Rising Trend of Use of Antidepressants Induced Non- Puerperal Lactation: A Case Report.

PubMed

Kukreti, Prerna; Ali, Wazid; Jiloha, R C

2016-06-01

Non puerperal lactation or galactorrhea is a well known side effect of antipsychotic drugs but has been infrequently described with the use of antidepressants. In past few decades, there have been emerging trend of isolated case reports of selective serotonin reuptake inhibitors induced non puerperal lactation. We report a case of non puerperal lactation following usage of second generation tricyclic antidepressant, nortriptyline and resolution on withdrawing the drug. Literature review has been done for antidepressant induced galactorrhea to understand the current trends, putative mechanism as different from one implicated for antipsychotics and its clinical utility.

Repeatability of metabolic responses to a nutrient deficiency in early and mid lactation and implications for robustness of dairy cows.

PubMed

Gross, J J; Bruckmaier, R M

2015-12-01

Nutrient partitioning toward the mammary gland during insufficient energy and nutrient supply is a strategy to ensure survival of the offspring in mammalian species. This homeorhetic priority of the mammary gland is also present in the modern dairy cow, in particular in early lactation. However, despite similar metabolic loads, the adaptive response to a given metabolic load varies considerably among animals. The aim of this study was to investigate if individual cows respond in a consistent manner to a negative energy balance (NEB) in early and mid lactation. Twenty-five dairy cows experienced the usual NEB after parturition and were subjected to a second 3-wk NEB induced by feed restriction in mid lactation. Animals were retrospectively ranked according to their highest plasma nonesterified fatty acid (NEFA) concentration in wk 1 to 4 postpartum. The animals with the 33% highest and 33% lowest values were selected and classified either as the high response (HR) or low response (LR) group. Before parturition, no differences in the studied parameters, dry matter intake, energy balance, concentrations of glucose, NEFA, β-hydroxybutyrate, cholesterol, triglycerides, growth hormone, and insulin-like growth factor-1, were detected between LR and HR. After parturition, milk yield and energy-corrected milk yield was higher for HR compared with LR in wk 2 to 14 and wk 1 to 6, respectively. During feed restriction in wk 15 to 17 postpartum, no differences in energy-corrected milk between LR and HR were found. Energy balance was more negative in HR during the NEB in early lactation, but not different from LR during feed restriction in mid lactation. Although plasma concentrations of glucose, growth hormone, triglycerides, and cholesterol showed group differences in early lactation, but not during feed restriction, the plasma concentrations of NEFA, β-hydroxybutyrate, and insulin-like growth factor-1 in HR changed repeatedly to a greater extent during the NEB at the 2

Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

PubMed Central

Morland, Cecilie; Andersson, Krister A.; Haugen, Øyvind P.; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne E.; Palibrk, Vuk; Diget, Elisabeth H.; Kennedy, Lauritz H.; Stølen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja; Offermanns, Stefan; Vervaeke, Koen; Bjørås, Magnar; Wisløff, Ulrik; Storm-Mathisen, Jon; Bergersen, Linda H.

2017-01-01

Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor. PMID:28534495

Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1.

PubMed

Morland, Cecilie; Andersson, Krister A; Haugen, Øyvind P; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne E; Palibrk, Vuk; Diget, Elisabeth H; Kennedy, Lauritz H; Stølen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja; Offermanns, Stefan; Vervaeke, Koen; Bjørås, Magnar; Wisløff, Ulrik; Storm-Mathisen, Jon; Bergersen, Linda H

2017-05-23

Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.

Cerebral blood flow changes during sodium-lactate-induced panic attacks

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

Stewart, R.S.; Devous, M.D. Sr.; Rush, A.J.

1988-04-01

Dynamic single-photon emission computed axial tomography (CAT) with inhaled xenon-133 was used to measure regional cerebral blood flow in 10 drug-free patients with DSM-III-diagnosed panic disorder and in five normal control subjects. All subjects underwent regional cerebral blood flow studies while at rest or during normal saline infusion and during sodium lactate infusion. Six of the 10 patients and none of the control subjects experienced lactate-induced panic attacks. Lactate infusion markedly raised hemispheric blood flow levels in both control subjects and patients who did not panic. Patients who did panic experienced either a minimal increase or a decrease in hemisphericmore » blood flow.« less

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

PubMed Central

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

2016-01-01

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

Fertilization and early embryonic development in heifers and lactating cows in summer and lactating and dry cows in winter.

PubMed

Sartori, R; Sartor-Bergfelt, R; Mertens, S A; Guenther, J N; Parrish, J J; Wiltbank, M C

2002-11-01

Two experiments in two seasons evaluated fertilization rate and embryonic development in dairy cattle. Experiment 1 (summer) compared lactating Holstein cows (n = 27; 97.3 +/- 4.1 d postpartum [dppl; 40.0 +/- 1.5 kg milk/d) to nulliparous heifers (n = 28; 11 to 17 mo old). Experiment 2 (winter) compared lactating cows (n = 27; 46.4 +/- 1.6 dpp; 45.9 +/- 1.4 kg milk/d) to dry cows (n = 26). Inseminations based on estrus included combined semen from four high-fertility bulls. Embryos and oocytes recovered 5 d after ovulation were evaluated for fertilization, embryo quality (1 = excellent to 5 = degenerate), nuclei/embryo, and accessory sperm. In experiment 1, 21 embryos and 17 unfertilized oocytes (UFO) were recovered from lactating cows versus 32 embryos and no UFO from heifers (55% vs. 100% fertilization). Embryos from lactating cows had inferior quality scores (3.8 +/- 0.4 vs. 2.2 +/- 0.3), fewer nuclei/embryo (19.3 +/- 3.7 vs. 36.8 +/- 3.0) but more accessory sperm (37.3 +/- 5.8 vs. 22.4 +/- 5.5/embryo) than embryos from heifers. Sperm were attached to 80% of UFO (17.8 +/- 12.1 sperm/UFO). In experiment 2, lactating cows yielded 36 embryos and 5 UFO versus 34 embryos and 4 UFO from dry cows (87.8 vs. 89.5% fertilization). Embryo quality from lactating cows was inferior to dry cows (3.1 +/- 0.3 vs. 2.2 +/- 0.3), but embryos had similar numbers of nuclei (27.2 +/- 2.7 vs. 30.6 +/- 2.1) and accessory sperm (42.0 +/- 9.4 vs. 36.5 +/- 6.3). From 53% of the flushings from lactating cows and 28% from dry cows, only nonviable embryos were collected. Thus, embryos of lactating dairy cows were detectably inferior to embryos from nonlactating females as early as 5 d after ovulation, with a surprisingly high percentage of nonviable embryos. In addition, fertilization rate was reduced only in summer, apparently due to an effect of heat stress on the oocyte.

Protein and nitrogen composition of equine (Equus caballus) milk during early lactation.

PubMed

Zicker, S C; Lonnerdal, B

1994-01-01

Separation of whey protein from casein in equine milk was achieved by adjustment of pH to 4.3 without addition of calcium, and by ultracentrifugation at 189,000 g for 1 hr. True protein, whey protein, and casein decreased significantly during the first 28 days of lactation with the magnitude of decrease being greatest for whey protein. The proportion of nitrogen in whey protein:casein decreased from 85:15 to 54:46 during the 28 day time period. The concentration of non-protein nitrogen remained relatively constant at 500 mg nitrogen/l but increased in proportion from 2 to 13% of the total nitrogen during the first 28 days of lactation. These results illustrate the unique nitrogen composition of equine milk, which is intermediate between human and ruminant milk, and how it changes during early lactation.

Molecular insights into the mechanisms of liver-associated diseases in early-lactating dairy cows: hypothetical role of endoplasmic reticulum stress.

PubMed

Ringseis, R; Gessner, D K; Eder, K

2015-08-01

The transition period represents the most critical period in the productive life of high-yielding dairy cows due to both metabolic and inflammatory stimuli, which challenge the liver and predispose dairy cows to develop liver-associated diseases such as fatty liver and ketosis. Despite the fact that all high-yielding dairy cows are affected by marked metabolic stress due to a severe negative energy balance (NEB) during early lactation, not all cows develop liver-associated diseases. Although the reason for this is largely unknown, this indicates that the capacity of the liver to cope with metabolic and inflammatory challenges varies between individual high-yielding dairy cows. Convincing evidence exists that endoplasmic reticulum (ER) stress plays a key role in the development of fatty liver, and it has been recently shown that ER stress occurs in the liver of high-yielding dairy cows. This indicates that ER stress may be involved in the development of liver-associated diseases in dairy cows. The present review shows that the liver of dairy cows during early lactation is exposed to several metabolic and inflammatory challenges, such as non-esterified fatty acids, tumour necrosis factor α, interleukin-1β, reactive oxygen species and lipopolysaccharides, which are known inducers of ER stress. Thus, ER stress may represent a molecular basis for fatty liver development and account for the frequent occurrence of fatty liver and ketosis in high-yielding dairy cows. Interindividual differences between dairy cows in the activation of hepatic stress response pathways, such as nuclear factor E2-related factor 2, which is activated during ER stress and reduces the sensitivity of tissues to oxidative and inflammatory damage, might provide an explanation at the molecular level for differences in the capacity to cope with pathological inflammatory challenges during early lactation and the susceptibility to develop liver-associated diseases between early-lactating dairy cows

Reduced serum vitamin D concentrations in healthy early-lactation dairy cattle.

PubMed

Holcombe, S J; Wisnieski, L; Gandy, J; Norby, B; Sordillo, L M

2018-02-01

Cattle obtain vitamin D by ingestion or cutaneous exposure to UV light. Dairy cattle diets are frequently supplemented with vitamin D to compensate for limited sun exposure or during times of increased metabolic demands, such as the periparturient period, to maintain calcium homeostasis. Whether housing and supplemental vitamin D practices supply adequate amounts of vitamin D to optimally support the transition from gestation to lactation in dairy cattle is unknown. Our objective was to determine how serum vitamin D concentrations of dairy cows change with season, age, parity, and stage of lactation. Clinically healthy cows (n = 183) from 5 commercial dairies were enrolled in the study. Serum samples were collected at dry off, within 7 d of entering the close-up group, and within 7 d after calving (calving+7). Vitamin D status was determined by measuring serum 25-hydroxyvitamin D [25(OH)D] by radioimmunoassay. We performed repeated-measures mixed-effects linear regression to determine the effects of season, age, parity, and lactation stage (dry off, close-up, and calving+7) on 25(OH)D concentrations in serum. Bivariable analysis indicated that parity, age, and season were not associated with serum 25(OH)D concentrations. Sample period affected 25(OH)D concentrations, with the highest 25(OH)D levels at dry off (99.7 ± 1.9 ng/mL) followed by close up (93.8 ± 2.1 ng/mL), with the lowest levels at calving+7 (82.6 ± 1.7 ng/mL). These data showed a large depletion of 25(OH)D in dairy cattle postpartum compared with late prepartum, although the biological significance of this change in these healthy cattle is unclear. Consumption of serum 25(OH)D by immune system functions and calcium homeostasis in early lactation likely caused the reduction in serum 25(OH)D concentrations after calving. These results suggest that determining whether serum 25(OH)D concentrations are associated with the incidence of transition period disease is an appropriate next step. Assessing the

Events occurring during the previous lactation, the dry period, and peripartum as risk factors for early lactation mastitis in cows receiving 2 different intramammary dry cow therapies.

PubMed

Pinedo, P J; Fleming, C; Risco, C A

2012-12-01

The objective of this study was to investigate the association between mastitis events occurring during the previous lactation, the dry period, and the peripartum period on the incidence of early lactation mastitis in cows receiving ceftiofur hydrochloride or penicillin dihydrostreptomycin as intramammary dry cow antibiotic therapy. Cows (n=402) from 2 large dairy farms in Central Florida were enrolled in the study at the time of dry-off processing and were randomly assigned to 1 of 2 dry cow therapies: ceftiofur hydrochloride or penicillin dihydrostreptomycin. Composite milk samples were collected at dry-off and after calving for bacteriological examination and somatic cell count. Peripartal health disorders were monitored during the first 30 d of lactation and included calving difficulty, metritis, ketosis, and left displaced abomasum. Milk production and individual somatic cell scores (SCS) were recorded monthly by the Dairy Herd Improvement Association. The main outcome variables were the risk of clinical mastitis during the first 30 and 60 d of lactation, and the risk of subclinical mastitis at the first 2 monthly Dairy Herd Improvement Association tests after calving (up to 70 d in milk). Additionally, the SCS and the presence of mastitis pathogens in milk at dry-off and at calving were analyzed. Explanatory variables consisted of events occurring during the previous lactation, at dry-off and during the dry period, at calving, and within the first 30 d after calving. Multiple events occurring during the previous lactation had a significant effect on the incidence of mastitis in the subsequent lactation. These events included low milk yield, intermediate lactation length, clinical mastitis, and lactation SCS average. Similarly, intramammary infections with environmental bacteria at dry-off increased the chances of clinical mastitis the first month after calving. Dry-off therapy had a significant effect on mastitis incidence; cows treated with ceftiofur

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

PubMed

Moosavi, Maede; Mirzaei, Abdolah; Ghavami, Mohsen; Tamadon, Amin

2014-01-01

The aim of the present study was to compare the occurrence and duration of clinical mastitis in different seasons, stages of lactation period and parities in a Holstein dairy farm in Iran. A retrospective epidemiological survey from April 2005 to March 2008 was conducted on 884 clinical mastitis cases of 7437 lactations. Data of each case including calendar-date of mastitis onset, days in milk (DIM) of mastitis onset (early: 0-74 DIM; middle: 75-150 DIM, and late ≥ 150 DIM), duration of mastitis, and parity (1, 2, and ≥ 3) were recorded. Based on date of mastitis onset, cases were classified into stages of lactation. Moreover, beginning of mastitis was seasonally categorized. Duration of clinical mastitis after treatment in early lactation was less than late lactation in the first-parity cows (p = 0.005). In early lactation period, the first-parity cows suffered clinical mastitis in days earlier than two other parity groups (p < 0.001). Moreover, in late lactation period, the first-parity cows had clinical mastitis in days later than cows in the third and more parities (p = 0.002). Occurrence of clinical mastitis in summer increased in late lactation period but in winter increased in early lactation period (p = 0.001). In addition, occurrence time of clinical mastitis in summer were in days later than in spring (p = 0.02) and winter (p = 0.03) in early lactation period. In conclusion, occurrence of mastitis in winter and spring during early lactation and in summer during late lactation period were more prevalent especially in lower parities.

