reduced after a withdrawal period of 7 days. Analysis of urine and milk residues showed the presence of similar metabolites in addition to the parent compound. The major part of the residue consisted of mono-, diethyl phosphate and 2 hydrophilic unknown metabolites. The erythrocyte cholinesterase activity was reduced to about 50% after 24 hours whereas the plasma enzyme was only slightly affected. The animals remained symptom-free during the experimental period. (author)

  20. IBD medications during pregnancy and lactation

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Maxwell, Cynthia; Hendel, Jakob

    2013-01-01

    pregnancy and breast-feeding, alternatives to ciprofloxacin, natalizumab and sodium phosphate should also be considered for pregnant women. Breast-feeding is also discouraged while on treatment with ciclosporin, metronidazole and ciprofloxacin. However, therapy with 5-aminosalicylic acid preparations......IBD often affects patients during their peak reproductive years. Several drugs are available for the treatment of IBD and new drugs are continuously in the pipeline. As long-term administration of medications is often necessary, the safety of drug therapy during pregnancy and breast-feeding needs...... to be considered in daily clinical practice. The aim of this Review is to summarize the latest information concerning the safety of medications used to treat IBD during pregnancy and lactation, as well as their effect on fertility. Although only thalidomide and methotrexate are absolutely contraindicated during...

  1. [Pregnancy and lactation-associated osteoporosis].

    Science.gov (United States)

    Gehlen, M; Lazarescu, A D; Hinz, C; Boncu, B; Schmidt, N; Pfeifer, M; Schwarz-Eywill, M; Pollähne, W; Minne, H W

    2017-04-01

    Pregnancy and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, which occurs in the last trimester or postpartum. So far 100 cases have been published. The leading symptoms are severe low back pain or less frequently hip pain. Many patients develop postpartum depression due to inability to care for the baby and vertebral fractures. The therapeutic decision has to be made individually but teriparatid and bisphosphonates seem to be the best option. We report the clinical course (16 years) of a 37-year-old patient with PLO, who suffered 6 vertebral fractures. There were severe physical limitations and mental problems caused by the disease. The patient was treated by multimodal therapy including physiotherapy and psychotherapy and bisphosphonates were given. The time between the onset of symptoms and diagnosis was 5 months. No further fractures occurred in the following 16 years. The physical and mental condition significantly improved.

  2. Glucose feeds the TCA cycle via circulating lactate.

    Science.gov (United States)

    Hui, Sheng; Ghergurovich, Jonathan M; Morscher, Raphael J; Jang, Cholsoon; Teng, Xin; Lu, Wenyun; Esparza, Lourdes A; Reya, Tannishtha; Le Zhan; Yanxiang Guo, Jessie; White, Eileen; Rabinowitz, Joshua D

    2017-11-02

    Mammalian tissues are fuelled by circulating nutrients, including glucose, amino acids, and various intermediary metabolites. Under aerobic conditions, glucose is generally assumed to be burned fully by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is itself also a potential nutrient for tissues and tumours. The quantitative relevance of circulating lactate or other metabolic intermediates as fuels remains unclear. Here we systematically examine the fluxes of circulating metabolites in mice, and find that lactate can be a primary source of carbon for the TCA cycle and thus of energy. Intravenous infusions of 13 C-labelled nutrients reveal that, on a molar basis, the circulatory turnover flux of lactate is the highest of all metabolites and exceeds that of glucose by 1.1-fold in fed mice and 2.5-fold in fasting mice; lactate is made primarily from glucose but also from other sources. In both fed and fasted mice, 13 C-lactate extensively labels TCA cycle intermediates in all tissues. Quantitative analysis reveals that during the fasted state, the contribution of glucose to tissue TCA metabolism is primarily indirect (via circulating lactate) in all tissues except the brain. In genetically engineered lung and pancreatic cancer tumours in fasted mice, the contribution of circulating lactate to TCA cycle intermediates exceeds that of glucose, with glutamine making a larger contribution than lactate in pancreatic cancer. Thus, glycolysis and the TCA cycle are uncoupled at the level of lactate, which is a primary circulating TCA substrate in most tissues and tumours.

  3. L-lactate transport in Ehrlich ascites-tumour cells.

    Science.gov (United States)

    Spencer, T L; Lehninger, A L

    1976-01-01

    Ehrlich ascites-tumour cells were investigated with regard to their stability to transport L-lactate by measuring either the distribution of [14C]lactate or concomitant H+ ion movements. The movement of lactate was dependent on the pH difference across the cell membrane and was electroneutral, as evidenced by an observed 1:1 antiport for OH- ions or 1:1 symport with H+ ions. 2. Kinetic experiments showed that lactate transport was saturable, with an apparent Km of approx. 4.68 mM and a Vmax. as high as 680 nmol/min per mg of protein at pH 6.2 and 37 degrees C. 3. Lactate transport exhibited a high temperature dependence (activation energy = 139 kJ/mol). 4. Lactate transport was inhibited competitively by (a) a variety of other substituted monocarboxylic acids (e.g. pyruvate, Ki = 6.3 mM), which were themselves transported, (b) the non-transportable analogues alpha-cyano-4-hydroxycinnamate (Ki = 0.5 mM), alpha-cyano-3-hydroxycinnamate (Ki = 2mM) and DL-p-hydroxyphenyl-lactate (Ki = 3.6 mM) and (c) the thiol-group reagent mersalyl (Ki = 125 muM). 5. Transport of simple monocarboxylic acids, including acetate and propionate, was insensitive to these inhibitors; they presumably cross the membrane by means of a different mechanism. 6. Experiments using saturating amounts of mersalyl as an "inhibitor stop" allowed measurements of the initial rates of net influx and of net efflux of [14C]lactate. Influx and efflux of lactate were judged to be symmetrical reactions in that they exhibited similar concentration dependence. 7. It is concluded that lactate transport in Ehrlich ascites-tumour cells is mediated by a carrier capable of transporting a number of other substituted monocarboxylic acids, but not unsubstituted short-chain aliphatic acids. PMID:7237

  4. Pilot scale anaerobic acidification of waste water containing sucrose and lactate

    Energy Technology Data Exchange (ETDEWEB)

    Zoetemeyer, R J; Borgerding, P H; Van den Heuvel, J C; Cohen, A; Boelhouwer, C

    1982-07-01

    The waste water from a sugar refinery, containing principally sucrose, lactate and ethanol as organic impurities, was anaerobically acidified at a pH of approximately 5.8 and an average temperature of 29 degrees C in a 1 meter cubed upflow reactor. The residence time was decreased, in steps, from 7.2 to 1.7 h. Sucrose was effectively metabolized in all cases, whereas lactate was only decomposed at longer residence times. Ethanol was not converted. The volume activity, and the sludge activity, could be increased to 250 kg/ cubic meters/d, and 14 kg/kg/d, respectively. Results indicated that in order to operate an acidification reactor at its maximum efficiency attention should be paid to the mixing system and to maintaining a constant pH. (Refs. 18).

  5. A rare cause of postpartum low back pain: pregnancy- and lactation-associated osteoporosis.

    Science.gov (United States)

    Terzi, Rabia; Terzi, Hasan; Özer, Tülay; Kale, Ahmet

    2014-01-01

    Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis. It results in severe low back pain in the last trimester of pregnancy and in the postpartum period, decreases in height, and fragility fractures, particularly in the vertebra. The current case report presents a 32-year-old patient who presented with back and low back pain that began in the last trimester of the pregnancy and worsened at two months postpartum and who was diagnosed with pregnancy- and lactation-associated osteoporosis after exclusion of other causes; the findings are discussed in view of the current literature. PLO is a rare clinical condition causing significant disability. PLO must be kept in mind in the differential diagnosis in patients presenting with low back pain during or after pregnancy. The patients must be evaluated for the risk factors of PLO, and an appropriate therapy must be initiated.

  6. A Rare Cause of Postpartum Low Back Pain: Pregnancy- and Lactation-Associated Osteoporosis

    Directory of Open Access Journals (Sweden)

    Rabia Terzi

    2014-01-01

    Full Text Available Pregnancy- and lactation-associated osteoporosis (PLO is a rare form of osteoporosis. It results in severe low back pain in the last trimester of pregnancy and in the postpartum period, decreases in height, and fragility fractures, particularly in the vertebra. The current case report presents a 32-year-old patient who presented with back and low back pain that began in the last trimester of the pregnancy and worsened at two months postpartum and who was diagnosed with pregnancy- and lactation-associated osteoporosis after exclusion of other causes; the findings are discussed in view of the current literature. PLO is a rare clinical condition causing significant disability. PLO must be kept in mind in the differential diagnosis in patients presenting with low back pain during or after pregnancy. The patients must be evaluated for the risk factors of PLO, and an appropriate therapy must be initiated.

  7. Lactate minimum in a ramp protocol and its validity to estimate the maximal lactate steady state

    Directory of Open Access Journals (Sweden)

    Emerson Pardono

    2009-01-01

    Full Text Available http://dx.doi.org/10.5007/1980-0037.2009v11n2p174   The objectives of this study were to evaluate the validity of the lactate minimum (LM using a ramp protocol for the determination of LM intensity (LMI, and to estimate the exercise intensity corresponding to maximal blood lactate steady state (MLSS. In addition, the possibility of determining aerobic and anaerobic fitness was investigated. Fourteen male cyclists of regional level performed one LM protocol on a cycle ergometer (Excalibur–Lode consisting of an incremental test at an initial workload of 75 Watts, with increments of 1 Watt every 6 seconds. Hyperlactatemia was induced by a 30-second Wingate anaerobic test (WAT (Monark–834E at a workload corresponding to 8.57% of the volunteer’s body weight. Peak power (11.5±2 Watts/kg, mean power output (9.8±1.7 Watts/kg, fatigue index (33.7±2.3% and lactate 7 min after WAT (10.5±2.3 mmol/L were determined. The incremental test identified LMI (207.8±17.7 Watts and its respective blood lactate concentration (2.9±0.7 mmol/L, heart rate (153.6±10.6 bpm, and also maximal aerobic power (305.2±31.0 Watts. MLSS intensity was identified by 2 to 4 constant exercise tests (207.8±17.7 Watts, with no difference compared to LMI and good agreement between the two parameters. The LM test using a ramp protocol seems to be a valid method for the identification of LMI and estimation of MLSS intensity in regional cyclists. In addition, both anaerobic and aerobic fitness parameters were identified during a single session.

  8. Associations between the time of conception and the shape of the lactation curve in early lactation in Norwegian dairy cattle

    DEFF Research Database (Denmark)

    Andersen, Fredrik; Østerås, Olav; Reksen, Olav

    2011-01-01

    This study was carried out to determine if an association exists between the shape of the lactation curve before it is influenced by the event of conception and the time from calving to conception in Norwegian dairy cattle. Lactation curves of Norwegian Red cows during 5 to 42 days in milk (DIM) ...

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

    Science.gov (United States)

    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

  10. Effects of pregnancy and lactation on the toxicity of 239Pu

    International Nuclear Information System (INIS)

    Mahlum, D.D.; Hess, J.O.; Sikov, M.R.

    1980-01-01

    Nulliparous, pregnant, or lactating Wistar rats were injected intravenously with 0, 0.5 or 2.0 μCi of 239 Pu per kilogram of body weight. Half of each group were repeatedly bred while the others were held for observation without further treatment. Treatment with either dose of 239 Pu decreased the median time to appearance of mammary tumors. Repeated breeding tended to increase the mean time to appearance. Longevity was decreased in a dose-related fashion by Pu administration. Repeated breeding did not influence survival in a major way

  11. Proteomic analysis of physiological function response to hot summer in liver from lactating dairy cows.

    Science.gov (United States)

    Wang, Qiangjun; Zhao, Xiaowei; Zhang, Zijun; Zhao, Huiling; Huang, Dongwei; Cheng, Guanglong; Yang, Yongxin

    2017-04-01

    Lactation performance of dairy cattle is susceptible to heat stress. The liver is one of the most crucial organs affected by high temperature in dairy cows. However, the physiological adaption by the liver to hot summer conditions has not been well elucidated in lactating dairy cows. In the present study, proteomic analysis of the liver in dairy cows in spring and hot summer was performed using a label-free method. In total, 127 differentially expressed proteins were identified; most of the upregulated proteins were involved in protein metabolic processes and responses to stimuli, whereas most of the downregulated proteins were related to oxidation-reduction. Pathway analysis indicated that 3 upregulated heat stress proteins (HSP90α, HSP90β, and endoplasmin) were enriched in the NOD-like receptor signaling pathway, whereas several downregulated NADH dehydrogenase proteins were involved in the oxidative phosphorylation pathway. The protein-protein interaction network indicated that several upregulated HSPs (HSP90α, HSP90β, and GRP78) were involved in more interactions than other proteins and were thus considered as central hub nodes. Our findings provide novel insights into the physiological adaption of liver function in lactating dairy cows to natural high temperature. Copyright © 2017. Published by Elsevier Ltd.

  12. Portable lactate analyzer for measuring lactate in cerebrospinal fluid (CSF and plasma ? method-comparison evaluations

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2014-07-01

    Full Text Available Increased plasma lactate levels can indicate the presence of metabolic disorders in HIV infected individuals. Objective: To determine whether a portable analyzer is valid for measuring cerebrospinal fluid (CSF and plasma lactate levels in HIV infected individuals. Method: CSF and plasma were collected from 178 subjects. Samples tested by the Accutrend® portable analyzer were compared to those tested by a reference device (SYNCHRON LX® 20. Results: The portable analyzer had in plasma sensitivity of 0.95 and specificity 0.87. For CSF the specificity was 0.95; the sensitivity 0.33; the negative predictive value was 95% and the positive predictive value 33%. Conclusions: These findings support the validity of the portable analyzer in measuring lactate concentrations in CSF that fall within the normal range. The relatively poor positive predictive value indicates that a result above the reference range may represent a “false positive test”, and should be confirmed by the reference device before concluding abnormality.

  13. Correlation of Lactate Concentration in Peripheral Plasma and Cerebrospinal Fluid with Glasgow Outcome Scale for Patients with Tuberculous Meningitis Complicated by Acute Hydrocephalus Treated with Fluid Diversions.

    Science.gov (United States)

    Faried, Ahmad; Arief, Gusman; Arifin, Muhammad Z; Nataprawira, Heda M

    2018-03-01

    Tuberculous meningitis (TBM) is an endemic infectious disease in developing countries, and it can become a serious illness in children. Treatment of TBM is more difficult and prone to failure than treatment of pulmonary tuberculosis. TBM causes hydrocephalus, cerebral edema, increased intracranial pressure, global ischemia, and neurologic deficits, which disturb cellular metabolism and increase lactate levels. A reliable, widely available clinical indicator of TBM severity is needed. Successful treatment of TBM is assessed using the Glasgow Outcome Scale (GOS). This prospective cohort study included 34 patients with TBM and acute hydrocephalus who had undergone fluid diversions and were admitted to Dr. Hasan Sadikin Hospital in Bandung from 2014 to 2015. A portable machine for blood glucose measurement was used to measure lactate concentrations. Statistical significance was defined as P ≤ 0.05. Average levels of plasma and cerebrospinal fluid (CSF) lactate were 1.99 ± 0.70 mmol/L and 3.04 ± 1.05 mmol/L, respectively. A significantly higher level of lactate was observed in CSF compared with plasma. Preoperative plasma lactate was negatively correlated to GOS (r = -0.539; P = 0.013), and CSF lactate was negatively correlated to GOS (r = -0.412; P = 0.027). Average lactate levels in CSF (central) were higher than plasma (peripheral) levels. GOS scale of patients decreased with increased plasma and CSF lactate levels. Examination of plasma and CSF lactate levels should be included in routine examinations to determine extent of cellular damage and GOS score in patients with TBM and acute hydrocephalus who have undergone fluid diversions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Effect of lactation stage on the concentration of essential and selected toxic elements in milk of Dubrovačka ruda - Croatian endangered breed

    Directory of Open Access Journals (Sweden)

    Zvonko Antunović

    2016-11-01

    Full Text Available The aim of the present study was to determine the lactation stage effect on the concentration of essential and selected toxic elements in the sheep’s milk of Dubrovačka ruda. The research was conducted with 23 sheep, average age of 4 years, of 3rd lactation, while the milk samples were taken during the early (60th day, middle (90th day and late (120th day lactation stage. The sheep were selected according to uniformed body development, adequate health status, body condition, equable age (4 years, parity (3rd lactation, stage of lactation (±7 days and litter size (single. Sheep were reared on the extensive Mediterranean pastures, reared indoors afterwards, fed with hay ad libitum and feed mixtures in average 0.5 kg/day. Milk sample was collected during morning milking from each sheep. The digested samples were analyzed with continuous flow hydride generation technique using inductively coupled plasma for Ca, Mg, K, P, Na, Cu, Fe, Zn, Mn, Ni, Mo, Co, Cr, Cd and Pb concentrations. Significant increase of Mg, Na, Se, Mn, Mo and Cd concentrations were found in milk as well as decrease of K concentration during the lactation. Although the concentration of Ca, Cu, Cr and As in milk during the lactation is increased, the differences between the lactation stages were not observed. Concentrations of P, Fe, Ni, Pb and Hg in milk of Dubrovačka ruda did not differ during the lactation. The low concentrations of Cr, Cd, Pb, As, Hg in milk indicate the safety for consumers and preserved environment of Dubrovnik-Neretva County.

  15. Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation.

    Science.gov (United States)

    Kajimoto, Masaki; Ledee, Dolena R; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G; Portman, Michael A

    2014-01-01

    Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. METHODS AND RESULTS: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon ((13)C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by(13)C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. T3 releases inhibition of lactate oxidation following IR injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

  16. Blood lactate recovery measurements, training, and performance during a 23-week period of competitive swimming.

    Science.gov (United States)

    Pelayo, P; Mujika, I; Sidney, M; Chatard, J C

    1996-01-01

    The purpose of this study was to relate measurements of blood lactate concentration, performance during a maximal anaerobic lactic test (MANLT) and training loads during a 23-week swimming season. Six elite 200-m freestyle male swimmers [mean age 19.5 (SD 1.6) years, height 184 (SD 5) cm and body mass 77.7 (SD 9.0) kg], participated in the study. The MANLT consisted of four all-out 50-m swims interspersed with 10-s recovery periods. Blood lactate concentrations were determined at 3 and 12-min post-exercise and were performed on weeks 2,6,10,14,18 and 21. Swimmers participated in 200-m freestyle competitions on weeks 1,7,13 and 23 (national championships). During weeks 1-10, training mostly involved aerobic exercise, while during weeks, 11-23, it involved anaerobic exercise. At 3-min and 12-min post-MANLT lactate concentrations varied throughout the season [range from 14.9 (SD 1.2) to 18.7 (SD 1.0) mmol.l-1] but demonstrated non-systematic variations. In contrast, the percentage of mean blood lactate decrease (% [La-]recovery) between min 3 and min 12 of the passive recovery post-MANLT increased from week 2 to 10 with aerobic training and decreased from week 10 to 21 with anaerobic training. The MANLT performance improved continuously throughout the season, while competition performance improved during the first three competitions but declined in the final championships, coinciding with the lowest % [La-]recovery and signs of overtraining, such as bad temper and increased sleeping heart rate. The results of this study indicated that % [La-]recovery could be an efficient marker for monitoring the impact of aerobic and anaerobic training and avoiding overtraining in elite 200-m swimmers.

  17. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

    1999-01-01

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  18. Arterial versus venous lactate: a measure of sepsis in children.

    Science.gov (United States)

    Samaraweera, Sahan Asela; Gibbons, Berwyck; Gour, Anami; Sedgwick, Philip

    2017-08-01

    This study assessed the agreement between arterial and venous blood lactate and pH levels in children with sepsis. This retrospective, three-year study involved 60 PICU patients, with data collected from electronic or paper patient records. The inclusion criteria comprised of children (≤17 years old) with sepsis and those who had a venous blood gas taken first with an arterial blood gas taken after within one hour. The lactate and pH values measured through each method were analysed. There is close agreement between venous and arterial lactate up to 2 mmol/L. As this value increases, this agreement becomes poor. The limits of agreement (LOA) are too large (±1.90 mmol/L) to allow venous and arterial lactate to be used interchangeably. The mean difference and LOA between both methods would be much smaller if derived using lactate values under 2.0 mmol/L. There is close agreement between arterial and venous pH (MD = -0.056, LOA ± 0.121). However, due to extreme variations in pH readings during sepsis, pH alone is an inadequate marker. A venous lactate ≤2 mmol/L can be used as a surrogate for arterial lactate during early management of sepsis in children. However, if the value exceeds 2 mmol/L, an arterial sample must confirm the venous result. What is known: • In children with septic shock, a blood gas is an important test to show the presence of acidosis and high lactic acid. Hyperlactataemia on admission is an early predictor of outcome and is associated with a greater mortality risk. • An arterial sample is the standard for lactate measurement, however getting a sample may be challenging in the emergency department or a general paediatric ward. Venous samples are quicker and easier to obtain. Adult studies generally advise caution in replacing venous lactate values for the arterial standard, whilst paediatric studies are limited in this area. What is new: • This is the first study assessing the agreement between arterial and peripheral venous

  19. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

    Science.gov (United States)

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

    2011-12-01

    Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

  20. Glucose homeostasis and metabolic adaptation in the pregnant and lactating sheep are affected by the level of nutrition previously provided during her late fetal life

    DEFF Research Database (Denmark)

    Husted, Sanne Munch; Nielsen, Mette Benedicte Olaf; Blache, D.

    2008-01-01

    during lactation. There was no effect of prenatal UN on glucose tolerance during G-IGTT, however, during RG-IGTT LOW was more glucose intolerant and apparently more insulin resistant compared to NORM. In conclusion, UN during late fetal life in sheep impairs subsequent pancreatic insulin secretory...... of a feed restriction period (RG-IGTT)), and a third around peak lactation (L-IGTT). LOW had lower basal insulin concentrations during lactation, and significantly decreased absolute insulin secretion during the L-IGTT in spite of similar glucose tolerance, indicating increased insulin sensitivity in LOW...... capacity during adult life, and reduces plasticity of down-regulation of insulin secretion in response to a metabolic challenge. Furthermore, prenatal UN appears to programme mechanisms, which in young adult females can shift the insulin hypersensitivity observed during early lactation into an insulin...