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

PubMed Central

Moosavi, Maede; Mirzaei, Abdolah; Ghavami, Mohsen; Tamadon, Amin

2014-01-01

The aim of the present study was to compare the occurrence and duration of clinical mastitis in different seasons, stages of lactation period and parities in a Holstein dairy farm in Iran. A retrospective epidemiological survey from April 2005 to March 2008 was conducted on 884 clinical mastitis cases of 7437 lactations. Data of each case including calendar-date of mastitis onset, days in milk (DIM) of mastitis onset (early: 0-74 DIM; middle: 75-150 DIM, and late ≥ 150 DIM), duration of mastitis, and parity (1, 2, and ≥ 3) were recorded. Based on date of mastitis onset, cases were classified into stages of lactation. Moreover, beginning of mastitis was seasonally categorized. Duration of clinical mastitis after treatment in early lactation was less than late lactation in the first-parity cows (p = 0.005). In early lactation period, the first-parity cows suffered clinical mastitis in days earlier than two other parity groups (p < 0.001). Moreover, in late lactation period, the first-parity cows had clinical mastitis in days later than cows in the third and more parities (p = 0.002). Occurrence of clinical mastitis in summer increased in late lactation period but in winter increased in early lactation period (p = 0.001). In addition, occurrence time of clinical mastitis in summer were in days later than in spring (p = 0.02) and winter (p = 0.03) in early lactation period. In conclusion, occurrence of mastitis in winter and spring during early lactation and in summer during late lactation period were more prevalent especially in lower parities. PMID:25568687

Induction of Lactation in the Biological Mother After Gestational Surrogacy of Twins: A Novel Approach and Review of Literature.

PubMed

Farhadi, Roya; Philip, Roy K

One of the important challenges in surrogate pregnancies is the early bonding of genetic mother with her infant and the establishment of breastfeeding. A combination of pharmacological and nonpharmacological methods is often used for the induction of lactation. Reports of induced lactation in surrogacy are limited and scattered. In this report, we present a case of induced lactation and initiation of breastfeeding in preterm twins by the genetic mother, through her novel approach after a gestational surrogate pregnancy. Thematic approach of maternal account is summarized with context and rigor. We reviewed the reported literature of induced lactation in similar cases with an aim to address the various methods adopted.

Somatic cell count-based selection reduces susceptibility to energy shortage during early lactation in a sheep model.

PubMed

Bouvier-Muller, J; Allain, C; Enjalbert, F; Farizon, Y; Portes, D; Foucras, G; Rupp, R

2018-03-01

During the transition from late gestation to early lactation ruminants experience a negative energy balance (NEB), which is considered to increase susceptibility to mammary infections. Our previous study in 2 divergent lines of sheep selected for high and low somatic cell score (SCS) suggested an association between the response to NEB and genetic susceptibility to mastitis. Forty-eight early-lactation primiparous dairy ewes from the 2 SCS genetic lines were allocated to 2 homogeneous subgroups-an NEB group, which was energy restricted and received 60% of the energy requirements for 15 d, and a control-fed group-to obtain 4 balanced groups of 12 ewes: high-SCS positive energy balance, low-SCS positive energy balance, high-SCS NEB, and low-SCS NEB. High-SCS ewes showed greater weight loss and increased plasmatic concentrations of β-hydroxybutyrate and nonesterified fatty acids than low-SCS ewes when confronted with an induced NEB. The aim of this study was to further characterize this interaction by combining transcriptomic and phenotypic data with a generalized partial least squares discriminant analysis using mixOmics package framework. A preliminary analysis using 3 blocks of phenotypes (fatty acids, weight and production, blood metabolites) revealed a high correlation between fat-to-protein ratio, β-hydroxybutyrate, and nonesterified fatty acids concentrations with milk long-chain fatty acid yields. These phenotypes allowed good discrimination of the energy-restricted high-SCS ewes and confirmed a high level of adipose tissue mobilization in this group. A second analysis, which included RNA-seq data, revealed high correlations between the long-chain fatty acid yields in milk and PDK4, CPT1A, SLC25A20, KLF10, and KLF11 expression, highlighting the relationship between mobilization of body reserves and enhanced fatty acids utilization for energy production in blood cells. Finally, analysis of milk composition measured in 1,025 ewes from the 2 genetic lines over

Increased plasma leptin attenuates adaptive metabolism in early lactating dairy cows.

PubMed

Ehrhardt, Richard A; Foskolos, Andreas; Giesy, Sarah L; Wesolowski, Stephanie R; Krumm, Christopher S; Butler, W Ronald; Quirk, Susan M; Waldron, Matthew R; Boisclair, Yves R

2016-05-01

Mammals meet the increased nutritional demands of lactation through a combination of increased feed intake and a collection of adaptations known as adaptive metabolism (e.g., glucose sparing via insulin resistance, mobilization of endogenous reserves, and increased metabolic efficiency via reduced thyroid hormones). In the modern dairy cow, adaptive metabolism predominates over increased feed intake at the onset of lactation and develops concurrently with a reduction in plasma leptin. To address the role of leptin in the adaptive metabolism of early lactation, we asked which adaptations could be countered by a constant 96-h intravenous infusion of human leptin (hLeptin) starting on day 8 of lactation. Compared to saline infusion (Control), hLeptin did not alter energy intake or milk energy output but caused a modest increase in body weight loss. hLeptin reduced plasma glucose by 9% and hepatic glycogen content by 73%, and these effects were associated with a 17% increase in glucose disposal during an insulin tolerance test. hLeptin attenuated the accumulation of triglyceride in the liver by 28% in the absence of effects on plasma levels of the anti-lipolytic hormone insulin or plasma levels of free fatty acids, a marker of lipid mobilization from adipose tissue. Finally, hLeptin increased the plasma concentrations of T4 and T3 by nearly 50% without affecting other neurally regulated hormones (i.e., cortisol and luteinizing hormone (LH)). Overall these data implicate the periparturient reduction in plasma leptin as one of the signals promoting conservation of glucose and energy at the onset of lactation in the energy-deficient dairy cow. © 2016 Society for Endocrinology.

Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.

PubMed

Wiegers, Evita C; Rooijackers, Hanne M; Tack, Cees J; Groenewoud, Hans J M M; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

2017-12-01

Since altered brain lactate handling has been implicated in the development of impaired awareness of hypoglycemia (IAH) in type 1 diabetes, the capacity to transport lactate into the brain during hypoglycemia may be relevant in its pathogenesis. High-intensity interval training (HIIT) increases plasma lactate levels. We compared the effect of HIIT-induced hyperlacticacidemia on brain lactate during hypoglycemia between 1 ) patients with type 1 diabetes and IAH, 2 ) patients with type 1 diabetes and normal awareness of hypoglycemia, and 3 ) healthy participants without diabetes ( n = 6 per group). All participants underwent a hypoglycemic (2.8 mmol/L) clamp after performing a bout of HIIT on a cycle ergometer. Before HIIT (baseline) and during hypoglycemia, brain lactate levels were determined continuously with J-difference-editing 1 H-MRS, and time curves were analyzed using nonlinear mixed-effects modeling. At the beginning of hypoglycemia (after HIIT), brain lactate levels were elevated in all groups but most pronounced in patients with IAH. During hypoglycemia, brain lactate decreased ∼30% below baseline in patients with IAH but returned to baseline levels and remained there in the other two groups. Our results support the concept of enhanced lactate transport as well as increased lactate oxidation in patients with type 1 diabetes and IAH. © 2017 by the American Diabetes Association.

Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk.

PubMed

Koch, Franziska; Lamp, Ole; Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

2016-01-01

Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production

Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy Cows: Implications to Liver-Muscle Crosstalk

PubMed Central

Eslamizad, Mehdi; Weitzel, Joachim; Kuhla, Björn

2016-01-01

Climate changes lead to rising temperatures during summer periods and dramatic economic losses in dairy production. Modern high-yielding dairy cows experience severe metabolic stress during the transition period between late gestation and early lactation to meet the high energy and nutrient requirements of the fetus or the mammary gland, and additional thermal stress during this time has adverse implications on metabolism and welfare. The mechanisms enabling metabolic adaptation to heat apart from the decline in feed intake and milk yield are not fully elucidated yet. To distinguish between feed intake and heat stress related effects, German Holstein dairy cows were first kept at thermoneutral conditions at 15°C followed by exposure to heat-stressed (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days; in late-pregnancy and again in early lactation. Liver and muscle biopsies and plasma samples were taken to assess major metabolic pathway regulation using real-time PCR and Western Blot. The results indicate that during heat stress, late pregnant cows activate Cahill but reduce Cori cycling, prevent increase in skeletal muscle fatty acid oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without altering ureagenesis despite reduced plane of nutrition. These homeorhetic adaptations are employed to reduce endogenous heat production while diverting amino acids to the growing fetus. Metabolic adaptation to heat stress in early lactation involves increased long-chain fatty acid degradation in muscle peroxisomes, allowance for muscle glucose utilization but diminished hepatic use of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty acid oxidation and ATP production in liver of HS compared to PF cows in early lactation. Consequently, metabolic adaptation to heat stress and reduced feed intake differ between late pregnancy and early lactation of dairy cows to maintain energy supply for fetus development or milk production

Effectiveness of potassium carbonate sesquihydrate to increase dietary cation-anion difference in early lactation cows.

PubMed

Harrison, J; White, R; Kincaid, R; Block, E; Jenkins, T; St-Pierre, N

2012-07-01

The effect of additional dietary potassium in early lactation dairy cows was evaluated with the addition of potassium carbonate sesquihydrate, which increased dietary K from 1.3 to 2.1% of dry matter (DM) from wk 3 to 12 of lactation. Cows fed potassium carbonate sesquihydrate in the form of DCAD Plus (Church & Dwight Co. Inc., Princeton, NJ) had increased DM intake, milk fat percentage and yield, energy-corrected milk, and efficiency of milk production per unit of DM intake. Milk fat of cows fed higher dietary K had a lower concentration of trans fatty acids, suggesting a role for potassium carbonate sesquihydrate in the rumen in the biohydrogenation processes converting linoleic to stearic acid. Cows fed the diet with 2.1% K had greater apparent balance of K, and no effects were noted on the concentration of blood Mg or amount of fecal Mg. The data support the feeding of greater amounts of K in the early lactation cow. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

PubMed Central

2010-01-01

Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.

PubMed

Koike, Terumoto; Yeung, Jonathan C; Cypel, Marcelo; Rubacha, Matthew; Matsuda, Yasushi; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Keshavjee, Shaf

2011-12-01

Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant. Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs. We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP. Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Metabolism of early-lactation dairy cows as affected by dietary starch and monensin supplementation.