  1. The fate of 131I-17-iodoheptadecanoic acid during lactate loading: Its oxidation is strongly inhibited in favor of its esterification

    International Nuclear Information System (INIS)

    Duwel, C.M.B.; Visser, F.C.; Eenige, M.J. van; Roos, J.P.; Hollander, W. den

    1990-01-01

    The influence of lactate loading on fatty acid metabolism (pH = 7.4) by the normal canine heart was investigated radiochemically using the radioiodinated fatty acid 131 I-17-iodoheptadecanoic acid ( 131 I-17-HDA). Fatty acid metabolism was studied during control conditions (n = 8) and after lactate loading (n = 7). In the canine heart total myocardial 131 I-17-HDA radioactivity (uptake) was not changed during the lactate intervention. The oxidation decreased fivefold (measured as free 131 I-iodide ion) from 70% to 14% (p 131 I-17-HDA was mainly stored in the triglycerides and phosphoglycerides. These results suggest that lactate inhibits cardiac 131 I-HDA oxidation. (orig.) [de

  2. N-Acetylcysteine Supplementation Controls Total Antioxidant Capacity, Creatine Kinase, Lactate, and Tumor Necrotic Factor-Alpha against Oxidative Stress Induced by Graded Exercise in Sedentary Men

    Directory of Open Access Journals (Sweden)

    Donrawee Leelarungrayub

    2011-01-01

    Full Text Available Aim of this study was to evaluate the effects of short-term (7 days N-acetylcysteine (NAC at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO2max, total antioxidant capacity (TAC, lactate, creatine kinase (CK, and tumor necrotic factor-alpha (TNF-α. Twenty-nine sedentary men (13 controls; 16 in the supplement group from a randomized control were included. At before and after supplementation, fatigue index (FI was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO2max. Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO2max increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO2max, maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  3. MICROBIOLOGY AND SENSITIVITY PATTERN OF LACTATIONAL AND NON-LACTATIONAL BREAST ABSCESS IN SOUTHERN ODISHA

    Directory of Open Access Journals (Sweden)

    Niranjan Sahoo

    2017-10-01

    Full Text Available BACKGROUND Breast abscess is one of the most frequently encountered cases in the General Surgery OPD among females. This fact can be supported by the fact that 4.6% and 11% of the women in developed and developing countries are affected by breast abscess. Breast abscesses are generally categorised as one of two types: Lactational abscesses and non-lactational abscesses. MATERIALS AND METHODS The present study was conducted from December 2015 to January 2017 on female patients visiting the General Surgery OPD of MKCG Medical College and Hospital with presumptive diagnosis of breast abscess. Both lactational and non-lactational females were included in the study. A total of 53 subjects with breast abscess were included in the study. The diagnosis of breast abscess was made from the clinical signs and symptoms of infection. Patients having any benign or malignant disease of breast were excluded from the study. RESULTS Of the 53 specimens found positive for bacterial yield, 43 were monomicrobial and only 10 were polymicrobial. Out of the 53 samples collected, only 6 showed anaerobic growth. Most common aerobic Gram positive isolate found in the sample was Staphylococcus aureus followed by Staphylococcus epidermidis. Most common aerobic Gram negative organism isolated was Pseudomonas aeruginosa found in 14 cases followed by Escherichia coli in 10 cases. Anaerobic bacteria were found only in nonlactational breast abscess. Of the anaerobic isolates, 5 are monomicrobial and 1 was polymicrobial. Aerobic Gram positive isolates showed sensitivity to most of the commonly used antibiotics. All the 4 gram negative isolates were found to be 100% sensitive to Piperacillin Tazobactam combination and Imipenem/Cilastatin combination. Pseudomonas was found to be somewhat resistant to Amikacin, Levofloxacin and Cephalosporins. Anaerobes were found to be fully sensitive to Metronidazole, Clindamycin and Piperacillin-Tazobactam combination. CONCLUSION Hence, this

  4. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...

  5. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

  6. Cow's milk quality and energy value during different lactation stages.

    Science.gov (United States)

    Salamończyk, Ewa

    2013-01-01

    The quality of dairy products, raw milk in particular, depends on many factors. Low bacterial and somatic cell counts are basic determinants of the appropriate raw milk quality. The objective of the work was to assess the effect of selected factors, that is, the age of cows and their daily milk performance, on cytological quality (somatic cell count) and energy value of milk produced at individual stages of lactation. Somatic cell count and energy value of cow's milk were assessed. A total of 229 792 milk samples were examined. Data for analysis were taken from milk records of 350 dairy herds. It was demonstrated that, of all the lactations studied, the fi rst lactation (from calving to the 100th day of lactation) was characterised by the highest daily milk performance (25.1 kg) and the lowest somatic cell count (356 thous./1 ml), fat, protein and dry matter contents (4.06, 2.96 and 12.41%, respectively) and milk calorific value (732 kcal/kg). The highest energy value was recorded in cow's milk produced towards the end of lactation, that is from day 300 till the end of lactation (842 kcal/kg). High milk calorific value in late lactation and high fat and protein contents were accompanied by low raw milk quality.

  7. Colonic lactate metabolism and D-lactic acidosis

    DEFF Research Database (Denmark)

    Hove, H; Mortensen, P B

    1995-01-01

    D-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic produced D-lactate accumulates. An intestinal bypassed patient with D-lactic acidosis had higher fecal D-lactate (122.4 mmol/liter) and L-lactate (90.1 mmol/liter) than described before in humans. D......-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal liter) and between 1.1 and 52.8 mmol/liter in urine (normal liter) within a few hours, indicating that the human organism do metabolize and excrete D-lactate. The patient with D-lactic acidosis had a 10-fold increased DL......-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient with D-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasma D-lactate, but intestinal continuity was reestablished 26 months later because D-lactic acidosis recurred (plasma 8...

  8. Blood lactate kinetics in normal and stress-susceptible pigs

    International Nuclear Information System (INIS)

    Darrah, P.S.; Beitz, D.C.; Topel, D.G.; Christian, L.L.

    1981-01-01

    In vitro rates of lactate metabolism were determined in stress-susceptible (SS) and stress-resistant (SR) pigs. Three SR and three SS pigs were given 20 muCi of [U-/sup 14/C] L-lactate by a single injection method and resting blood lactate kinetics were measured. Seventeen blood samples were taken during the 60 min after injection. Lactate was separated from the deproteinized plasma by silicic acid column chromatography, and specific radioactivity was determined. Kinetic characteristics were calculated from plots of specific activity versus time. Pigs met steady-state requirements during the sampling period. There were no differences in kinetic characteristics of resting SS and SR pigs. Later, a second isotope injection was given after 5 min of electrical stress. Lactate pool sizes increased similarly in both types of pigs after stress; however, SS pigs had greater plasma lactate concentrations after stress. It is concluded that SS and SR pigs respond differently to stress but have similar capacities to metabolize lactate while resting

  9. Kinetics of lactate turnover and oxidation in man

    International Nuclear Information System (INIS)

    Searle, G.L.; Shames, D.; Cavalieri, R.R.; DeGrazia, J.; Zarcone, V.; Porte, D. Jr.; Bagdade, J.D.

    1975-01-01

    The turnover and oxidation of lactic acid have been studied in man by means of 14 C-lactic acid, 14 C-glucose, and 14 C-alanine. The use of these labels in separate studies has enabled us to describe a complete scheme for the kinetics of lactic acid in man. We have determined that lactate arises from a minimum of two sources in overnight fasted man. 66% of lactate at this time arises from the metabolism of glucose while approximately 15% is derived from alanine. These sources and others unidentified supply lactate to the body pool at a rate of approximately 95 mg per kg per h. The disposal of this quantity of lactate is achieved through a minimum of three routes. Approximately 57% of the lactate turnover is oxidized to carbon dioxide, 15% is reduced to glucose, and approximately 25% is converted to alanine. The quantitative changes in the kinetics of this system that are brought on by fasting add an interesting dimension to the system. In agreement with the concepts of fuel economy in fasting the contribution of glucose carbon to lactic acid falls and, in turn, the contribution of lactate carbon to body glucose rises. The study of additional permutations of this system suggest that lactate, with pyruvate, is in the main stream of the intermediary metabolism of the body. The authors suggest that the study of this system offers promise of a fuller understanding of the derangements of metabolic disease. (author)

  10. Effect of Glucogenic vs. Lipogenic Diets on Energy Balance, Blood Metabolites, and Reproduction in Primiparous and Multiparous Dairy Cows in Early Lactation

    NARCIS (Netherlands)

    Knegsel, van A.T.M.; Brand, van den H.; Dijkstra, J.; Straalen, van W.M.; Jorritsma, R.; Tamminga, S.; Kemp, B.

    2007-01-01

    Increasing the availability of glucogenic nutrients relative to lipogenic nutrients has been hypothesized to decrease the production of milk fat, to improve the energy balance (EB), and to decrease the incidence and severity of metabolic and reproductive disorders in dairy cows in early lactation.

  11. Cerebrospinal fluid lactate and pyruvate concentrations and their ratio.

    Science.gov (United States)

    Zhang, Wan-Ming; Natowicz, Marvin R

    2013-05-01

    Determinations of cerebrospinal fluid (CSF) lactate and pyruvate concentrations and CSF lactate:pyruvate (L/P) ratios are important in several clinical settings, yet published normative data have significant limitations. We sought to determine a large dataset of stringently-defined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios. We evaluated data from 627 patients who had determinations of CSF lactate and/or CSF pyruvate from 2001 to 2011 at the Cleveland Clinic. Inclusion in the normal reference population required normal CSF cell counts, glucose and protein and routine serum chemistries and absence of progressive brain disorder, epilepsy, or seizure within 24h. Brain MRI, if done, showed no evidence of tumor, acute changes or basal ganglia abnormality. CSF cytology, CSF alanine and immunoglobulin levels, and oligoclonal band analysis were required to be normal, if done. Various inclusion/exclusion criteria were compared. 92 patients fulfilled inclusion/exclusion criteria for a reference population. The 95% central intervals (2.5%-97.5%) for CSF lactate and pyruvate levels were 1.01-2.09mM and 0.03-0.15mM, respectively, and 9.05-26.37 for CSF L/P. There were no significant gender-related differences of CSF lactate or pyruvate concentrations or of CSF L/P. Weak positive correlations between the concentration of CSF lactate or pyruvate and age were noted. Using stringent inclusion/exclusion criteria, we determined normative data for CSF lactate and pyruvate concentrations and CSF L/P ratios in a large, well-characterized reference population. Normalcy of routine CSF and blood analytes are the most important parameters in determining reference intervals for CSF lactate and pyruvate. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. Breast cancer during pregnancy and lactation

    International Nuclear Information System (INIS)

    Meshikhes, Abdul-Wahed N.; Al-Mubarek, Mohammed A.; Al-Tufaif, Ahmed A.

    2004-01-01

    We report 3 cases of gestational breast cancer that were encountered by the authors over a year period (1998) and discuss the diagnostic dilemma and modern management options. The first case was a 38-year-old Saudi female who was 8 month pregnant presented with 3 month history of left breast lump and intermittent bloody nipple discharge. She started menarche at the age of 13 years and denied any past history of benign breast diseases or oral contraceptive pill. There was no family history of malignant breast disease. Clinical examination revealed an irregular hard lump (3x3 cm) in the subareolar area of the left breast with no palpable axillary or supraclavicular lymph nodes. Fine needle aspiration cytology (FNAC) showed infiltrating ductal carcinoma. She underwent left simple mastectomy and axillary clearance together with cesarian section (CS) and tubal ligation at the same time. Histology revealed grade II infiltrating ductal carcinoma with 2 of the 11 level I nodes were positive for malignancy. She later underwent adjuvant chemoradiation and remained well with no evidence of locoregional recurrence 34 months later. The second case was a 40-year-old Saudi female who has been lactating for 10 months presented with a left breast lump of one week duration. There was no history of breast pain or nipple discharge and denied any past history of benign breast disease. There was no family history of breast cancer. Clinically, there was a 2x3 cm irregular left breast mass, in the upper outer quadrant with no palpable axillary lymphadenopathy. Mammography revealed suspicious opacity in the left breast but bone scan and ultrasonography showed no bone or liver metastases. Fine needle aspiration cytology showed suspicious of malignancy. She underwent a wide excision and left axillary clearance. Histopathology showed grade II medullary carcinoma and 2 out of 20 axillary lymph nodes were malignant. She later underwent systemic chemotherapy and radiation to left breast and

  13. Blood lactate levels in 31 female dogs with pyometra

    Directory of Open Access Journals (Sweden)

    Karlstam Erika

    2009-01-01

    Full Text Available Abstract Background Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1 the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2 if these levels are related with the clinical status or other biochemical or hematological disorders. Methods In total 31 female dogs with pyometra admitted for surgical ovariohysterectomy and 16 healthy female control dogs were included in the present study. A complete physical examination including SIRS-status determination was performed. Blood samples for lactate concentrations, hematological and biochemical parameters, acid-base and blood gas analysis and other laboratory parameters were collected and subsequently analysed. The diagnosis pyometra was verified with histopathological examination of the uterus and ovaries. Increased hospitalisation length and presence of SIRS were used as indicators of outcome. Results In the pyometra group the median blood lactate level was 1,6 mmol l-1 (range -1. In the control group the median lactate level was 1,2 mmol l-1 (range -1. Of the 31 bitches 19 (61% fulfilled 2 or more criteria for SIRS at inclusion, 10 bitches (32% fulfilled 3 of the SIRS criteria whereas none accomplished more than 3 criteria. Lactate levels did not differ significantly between the pyometra and control group, or between the SIRS positive and SIRS negative dogs with pyometra. Increased lactate concentration (>2.5 mmol l-1 was demonstrated in one female dog with pyometra (3%, and was not associated with longer hospitalisation or presence of SIRS. Lactate

  14. Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

    Science.gov (United States)

    Farney, Jaymelynn K.; Mamedova, Laman K.; Coetzee, Johann F.; KuKanich, Butch; Sordillo, Lorraine M.; Stoakes, Sara K.; Minton, J. Ernest; Hollis, Larry C.

    2013-01-01

    Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation. PMID:23678026

  15. Effects of niacin supplementation on the insulin resistance in Holstein cows during early lactation

    Directory of Open Access Journals (Sweden)

    Talija Hristovska

    2017-01-01

    Full Text Available Insulin resistance in early lactation includes low glucose concentration, low insulin release and responsiveness and high lipolysis. Niacin is important antilipolytic agent and leads to increase glucose and insulin concentration. The objectives of this study were to determine the influence of niacin on the insulin resistance in cows during early lactation using the difference of value and regression analysis between blood non-esterified fatty acid (NEFA, glucose and insulin concentrations, revised quantitative insulin sensitivity check index and glucose-to-insulin ratio. Niacin supplementation led to a decrease of NEFA concentration and an increase of glucose and insulin concentrations during the first three weeks after calving. Cows in the niacin group which were more resistant to insulin showed higher concentrations of non-esterified fatty acid in comparison with more sensitive cows from the same group, but still lower than the control. The regression analyses suggest the following characteristics of cows supplemented with niacin in comparison with the control group: the insulin response to glucose was more intense; the antilipolytic effect of insulin was lower; insulin efficiency expressed as glucose-to-insulin ratio increase with a decrease in NEFA. The metabolic changes due to niacin supplementation showed a dual influence on the insulin resistance in dairy cows during early lactation: decreased NEFA concentrations led to a decrease in the insulin resistance (due to an increase in insulin efficiency and insulin sensitivity index, but increased concentrations of insulin and glucose possibly caused an increase in the insulin resistance in dairy cows (due to lower insulin sensitivity index and possibly lower antilipolytic effects of insulin.

  16. Short- and long-term effects of high milking frequency during the first 21 days of lactation on production and reproductive performance in high-lactating cows.

    Science.gov (United States)

    Shoshani, E; Cohen, M; Doekes, J J

    2017-01-01

    We examined short- and long-term effects of high milking frequency (HMF) for the first 21 days of lactation. The study included 122 Israeli Holstein cows - 32 pregnant heifers, 40 cows in second lactation and 50 cows in >second lactation. Heifers were paired according to predicted transmitting ability and cows according to energy-corrected milk (ECM) production, age, days in milk and expected calving date. Thin cows (body condition score second lactation cows relative to their control counterparts (-0.37%); ECM production was also higher in 6× milking first and second lactation (7.6% and 5%, respectively) but not for >second lactation cows. Furthermore, HMF had long-lasting effects, expressed as significantly higher milk production through the succeeding lactation in the previous first lactation cows (10%); a tendency toward significance in the second lactation cows relative to the controls (4.7%), but a deleterious effect on the >second lactation cows, reflected by lower milk production (-5.25%) than in controls; similar patterns were found for the ECM. For the entire 305 days of lactation, fat and protein yields were higher for first and second lactation cows, whereas protein yield for >second lactation cows was lower in the 6× milking v. Given that HMF during the first 21 days of first or second lactation increases milk and ECM yields throughout the concurrent and successive lactation with no adverse effect on energy balance, mastitis, metabolic diseases or reproduction, it seems to be economically beneficial. However, caution should be paid for >second lactation cows due to absence of significant effect in the entire of the first HMF applied lactation and the deleterious effect in the succeeding lactation.

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

    Directory of Open Access Journals (Sweden)

    Jiayang Qin

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  19. Insulin signaling disruption in male mice due to perinatal bisphenol A exposure: Role of insulin signaling in the brain.

    Science.gov (United States)

    Fang, Fangfang; Gao, Yue; Wang, Tingwei; Chen, Donglong; Liu, Jingli; Qian, Wenyi; Cheng, Jie; Gao, Rong; Wang, Jun; Xiao, Hang

    2016-03-14

    Bisphenol A (BPA), an environmental estrogenic endocrine disruptor, is widely used for producing polycarbonate plastics and epoxy resins. Available data have shown that perinatal exposure to BPA contributes to peripheral insulin resistance, while in the present study, we aimed to investigate the effects of perinatal BPA exposure on insulin signaling and glucose transport in the cortex of offspring mice. The pregnant mice were administrated either vehicle or BPA (100 μg/kg/day) at three perinatal stages. Stage I: from day 6 of gestation until parturition (P6-PND0 fetus exposure); Stage II: from lactation until delactation (PND0-PND21 newborn exposure) and Stage III: from day 6 of pregnancy until delactation (P6-PND21 fetus and newborn exposure). At 8 months of age for the offspring mice, the insulin signaling pathways and glucose transporters (GLUTs) were detected. Our data indicated that the insulin signaling including insulin, phosphorylated insulin receptor (IR), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular signal regulated protein kinase (p-ERK) were significantly decreased in the brain. In parallel, GLUTs (GLUT1/3/4) were obviously decreased as well in BPA-treated group in mice brain. Noteworthily, the phosphorylated tau (p-tau) and amyloid precursor protein (APP) were markedly up-regulated in all BPA-treated groups. These results, taken together, suggest the adverse effects of BPA on insulin signaling and GLUTs, which might subsequently contribute to the increment of p-tau and APP in the brain of adult offspring. Therefore, perinatal BPA exposure might be a risk factor for the long-term neurodegenerative changes in offspring male mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. EVALUATION OF OXIDATIVE STRESS IN DAIRY GOATS LACTATING NATURALLY OR BY HORMONAL INDUCTION

    Directory of Open Access Journals (Sweden)

    Rocio Teresa García-Balcázar

    2016-08-01

    Full Text Available The objective was to evaluate the oxidative stress (OS and its association with performance and serum cortisol in dairy goats under induced (IL and natural lactation (NL. Six goats programmed to be eliminated due to reproductive problems were IL as follows: a days 1-7, estradiol plus progesterone; b days 8-14, estradiol; c days 18-20, flumetasone; d every seven days bovine somatotropin; f on day 21 milking began. Cortisol, antioxidant capacity and Glutathione Peroxidase activity (GHS-Px were determined in serum. During the first two weeks in milk, NL goats had higher cortisol (P0.05. Milk yield/day between groups (NL=2.54+0.2; IL= 2.12+0.2kg and proportion of pregnant goats (NL=100%; IL=83.3% were similar (P>0.05. The treatment was effective as inductor of lactation; besides most of the IL animals became pregnant despite their previous reproductive problems, prolonging their productive life with a natural lactation plus the additional benefit of at least one more kid. Because the antioxidant capacity increased and cortisol decreased in IL goats, apparently their welfare was more adequate than in NL animals.

  1. Lactate Transporters Expression in Tumor of Balb/c Mice Bearing Breast Cancer after Endurance Training

    Directory of Open Access Journals (Sweden)

    M Aveseh

    2014-10-01

    Full Text Available Background & aim: Changes in the metabolism of cancer cells plays a major role in the survival and their expansion. The aim of this study was to determine expression of lactate transmitters in Balb/c mice with breast cancer after endurance training. Methods: In this experimental study twenty-five Balb C mice were randomly divided into two groups of breast cancer control (N=13 and breast cancer training (N=12. Breast cancer was induced in mammary fat pad by injection of cancer cells (MC4L2 in mice and endurance training protocol was applied for 7 weeks in the experimental group. Tumor volume and MCT1, MCT4, and CD147 expression were measured by micro digital caliper and western blotting technique respectively. Data were analyzed statistically using Student t and Pearson. Results: Significant decreases was found in weight and CD147 expression of tumor after 7 weeks of endurance training in the exercise group compared to the control group. No significant differences were seen in MCT4 expression and tumor volume between the groups (05 / 0p>0.05. Significant correlation was found between tumor MCT1 and CD147 expression (P < 0.05, while the relationship between MCT4 and CD147 expression in tumors was not statistically significant. Conclusion: Endurance training can reduce lactate metabolism in cancer cells through suppression of lactate transporters expression and provides a useful tool in breast cancer treatment or prevention.

  2. Radioimmunoassay of lactate dehydrogenase, H forms

    International Nuclear Information System (INIS)

    Malvano, R.; Massaglia, A.; Zannino, M.; Palmucci, F.; Cali, V.; Zucchelli, G.C.; Consiglio Nazionale delle Ricerche, Pisa

    1979-01-01

    Antisera to H 4 -lactate dehydrogenase (LDH) were elicited in rabbits, against both human (h) and porcine (p) isoenzymes. 125 I-labelled H 4 -LDH was prepared by electrolytic iodination. A simple and fast procedure (1-h incubation for clinical assays) was set up by using polyethylene glycol for the bound-free separation. The results obtained in the antiserum characterization indicated that the heterologous homotetramer, M 4 was completely discriminated in the porcine system, while a weak cross-reaction with human antisera resulted. In both cases, for the hybrid forms, a cross-reactivity level related to the stoichiometric contents of the H-subunit in the tetramers was observed. The H 4 -LDH from other species was found to be much more effectively distinguished in the procine than in the human system. The assay for human LDH was further validated in terms of analytical suitability and clinical response. For healthy subjects the mean concentration was 0.46 +- 0.19 μg/ml (mean +- SD). Patients with acute myocardial infarction had levels ranging from 1.2 to 5.9 μg/ml. (orig.) [de

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

    Science.gov (United States)

    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.

  4. The effect of CPAP treatment on venous lactate and arterial blood gas among obstructive sleep apnea syndrome patients.

    Science.gov (United States)

    Lin, Ting; Huang, Jie-Feng; Lin, Qi-Chang; Chen, Gong-Ping; Wang, Bi-Ying; Zhao, Jian-Ming; Qi, Jia-Chao

    2017-05-01

    The aim of this observational study was to investigate the influence of continuous positive airway pressure (CPAP) on arterial blood gas and venous lactate, markers of tissue hypoxia, among obstructive sleep apnea syndrome (OSAS) patients, and determine the risk factor of serum lactate and hydrogen ion concentration (PH) in OSAS patients. One-hundred and nine patients with newly diagnosed OSAS were enrolled in the study. All individuals were treated with CPAP for one night. Venous lactate and arterial blood gas were gathered from all subjects in the morning at the end of polysomnography and the next morning after CPAP treatment. Of the 109 selected subjects, the average lactate level was 2.23 ± 0.59 mmol/L, and the mean PH, PaO 2 , and PaCO 2 were 7.380 ± 0.23, 88.14 ± 17.83 mmHg, and 38.70 ± 4.28 mmHg, respectively. Compared to baseline, lactic acid significantly decreased (2.10 ± 0.50 mmol/L, p = 0.03), while PH increased (7.388 ± 0.27, p treatment. In addition, neck circumference and the polysomnographic parameters, including apnea-hypopnea index, oxygen desaturation index (ODI), mean oxygen saturation (SpO 2 ), and the percentage of sleep time with SpO 2 treatment could reduce serum lactate and increase PH in OSAS patients and might alleviate acid-base balance disorders in OSAS. Furthermore, TS90 % was a risk factor for elevated lactate, and age was independently associated with PH.

  5. Effects of high ambient temperature on urea-nitrogen recycling in lactating dairy cows.

    Science.gov (United States)

    Obitsu, Taketo; Kamiya, Mitsuru; Kamiya, Yuko; Tanaka, Masahito; Sugino, Toshihisa; Taniguchi, Kohzo

    2011-08-01

    Effects of exposure to hot environment on urea metabolism were studied in lactating Holstein cows. Four cows were fed ad libitum a total mixed ration and housed in a temperature-controlled chamber at constant moderate (18°C) or high (28°C) ambient temperatures in a cross-over design. Urea nitrogen (N) kinetics was measured by determining urea isotopomer in urine after single injection of [(15) N(2) ]urea into the jugular vein. Both dry matter intake and milk yield were decreased under high ambient temperature. Intakes of total N and digestible N were decreased under high ambient temperature but urinary urea-N excretion was increased. The ratio of urea-N production to digestible N was increased, whereas the proportion of gut urea-N entry to urea-N production tended to be decreased under high ambient temperature. Neither return to the ornithine cycle, anabolic use nor fecal excretion of urea-N recycled to the gut was affected by ambient temperature. Under high ambient temperature, renal clearance of plasma urea was not affected but the gut clearance was decreased. Increase of urea-N production and reduction of gut urea-N entry, in relative terms, were associated with increased urinary urea-N excretion of lactating dairy cows in higher thermal environments. 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  6. Quantified Effects of Late Pregnancy and Lactation on the Osmotic ...