PubMed

McCarthy, M M; Yasui, T; Ryan, C M; Pelton, S H; Mechor, G D; Overton, T R

2015-05-01

The objective of this study was to evaluate the effect of dietary starch content and monensin (MON) on metabolism of dairy cows during early lactation. Before parturition, primiparous (n=21) and multiparous (n=49) Holstein cows were fed a common controlled-energy close-up diet with a daily topdress of either 0 or 400mg/d monensin. From d 1 to 21 postpartum, cows were fed a high-starch (HS; 26.2% starch, 34.3% neutral detergent fiber, 22.7% acid detergent fiber, 15.5% crude protein) or low-starch (LS; 21.5% starch, 36.9% neutral detergent fiber, 25.2% acid detergent fiber, 15.4% crude protein) total mixed ration with a daily topdress of either 0mg/d monensin (CON) or 450mg/d monensin (MON), continuing with prepartum topdress assignment. From d 22 through 63 postpartum, all cows were fed HS and continued with the assigned topdress treatment until d 63. Cows fed HS had higher plasma glucose and insulin and lower nonesterified fatty acids (NEFA) than cows fed LS during d 1 to 21 postpartum. Cows fed LS had elevated early-lactation β-hydroxybutyrate (BHBA) compared with cows fed HS. Cows fed HS had greater insulin resistance and increased plasma haptoglobin in the early lactation period. There was no effect of MON on postpartum plasma NEFA. Cows fed MON had higher plasma glucose compared with CON cows, which was driven by a MON × parity interaction in which primiparous cows fed MON had greater plasma glucose concentrations than cows fed CON. Cows fed MON had lower plasma BHBA compared with CON, which was contributed to by a MON × parity interaction in which primiparous cows fed MON had lower BHBA concentrations than CON. Starch treatment had no effect on overall liver triglyceride content. Primiparous cows fed MON had increased liver triglyceride content compared with CON primiparous cows, and multiparous cows fed MON had decreased liver triglyceride content compared with CON cows. Multiparous cows fed LS with MON had higher liver glycogen content than multiparous

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

PubMed

Collier, R J; Bauman, D E

2017-12-01

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

Symposium review: Modulating adipose tissue lipolysis and remodeling to improve immune function during the transition period and early lactation of dairy cows.

PubMed

Contreras, G Andres; Strieder-Barboza, Clarissa; De Koster, Jenne

2018-03-01

Despite major advances in our understanding of transition and early lactation cow physiology and the use of advanced dietary, medical, and management tools, at least half of early lactation cows are reported to develop disease and over half of cow deaths occur during the first week of lactation. Excessive lipolysis, usually measured as plasma concentrations of free fatty acids (FFA), is a major risk factor for the development of displaced abomasum, ketosis, fatty liver, and metritis, and may also lead to poor lactation performance. Lipolysis triggers adipose tissue (AT) remodeling that is characterized by enhanced humoral and cell-mediated inflammatory responses and changes in its distribution of cellular populations and extracellular matrix composition. Uncontrolled AT inflammation could perpetuate lipolysis, as we have observed in cows with displaced abomasum, especially in those animals with genetic predisposition for excessive lipolysis responses. Efficient transition cow management ensures a moderate rate of lipolysis that is rapidly reduced as lactation progresses. Limiting FFA release from AT benefits immune function as several FFA are known to promote dysregulation of inflammation. Adequate formulation of pre- and postpartum diet reduces the intensity of AT lipolysis. Additionally, supplementation with niacin, monensin, and rumen-protected methyl donors (choline and methionine) during the transition period is reported to minimize FFA release into systemic circulation. Targeted supplementation of energy sources during early lactation improves energy balance and increases insulin concentration, which limits AT lipolytic responses. This review elaborates on the mechanisms by which uncontrolled lipolysis triggers inflammatory disorders. Details on current nutritional and pharmacological interventions that aid the modulation of FFA release from AT and their effect on immune function are provided. Understanding the inherent characteristics of AT biology in

Effects of substitution of different levels of steam-flaked corn for finely ground corn on lactation and digestion in early lactation dairy cows.

PubMed

Zhong, R Z; Li, J G; Gao, Y X; Tan, Z L; Ren, G P

2008-10-01

Eight multiparous Holstein cows, 4 of them fitted with rumen cannulas, were used to test the effects of substitution of steam-flaked corn (SFC) for equal amounts of finely ground corn (FGC) in diets on feed intake and digestion, blood metabolites, and lactation performance in early lactation dairy cows. Cows were fed 4 diets in a replicated 4 x 4 Latin square design. The fistulated cows formed 1 replicate. Each experimental period lasted for 3 wk. The 4 diets contained 0, 10, 20, or 40% SFC and 40, 30, 20, or 0% FGC (dry matter basis), respectively. The milk protein content and yield, milk solid nonfat content and yield, plasma glucose concentration, and dry matter intake increased as the proportion of SFC increased in diets. Apparent total tract digestibilities of dry matter, organic matter, neutral detergent fiber, acid detergent fiber, and average ruminal fluid NH(3)-N concentration decreased with increasing levels of SFC. The ruminal fluid pH was not affected by the substitution of SFC for FGC. The 20% SFC substitution improved digestion of crude protein, yield of fat-corrected milk, milk lactose content, fat, and fat yield. The 40% SFC substitution increased urea concentration in both plasma and milk. It was concluded that 20% of SFC substitution for FGC appeared to be an appropriate level in diet for early lactation dairy cows.

Early Lactation and Infant Feeding Practices Differ by Maternal Gestational Diabetes History.

PubMed

Oza-Frank, Reena; Moreland, Jennifer J; McNamara, Kelly; Geraghty, Sheela R; Keim, Sarah A

2016-11-01

Detailed data on lactation practices by gestational diabetes mellitus (GDM) history are lacking, precluding potential explanations and targets for interventions to improve lactation intensity and duration and, ultimately, long-term maternal and child health. This study aimed to examine breastfeeding practices through 12 months postpartum by GDM history. Women who delivered a singleton, liveborn infant at The Ohio State University Wexner Medical Center (Columbus, OH), in 2011 completed a postal questionnaire to assess lactation and infant feeding practices and difficulties. Bivariate and multivariate associations between GDM history and lactation and infant feeding practices were examined. The sample included 432 women (62% response rate), including 7.9% who had GDM during the index pregnancy. Women with GDM initiated breastfeeding (at-the-breast or pumping) as often as women without any diabetes but were more likely to report introduction of formula within the first 2 days of life (79.4% vs 53.8%, P < .01; adjusted odds ratio: 3.48; 95% confidence interval, 1.47-8.26). Women with GDM initiated pumping 4 days earlier than women without diabetes ( P < .05), which was confirmed in adjusted analyses. There was no difference in the proportion of women reporting breastfeeding difficulty (odds ratio: 2.08; 95% confidence interval, 0.78-5.52). However, there was a trend toward women with GDM reporting more formula feeding and less at-the-breast feeding as strategies to address difficulty compared with women without diabetes. Additional research is needed to understand why women with GDM engage in different early lactation and infant feeding practices, and how best to promote and sustain breastfeeding among these women.

Effect of maternal Chlorella supplementation on carotenoid concentration in breast milk at early lactation.

PubMed

Nagayama, Junya; Noda, Kiyoshi; Uchikawa, Takuya; Maruyama, Isao; Shimomura, Hiroshi; Miyahara, Michiyoshi

2014-08-01

Breast milk carotenoids provide neonates with a source of vitamin A and potentially, oxidative stress protection and other health benefits. Chlorella, which has high levels of carotenoids such as lutein, zeaxanthin and β-carotene, is an effective dietary source of carotenoids for humans. In this study, the effect of maternal supplementation with Chlorella on carotenoid levels in breast milk at early lactation was investigated. Ten healthy, pregnant women received 6 g of Chlorella daily from gestational week 16-20 until the day of delivery (Chlorella group); ten others did not (control group). Among the carotenoids detected in breast milk, lutein, zeaxanthin and β-carotene concentrations in the Chlorella group were 2.6-fold (p = 0.001), 2.7-fold (p = 0.001) and 1.7-fold (p = 0.049) higher, respectively, than those in the control group. Our study shows that Chlorella intake during pregnancy is effective in improving the carotenoid status of breast milk at early lactation.

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

PubMed

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

2018-05-01

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

Risk factors for early lactation problems among Peruvian primiparous mothers.

PubMed

Matias, Susana L; Nommsen-Rivers, Laurie A; Creed-Kanashiro, Hilary; Dewey, Kathryn G

2010-04-01

The aim of this study was to determine the incidence and risk factors for early lactation problems [suboptimal infant breastfeeding behaviour (SIBB), delayed onset of lactogenesis (OL) and excessive neonatal weight loss] among mother-infant pairs in Lima, Peru. All primiparous mothers who gave birth to a healthy, single, term infant at a government hospital in a peri-urban area of Lima during the 8-month recruitment period were invited to participate in the study. Data were collected at the hospital (day 0) and during a home visit (day 3). Infant breastfeeding behaviour was evaluated using the Infant Breastfeeding Assessment Tool; SIBB was defined as < or = 10 score. OL was determined by maternal report of breast fullness changes; delayed OL was defined as perceived after 72 h. Excessive neonatal weight loss was defined as > or = 10% of birthweight by day 3. One hundred seventy-one mother-infant pairs participated in the study. SIBB prevalence was 52% on day 0 and 21% on day 3; it was associated with male infant gender (day 0), < 8 breastfeeds during the first 24 h (days 0 and 3), and gestational age < 39 weeks (day 3). Delayed OL incidence was 17% and was associated with infant Apgar score < 8. Excessive neonatal weight loss occurred in 10% of neonates and was associated with maternal overweight and Caesarean-section delivery. Early lactation problems may be influenced by modifiable factors such as delivery mode and breastfeeding frequency. Infant status at birth and maternal characteristics could indicate when breastfeeding dyads need extra support.

Prognostic significance of blood lactate and lactate clearance in trauma patients.

PubMed

Régnier, Marie-Alix; Raux, Mathieu; Le Manach, Yannick; Asencio, Yves; Gaillard, Johann; Devilliers, Catherine; Langeron, Olivier; Riou, Bruno

2012-12-01

Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

Non-targeted plasma metabolomic profile at early and late lactation in parity 1 dams with diverging body composition at weaning

USDA-ARS?s Scientific Manuscript database

Lactation is an extremely energy demanding event, impacting naïve dams to a greater extent as they are still physiologically immature. The objective of the current study was to determine if a unique plasma metabolome exists at early and late lactation from first parity gilts having similar body meas...

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

PubMed

Janjanam, Jagadeesh; Singh, Surender; Jena, Manoj K; Varshney, Nishant; Kola, Srujana; Kumar, Sudarshan; Kaushik, Jai K; Grover, Sunita; Dang, Ajay K; Mukesh, Manishi; Prakash, B S; Mohanty, Ashok K

2014-01-01

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.

Comparative 2D-DIGE Proteomic Analysis of Bovine Mammary Epithelial Cells during Lactation Reveals Protein Signatures for Lactation Persistency and Milk Yield

PubMed Central

Janjanam, Jagadeesh; Singh, Surender; Jena, Manoj K.; Varshney, Nishant; Kola, Srujana; Kumar, Sudarshan; Kaushik, Jai K.; Grover, Sunita; Dang, Ajay K.; Mukesh, Manishi; Prakash, B. S.; Mohanty, Ashok K.

2014-01-01

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. PMID:25111801

Effect of Lactation on myocardial vulnerability to ischemic insult in rats

PubMed Central

Askari, Sahar; Imani, Alireza; Sadeghipour, Hamidreza; Faghihi, Mahdieh; Edalatyzadeh, Zohreh; Choopani, Samira; Karimi, Nasser; Fatima, Sulail

2017-01-01

Background Cardiovascular diseases are the leading cause of mortality and long-term disability worldwide. Various studies have suggested a protective effect of lactation in reducing the risk of cardiovascular diseases. Objective This study was designed to assess the effects of pregnancy and lactation on the vulnerability of the myocardium to an ischemic insult. Methods Eighteen female rats were randomly divided into three groups: ischemia-reperfusion (IR), in which the hearts of virgin rats underwent IR (n = 6); lactating, in which the rats nursed their pups for 3 weeks and the maternal hearts were then submitted to IR (n = 6); and non-lactating, in which the pups were separated after birth and the maternal hearts were submitted to IR (n = 6). Outcome measures included heart rate (HR), left ventricular developed pressure (LVDP), rate pressure product (RPP), ratio of the infarct size to the area at risk (IS/AAR %), and ventricular arrhythmias - premature ventricular contraction (PVC) and ventricular tachycardia (VT). Results The IS/AAR was markedly decreased in the lactating group when compared with the non-lactating group (13.2 ± 2.5 versus 39.7 ± 3.5, p < 0.001) and the IR group (13.2 ± 2.5 versus 34.0 ± 4.7, p < 0.05). The evaluation of IR-induced ventricular arrhythmias indicated that the number of compound PVCs during ischemia, and the number and duration of VTs during ischemia and in the first 5 minutes of reperfusion in the non-lactating group were significantly (p < 0.05) higher than those in the lactating and IR groups. Conclusion Lactation induced early-onset cardioprotective effects, while rats that were not allowed to nurse their pups were more susceptible to myocardial IR injury. PMID:28444063

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

PubMed

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.

Protective role of zinc against the neurotoxicity induced by exposure to cadmium during gestation and lactation periods on hippocampal volume of pups tested in early adulthood.

PubMed

Ben Mimouna, Safa; Chemek, Marouane; Boughammoura, Sana; Haouas, Zohra; Messaoudi, Imed

2018-05-03

The present study was conducted to assess the possible effect of cadmium (Cd) throughout gestation and lactation on the volume of the subregion of the hippocampus as well as the potential protective role of zinc (Zn) against Cd neurotoxicity. For this purpose, female rats received either tap water, Cd, Zn or Cd + Zn in their drinking water during gestation and lactation. At postnatal day 35 (PND35), the male pups were sacrificed, and their brains were taken for histologic, chemical, and biochemical analysis. Hippocampal volume was measured in histologic brain slices using Cavalieri's principle. Zn depletion was observed in the brains of pups issued from mothers exposed to Cd. Biochemical analysis further revealed that Cd exposure significantly increases the superoxide dismutase (SOD) activity, as well as the metallothionein (MT) level. During histologic investigation, our results showed that gestational and lactational exposure to Cd significantly altered and decreased the volume of CA1, CA3 pyramidal cell layer and the dentate gyrus. However, there were no marked differences shown in CA2 subfield. Compared to Cd group, co-treatment with Cd and Zn provided correction of the changes induced by the Cd exposure. These results highlight the protective role of Zn against Cd-induced alteration in the hippocampus which is a crucial structure implicated in learning and memory processes.