    African Journals Online (AJOL)

    Quantified Effects of Late Pregnancy and Lactation on the Osmotic Stability of ... in the composition of erythrocyte membranes associated with the physiologic states. Keywords: Erythrocyteosmotic stability, osmotic fragility, late pregnancy, ...

  7. Antioxidant treatment attenuates lactate production in diabetic nephropathy

    DEFF Research Database (Denmark)

    Laustsen, Christoffer; Nielsen, Per Mose; Stokholm Nørlinger, Thomas

    2017-01-01

    -IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels......, indicating an intact glucose-alanine cycle, or [13C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment......The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying...

  8. Pregnant & Lactating Populations Research - NCS Dietary Assessment Literature Review

    Science.gov (United States)

    Identifying and studying additional biomarkers of energy and nutrient intake will advance validation efforts and lead to a better understanding of the biases and sources of measurement error in dietary assessment instruments in pregnant or lactating populations.

  9. Correlation of the association of serum lactate, random blood sugar ...

    African Journals Online (AJOL)

    Correlation of the association of serum lactate, random blood sugar, and revised trauma score as predictors of outcome in hemodynamically unstable abdominal emergencies. E Allwell‑Brown, OO Afuwape, O Ayandipo, T Alonge ...

  10. The pρT behaviour of the lactate family

    International Nuclear Information System (INIS)

    Lomba, Laura; Pino, M. Rosa; Lafuente, Carlos; Lopez, M. Carmen; Giner, Beatriz

    2013-01-01

    Highlights: ► PrhoT behaviour of three lactates are reported. ► The experimental results have been compared with the available literature data. ► TRIDENT model has been used to correlate experimental data of the compounds. ► Derived properties have been calculated from densities using Tait equation. -- Abstract: The densities of methyl lactate, ethyl lactate and butyl lactate have been measured using a high-pressure, high-temperature vibrating tube densimeter system over a temperature range from T = (283.15 to 338.15) K and a pressure range from p = (0.1 to 60.0) MPa. The experimental densities have been satisfactorily correlated with temperature and pressure using the TRIDEN equation. Finally, from the experimental densities, properties such as isobaric expansibility and isothermal compressibility have been calculated

  11. Calcium homeostasis during pregnancy and lactation: role of vitamin ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    skinned but also even Caucasian women tend to go into vitamin D deficiency during ... homeostasis in this phase of life is still controversial. Studies are .... calcium balance in lactating women. .... work on vitamin D. In general these authors.

  12. Lactational Vitamin E Protects Against the Histotoxic Effects of ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: The work investigated the protective role of lactational vitamin E administration on vanadium-induced histotoxicity. ... includes vitamin C, glutathione, selenium, and .... Int. J. Cancer: 120: 13-23. ... Vanadium (IV) mediated free radical.

  13. Ultrasonographic findings of breast diseases during pregnancy and lactating period

    International Nuclear Information System (INIS)

    Lee, Yeon Hee; Park, Yong Hyun; Kwon, Tae Hee

    1995-01-01

    To evaluate ultrasonographic findings and usefulness in the diagnosis of breast diseases during pregnancy and lactating period. The authors evaluated the ultrasonographic findings of 18 breast diseases during pregnancy and lactation retrospectively. The ultrasonographic examinations were performed with linear-array 5 MHz transducer (ATL). Final diagnoses were obtained by the excisional biopsy, fine needle aspiration and clinical follow-up. Total 18 cases of breast diseases were consisted of 8 cases of galactocele, 4 cases of fibroadenoma, 3 cases of axillary accessory breast, 2 cases of lactating adenoma, and 1 case of phylloides tumor. The ultrasonographic findings of the above breast diseases were valuable in the diagnosis and therapeutic planning. Ultrasonography is the initial and useful method of diagnosing breast diseases during pregnancy and lactating period

  14. Lactate transport and receptor actions in cerebral malaria

    DEFF Research Database (Denmark)

    Mariga, Shelton T; Kolko, Miriam; Gjedde, Albert

    2014-01-01

    in order to identify therapeutic targets. Here, we argue that cerebral energy metabolic defects are probable etiological factors in CM pathogenesis, because malaria parasites consume large amounts of glucose metabolized mostly to lactate. Monocarboxylate transporters (MCTs) mediate facilitated transfer...

  15. Ultrasonographic findings of breast diseases during pregnancy and lactating period

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeon Hee [Dnakook University College of Medicine, Cheonan (Korea, Republic of); Park, Yong Hyun; Kwon, Tae Hee [Cha Women' s Hospital of Seoul, Seoul (Korea, Republic of)

    1995-09-15

    To evaluate ultrasonographic findings and usefulness in the diagnosis of breast diseases during pregnancy and lactating period. The authors evaluated the ultrasonographic findings of 18 breast diseases during pregnancy and lactation retrospectively. The ultrasonographic examinations were performed with linear-array 5 MHz transducer (ATL). Final diagnoses were obtained by the excisional biopsy, fine needle aspiration and clinical follow-up. Total 18 cases of breast diseases were consisted of 8 cases of galactocele, 4 cases of fibroadenoma, 3 cases of axillary accessory breast, 2 cases of lactating adenoma, and 1 case of phylloides tumor. The ultrasonographic findings of the above breast diseases were valuable in the diagnosis and therapeutic planning. Ultrasonography is the initial and useful method of diagnosing breast diseases during pregnancy and lactating period.

  16. Histomorphormetric studies on lactational lead intoxication in testes

    African Journals Online (AJOL)

    2018-02-28

    Feb 28, 2018 ... This research work was designed to investigate the impact of lactational lead exposure on ..... How did lead get into our gasoline:retrieved from www. ... Supplementation against Damage Caused by Lead in the Testes of Mice.

  17. Correlation of the association of serum lactate, random blood sugar ...

    African Journals Online (AJOL)

    2015-09-21

    Sep 21, 2015 ... reversal of the physiologic and metabolic changes associated with consequent .... reduction in serum lactate levels, as well as RBG levels with a transient ... in our environment considering the cost and logistics in developing ...

  18. Muscle glycogen depletion and lactate concentration during downhill skiing.

    Science.gov (United States)

    Tesch, P; Larsson, L; Eriksson, A; Karlsson, J

    1978-01-01

    Skilled and unskilled skiers were studied during downhill skiing. Muscle glycogen and muscle lactate concentrations in the vastus lateralis muscle were determined following different skiing conditions. Heavy glycogen utilization was found in the groups studied during a day of skiing. The skilled and unskilled skiers differed with respect to selective glycogen depletion pattern and the skilled subjects demonstrated greater depletion of slow twitch fibers than the unskilled subjects. Lactate concentrations ranged from approximately 5-26 mmoles x kg-1 wet muscle after approximately one minute of maximal skiing. This wide range was not found to be related to the level of skiing proficiency. However, skiing with varyingly angled boots, resulting in different knee angles, did affect lactate concentration. Lactate concentration was positively correlated to individual muscle fiber composition expressed as a percent of fast twitch fibers. The results suggest more pronounced involvement of aerobic energy metabolism in skilled skiers than in unskilled skiers.

  19. Histomorphormetric studies on lactational lead intoxication in testes ...

    African Journals Online (AJOL)

    damped cotton wool in a vacuum (air-tight chamber). ... The animal was then perfused to clear blood from the organs before the organs were harvested, the testes of the pups exposed via lactation were observed via histological methods.

  20. Atraumatic femoral neck fracture secondary to prolonged lactation induced osteomalacia

    Directory of Open Access Journals (Sweden)

    Dhammapal Sahebrao Bhamare

    2013-01-01

    Full Text Available Presenting a case of atraumatic fracture neck femur secondary to 2 years of prolonged lactation. A 26-year-old lactating mother presented with pain in left hip from last 12 months. She was apparently alright before and during pregnancy. Plain radiograph showed a complete undisplaced fracture of femoral neck. Osteomalacia was diagnosed by radiological and serological investigations. The fracture was fixed using AO type cannulated cancellous screws. The fracture showed good clinical and radiological union at 3 months. Literature review shows that this is a first case of atraumatic fracture of neck femur due to prolonged lactational osteomalacia. It showed that even apparently healthy Indians are susceptible to osteomalacia, more so during pregnancy and lactation and can be presented as atraumatic fracture. Although considered relatively stable, a compression type incomplete fracture neck femur may progress to a complete fracture if not treated in time.

  1. Intravenous lipid infusion affects dry matter intake, methane yield, and rumen bacteria structure in late-lactating Holstein cows.

    Science.gov (United States)

    Lamp, Ole; Reyer, Henry; Otten, Winfried; Nürnberg, Gerd; Derno, Michael; Wimmers, Klaus; Metges, Cornelia C; Kuhla, Björn

    2018-03-28

    Increasing the dietary fat content of ruminant diets decreases methane (CH 4 ) production. This effect is caused by the toxic properties of fatty acids on rumen microbial populations, coating of feed particles diminishing the accessibility for microbes, and a reduction in dry matter intake (DMI). The latter effect is caused by postabsorptive long-chain fatty acids eliciting anorexic signaling; however, whether circulating long-chain fatty acids affect rumen CH 4 production alike is unknown. To approach this question, 5 rumen-cannulated Holstein cows in late lactation received 2 jugular catheters and were kept in respiration chambers to measure CH 4 production and DMI for 48 h. In a crossover design, cows were intravenously infused with a 20% lipid emulsion (LIPO) or 0.9% NaCl (CON). The LIPO cows received 2.1 kg of triglycerides/d [0.152 ± 0.007 g of triglycerides/(kg of BW × h) -1 ] consisting of 12.1% palmitic acid, 4.2% stearic acid, 31.1% oleic acid, and 52.7% linoleic acid. Blood and rumen fluid samples were taken hourly during the day. Results showed that LIPO compared with CON infusion increased plasma triglyceride as well as free fatty acid and serotonin concentrations but reduced the proportion of de novo synthesized milk fatty acids (sum of C6 to C16). Daily CH 4 production and DMI were lower, whereas daily CH 4 yield (CH 4 /DMI) was greater in LIPO than CON cows, although CH 4 yield decreased from d 1 to d 2 by 2 to 14% in LIPO-infused cows only. This effect was associated with a higher (acetate + butyrate)/propionate ratio, tending lower propionate concentrations between 24 and 34 h of infusion, reduced relative abundances of genera belonging to Succinivibrio, Ruminococcaceae, and Ruminiclostridium, and greater relative Bacteroidetes genus abundances in the rumen. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Hypergravity disruption of homeorhetic adaptations to lactation in rat dams include changes in circadian clocks

    Directory of Open Access Journals (Sweden)

    Theresa Casey

    2012-04-01

    Altered gravity load induced by spaceflight (microgravity and centrifugation (hypergravity is associated with changes in circadian, metabolic, and reproductive systems. Exposure to 2-g hypergravity (HG during pregnancy and lactation decreased rate of mammary metabolic activity and increased pup mortality. We hypothesize HG disrupted maternal homeorhetic responses to pregnancy and lactation are due to changes in maternal metabolism, hormone concentrations, and maternal behavior related to gravity induced alterations in circadian clocks. Effect of HG exposure on mammary, liver and adipose tissue metabolism, plasma hormones and maternal behavior were analyzed in rat dams from mid-pregnancy (Gestational day [G]11 through early lactation (Postnatal day [P]3; comparisons were made across five time-points: G20, G21, P0 (labor and delivery, P1 and P3. Blood, mammary, liver, and adipose tissue were collected for analyzing plasma hormones, glucose oxidation to CO2 and incorporation into lipids, or gene expression. Maternal behavioral phenotyping was conducted using time-lapse videographic analyses. Dam and fetal-pup body mass were significantly reduced in HG in all age groups. HG did not affect labor and delivery; however, HG pups experienced a greater rate of mortality. PRL, corticosterone, and insulin levels and receptor genes were altered by HG. Mammary, liver and adipose tissue metabolism and expression of genes that regulate lipid metabolism were altered by HG exposure. Exposure to HG significantly changed expression of core clock genes in mammary and liver and circadian rhythms of maternal behavior. Gravity load alterations in dam's circadian system may have impacted homeorhetic adaptations needed for a successful lactation.