Adipose tissue remodeling in late-lactation dairy cows during feed-restriction-induced negative energy balance.

PubMed

Contreras, G Andres; Thelen, Kyan; Schmidt, Sarah E; Strieder-Barboza, Clarissa; Preseault, Courtney L; Raphael, William; Kiupel, Matti; Caron, John; Lock, Adam L

2016-12-01

Excessive rates of demand lipolysis in the adipose tissue (AT) during periods of negative energy balance (NEB) are associated with increased susceptibility to disease and limited lactation performance. Lipolysis induces a remodeling process within AT that is characterized by an inflammatory response, cellular proliferation, and changes in the extracellular matrix (ECMT). The adipose tissue macrophage (ATM) is a key component of the inflammatory response. Infiltration of ATM-forming cellular aggregates was demonstrated in transition cows, suggesting that ATM trafficking and phenotype changes may be associated with disease. However, it is currently unknown if ATM infiltration occurs in dairy cows only during NEB states related to the transition period or also during NEB-induced lipolysis at other stages of lactation. The objective of this study was to evaluate changes in ATM trafficking and inflammatory phenotypes, and the expression of genetic markers of AT remodeling in healthy late-lactation cows during feed restriction-induced NEB. After a 14-d (d -14 to d -1) preliminary period, Holstein cows were randomly assigned to 1 of 2 feeding protocols, ad libitum (AL) or feed restriction (FR), for 4 d (d 1-4). Caloric intake was reduced in FR to achieve a targeted energy balance of -15 Mcal/d of net energy for lactation. Omental and subcutaneous AT samples were collected laparoscopically to harvest stromal vascular fraction (SVF) cells on d -3 and 4. The FR induced a NEB of -14.1±0.62 Mcal/d of net energy for lactation, whereas AL cows remained in positive energy balance (3.2±0.66 Mcal/d of NE L ). The FR triggered a lipolytic response reflected in increased plasma nonesterified fatty acids (0.65±0.05 mEq/L on d 4), enhanced phosphorylation of hormone sensitive lipase, and reduced adipocyte diameter. Flow cytometry and immunohistochemistry analysis revealed that on d 4, FR cows had increased numbers of CD172a + , an ATM (M1 and M2) surface marker, cells in SVF that

Effect of concentrate feeding method on the performance of dairy cows in early to mid lactation.

PubMed

Purcell, P J; Law, R A; Gordon, A W; McGettrick, S A; Ferris, C P

2016-04-01

The objective of the current study was to determine the effects of concentrate feeding method on milk yield and composition, dry matter (DM) intake (DMI), body weight and body condition score, reproductive performance, energy balance, and blood metabolites of housed (i.e., accommodated indoors) dairy cows in early to mid lactation. Eighty-eight multiparous Holstein-Friesian cows were managed on 1 of 4 concentrate feeding methods (CFM; 22 cows per CFM) for the first 21 wk postpartum. Cows on all 4 CFM were offered grass silage plus maize silage (in a 70:30 ratio on a DM basis) ad libitum throughout the study. In addition, cows had a target concentrate allocation of 11 kg/cow per day (from d 13 postpartum) via 1 of 4 CFM, consisting of (1) offered on a flat-rate basis via an out-of-parlor feeding system, (2) offered based on individual cow's milk yields in early lactation via an out-of-parlor feeding system, (3) offered as part of a partial mixed ration (target intake of 5 kg/cow per day) with additional concentrate offered based on individual cow's milk yields in early lactation via an out-of-parlor feeding system, and (4) offered as part of a partial mixed ration containing a fixed quantity of concentrate for each cow in the group. In addition, all cows were offered 1 kg/cow per day of concentrate pellets via an in-parlor feeding system. We detected no effect of CFM on concentrate or total DMI, mean daily milk yield, concentrations and yields of milk fat and protein, or metabolizable energy intakes, requirements, or balances throughout the study. We also found no effects of CFM on mean or final body weight, mean or final body condition score, conception rates to first service, or any of the blood metabolites examined. The results of this study suggest that CFM has little effect on the overall performance of higher-yielding dairy cows in early to mid lactation when offered diets based on conserved forages. Copyright © 2016 American Dairy Science Association

Relationships between early-life growth, intake, and birth season with first-lactation performance of Holstein dairy cows.

PubMed

Chester-Jones, H; Heins, B J; Ziegler, D; Schimek, D; Schuling, S; Ziegler, B; de Ondarza, M B; Sniffen, C J; Broadwater, N

2017-05-01

The objective was to determine the relationships between early-life parameters [including average daily gain (ADG), body weight (BW), milk replacer intake, starter intake, and birth season] and the first-lactation performance of Holstein cows. We collected data from birth years 2004 to 2012 for 2,880 Holstein animals. Calves were received from 3 commercial dairy farms and enrolled in 37 different calf research trials at the University of Minnesota Southern Research and Outreach Center from 3 to 195 d. Upon trial completion, calves were returned to their respective farms. Milk replacer options included varying protein levels and amounts fed, but in the majority of studies, calves were fed a milk replacer containing 20% crude protein and 20% fat at 0.57 kg/calf daily. Most calves (93%) were weaned at 6 wk. Milk replacer dry matter intake, starter intake, ADG, and BW at 6 wk were 21.5 ± 2.2 kg, 17.3 ± 7.3 kg, 0.53 ± 0.13 kg/d, and 62.4 ± 6.8 kg, respectively. Average age at first calving and first-lactation 305-d milk yield were 715 ± 46.5 d and 10,959 ± 1,527 kg, respectively. We conducted separate mixed-model analyses using the REML model-fitting protocol of JMP (SAS Institute Inc., Cary, NC) to determine the effect of early-life BW or ADG, milk replacer and starter intake, and birth season on first-lactation 305-d milk, fat, and true protein yield. Greater BW and ADG at 6 wk resulted in increased first-lactation milk and milk component yields. Intake of calf starter at 8 wk had a significant positive relationship with first-lactation 305-d yield of milk and milk components. Milk replacer intake, which varied very little in this data set, had no effect on first-lactation 305-d yield of milk and milk components. Calves born in the fall and winter had greater starter intake, BW, and ADG at 8 wk. However, calves born in the summer had a higher 305-d milk yield during their first lactation than those born in the fall and winter. Improvements were modest, and

Neuronal Cell Death Induced by Mechanical Percussion Trauma in Cultured Neurons is not Preceded by Alterations in Glucose, Lactate and Glutamine Metabolism.

PubMed

Jayakumar, A R; Bak, L K; Rama Rao, K V; Waagepetersen, H S; Schousboe, A; Norenberg, M D

2016-02-01

Traumatic brain injury (TBI) is a devastating neurological disorder that usually presents in acute and chronic forms. Brain edema and associated increased intracranial pressure in the early phase following TBI are major consequences of acute trauma. On the other hand, neuronal injury, leading to neurobehavioral and cognitive impairments, that usually develop months to years after single or repetitive episodes of head trauma, are major consequences of chronic TBI. The molecular mechanisms responsible for TBI-induced injury, however, are unclear. Recent studies have suggested that early mitochondrial dysfunction and subsequent energy failure play a role in the pathogenesis of TBI. We therefore examined whether oxidative metabolism of (13)C-labeled glucose, lactate or glutamine is altered early following in vitro mechanical percussion-induced trauma (5 atm) to neurons (4-24 h), and whether such events contribute to the development of neuronal injury. Cell viability was assayed using the release of the cytoplasmic enzyme lactate dehydrogenase (LDH), together with fluorescence-based cell staining (calcein and ethidium homodimer-1 for live and dead cells, respectively). Trauma had no effect on the LDH release in neurons from 1 to 18 h. However, a significant increase in LDH release was detected at 24 h after trauma. Similar findings were identified when traumatized neurons were stained with fluorescent markers. Additionally (13)C-labeling of glutamate showed a small, but statistically significant decrease at 14 h after trauma. However, trauma had no effect on the cycling ratio of the TCA cycle at any time-period examined. These findings indicate that trauma does not cause a disturbance in oxidative metabolism of any of the substrates used for neurons. Accordingly, such metabolic disturbance does not appear to contribute to the neuronal death in the early stages following trauma.

Lactation Biology Symposium: maternal nutrition during early and mid-to-late pregnancy: Comparative effects on milk production of twin-born ewe progeny during their first lactation.

PubMed

Paten, A M; Kenyon, P R; Lopez-Villalobos, N; Peterson, S W; Jenkinson, C M C; Pain, S J; Blair, H T

2013-02-01

Studies using sheep models indicate that the fetal mammary gland is sensitive to maternal nutrition during gestation; however, results have been inconsistent and do not identify critical feeding periods. This study aimed to clarify previous findings by partitioning the period of maternal nutritional manipulation into 2 stages: early and mid-to-late pregnancy. Sixty-six twin-born, twin-bearing ewes, born to dams that were fed either submaintenance, maintenance, or ad libitum during early pregnancy (d 21 to 50 of pregnancy; SmP21-50, MP21-50, or AdP21-50, respectively) and then either maintenance or ad libitum during mid-to-late pregnancy (d 50 to 140 of pregnancy; MP50-140 or AdP50-140, respectively) were milked once a week, starting from d 7 ± 1 postpartum, for 7 subsequent weeks to enable estimation of daily milk yield and composition. Their lambs were weighed weekly. Ewes born to dams fed MP21-50 tended to have greater accumulated milk (P = 0.10), fat (P = 0.07), and NE (P = 0.06) yields over 50 d compared with ewes born to dams fed SmP21-50 and AdP21-50. In contrast, ewes born to dams fed AdP50-140 tended to have greater accumulated milk (P = 0.10) and lactose (P = 0.09) yields compared with ewes born to dams fed MP50-140. Grandoffspring birth weights were unaffected by granddam nutrition during pregnancy. Ewes born to dams fed AdP21-50 weaned lighter lambs (P = 0.05) than ewes born to dams fed AmP21-50 and tended to wean lighter lambs (P = 0.07) than ewes born to dams fed MP21-50 whereas there were no differences between the weaning weights of lambs (P = 0.43) from ewes born to dams fed AdP50-140 and MP50-140. Maintenance nutrition of dams during early pregnancy appears to be associated with an improved lactation performance of ewe offspring. Higher levels of nutrition during mid-to-late pregnancy also appears to improve the first-lactation performance of ewe offspring. Interestingly, although grandoffspring birth weights were unaffected, weaning weight

Bovine Milk Comparative Proteome Analysis from Early, Mid, and Late Lactation in the Cattle Breed, Malnad Gidda (Bos indicus).

PubMed

Mol, Praseeda; Kannegundla, Uday; Dey, Gourav; Gopalakrishnan, Lathika; Dammalli, Manjunath; Kumar, Manish; Patil, Arun H; Basavaraju, Marappa; Rao, Akhila; Ramesha, Kerekoppa P; Prasad, Thottethodi Subrahmanya Keshava

2018-03-01

Bovine milk is important for both veterinary medicine and human nutrition. Understanding the bovine milk proteome at different stages of lactation has therefore broad significance for integrative biology and clinical medicine as well. Indeed, different lactation stages have marked influence on the milk yield, milk constituents, and nourishment of the neonates. We performed a comparative proteome analysis of the bovine milk obtained at different stages of lactation from the Indian indigenous cattle Malnad Gidda (Bos indicus), a widely available breed. The milk differential proteome during the lactation stages in B. indicus has not been investigated to date. Using high-resolution mass spectrometry-based quantitative proteomics of the bovine whey proteins at early, mid, and late lactation stages, we identified a total of 564 proteins, out of which 403 proteins were found to be differentially abundant at different lactation stages. As is expected of any body fluid proteome, 51% of the proteins identified in the milk were found to have signal peptides. Gene ontology analyses were carried out to categorize proteins altered across different lactation stages based on biological process and molecular function, which enabled us to correlate their significance in each lactation stage. We also investigated the potential pathways enriched in different lactation stages using bioinformatics pathway analysis tools. To the best of our knowledge, this study represents the first and largest inventory of milk proteins identified to date for an Indian cattle breed. We believe that the current study broadly informs both veterinary omics research and the emerging field of nutriproteomics during lactation stages.

Short communication: Effects of dietary 5,6-dimethylbenzimidazole supplementation on vitamin B12 supply, lactation performance, and energy balance in dairy cows during the transition period and early lactation.

PubMed

Wang, D M; Zhang, B X; Wang, J K; Liu, H Y; Liu, J X

2018-03-01

The current study was conducted to investigate the effects of 5,6-dimethylbenzimidazole (DMB) supplementation to the feed during the transition period and early lactation on the vitamin B 12 supply, lactation performance, and energy balance in postpartum cows. Twenty-four prepartum Holstein dairy cows were divided into 12 blocks based on their parity and milk yield at the last lactation and were then randomly allocated to 1 of 2 treatments: a basal diet without DMB (control) or a treatment diet that contained 1.5 g of DMB/d per cow. The study started at wk 3 before the expected calving day and ended at wk 8 postpartum. The feed intake and the lactation performance were measured weekly after calving. Blood parameters were measured on d -10, 0, 8, 15, 29, 43, and 57 relative to the calving day. Body weight was measured on the calving day and on d 57 after calving. The yields of milk, protein, and lactose in cows fed DMB were higher than in the control throughout the whole postpartum stage. On wk 8 postpartum, the vitamin B 12 content in the milk and sera was greater in cows fed DMB than in the control. The overall body weight loss from wk 1 to 8 postpartum was less in cows fed DMB than in the control. The plasma content of nonesterified fatty acids and β-hydroxybutyric acid was significantly lower in cows fed DMB than in the control throughout the whole experimental stage. In conclusion, dietary DMB fed during the transition period and early lactation improved the vitamin B 12 supply, milk production, and energy balance of postpartum dairy cows. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of dietary starch level and high rumen-undegradable protein on endocrine-metabolic status, milk yield, and milk composition in dairy cows during early and late lactation.

PubMed

Piccioli-Cappelli, F; Loor, J J; Seal, C J; Minuti, A; Trevisi, E

2014-12-01

Diet composition defines the amount and type of nutrients absorbed by dairy cows. Endocrine-metabolic interactions can influence these parameters, and so nutrient availability for the mammary gland can significantly vary and affect milk yield and its composition. Six dairy cows in early and then late lactation received, for 28 d in a changeover design, 2 diets designed to provide, within the same stage of lactation, similar amounts of rumen fermentable material but either high starch plus sugar (HS) content or low starch plus sugar content (LS). All diets had similar dietary crude protein and calculated supply of essential amino acids. Dry matter intake within each stage of lactation was similar between groups. Milk yield was similar between groups in early lactation, whereas a higher milk yield was observed in late lactation when feeding HS. At the metabolic level, the main difference observed between the diets in both stages of lactation was lower blood glucose in cows fed LS. The lower glucose availability during consumption of LS caused substantial modifications in the circulating and postprandial pattern of metabolic hormones. Feeding LS versus HS resulted in an increase in the ratio of bovine somatotropin to insulin. This increased mobilization of lipid reserves resulted in higher blood concentrations of nonesterified fatty acids and β-hydroxybutyrate, which contributed to the higher milk fat content in both stages of lactation in the LS group. This greater recourse to body fat stores was confirmed by the greater loss of body weight during early lactation and the slower recovery of body weight in late lactation in cows fed LS. The lower insulin to glucagon ratio observed in cows fed LS in early and late lactation likely caused an increase in hepatic uptake and catabolism of amino acids, as confirmed by the higher blood urea concentrations. Despite the higher catabolism of amino acids in LS in early lactation, similar milk protein output was observed for both

Brown midrib corn silage and Tifton 85 bermudagrass in rations for early-lactation cows.

PubMed

Castro, J J; Bernard, J K; Mullis, N A; Eggleston, R B

2010-05-01

Forty Holstein cows were used in an 8-wk randomized trial to evaluate the effects of feeding combinations of forages with improved fiber digestibility on performance during early lactation. Treatments were arranged as a 2 x 2 factorial to include silage from normal (NCS) or brown midrib (BMR) corn silage with or without 10% Tifton 85 bermudagrass hay (T85). In a simultaneous digestion trial, degradation and passage kinetics and ruminal fermentation parameters were evaluated in a 4 x 4 Latin square design trial using late-lactation Holstein cows fitted with ruminal cannulas. Dry matter intake (DMI) and neutral detergent fiber (NDF) intake were greater with BMR than with NCS; however, milk yield and composition were similar among corn silage types. Inclusion of T85 reduced milk yield but supported higher milk fat percentage, resulting in similar yields of energy-corrected milk. Blood glucose concentrations were higher for BMR compared with NCS, and inclusion of T85 increased blood urea N concentrations. Treatments did not alter liquid or solid phase passage rates or rumen turnover. Corn silage type did not affect ruminal pH or volatile fatty acid concentrations, but inclusion of T85 increased pH and molar proportion of acetate but decreased butyrate. Molar proportions of propionate were greater for NCS and T85 compared with BMR and T85, resulting in an interaction. Results of this trial indicate that combinations of forages with improved fiber digestibility can be used to support intake and performance of cows during early lactation. Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Screening of miRNA profiles and construction of regulation networks in early and late lactation of dairy goat mammary glands.

PubMed

Ji, Zhibin; Liu, Zhaohua; Chao, Tianle; Hou, Lei; Fan, Rui; He, Rongyan; Wang, Guizhi; Wang, Jianmin

2017-09-20

In recent years, studies related to the expression profiles of miRNAs in the dairy goat mammary gland were performed, but regulatory mechanisms in the physiological environment and the dynamic homeostasis of mammary gland development and lactation are not clear. In the present study, sequencing data analysis of early and late lactation uncovered a total of 1,487 unique miRNAs, including 45 novel miRNA candidates and 1,442 known and conserved miRNAs, of which 758 miRNAs were co-expressed and 378 differentially expressed with P < 0.05. Moreover, 76 non-redundant target genes were annotated in 347 GO consortiums, with 3,143 candidate target genes grouped into 33 pathways. Additionally, 18 predicted target genes of 214 miRNAs were directly annotated in mammary gland development and used to construct regulatory networks based on GO annotation and the KEGG pathway. The expression levels of seven known miRNAs and three novel miRNAs were examined using quantitative real-time PCR. The results showed that miRNAs might play important roles in early and late lactation during dairy goat mammary gland development, which will be helpful to obtain a better understanding of the genetic control of mammary gland lactation and development.

Glucose, Lactate and Glutamine but not Glutamate Support Depolarization-Induced Increased Respiration in Isolated Nerve Terminals.

PubMed

Hohnholt, Michaela C; Andersen, Vibe H; Bak, Lasse K; Waagepetersen, Helle S

2017-01-01

Synaptosomes prepared from various aged and gene modified experimental animals constitute a valuable model system to study pre-synaptic mechanisms. Synaptosomes were isolated from whole brain and the XFe96 extracellular flux analyzer (Seahorse Bioscience) was used to study mitochondrial respiration and glycolytic rate in presence of different substrates. Mitochondrial function was tested by sequentially exposure of the synaptosomes to the ATP synthase inhibitor, oligomycin, the uncoupler FCCP (carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone) and the electron transport chain inhibitors rotenone and antimycin A. The synaptosomes exhibited intense respiratory activity using glucose as substrate. The FCCP-dependent respiration was significantly higher with 10 mM glucose compared to 1 mM glucose. Synaptosomes also readily used pyruvate as substrate, which elevated basal respiration, activity-dependent respiration induced by veratridine and the respiratory response to uncoupling compared to that obtained with glucose as substrate. Also lactate was used as substrate by synaptosomes but in contrast to pyruvate, mitochondrial lactate mediated respiration was comparable to respiration using glucose as substrate. Synaptosomal respiration using glutamate and glutamine as substrates was significantly higher compared to basal respiration, whereas oligomycin-dependent and FCCP-induced respiration was lower compared to the responses obtained in the presence of glucose as substrate. We provide evidence that synaptosomes are able to use besides glucose and pyruvate also the substrates lactate, glutamate and glutamine to support their basal respiration. Veratridine was found to increase respiration supported by glucose, pyruvate, lactate and glutamine and FCCP was found to increase respiration supported by glucose, pyruvate and lactate. This was not the case when glutamate was the only energy substrate.

Constant light during lactation programs circadian and metabolic systems.

PubMed

Madahi, Palma-Gómez; Ivan, Osnaya; Adriana, Balderas; Diana, Ortega; Carolina, Escobar

2018-04-24

Exposure to light at night is a disruptive condition for the adult circadian system, leading to arrhythmicity in nocturnal rodents. Circadian disruption is a risk factor for developing physiological and behavioral alterations, including weight gain and metabolic disease. During early stages of development, the circadian system undergoes a critical period of adjustment, and it is especially vulnerable to altered lighting conditions that may program its function, leading to long-term effects. We hypothesized that during lactation a disrupted light-dark cycle due to light at night may disrupt the circadian system and in the long term induce metabolic disorders. Here we explored in pups, short- and long-term effects of constant light (LL) during lactation. In the short term, LL caused a loss of rhythmicity and a reduction in the immunopositive cells of VIP, AVP, and PER1 in the suprachiasmatic nucleus (SCN). In the short term, the affection on the circadian clock in the pups resulted in body weight gain, loss of daily rhythms in general activity, plasma glucose and triglycerides (TG). Importantly, the DD conditions during development also induced altered daily rhythms in general activity and in the SCN. Exposure to LD conditions after lactation did not restore rhythmicity in the SCN, and the number of immunopositve cells to VIP, AVP, and PER1 remained reduced. In the long term, daily rhythmicity in general activity was restored; however, daily rhythms in glucose and TG remained disrupted, and daily mean levels of TG were significantly increased. Present results point out the programming role played by the LD cycle during early development in the function of the circadian system and on metabolism. This study points out the risk represented by exposure to an altered light-dark cycle during early stages of development. AVP: arginine vasopressin peptide; CRY: cryptochrome; DD: constant darkness; DM: dorsomedial; LD: light-dark cycle; LL: constant light; NICUs: neonatal

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

PubMed

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

2016-07-01

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

Characterization of porcine milk oligosaccharides during early lactation and their relation to the fecal microbiome

PubMed Central

Salcedo, J.; Frese, S. A.; Mills, D. A.; Barile, D.

2017-01-01

The composition of porcine milk oligosaccharides (PMO) was analyzed during early lactation and their relation to piglet gut microbiome was investigated. Pigs are considered ideal intestinal models to simulate humans because of the striking similarity in intestinal physiopathology to humans. The evolution of PMO was investigated in the milk from 3 healthy sows at prefarrowing, farrowing, and d 7 and 14 postpartum by Nano-LC Chip Quadrupole-Time-of-Flight mass spectrometer (Agilent Technologies, Santa Clara, CA). Previously sequenced metagenome libraries were reanalyzed to examine changes with specific gut bacterial populations. Over 30 oligosaccharides (OS) were identified in the milk, with 3′-sialyllactose, lacto-N-tetraose, α1–3,β1–4-d-galactotriose, 2′-fucosyllactose, and 6′-sialyllactose being the most abundant species (accounting for ~70% of the total OS). Porcine milk had lower OS diversity (number of unique structures) than human milk, and appeared closer to bovine and caprine milk. In agreement with previous studies, only 3 fucosylated OS were identified. Surprisingly, their contribution to total OS abundance was greater than in bovine milk (9 vs. 1%). Indeed, fucosylated PMO increased during lactation, mirroring a similar trend observed for neutral and type I OS content during early lactation. Taken together, these results suggest that, in terms of abundance, PMO are closer to human milk than other domestic species, such as bovine and caprine milks. Metagenomic sequencing revealed that fucose-consuming bacterial taxa in the gut microbiota of piglets were qualitatively but not quantitatively different between nursing and weaning stages, suggesting that both the composition and structure of dietary glycans may play a critical role in shaping the distal gut microbiome. The similarity of both intestinal physiopathology and milk OS composition in human and porcine species suggests similar effects on gastrointestinal development of early nutrition

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate.

PubMed

Lange, Sofie C; Winkler, Ulrike; Andresen, Lars; Byhrø, Mathilde; Waagepetersen, Helle S; Hirrlinger, Johannes; Bak, Lasse K

2015-12-01

We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

Induction of triglyceride accumulation and mitochondrial maintenance in muscle cells by lactate

PubMed Central

Sun, Jingquan; Ye, Xin; Xie, Minhao; Ye, Jianping

2016-01-01

Muscle exercise induces intramuscular triglyceride (TG) accumulation and promotes mitochondrial maintenance in myotubes. However, the mechanism underlying exercise effects remains unknown. In this study, lactic acid was tested as a signaling molecule in C2C12 myotubes to understand the mechanism. Intracellular TG storage was induced in the cells by sodium lactate. The lactate activity was observed with an inhibition of the cAMP-PKA pathway as indicated by a reduction in the phosphorylation status of CREB (pCREB). Induction of pCREB signal by forskolin was blocked by pretreatment of cells with lactate. The impact of lactate on mitochondrial function was examined with a focus on the activities of two enzymes, MCAT (malonylCoA:ACP transferase) and PDH (pyruvate dehydrogenase). The enzyme activities were induced in the cells by lactate. Expression of the lactate receptor (GPR81) and lactate transporters (MCT1/4) were induced as well by lactate. The lactate activities were observed at concentrations between 4–64 mM, and were not dependent on the increase in intracellular pyruvate. Pyruvate treatment did not generate the same effects in the cells. Those results suggest that lactate may induce intramuscular TG storage and mitochondrial maintenance in myotubes through inhibition of the cAMP pathway by activation of GPR81 in a positive feedback manner. PMID:27645401

[Prevalence and severity of lameness in early lactation in dairy cows and the effect on reproductive performance].