  3. Conventional hemofiltration during cardiopulmonary bypass increases the serum lactate level in adult cardiac surgery

    Directory of Open Access Journals (Sweden)

    Rabie Soliman

    2016-01-01

    Full Text Available Objective: To evaluate the effect of hemofiltration during cardiopulmonary bypass on lactate level in adult patients who underwent cardiac surgery. Design: An observational study. Setting: Prince Sultan cardiac center, Riyadh, Saudi Arabia. Participants: The study included 283 patients classified into two groups: Hemofiltration group (n=138, hemofiltration was done during CPB. Control group (n = 145, patients without hemofiltration. Interventions: Hemofiltration during cardiopulmonary bypass. Measurements and Main Results: Monitors included hematocrit, lactate levels, mixed venous oxygen saturation, amount of fluid removal during hemofiltration and urine output. The lactate elevated in group H than group C (P < 0.05, and the PH showed metabolic acidosis in group H (P < 0.05. The mixed venous oxygen saturation decreased in group H than group C (P < 0.05. The number of transfused packed red blood cells was lower in group H than group C (P < 0.05. The hematocrit was higher in group H than group C (P < 0.05. The urine output was lower in group H than group C (P < 0.05. Conclusions: Hemofiltration during cardiopulmonary bypass leads to hemoconcentration, elevated lactate level and increased inotropic support. There are some recommendations for hemofiltration: First; Hemofiltration should be limited for patients with impaired renal function, positive fluid balance, reduced response to diuretics or prolonged bypass time more than 2 hours. Second; Minimal amount of fluids should be administered to maintain adequate cardiac output and reduction of priming volumes is preferable to maintain controlled hemodilution. Third; it should be done before weaning of or after cardiopulmonary bypass and not during the whole time of cardiopulmonary bypass.

  4. Prognostic value of lactate clearance in severe community acquired pneumonia

    OpenAIRE

    Mohamed, Kamel Abd Elaziz; Ahmed, Dief Abd Elgalil

    2014-01-01

    Introduction: Severe community acquired pneumonia (SCAP) occurs in approximately 18–36% of all CAP and the mortality rate could be as high as 67% in patients with SCAP. Several studies have described a correlation between baseline lactate concentration and mortality of ICU patients. Aim of the work: To follow lactate clearance after admission for 24 h which could be an indicator of outcome in severe community acquired pneumonia. Patients and methods: Forty-six consecutively admitted adu...

  5. Survey Of Ketosis In Lactating Wadara Cows | Igbokwe | Tropical ...

    African Journals Online (AJOL)

    Milk samples collected from 203 lactating Wadara cows at various periods of lactation from April to August, 1999, in Borno State, Nigeria, were negative for ketones by Rothera\\'s test. The protein, lactose, fat and total solids contents of 30 milk samples were 12.5 6.7mg/ml, 12.3 2.0mg/ml, 3.2 1.2% and 12.9 2.8%, ...

  6. Methods for early prediction of lactation flow in Holstein heifers

    Directory of Open Access Journals (Sweden)

    Vesna Gantner

    2010-12-01

    Full Text Available The aim of this research was to define methods for early prediction (based on I. milk control record of lactation flow in Holstein heifers as well as to choose optimal one in terms of prediction fit and application simplicity. Total of 304,569 daily yield records automatically recorded on a 1,136 first lactation Holstein cows, from March 2003 till August 2008., were included in analysis. According to the test date, calving date, the age at first calving, lactation stage when I. milk control occurred and to the average milk yield in first 25th, T1 (and 25th-45th, T2 lactation days, measuring monthcalving month-age-production-time-period subgroups were formed. The parameters of analysed nonlinear and linear methods were estimated for each defined subgroup. As models evaluation measures,adjusted coefficient of determination, and average and standard deviation of error were used. Considering obtained results, in terms of total variance explanation (R2 adj, the nonlinear Wood’s method showed superiority above the linear ones (Wilmink’s, Ali-Schaeffer’s and Guo-Swalve’s method in both time-period subgroups (T1 - 97.5 % of explained variability; T2 - 98.1 % of explained variability. Regarding the evaluation measures based on prediction error amount (eavg±eSD, the lowest average error of daily milk yield prediction (less than 0.005 kg/day, as well as of lactation milk yield prediction (less than 50 kg/lactation (T1 time-period subgroup and less than 30 kg/lactation (T2 time-period subgroup; were determined when Wood’s nonlinear prediction method were applied. Obtained results indicate that estimated Wood’s regression parameters could be used in routine work for early prediction of Holstein heifer’s lactation flow.

  7. Lactate dehydrogenase activity is inhibited by methylmalonate in vitro.

    Science.gov (United States)

    Saad, Laura O; Mirandola, Sandra R; Maciel, Evelise N; Castilho, Roger F

    2006-04-01

    Methylmalonic acidemia (MMAemia) is an inherited metabolic disorder of branched amino acid and odd-chain fatty acid metabolism, involving a defect in the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A. Systemic and neurological manifestations in this disease are thought to be associated with the accumulation of methylmalonate (MMA) in tissues and biological fluids with consequent impairment of energy metabolism and oxidative stress. In the present work we studied the effect of MMA and two other inhibitors of mitochondrial respiratory chain complex II (malonate and 3-nitropropionate) on the activity of lactate dehydrogenase (LDH) in tissue homogenates from adult rats. MMA potently inhibited LDH-catalyzed conversion of lactate to pyruvate in liver and brain homogenates as well as in a purified bovine heart LDH preparation. LDH was about one order of magnitude less sensitive to inhibition by MMA when catalyzing the conversion of pyruvate to lactate. Kinetic studies on the inhibition of brain LDH indicated that MMA inhibits this enzyme competitively with lactate as a substrate (K (i)=3.02+/-0.59 mM). Malonate and 3-nitropropionate also strongly inhibited LDH-catalyzed conversion of lactate to pyruvate in brain homogenates, while no inhibition was observed by succinate or propionate, when present in concentrations of up to 25 mM. We propose that inhibition of the lactate/pyruvate conversion by MMA contributes to lactate accumulation in blood, metabolic acidemia and inhibition of gluconeogenesis observed in patients with MMAemia. Moreover, the inhibition of LDH in the central nervous system may also impair the lactate shuttle between astrocytes and neurons, compromising neuronal energy metabolism.

  8. Serum and breast-milk vitamin A in women during lactation in rural Chiang Mai, Thailand

    NARCIS (Netherlands)

    Panpanich, Ratana; Vitsupakorn, Kannika; Harper, Gregory; Brabin, Bernard

    2002-01-01

    Vitamin A deficiency can occur during lactation and breast-milk vitamin A has been recommended for monitoring the vitamin A status of lactating women and their infants. This study aimed to investigate the vitamin A status of lactating women in relation to race, age, parity, duration of lactation and

  9. Decreasing Fires in Mediterranean Europe.

    Directory of Open Access Journals (Sweden)

    Marco Turco

    Full Text Available Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value. These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011 and a mixed trend in Portugal (1980-2011. Similar overall results were found for the annual number of fires (NF, which globally decreased by about 12600 in the study period (about -59%, except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  10. Decreasing Fires in Mediterranean Europe.

    Science.gov (United States)

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  11. Excretion of Calcium, Phosphorus, Magnesium and Sodium in Lactating Sows

    Directory of Open Access Journals (Sweden)

    Novotný J.

    2016-06-01

    Full Text Available The aim of this study was to evaluate the excretion of calcium (Ca, phosphorus (P, magnesium (Mg and sodium (Na via milk, urine and faeces during the lactation period of sows. Six clinically healthy lactating sows (crossbreed Large White × Landrace were selected for these experiments and were housed in standard conditions and fed with commercially prepared dry mixture for this category of sows. The blood serum, milk, urine and faecal samples were collected on the 7th, 14th, 21st, and 28th day of lactation. During four weeks of lactation, we recorded the relatively stable and physiological concentrations of Ca, P, Mg and Na in blood serum. The analysis of the sow’s milk showed the highest concentration of Ca and P at the end of lactation, while the highest concentration of Mg and Na was observed on the 7th lactation day. The following macro-mineral excretion was recorded in urine: 98.83-194.00 mg.l-1 for Ca; 11.88- 53.09 mg.l-1 for P; 171.67-344.05 mg.l-1 for Mg; and 56.50-74.83 mg.l-1 for Na; and in the faeces, 1824.5- 3045.5 mg.kg-1 for Ca; 1566.93-2483.2 mg.kg-1 for P; 1916.2-2505.2 mg.kg-1 for Mg; and 516.8-748.2 mg. kg-1 for Na.

  12. ARALAR/AGC1 deficiency, a neurodevelopmental disorder with severe impairment of neuronal mitochondrial respiration, does not produce a primary increase in brain lactate.

    Science.gov (United States)

    Juaristi, Inés; García-Martín, María L; Rodrigues, Tiago B; Satrústegui, Jorgina; Llorente-Folch, Irene; Pardo, Beatriz

    2017-07-01

    ARALAR/AGC1 (aspartate-glutamate mitochondrial carrier 1) is an important component of the NADH malate-aspartate shuttle (MAS). AGC1-deficiency is a rare disease causing global cerebral hypomyelination, developmental arrest, hypotonia, and epilepsy (OMIM ID #612949); the aralar-KO mouse recapitulates the major findings in humans. This study was aimed at understanding the impact of ARALAR-deficiency in brain lactate levels as a biomarker. We report that lactate was equally abundant in wild-type and aralar-KO mouse brain in vivo at postnatal day 17. We find that lactate production upon mitochondrial blockade depends on up-regulation of lactate formation in astrocytes rather than in neurons. However, ARALAR-deficiency decreased cell respiration in neurons, not astrocytes, which maintained unchanged respiration and lactate production. As the primary site of ARALAR-deficiency is neuronal, this explains the lack of accumulation of brain lactate in ARALAR-deficiency in humans and mice. On the other hand, we find that the cytosolic and mitochondrial components of the glycerol phosphate shuttle are present in astrocytes with similar activities. This suggests that glycerol phosphate shuttle is the main NADH shuttle in astrocytes and explains the absence of effects of ARALAR-deficiency in these cells. © 2017 International Society for Neurochemistry.

  13. Effects of ultrasound treatment on physico-chemical, functional properties and antioxidant activity of whey protein isolate in the presence of calcium lactate.