PubMed

Orgel, Corina; Ruddat, Inga; Hoedemaker, Martina

2016-08-17

To examine the impact of different degrees of lameness on the fertility of dairy cows. Seven dairy herds housed in free stall barns with cubicles were visited at 4-week intervals and all cows were examined for locomotion characteristics using a locomotion scoring system. The cows received scores from 1 (normal gait) to 5 (severely lame). During the study period of 18 months, 893 cows in the first month of lactation and 944 cows in the second, third and fourth months of lactation were evaluated. Reproductive measures between non-lame cows (score 1), mild lame cows (score 2) and cows with clear lameness (score ≥ 3) were compared. Independent of parity and herd effects, cows with scores ≥ 3 in the first month of lactation displayed a 6 days longer calving to first service interval (CFSI) (86.2 ± 35.6 vs. 80.2 ± 34.1 days; p = 0.002) and a 16 days longer calving to conception interval (CCI) (119.7 ± 51.4 vs. 103.8 ± 55.5 days; p = 0.048) than non-lame cows. Additionally, the risk for non-conception was significantly higher in cows suffering from lameness in the first month of lactation (odds ratio: 2.1, 95% confidence interval: 1.095, 4.040; p = 0.026). Cows affected by mild lameness in the third month of lactation had a 4 days longer CFSI (84.7 ± 35.6 vs. 80.1 ± 30.5 days; p = 0.026) and a 18 days longer CCI (120.1 ± 55.4 vs. 102.3 ± 47.6 days; p = 0.016) than non-lame cows, while the CSFI in distinct lame cows was extended by 7 days compared to non-lame cows (87.2 ± 34.9 vs. 80.1 ± 30.5 days; p = 0.002). Cows with the score 1 in the first month and score 3 in the third month of lactation showed the longest CSFI (94.3 ± 33.9 vs. 76.5 ± 16.0 days in non-lame cows; p = 0.046). This study suggests that both distinct and mild lameness in early lactation lead to a decline in reproduction in dairy herds. A regular determination of the lameness prevalence in dairy herds and optimizing claw health management

Lutein concentration in human milk during early lactation and its relationship with dietary lutein intake.

PubMed

Cena, Hellas; Castellazzi, Anna Maria; Pietri, Amedeo; Roggi, Carla; Turconi, Giovanna

2009-10-01

The present study aimed to estimate the lutein concentration in human milk during early lactation and its relationship with dietary lutein intake measured through the administration of a short FFQ. A cross-sectional study in which an FFQ was administered twice: on day 3 (T0) and day 30 (T1) postpartum; meanwhile two breast milk samples were collected. Maternal plasma samples were obtained at T0. The comparison of dietary lutein intakes and likewise lutein concentrations in breast milk at T0 and T1 were analysed with Student's t test. Pearson's correlation coefficient was used to determine the association between dietary lutein intake and lutein concentration in milk and plasma, respectively, as well as the correlation between breast milk and plasma lutein concentrations at T0. Pavia, northern Italy. Twenty-one pregnant women, age range 24-42 years, were recruited during their last trimester on a voluntary basis. Both breast milk and plasma lutein concentrations were significantly correlated with dietary lutein intake (r = 0.86, P = 0.0001 and r = 0.94, P = 0.0001, respectively). There was a clear significant correlation between milk and plasma lutein concentrations (r = 0.87, P = 0.0001). Mature milk lutein concentration, although significantly reduced at T1 (P < 0.01), maintained a fairly high correlation with dietary lutein intake (r = 0.82, P = 0.0001). Even though milk lutein concentration decreased during early lactation, it remained significantly correlated with daily lutein intake. Therefore, while awaiting further research, dietary recommendations advising intake of fresh fruit and vegetables rich in lutein, throughout the whole duration of pregnancy and lactation, are extremely useful.

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

PubMed

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

2017-10-01

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

Lactate storm marks cerebral metabolism following brain trauma.

PubMed

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.

Hepatic thyroid signaling of heat-stressed late pregnant and early lactating cows

PubMed Central

Weitzel, Joachim M; Viergutz, Torsten; Albrecht, Dirk; Bruckmaier, Rupert; Schmicke, Marion; Tuchscherer, Armin; Koch, Franziska

2017-01-01

During the transition between late gestation and early lactation, dairy cows experience severe metabolic stress due to the high energy and nutrient requirements of the fetus and the mammary gland. Additional thermal stress that occurs with rising temperatures during the ongoing climate change has further adverse implications on energy intake, metabolism and welfare. The thyroid hormone (TH)-mediated cellular signaling has a pivotal role in regulation of body temperature, energy intake and metabolic adaptation to heat. To distinguish between energy intake and heat stress-related effects, Holstein cows were first kept at thermoneutrality at 15°C followed by exposure to heat stress (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days, in late pregnancy and again in early lactation. Herein, we focused on hepatic metabolic changes associated with alterations in the hypothalamic–pituitary–thyroid axis in HS and PF animals. T3 and T4 levels dropped with HS or PF; however, in HS animals, this decline was more pronounced. Thyroid-stimulating hormone (TSH) levels remain unaffected, while plasma cholesterol concentrations were lower in HS than PF animals. Hepatic marker genes for TH action (THRA, DIO1 and PPARGC1) decreased after HS and were lower compared to PF cows but only post-partum. Proteomics data revealed reduced hepatic amino acid catabolism ante-partum and a shift toward activated beta-oxidation and gluconeogenesis but declined oxidative stress defense post-partum. Thus, liver metabolism of HS and PF cows adapts differently to diminished energy intake both ante-partum and post-partum, and a different TH sensitivity is involved in the regulation of catabolic processes. PMID:28500083

Non-puerperal induced lactation: an infant feeding option in paediatric HIV/AIDS in tropical Africa.

PubMed

Ogunlesi, Tinuade A; Adekanmbi, Folasade A; Fetuga, Bolanle M; Ogundeyi, Mojisola M

2008-09-01

A major problem in the management of infants exposed to HIV is the issue of feeding, which stems from the need to avoid transmission of the virus via breast milk. Other important issues in the nutrition of infants exposed to the virus include severe maternal illness, which makes suckling extremely difficult, and feeding orphans. Wet nursing is one of the recommended steps in addressing the feeding problems of such infants but for reasons of sociocultural disapproval, it appears not to be popular in traditional African settings. Non-puerperal induced lactation or re-lactation of a close relation, usually a grandmother, which hitherto has been used to rehabilitate severely malnourished motherless infants, may be equally useful. The procedure of re-lactation and the limitations of the method are highlighted. Also, the need to employ information, education and communication in improving the sociocultural acceptability of this veritable infant feeding method in tropical Africa is discussed.

Hypothyroxinemia induced by mild iodine deficiency deregulats thyroid proteins during gestation and lactation in dams.

PubMed

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2013-08-02

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I- symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels.

Maternal Exposure to Ethanol During Pregnancy and Lactation Affects Glutamatergic System and Induces Oxidative Stress in Offspring Hippocampus.

PubMed

Cesconetto, Patricia A; Andrade, Camila M; Cattani, Daiane; Domingues, Juliana T; Parisotto, Eduardo B; Filho, Danilo W; Zamoner, Ariane

2016-01-01

Alcohol abuse during pregnancy leads to intellectual disability and morphological defects in the offspring. The aim of this study was to determine the effect of chronic maternal ethanol (EtOH) consumption during pregnancy and lactation on glutamatergic transmission regulation, energy deficit, and oxidative stress in the hippocampus of the offspring. EtOH was administered to dams in drinking water at increasing doses (2 to 20%) from the gestation day 5 to lactation day 21. EtOH and tap water intake by treated and control groups, respectively, were measured daily. Results showed that EtOH exposure does not affect fluid intake over the course of pregnancy and lactation. The toxicity of maternal exposure to EtOH was demonstrated by decreased offspring body weight at experimental age, on postnatal day 21. Moreover, maternal EtOH exposure decreased (45) Ca(2+) influx in the offspring's hippocampus. Corroborating this finding, EtOH increased both Na(+) -dependent and Na(+) -independent glial [(14) C]-glutamate uptake in hippocampus of immature rats. Also, maternal EtOH exposure decreased glutamine synthetase activity and induced aspartate aminotransferase enzymatic activity, suggesting that in EtOH-exposed offspring hippocampus, glutamate is preferentially used as a fuel in tricarboxylic acid cycle instead of being converted into glutamine. In addition, EtOH exposure decreased [U-14C]-2-deoxy-D-glucose uptake in offspring hippocampus. The decline in glucose transport coincided with increased lactate dehydrogenase activity, suggesting an adaptative response in EtOH-exposed offspring hippocampus, using lactate as an alternative fuel. These events were associated with oxidative damage, as demonstrated by changes in the enzymatic antioxidant defense system and lipid peroxidation. Taken together, the results demonstrate that maternal exposure to EtOH during pregnancy and lactation impairs glutamatergic transmission, as well as inducing oxidative stress and energy deficit in

Induction of lactation in the intended mother of a surrogate pregnancy: case report.

PubMed

Biervliet, F P; Maguiness, S D; Hay, D M; Killick, S R; Atkin, S L

2001-03-01

A case of a successful induction of lactation in a commissioning mother of a surrogate pregnancy is reported. Induction of lactation was achieved with oral metoclopramide which was well tolerated. Alternative methods to induce lactation are reviewed. The advantages of breast-feeding and the relative ease with which lactation can be induced after a surrogate pregnancy would suggest that this could be offered to all commissioning mothers.

Bromocriptine modulates the expression of PTHrP receptor, Indian hedgehog, and Runx2 proteins in the growth plate of lactating rats.

PubMed

Wongdee, Kannikar; Thonapan, Natchayaporn; Saengamnart, Wasana; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2013-09-01

In lactating rats, the endochondral bone growth is markedly enhanced, leading to the lengthening of long bone. This lactation-induced bone elongation could be abolished by a dopaminergic D2 receptor agonist bromocriptine, but how bromocriptine altered the expression of major chondroregulatory proteins in the growth plate cartilage was elusive. Here, we performed a quantitative immunohistochemical analysis to determine the expression of various peptides and transcription factors known to control the growth plate chondrocyte proliferation and differentiation [i.e., parathyroid hormone-related protein (PTHrP), PTHrP receptor, Indian hedgehog (Ihh), and runt-related transcription factor 2 (Runx2)], in bromocriptine-treated lactating rats. The results showed that bromocriptine markedly increased Ihh expression in hypertrophic chondrocytes during early and mid-lactation, while the expression of PTHrP receptor, but not its ligand PTHrP, was upregulated in the proliferative and hypertrophic zones during mid and late lactation. In contrast, the expression of Runx2, an important transcription factor for chondrocyte differentiation, was suppressed in the hypertrophic chondrocytes of bromocriptine-treated rats. In conclusion, bromocriptine increased Ihh and PTHrP receptor expressions and decreased Runx2 expression, which might, in turn, enhance chondrocyte proliferation and delay chondrocyte hypertrophy, thereby slowing down endochondral bone growth. This finding could explain how bromocriptine compromised the lactation-induced bone elongation.

Hypothyroxinemia Induced by Mild Iodine Deficiency Deregulats Thyroid Proteins during Gestation and Lactation in Dams

PubMed Central

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2013-01-01

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I− symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels. PMID:23917811

Early changes in coagulation profiles and lactate levels in patients with septic shock undergoing extracorporeal membrane oxygenation

PubMed Central

Kim, Hyoung Soo; Cheon, Dae Young; Ha, Sang Ook; Han, Sang Jin; Kim, Hyun-Sook; Lee, Sun Hee; Kim, Sung Gyun

2018-01-01

Background To investigate the impact of coagulation profiles and lactate levels in patients with septic shock undergoing extracorporeal membrane oxygenation (ECMO). Methods A retrospective analysis of coagulation profiles, including disseminated intravascular coagulation (DIC) score, before and during 48 h of ECMO support [on day 0 (pre-ECMO), day 1, and day 2], was conducted in patients with septic shock undergoing ECMO. Results A total of 37 patients were included, and 15 (40.5%) patients survived. The initial DIC scores did not change in either the pre-ECMO overt-DIC (n=15) or non-overt-DIC (n=22) group after ECMO commencement. However, the DIC scores were significantly higher, at all three time-points, in non-survivors than in survivors. Additionally, the lactate levels improved considerably in the pre-ECMO non-overt-DIC group and in survivors during ECMO support, but not in the pre-ECMO overt DIC group or non-survivors. On a multivariate analysis, the pre-ECMO DIC score was significantly associated with hospital death [odds ratio (OR), 3.935; 95% confidence interval (CI), 1.170–13.230]. Receiver operating characteristic (ROC) curves revealed that the combination of pre-ECMO DIC score plus lactate level was the best predictor of hospital death (area under the curve, 0.879; 0.771–0.987); patients with combined scores >9.35 (the optimal cut-off) exhibited a three-fold higher mortality rate than did those with lower scores (81.8% vs. 26.7%, P=0.001). Conclusions During the early period of ECMO support, the coagulation profiles and lactate levels exhibited different trajectories in survivors and non-survivors. Furthermore, the pre-ECMO DIC score plus lactate level was the best predictor of hospital death. PMID:29707291

Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

PubMed Central

Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

2016-01-01

ABSTRACT Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling. PMID:26636483

Intramammary infections in heifers during early lactation following intramammary infusion of pirlimycin hydrochloride or penicillin-novobiocin at the first milking after parturition.

PubMed

Oliver, Stephen P; Headrick, Susan I; Gillespie, Barbara E; Lewis, Mark J; Johnson, David L; Lamar, Kenneth C; Moorehead, Hugh; Dowlen, Henry H; Hallberg, John W

2007-05-01

A study was conducted to determine whether intramammary antibiotic treatment of heifer mammary glands following the first milking after calving was effective for reducing the percentage of mammary quarters infected during early lactation. Jersey and Holstein heifers from two research herds were assigned to one of three treatment groups: (1) no intramammary infusion following the first milking after parturition, (2) intramammary infusion of all quarters with pirlimycin hydrochloride following the first milking after parturition and (3) intramammary infusion of all quarters with novobiocin sodium plus penicillin G procaine following the first milking after parturition. Almost 93% of Jersey heifers (40/43) and 73.1% of quarters (125/171) were infected at the first milking. Almost 77% of quarters (33/43) were cured following treatment with pirlimycin, 61.8% (21/34) were cured following treatment with penicillin-novobiocin and 39.6% (19/48) of infections were eliminated spontaneously in the untreated control group. Significantly fewer infections were observed in pirlimycin or penicillin-novobiocin treated mammary glands of Jersey heifers during early lactation than in untreated control mammary glands. Almost 89% of Holstein heifers (32/36) and 52.8% of quarters (76/144) were infected at the first milking. About 57% (12/21) of quarters were cured following treatment with pirlimycin, 41.4% (12/29) were cured following treatment with penicillin-novobiocin and 23.1% (6/26) of infections were eliminated spontaneously in the untreated negative control group. Significantly fewer infections were observed in pirlimycin treated mammary glands of Holstein heifers during early lactation than in untreated control mammary glands. However, no significant differences were observed following penicillin-novobiocin treatment of Holstein heifers after the first milking of lactation compared with untreated control quarters. Coagulase-negative staphylococci, Streptococcus uberis and

High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice.

PubMed

Tsuduki, Tsuyoshi; Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu

2015-07-17

This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.

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

PubMed

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

2012-05-01

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

First report about the mode of action of combined butafosfan and cyanocobalamin on hepatic metabolism in nonketotic early lactating cows.

PubMed

Kreipe, L; Deniz, A; Bruckmaier, R M; van Dorland, H A

2011-10-01

The primary aim was to investigate the effect of combined butafosfan and cyanocobalamin on liver metabolism in early lactating cows through mRNA expression measurements of genes encoding 31 enzymes and transport proteins of major metabolic processes in the liver using 16 multiparous early lactating dairy cows. The treatments included i.v. injection of 10 mL/100 kg of body weight combined butafosfan and cyanocobalamin (TG, n = 8) on 3 d consecutively at 25 ± 3 d in milk or injection with physiological saline solution similarly applied (CG, n = 8). Results include a higher daily milk production for TG cows (41.1 ± 0.9 kg, mean ± SEM) compared with CG cows (39.5 ± 0.7 kg). In plasma, the concentration of inorganic phosphorus was lower in the TG cows (1.25 ± 0.08 mmol/L) after the treatment than in the CG cows (1.33 ± 0.07 mmol/L). The plasma β-hydroxybutyrate concentration was 0.65 ± 0.13 mmol/L for all cows before the treatment, and remained unaffected post treatment. The unique result was that in the liver, the mRNA abundance of acyl-coenzyme A synthetase long-chain family member 1, involved in fatty acid oxidation and biosynthesis, was lower across time points after the treatment for TG compared with CG cows (17.5 ± 0.15 versus 18.1 ± 0.24 cycle threshold, log(2), respectively). In conclusion, certain effects of combined butafosfan and cyanocobalamin were observed on mRNA abundance of a gene in the liver of nonketotic early lactating cows. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

PubMed

Peetz, Jan; Barros, L Felipe; San Martín, Alejandro; Becker, Holger M

2015-07-01

Blood-derived lactate is a precious energy substrate for the heart muscle. Lactate is transported into cardiomyocytes via monocarboxylate transporters (MCTs) together with H(+), which couples lactate uptake to cellular pH regulation. In this study, we have investigated how the interplay between different acid/base transporters and carbonic anhydrases (CA), which catalyze the reversible hydration of CO2, modulates the uptake of lactate into isolated mouse cardiomyocytes. Lactate transport was estimated both as lactate-induced acidification and as changes in intracellular lactate levels measured with a newly developed Förster resonance energy transfer (FRET) nanosensor. Recordings of intracellular pH showed an increase in the rate of lactate-induced acidification when CA was inhibited by 6-ethoxy-2-benzothiazolesulfonamide (EZA), while direct measurements of lactate flux demonstrated a decrease in MCT transport activity, when CA was inhibited. The data indicate that catalytic activity of extracellular CA increases lactate uptake and counteracts intracellular lactate-induced acidification. We propose a hypothetical model, in which HCO3 (-), formed from cell-derived CO2 at the outer surface of the cardiomyocyte plasma membrane by membrane-anchored, extracellular CA, is transported into the cell via Na(+)/HCO3 (-) cotransport to counteract intracellular acidification, while the remaining H(+) stabilizes extracellular pH at the surface of the plasma membrane during MCT activity to enhance lactate influx into cardiomyocytes.

MATERNAL EXPOSURE TO ATRAZINE DURING LACTATION SUPPRESSES SUCKLING-INDUCED PROLACTIN RELEASE AND RESULTS IN PROSTATITIS IN THE ADULT OFFSPRING

EPA Science Inventory

The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), ...

Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats

PubMed Central

Zou, Mi; Arentson, Emily J.; Teegarden, Dorothy; Koser, Stephanie L.; Onyskow, Laurie; Donkin, Shawn S.

2015-01-01

Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose and low protein diets are linked to hepatic steatosis and insulin resistance in non-pregnant animals. We hypothesized that dietary fructose or low protein intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of low protein or fructose intake on hepatic steatosis and insulin resistance in unmated controls and pregnant and lactating rats. Sprague-Dawley rats were fed either a control (CT), a 63% fructose (FR) or an 8% protein (LP) diet. Glucose tolerance test at day 17 of the study revealed greater (P < 0.05) blood glucose at 10 (75.6 vs. 64.0 ± 4.8 mg/dl) and 20 (72.4 vs. 58.6 ± 4.0 mg/dl) min after glucose dose and greater area under the curve (4302.3 vs. 3763.4 ± 263.6 mg·dl−1·min−1) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < 0.05) livers (9.3, 7.1 vs. 4.8 ± 0.2 % body weight) and elevated (P < 0.05) liver triacylglycerol (216.0, 130.0 vs. 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. FR induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated control rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than a LP diet. PMID:22935342

[Temperature-switched high-efficiency D-lactate production from glycerol].

PubMed

Tian, Kangming; Zhou, Li; Chen, Xianzhong; Shen, Wei; Shi, Guiyang; Singh, Suren; Lu, Fuping; Wang, Zhengxiang

2013-01-01

Glycerol from oil hydrolysis industry is being considered as one of the abundent raw materials for fermentation industry. In present study, the aerobic and anaerobic metabolism and growth properties on glycerol by Esherichia coli CICIM B0013-070, a D-lactate over-producing strain constructed previously, at different temperatures were investigated, followed by a novel fermentation process, named temperature-switched process, was established for D-lactate production from glycerol. Under the optimal condition, lactate yield was increased from 64.0% to 82.6%. Subsequently, the yield of D-lactate from glycerol was reached up to 88.9% while a thermo-inducible promoter was used to regulate D-lactate dehydrogenase transcription.

Epidemiology of subclinical ketosis in early lactation dairy cattle.

PubMed

McArt, J A A; Nydam, D V; Oetzel, G R

2012-09-01

The purpose of this study was to describe the epidemiology of subclinical ketosis (SCK) in dairy cows in early lactation and determine the association of (1) days in milk (DIM) at onset of SCK, and (2) blood β-hydroxybutyrate (BHBA) concentration at onset of SCK with development of displaced abomasum (DA) and removal from herd in the first 30 DIM, conception to first service, days to conception within 150 DIM, and early lactation milk yield. Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 DIM using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Subclinical ketosis was defined as a BHBA concentration of 1.2 to 2.9 mmol/L. Mixed-effects multivariable Poisson regression was used to assess DA, removal from herd, and conception to first service. Semiparametric proportional hazards models were used to evaluate days to conception, and repeated-measures ANOVA was used to evaluate milk yield in the first 30 DIM. A total of 741 of 1,717 (43.2%) eligible cows had a least one BHBA test of 1.2 to 2.9 mmol/L. Peak incidence of SCK occurred at 5 DIM, when 22.3% of cows had their first SCK-positive test. Peak prevalence of SCK occurred at 5 DIM, when 28.9% of cows had a SCK-positive test. Median time from first positive SCK test until BHBA test <1.2 mmol/L was 5d. Cows first testing SCK positive from 3 to 5 DIM were 6.1 times more likely [95% confidence interval (CI) = 2.3 to 16.0] to develop a DA than cows first testing SCK positive at 6 DIM or later. Cows first testing SCK positive from 3 to 7 DIM were 4.5 times more likely (95% CI = 1.7 to 11.7) to be removed from the herd, were 0.7 times as likely (95% CI = 0.6 to 0.8) to conceive to first service, and produced 2.2 kg less milk per day for the first 30 DIM than cows first testing positive at 8 DIM or later. Each 0.1 mmol/L increase in BHBA at first SCK-positive test increased the risk of developing a DA by a factor of 1.1 (95% CI = 1.0 to 1

Arterial versus venous lactate: a measure of sepsis in children.

PubMed

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

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

PubMed

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

2010-01-01

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

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

PubMed

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

2017-10-01

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

CD147 Required for Corneal Endothelial Lactate Transport

PubMed Central

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

2014-01-01

Purpose. 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. Methods. 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. Results. 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. Conclusions. 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. PMID:24970254

CD147 required for corneal endothelial lactate transport.

PubMed

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.

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

PubMed

Ling, Binbing; Alcorn, Jane

2008-07-01

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

Selenium and Antioxidant Status in Dairy Cows at Different Stages of Lactation.

PubMed

Gong, Jian; Xiao, Min

2016-05-01

Thirty-five multiparous Holstein cows averaging 550 ± 50 kg of body weight and in 2 to 4 parity were divided into three groups according to lactation stage (group A: nine cows from 4 to 1 weeks prepartum; group B: 11 cows from 1 to 30 days postpartum; group C: 15 cows from 30 to 100 days postpartum). Selenium concentration, malondialdehyde (MDA) level, glutathione peroxidase (GSH-Px) activity, thioredoxin reductase (TrxR) activity, and total antioxidant status (TAS) in serum were determined to evaluate selenium and antioxidant status in dairy cows at different stages of lactation. The results showed that mean serum selenium concentration, MDA level, and GSH-Px activity of cows in early lactation increased significantly (P < 0.05) when compared with cows in the dry period and peak lactation. Conversely, serum TrxR activity and TAS declined during this period (P < 0.05). The increase of serum MDA level during early lactation indicate that the reactive oxygen species, including lipid hydroperoxides, increase in this period, thus placing the cows at a greater risk of oxidative stress. The significant decrease in TrxR activity that is accompanied with a decrease in TAS during early lactation suggests that dairy cows have low antioxidant defense in this period and TrxR may be an important antioxidant defense mechanism in transition dairy cows.

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

PubMed

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

2008-06-01

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

High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

PubMed

Heireman, Laura; Mahieu, Boris; Helbert, Mark; Uyttenbroeck, Wim; Stroobants, Jan; Piqueur, Marian

2017-07-27

Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a  HAGMA. L-lactate, D-lactate, β-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified.

Mammary cell-activating factor regulates the hormone-independent transcription of the early lactation protein (ELP) gene in a marsupial.

PubMed

Pharo, Elizabeth A; Renfree, Marilyn B; Cane, Kylie N

2016-11-15

The regulation of the tammar wallaby (Macropus eugenii) early lactation protein (ELP) gene is complex. ELP is responsive to the lactogenic hormones; insulin (I), hydrocortisone (HC) and prolactin (PRL) in mammary gland explants but could not be induced with lactogenic hormones in tammar primary mammary gland cells, nor in KIM-2 conditionally immortalised murine mammary epithelial cells. Similarly, ELP promoter constructs transiently-transfected into human embryonic kidney (HEK293T) cells constitutively expressing the prolactin receptor (PRLR) and Signal Transducer and Activator of Transcription (STAT)5A were unresponsive to prolactin, unlike the rat and mouse β-casein (CSN2) promoter constructs. Identification of the minimal promoter required for the hormone-independent transcription of tammar ELP in HEK293Ts and comparative analysis of the proximal promoters of marsupial ELP and the orthologous eutherian colostrum trypsin inhibitor (CTI) gene suggests that mammary cell-activating factor (MAF), an E26 transformation-specific (ETS) factor, may bind to an AGGAAG motif and activate tammar ELP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid.