    Science.gov (United States)

    Jiang, Zhanmei; Yao, Kun; Yuan, Xiangying; Mu, Zhishen; Gao, Zengli; Hou, Juncai; Jiang, Lianzhou

    2018-03-01

    The aim of this study was to investigate the effects of ultrasound applied at various powers (0, 200, 400, 600 or 800 W) and for different times (20 or 40 min) on the physico-chemical, functional properties and antioxidant activities of whey protein isolate (WPI) dispersions in the presence of 1.20 mmol L -1 calcium lactate. Surface hydrophobicity and free sulfhydryl group of the WPI dispersions containing 1.2 mmol L -1 calcium lactate were significantly enhanced after sonication. Furthermore, particle size of WPI dispersions containing 1.20 mmol L -1 calcium lactate was minimised after sonication. Scanning electron microscopy of sonicated WPI suspensions containing 1.20 mmol L -1 calcium lactate showed that WPI microstructure had significantly changed. After WPI dispersions were treated by sonication assisted with calcium lactate, its gel strength enhanced and solubility decreased. Gel strength of sonicated WPI dispersions (600 W, 40 min) was the maximum among all the WPI treatments. Emulsification activity of sonicated WPI dispersions reduced while its emulsion stability increased. The DPPH radical scavenging activity and ferrous reducing power of sonicated WPI dispersions mostly increased. Ultrasound treatments induced structural changes in WPI molecules, leading to different microstructure and improved gel strength of WPI in the presence of calcium lactate. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  14. Milk yield, composition and qua­li­ty of organic milk of ewes crossbreeds of Lacaune, East Friesian and Improved Wallachian during lactation

    Directory of Open Access Journals (Sweden)

    Michaela Pokorná

    2009-01-01

    Full Text Available Evaluation of milk yield, composition and quality of organic milk of crossbreeds of Lacaune (L, East Friesian (EF and Improved Wallachian (IW, (n = 10, L 50 EF 43.75 IW 6.25 during lactation was carried out on organic farm in Valašská Bystřice in 2007. All sheep were on the third lactation and during study they were reared on permanent pasture. The stage of lactation (SL had a highly significant effect on milk yield (MY and contents of total solids (TS, fat (F, protein (P, casein (C, lactose (L and urea (U. The SL had also a highly significant effect on pH and titrable acidity (TA, whereas on rennet clotting time (RCT the SL had a significant effect. On the other hand the SL had not a significant effect on somatic cell counts (SCC and rennet curd quality (RCQ. The highest contents of TS, F and C were found at the end of the lactation, whereas their lowest contents were found on the 120th day. Between the second and the last sampling the lactose content decreased. The content of U and RCT were the most variable indicators whithin the frame of our study. On the other hand SCCs were, during the whole lactation, very well-balanced and relatively low. Between pH and SCC was found positive correlation. TA gradually increased and RCT gradually prolonged with advanced lactation.

  15. Application of L-lactate-cytochrome c-oxidoreductase for development of amperometric biosensor for L-lactate determination

    Directory of Open Access Journals (Sweden)

    Dzyadevych S. V.

    2009-06-01

    Full Text Available Aim. Development of amperometric biosensor based on L-lactate-cytochrome c-oxidoreductase (flavocytochrome b2, FC b2 for lactate determination. Methods. All experiments were performed using the amperometric method of detection. The methods of electrochemical polymerization and immobilization in glutaraldehyde vapors were used for FC b2 immobilization on the surface of electrodes. Results. The FC b2 preparation, which demonstrated the best operational characteristics after immobilization in poly (3,4-ethylen dioxythiophene, was selected. The selectivity, operational and storage stability, and pH-optimum for operation of the created biosensor were determined. The analysis of L-lactate in the model solutions and wine samples was carried outusing the developed biosensor. Conclusion. The FC b2-based biosensor due to its high stability can be effectively used for lactate determination in blood and other liquids containing no ethanol. After the selectivity optimization, the devise can be also applied for wine analysis.

  16. The effect of extracellular alkalinization on lactate metabolism of breast cancer stem cells: Overview of LDH-A, LDH-B, MCT1 and MCT4 gene expression

    Science.gov (United States)

    Neolaka, G. M. G.; Yustisia, I.; Sadikin, M.; Wanandi, S. I.

    2017-08-01

    Changes in the metabolic status of cancer cells are presumed to be correlated with the adjustment of these cells to extracellular changes. Cell glycolysis increases the production of intracellular lactate catalyzed by the lactate dehydrogenases, both LDH-A and LDH-B. An increase in intracellular lactate can affect extracellular pH balance through monocarboxylate transporters, particularly MCT1 and MCT4. This study aimed to analyze the effects of extracellular alkalinization on the lactate metabolism of human breast cancer stem cells (BCSCs). In this study, human primary BCSCs (CD24-/CD44+ cells) were treated with 100 mM sodium bicarbonate for 0.5, 24, and 48 h in DMEM F12/HEPES. After incubation, extracellular pH was measured and cells were harvested to extract the total RNA and protein. The expression of LDH-A, LDH-B, MCT1, and MCT4 mRNA genes were analyzed using qRT-PCR method. Our study shows that administration of sodium bicarbonate in the BCSC culture medium could increase extracellular pH. To balance the increase of extracellular pH, BCSCs regulated the expression of LDH-A, LDH-B, MCT1, and MCT4 genes. As the extracellular pH increases, the expression of LDH-A that converts pyruvate to lactate increased along with the increase of MCT 4 and MCT 1 expression, which act as lactate transporters. As the incubation time increases, the pH decreases, leading to the suppression of LDH-A and increase of LDH-B expression that converts lactate into pyruvate. Therefore, we suggest that the extracellular alkalinization by sodium bicarbonate in BCSCs affected the genes that regulate lactate metabolism.

  17. Non-Invasive Detection of Lactate as a Biomarker of Response using Spectral Selective Multiple Quantum Editing Sequence (SS-SelMQC)

    Science.gov (United States)

    2013-11-01

    phantoms with known concentrations (Lac with without Gd-DTPA doping , and Lac/Lip solutions). Once the RF coils are optimized, signal to noise (SNR...cylindrical phantoms (10mm and 15mm diameter) with 5, 15 and 30 mM lactate/ saline doped with and without 25 μΜ Gd-DPTA solutions. For Lac/Lip...approach to lactate production in human skeletal muscle during exercise. Med Sci Sports Exerc 2000;32:756–63. 51. Maekawa M, Sudo K, Li SS, Kanno T

  18. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  19. Measurand transient signal suppressor

    Science.gov (United States)

    Bozeman, Richard J., Jr. (Inventor)

    1994-01-01

    A transient signal suppressor for use in a controls system which is adapted to respond to a change in a physical parameter whenever it crosses a predetermined threshold value in a selected direction of increasing or decreasing values with respect to the threshold value and is sustained for a selected discrete time interval is presented. The suppressor includes a sensor transducer for sensing the physical parameter and generating an electrical input signal whenever the sensed physical parameter crosses the threshold level in the selected direction. A manually operated switch is provided for adapting the suppressor to produce an output drive signal whenever the physical parameter crosses the threshold value in the selected direction of increasing or decreasing values. A time delay circuit is selectively adjustable for suppressing the transducer input signal for a preselected one of a plurality of available discrete suppression time and producing an output signal only if the input signal is sustained for a time greater than the selected suppression time. An electronic gate is coupled to receive the transducer input signal and the timer output signal and produce an output drive signal for energizing a control relay whenever the transducer input is a non-transient signal which is sustained beyond the selected time interval.

  20. Exercise Increases Cystathionine-γ-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats.

    Science.gov (United States)

    Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Lu, Jianqiang

    2016-01-01

    Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling.

  1. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-09-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  2. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-12-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  3. Vitamin D Levels Among Pregnant and Lactating Women

    International Nuclear Information System (INIS)

    Sharif, S.; Farasat, T.; Fazal, S.

    2013-01-01

    Objective: To assess the serum level of vitamin D in pregnant and lactating women. Study Design: Case-control study. Place and Duration of Study: Gynaecological Unit 1 of Jinnah Hospital, Lahore, from December 2010 to May 2011. Methodology: A total of 100 women comprised of three groups: pregnant (n = 40), lactating (n = 40) and control (n = 20) groups. The information regarding age, educational level, socioeconomic status, exposure to sunlight and dietary vitamin D intake were collected through self-structured questionnaire. Serum concentration of vitamin D was measured by ELISA and serum calcium and phosphate levels were measured by chemistry analyzer. Statistical analysis was done using SPSS (version 13). The values were considered significant at 0.05 level of significance. Results: The mean serum vitamin D level in the pregnant and lactating mothers was 26.5 +- 17.1 nmol/L and 21.4 +- 16.3 nmol/L respectively and in control group was 33.8 +- 21.1 nmol/L. The mean calcium level in the pregnant, lactating and control group was 10.3 +- 1.2 mg/dL, 9.7 +- 1.3 mg/dL and 9.7 +- 1.3 mg/dL respectively. The mean phosphate in pregnant was 3.2 +- 0.76 mg/dl, in lactating was 3.3 +- 0.76 mg/dl and in control was 3.5 +- 0.92 mg/dl. Significant difference (p = 0.041 and p = 0.037 respectively) in the serum levels of vitamin D and calcium was observed among the pregnant and lactating women as compared to control group. Conclusion: Low serum vitamin D concentration was observed in lactating women and pregnant women as compared to control group. (author)

  4. Vitamin D levels among pregnant and lactating women.

    Science.gov (United States)

    Sharif, Saima; Farasat, Tasnim; Shoaib, Hamna; Saqib, Muhammad; Fazal, Sabiha

    2013-12-01

    To assess the serum level of vitamin D in pregnant and lactating women. Case-control study. Gynaecological Unit 1 of Jinnah Hospital, Lahore, from December 2010 to May 2011. A total of 100 women comprised of three groups: pregnant (n = 40), lactating (n = 40) and control (n = 20) groups. The information regarding age, educational level, socioeconomic status, exposure to sunlight and dietary vitamin D intake were collected through self-structured questionnaire. Serum concentration of vitamin D was measured by ELISA and serum calcium and phosphate levels were measured by chemistry analyzer. Statistical analysis was done using SPSS (version 13). The values were considered significant at 0.05 level of significance. The mean serum vitamin D level in the pregnant and lactating mothers was 26.5 ± 17.1 nmol/L and 21.4 ± 16.3 nmol/L respectively and in control group was 33.8 ± 21.1 nmol/L. The mean calcium level in the pregnant, lactating and control group was 10.3 ± 1.2 mg/dL, 9.7 ± 1.3 mg/dL and 9.7 ± 1.3 mg/dL respectively. The mean phosphate in pregnant was 3.2 ± 0.76 mg/dl, in lactating was 3.3 ± 0.76 mg/dl and in control was 3.5 ± 0.92 mg/dl. Significant difference (p = 0.041 and p = 0.037 respectively) in the serum levels of vitamin D and calcium was observed among the pregnant and lactating women as compared to control group. Low serum vitamin D concentration was observed in lactating women and pregnant women as compared to control group.

  5. Substitution of Tyr254 with Phe at the active site of flavocytochrome b2: consequences on catalysis of lactate dehydrogenation

    International Nuclear Information System (INIS)

    Dubois, J.; Chapman, S.K.; Mathews, F.S.; Reid, G.A.; Lederer, F.

    1990-01-01

    A role for Tyr254 in L-lactate dehydrogenation catalyzed by flavocytochrome b2 has recently been proposed on the basis of the known active-site structure and of studies that had suggested a mechanism involving the initial formation of a lactate carbanion. This role is now examined after replacement of Tyr254 with phenylalanine. The kcat is decreased about 40-fold, Km for lactate appears unchanged, and the mainly rate-limiting step is still alpha-hydrogen abstraction, as judged from the steady-state deuterium isotope effect. Modeling studies with lactate introduced into the active site indicate two possible substrate conformations with different hydrogen-bonding partners for the substrate hydroxyl. If the hydrogen bond is formed with Tyr254, as was initially postulated, the mechanism must involve removal by His373 of the C2 hydrogen, with carbanion formation. If, in the absence of the Tyr254 phenol group, the hydrogen bond is formed with His373 N3, the substrate is positioned in such a way that the reaction must proceed by hydride transfer. Therefore the mechanism of the Y254F enzyme was investigated so as to distinguish between the two mechanistic possibilities. 2-Hydroxy-3-butynoate behaves with the mutant as a suicide reagent, as with the wild-type enzyme. Similarly, the mutant protein also catalyzes the reduction and the dehydrohalogenation of bromopyruvate under transhydrogenation conditions

  6. Dietary verbascoside supplementation in donkeys: effects on milk fatty acid profile during lactation, and serum biochemical parameters and oxidative markers.

    Science.gov (United States)

    D'Alessandro, A G; Vizzarri, F; Palazzo, M; Martemucci, G

    2017-09-01

    Various uses of donkeys' milk have been recently proposed for human consumption on the basis of its nutritional characteristics. Improvements in milk fatty acid profile and animal oxidative status can be induced through dietary supplementation of phenolic compounds. The study aimed to evaluate in donkeys the effects of dietary supplementation with verbascoside (VB) on: (i) the fatty acid profile and vitamins A and E contents of milk during a whole lactation, and (ii) blood biochemical parameters and markers of oxidative status of the animals. At foaling, 12 lactating jennies were subdivided into two groups (n 6): control, without VB supplement; VB, receiving a lipid-encapsulated VB supplement. Gross composition, fatty acid profile and vitamins A and E contents in milk were assessed monthly over the 6 months of lactation. Serum total cholesterol, high-density lipoproteins cholesterol and low-density lipoproteins cholesterol, tryglicerides, non-esterified fatty acid, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase, reactive oxygen metabolites, thiobarbituric acid reactive substances (TBARs), vitamin A and vitamin E were evaluated at 8 days after foaling (D0) and then at D90, D105 and D120 of lactation. In milk, the VB supplementation decreased the saturated fatty acids (Pdonkey's milk with a benefit on the oxidative status and serum lipidic profile of the animals.

  7. Increasing milk solids production across lactation through genetic selection and intensive pasture-based feed system.

    Science.gov (United States)

    Coleman, J; Pierce, K M; Berry, D P; Brennan, A; Horan, B

    2010-09-01

    The objective of the study was to quantify the effect of genetic improvement using the Irish total merit index, the Economic Breeding Index (EBI), on overall performance and lactation profiles for milk, milk solids, body weight (BW), and body condition score (BCS) within 2 pasture-based systems of milk production likely to be used in the future, following abolition of the European Union's milk quota system. Three genotypes of Holstein-Friesian dairy cattle were established from within the Moorepark dairy research herd: LowNA, indicative of animals with North American origin and average or lower genetic merit at the time of the study; HighNA, North American Holstein-Friesians of high genetic merit; and HighNZ, New Zealand Holstein-Friesians of high genetic merit. Animals from within each genotype were randomly allocated to 1 of 2 possible pasture-based feeding systems (FS): 1) The Moorepark pasture (MP) system (2.64 cows/ha and 344 kg of concentrate supplement per cow per lactation) and 2) a high output per hectare (HC) system (2.85 cows/ha and 1,056 kg of concentrate supplement per cow per lactation). Pasture was allocated to achieve similar postgrazing residual sward heights for both treatments. A total of 126, 128, and 140 spring-calving dairy cows were used during the years 2006, 2007, and 2008, respectively. Each group had an individual farmlet of 17 paddocks and all groups were managed similarly throughout the study. The effects of genotype, FS, and the interaction between genotype and FS on milk production, BW, and BCS across lactation were studied using mixed models with factorial arrangements of genotype and FS accounting for the repeated cow records across years. No significant genotype by FS interaction was observed for any of the variables measured. Results show that milk solids production of the national average dairy cow can be increased across lactation through increased EBI. High EBI genotypes (HighNA and HighNZ) produced more milk solids per cow and

  8. Myocardial oxygenation and transmural lactate metabolism during experimental acute coronary stenosis in pigs.

    Science.gov (United States)

    Gonschior, P; Gonschior, G M; Conzen, P F; Hobbhahn, J; Goetz, A E; Peter, K; Brendel, W

    1992-01-01

    Measurement of surface tissue pO2 (ptO2) with surface electrodes is increasingly applied in experimental medicine. Its use on the beating heart may seem to be problematic because transmural gradients of tissue pO2 would reduce the validity of pO2 determinations in the epicardial layers. This study attempted to determine whether ptO2 may be a valid and sensitive indicator of transmural myocardial oxygenation. In order to measure ptO2, two eight-channel Clark-type electrodes were placed on a beating porcine left ventricle (n = 13). Measurements were made at different degrees of acute stenosis of the left anterior descending artery (LAD). A 24-F cannula was inserted into the great cardiac vein, draining the poststenotic myocardium to obtain coronary venous blood samples. Transmural metabolic changes were detected simultaneously by coronary venous blood gas parameters and lactate levels. Epicardial tissue pO2 was 49 +/- 2 mm Hg (mean +/- SEM) before stenosis and decreased to a mean value of 25 +/- 2 mm Hg during stenosis. Different degrees of LAD stenosis (ptO2 range: 12-35 mm Hg) were substantial enough to alter arterio-coronary venous lactate difference (avd lactate) from +0.31 +/- 0.07 mmol/l (control) to -0.62 +/- 0.15 mmol/l (stenosis). A significant linear correlation between changes of ptO2 (delta ptO2) and changes of avd lactate (delta avd lactate) resulted (y = 0.59 + 0.62x; r = 0.86; p less than or equal to 0.001). However, linear regression analysis between delta ptO2 correlated with the corresponding data from coronary venous pO2 (delta pO2cv) oxygen content (delta O2contcv), and oxygen saturation (delta O2satcv) showed no significant correlations. We conclude that measurement of ptO2 is a sensitive and valuable indicator of transmural oxygenation in ischemic myocardium, whereas pO2cv, O2contcv and O2satcv do not seem to be valid predictors of ischemia in myocardial oxygenation.

  9. Relationship between muscle oxygenation by NIRS and blood lactate

    Energy Technology Data Exchange (ETDEWEB)

    Xu Guodong [School of Physical Education, Jianghan University, Hubei Wuhan 430056 (China); Mao Zongzhen; Ye Yanjie; Lv Kunru, E-mail: xguodong@wipe.edu.cn [School of Health Sciences, Wuhan Institute of Physical Education, Hubei Wuhan 430079 (China)

    2011-01-01

    The aim of the study was to investigate the relationship of muscle oxygenation in term of oxy-hemoglobin concentration change ({Delta}HbO{sub 2}) by NIRS and blood lactate (BLA) in local skeletal muscle and evaluate the capability of NIRS in the research of exercise physiology Twenty-three athlete in the national fin-swimming team took the increasing load training on the power bicycle while their {Delta}HbO{sub 2} and BLA were simultaneously recorded. The initial powers used in the training were set as 100 w for males and 40 w for females. During the experiment, the power kept constant for 3 min before each abrupt increment of 30 w until the limit of the athlete's capability. Statistical analysis and data visualization were performed. Following the increasing load training, {Delta}HbO{sub 2} step-likely increased in the phase of aerobic metabolism but linearly decreased in the phase of anaerobic metabolism. The variation tendency of BLA was the same as {Delta}HbO{sub 2} and the concurrency of crucial turning points between {Delta}HbO{sub 2} and BLA was revealed. This relationship between {Delta}HbO{sub 2} and BLA presented in the increasing load training suggested that {Delta}HbO{sub 2} might be capable for taking the place of the invasively measured parameter BLA. Considering that {Delta}HbO{sub 2} can be noninvasively measured by NIRS, {Delta}HbO{sub 2} has the potential in the evaluation of athletes' physiological function and training effect on the athletes and accordingly NIRS can be well used in this field.

  10. Relationship between muscle oxygenation by NIRS and blood lactate

    International Nuclear Information System (INIS)

    Xu Guodong; Mao Zongzhen; Ye Yanjie; Lv Kunru

    2011-01-01

    The aim of the study was to investigate the relationship of muscle oxygenation in term of oxy-hemoglobin concentration change (ΔHbO 2 ) by NIRS and blood lactate (BLA) in local skeletal muscle and evaluate the capability of NIRS in the research of exercise physiology Twenty-three athlete in the national fin-swimming team took the increasing load training on the power bicycle while their ΔHbO 2 and BLA were simultaneously recorded. The initial powers used in the training were set as 100 w for males and 40 w for females. During the experiment, the power kept constant for 3 min before each abrupt increment of 30 w until the limit of the athlete's capability. Statistical analysis and data visualization were performed. Following the increasing load training, ΔHbO 2 step-likely increased in the phase of aerobic metabolism but linearly decreased in the phase of anaerobic metabolism. The variation tendency of BLA was the same as ΔHbO 2 and the concurrency of crucial turning points between ΔHbO 2 and BLA was revealed. This relationship between ΔHbO 2 and BLA presented in the increasing load training suggested that ΔHbO 2 might be capable for taking the place of the invasively measured parameter BLA. Considering that ΔHbO 2 can be noninvasively measured by NIRS, ΔHbO 2 has the potential in the evaluation of athletes' physiological function and training effect on the athletes and accordingly NIRS can be well used in this field.

  11. The Effect of Maternal Thyroid Disorders (Hypothyroidism and Hyperthyroidism During Pregnancy and Lactation on Skin Development in Wistar Rat Newborns

    Directory of Open Access Journals (Sweden)

    Maryam Amerion

    2013-05-01

    Full Text Available   Objective(s: Previous studies have shown that thyroid hormones are necessary for normal development of many organs and because of the importance of skin as the largest and the most important organ in human body protection in spite of external environment, the study of thyroid hormones effects on skin development is considerable. In this survey we have tried to study the effects of maternal hypothyroidism on skin development in fetus during pregnancy and lactation by immunohistochemistry technique.   Materials and Methods: Rats were divided into 4 groups, hypothyroids, hyperthyroids, hypothyroids are treated with levothyroxin and a control group. The rat mothers were exposed to PTU with 50 mg/lit dosage and levothyroxin with 1 mg/lit dosage and PTU and levothyroxin simultaneously and with the same dosage respectively in hypothyroid, hyperthyroid and treated hypothyroids with levothyroxin groups. After 14 days, blood sample was taken from mothers, and if thyroid hormones level had change well, mating was allowed. After pregnancy and delivery, 1th day dorsal skin (as the sample for pregnancy assay and 10th day skin (as for lactation assay was used for immunohystochemical and morphometric studies. Results: In this study it was observed that maternal hypothyroidism during pregnancy and lactation causes significant increase in laminin expression, in most areas of skin, and maternal hyperthyroidism during pregnancy and lactation causes significant decrease in laminin expression. Also significant decrease was observed in hair follicles number and epidermis thickness in hypothyroidism groups. Conclusion: This study showed maternal hypothyroidism causes significant decrease in epidermis thickness and hair follicles number and it causes less hair in fetus. Also maternal hypothyroidism causes large changes in laminin expression in different parts of skin. At the same time,maternal hyperthyroidism causes opposite results. In fact, thyroid hormones

  12. Changes in serum metabolic hormone levels after glucose infusion during lactation cycles in Holstein cows

    Directory of Open Access Journals (Sweden)

    Aliasghar Chalmeh

    2015-02-01

    Full Text Available Negative energy balance can impair the metabolism of high producing dairy cows and supplying the glucose, as an energy source; can prevent the metabolic disorders in these animals. Hence, we hypothesized that bolus intravenous glucose administration may change the concentrations of metabolic hormones in order to prevent and control of metabolic dysfunctions of dairy cows. Twenty five multiparous Holstein dairy cows were divided to 5 equal groups containing early, mid and late lactations, far-off and close-up dry periods. All cows were received dextrose 50% intravenously at 500 mg/kg, 10 mL/kg/h. Blood samples were collected from all animals prior to and 1, 2, 3 and 4 after dextrose 50% infusion and sera were separated to determine glucose, triiodothyronine (T3, thyroxine (T4, serum free T3 (fT3, free T4 (fT4, cortisol and insulin like growth factor-1 (IGF-1. The decreasing pattern of T3 concentration was detected in all studied animals following intravenous glucose infusion (P<0.05. The significant increasing pattern of T4 levels was seen in early and mid lactation cows after glucose administration (P<0.05. The significant decreasing pattern of IGF-1 was detected in mid and late lactations and far-off dry groups (P<0.05. There were no significant alterations in fT3, fT4 and cortisol concentrations following glucose infusion in all experimental groups. In conclusion, bolus intravenous glucose infusion could influence the metabolic hormones in high producing Holstein dairy cows. Alterations of metabolic hormones following bolus intravenous glucose administration indicated that glucose is an important direct controller of metabolic interactions and responses in dairy cows during different physiological states.

  13. Hexavalent chromium reduction under fermentative conditions with lactate stimulated native microbial communities.

    Science.gov (United States)

    Somenahally, Anil C; Mosher, Jennifer J; Yuan, Tong; Podar, Mircea; Phelps, Tommy J; Brown,