PubMed

Fernández, Silvina; Córdoba, Mariana

2017-04-01

Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium. Capacitation and acrosome reaction were evaluated by chlortetracycline technique, while plasma membrane and acrosome integrity were determined by trypan blue stain/differential interference contrast microscopy. Heparin capacitated samples had a significant decrease in LDH and CK activities, while in hyaluronic acid capacitated samples LDH and CK activities both increased compared to control samples, in heparin and hyaluronic acid capacitation conditions, respectively. A significant increase in lactate concentration in the incubation medium occurred in hyaluronic acid-treated sperm samples compared to heparin treatment, indicating this energetic metabolite is produced during capacitation. The LDH and CK enzyme activities and lactate concentrations in the incubation medium were decreased with 2',5'-dideoxyadenosine treatment in hyaluronic acid samples. The mAC inhibitor significantly inhibited heparin-induced capacitation of sperm cells, but did not completely inhibit hyaluronic acid capacitation. Therefore, hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a mAC. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by mAC. Copyright © 2017 Elsevier B.V. All

Prevalence and incidence of intramammary infections in lactating dairy goats.

PubMed

McDougall, S; Malcolm, D; Prosser, Cg

2014-05-01

To determine the prevalence of intramammary infection (IMI) of lactating dairy goats between 0 and 4 days postpartum, the prevalence and incidence rate of new IMI at Weeks 2, 14 and 27 of lactation, and the relationship between herd-level prevalence of IMI and bulk tank somatic cell count (BTSCC). Milk samples were collected from 8% of a herd (total 624 does) from 18 dairy goat herds in the Waikato region of New Zealand, for bacteriology and somatic cell count (SCC) determination, from both glands within 4 days of kidding (Week 0) and again at Weeks 2, 14 and 27. Prevalence of IMI was determined at each time point and incidence rate calculated for Weeks 0-2, 2-14, and 14-27. Greenwood and Reed-Frost models were compared for estimation of the transmission parameter for all pathogens, and for Staphylococcus aureus, coagulase negative staphylococci (CNS) and Corynebacterium spp. separately. Bacteria were isolated from 1,122/4,814 (23.3%) glands, with CNS (13.4%) and Corynebacterium spp. (7.3%) being the most common isolates. Prevalence of any IMI increased with stage of lactation, varied among herds, and increased with age (all p<0.05). Incidence rate was 80, 24 and 7 new IMI/10,000 gland days for Weeks 0-2, 2-14 and 14-27, respectively. Incidence rate for any IMI increased with age and with the presence of an IMI in the contralateral gland, and varied among herds (p<0.001). The transmission of each pathogen was better modelled assuming contagiousness (Reed-Frost models), than not (Greenwood models). At gland level, IMI increased SCC at all stages of lactation (p<0.001). The gland prevalence of IMI within herds was positively associated with ln BTSCC at Week 2 (p=0.02), but not Weeks 14 or 27 (p>0.05). Prevalence of IMI increased with stage of lactation, but the highest incidence rate of new IMI occurred in early lactation. Models accounting for the contagious nature of infection fitted better than those not accounting for contagiousness. BTSCC was only associated

The “metabolic sensor” function of rat supraoptic oxytocin and vasopressin neurons is attenuated during lactation but not in diet-induced obesity

PubMed Central

Stevens, Wanida; Song, Zhilin; Johnson, Ginger C.; MacLean, Paul S.

2015-01-01

The oxytocin (OT) and vasopressin (VP) neurons of the supraoptic nucleus (SON) demonstrate characteristics of “metabolic sensors”. They express insulin receptors and glucokinase (GK). They respond to an increase in glucose and insulin with an increase in intracellular [Ca2+] and increased OT and VP release that is GK dependent. Although this is consistent with the established role of OT as an anorectic agent, how these molecules function relative to the important role of OT during lactation and whether deficits in this metabolic sensor function contribute to obesity remain to be examined. Thus, we evaluated whether insulin and glucose-induced OT and VP secretion from perifused explants of the hypothalamo-neurohypophyseal system are altered during lactation and by diet-induced obesity (DIO). In explants from female day 8 lactating rats, increasing glucose (Glu, 5 mM) did not alter OT or VP release. However, insulin (Ins; 3 ng/ml) increased OT release, and increasing the glucose concentration in the presence of insulin (Ins+Glu) resulted in a sustained elevation in both OT and VP release that was not prevented by alloxan, a GK inhibitor. Explants from male DIO rats also responded to Ins+Glu with an increase in OT and VP regardless of whether obesity had been induced by feeding a high-fat diet (HFD). The HFD-DIO rats had elevated body weight, plasma Ins, Glu, leptin, and triglycerides. These findings suggest that the role of SON neurons as metabolic sensors is diminished during lactation, but not in this animal model of obesity. PMID:26661099

Mitochondrial Respiratory Defect Causes Dysfunctional Lactate Turnover via AMP-activated Protein Kinase Activation in Human-induced Pluripotent Stem Cell-derived Hepatocytes*

PubMed Central

Im, Ilkyun; Jang, Mi-jin; Park, Seung Ju; Lee, Sang-Hee; Choi, Jin-Ho; Yoo, Han-Wook; Kim, Seyun; Han, Yong-Mahn

2015-01-01

A defective mitochondrial respiratory chain complex (DMRC) causes various metabolic disorders in humans. However, the pathophysiology of DMRC in the liver remains unclear. To understand DMRC pathophysiology in vitro, DMRC-induced pluripotent stem cells were generated from dermal fibroblasts of a DMRC patient who had a homoplasmic mutation (m.3398T→C) in the mitochondrion-encoded NADH dehydrogenase 1 (MTND1) gene and that differentiated into hepatocytes (DMRC hepatocytes) in vitro. DMRC hepatocytes showed abnormalities in mitochondrial characteristics, the NAD+/NADH ratio, the glycogen storage level, the lactate turnover rate, and AMPK activity. Intriguingly, low glycogen storage and transcription of lactate turnover-related genes in DMRC hepatocytes were recovered by inhibition of AMPK activity. Thus, AMPK activation led to metabolic changes in terms of glycogen storage and lactate turnover in DMRC hepatocytes. These data demonstrate for the first time that energy depletion may lead to lactic acidosis in the DMRC patient by reduction of lactate uptake via AMPK in liver. PMID:26491018

The economic benefit of treating subclinical Streptococcus agalactiae mastitis in lactating cows.

PubMed

Yamagata, M; Goodger, W J; Weaver, L; Franti, C

1987-12-15

The economic benefits of treating lactating cows for Streptococcus agalactiae mastitis were studied at a large (689 milking cows) central California dairy. Postcure milk production of case cows (infected, treated, and cured) was compared with production of paired control cows (uninfected) and was matched for yield, days in milk, days in gestation, and parity. A simulation was used to plot expected lactation curves for mastitic cows (infected, not treated) with characteristics similar to those of each control cow, and these curves were compared with actual case-cow lactation curves. The difference in actual and expected production was used to calculate net economic benefits of treatment. Comparison of expected with actual production indicated a net benefit from treatment of $396/cow for cows treated in early lactation and $237 for cows treated in midlactation, but a net loss of $55 for cows treated in late lactation. Lactation number did not have a significant impact on economic benefits of treatment. In contrast to other studies indicating no economic benefit from treating mastitis during lactation, this study's positive results may have been attributable to the high cure rate (98%) and the subclinical form of mastitis being treated. Streptococcus agalactiae mastitis treatment during early and midlactation would appear to be an economically justifiable option for dairy managers.

Comparison of the alkalizing effects of bicarbonate precursors in calves with experimentally induced metabolic acidosis.

PubMed

Nakagawa, Mitsuhide; Suzuki, Kazuyuki; Takahashi, Fumito; Kamikatano, Kazuhiro; Koiwa, Masateru; Taguchi, Kiyoshi

2009-06-01

The aims of this study were to confirm whether commercial acetated Ringer's solution, which contains 28 mM of sodium acetate, is superior to commercial lactated Ringer's solution in alkalizing effects in calves with experimentally induced metabolic acidosis. Twenty calves with experimentally induced mild acidosis were intravenously administered isotonic saline, DL-lactated, L-lactated or acetated Ringer's solution at a dose of 80 ml/kg body weight (BW). The acetated Ringer's solution induced a significantly greater increase in venous HCO(3)(-) and base excess concentrations than the other fluids during the early phases of extracellular fluid replacement in mild metabolic acidosis. Therefore, the alkalizing effect of commercial acetated Ringer's solution is superior to commercial DL- and L-lactated Ringer's solution in treatment of mild metabolic acidosis in calves.

Effect of level of chronic immune system activation on the lactational performance of sows.

PubMed

Sauber, T E; Stahly, T S; Nonnecke, B J

1999-08-01

The effect of the level of chronic immune system (IS) activation on sow lactational performance was determined in 11 pairs of littermate, primiparous sows. Sows with a low level of IS activation were created by rearing the animals via early weaning, isolated rearing schemes. During lactation, two levels of IS activation were achieved in each littermate sow pair by subcutaneous administration of either 0 (saline) or 5 microg/kg of sow BW of Escherichia coli lipopolysaccharide (LPS) in a mineral oil adjuvant emulsion on d 2 and 10 of lactation. Litters were standardized to 13 pigs by 8 h postpartum. Sows were offered daily 6.0 kg of a corn-soy diet formulated to contain a minimum of 250% of the dietary nutrient concentrations estimated to be needed by lactating sows. Based on antibody titers to LPS and serum concentrations of alpha-1 acid glycoprotein (AGP), high IS sows mounted an immune response to the LPS during lactation, and low IS sows maintained a low level of IS activation. Over an 18-d lactation, a high level of chronic activation of the sows' immune systems depressed daily sow feed intakes by .56 kg, litter weight gains by .32 kg, and daily milk by 1.4 kg, milk energy by 1.7 Mcal, and milk protein yields by 71 g, but did not alter sow body weight loss. The reductions in yields of milk and milk nutrients likely were because of proinflammatory cytokine-induced inhibition of the lactogenic hormones resulting from high chronic IS activation. Based on these data, the level of chronic IS activation alters the lactational performance of sows.

Importance of measuring lactate levels in children with sepsis.

PubMed

Anil, Nisha

2017-10-10

Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Exposure to a glyphosate-based herbicide during pregnancy and lactation induces neurobehavioral alterations in rat offspring.

PubMed

Gallegos, Cristina E; Bartos, Mariana; Bras, Cristina; Gumilar, Fernanda; Antonelli, Marta C; Minetti, Alejandra

2016-03-01

The impact of sub-lethal doses of herbicides on human health and the environment is a matter of controversy. Due to the fact that evidence particularly of the effects of glyphosate on the central nervous system of rat offspring by in utero exposure is scarce, the purpose of the present study was to assess the neurobehavioral effects of chronic exposure to a glyphosate-containing herbicide during pregnancy and lactation. To this end, pregnant Wistar rats were exposed through drinking water to 0.2% or 0.4% of a commercial formulation of glyphosate (corresponding to a concentration of 0.65 or 1.30g/L of glyphosate, respectively) during pregnancy and lactation and neurobehavioral alterations in offspring were analyzed. The postnatal day on which each pup acquired neonatal reflexes (righting, cliff aversion and negative geotaxis) and that on which eyes and auditory canals were fully opened were recorded for the assessment of sensorimotor development. Locomotor activity and anxiety levels were monitored via open field test and plus maze test, respectively, in 45- and 90-day-old offspring. Pups exposed to a glyphosate-based herbicide showed early onset of cliff aversion reflex and early auditory canal opening. A decrease in locomotor activity and in anxiety levels was also observed in the groups exposed to a glyphosate-containing herbicide. Findings from the present study reveal that early exposure to a glyphosate-based herbicide affects the central nervous system in rat offspring probably by altering mechanisms or neurotransmitter systems that regulate locomotor activity and anxiety. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative composition, diversity, and abundance of oligosaccharides in early lactation milk from commercial dairy and beef cows

PubMed Central

Sischo, William M.; Short, Diana M.; Geissler, Mareen; Bunyatratchata, Apichaya; Barile, Daniela

2017-01-01

Prebiotics are nondigestible dietary ingredients, usually oligosaccharides (OS), that provide a health benefit to the host by directly modulating the gut microbiota. Although there is some information describing OS content in dairy-source milk, no information is available to describe the OS content of beef-source milk. Given the different trait emphasis between dairy and beef for milk production and calf survivability, it is plausible that OS composition, diversity, and abundance differ between production types. The goal of this study was to compare OS in milk from commercial dairy and beef cows in early lactation. Early-lactation multiparous cows (5–12 d in milk) from 5 commercial Holstein dairy herds and 5 Angus or Angus hybrid beef herds were sampled once. Milk was obtained from each enrolled cow and frozen on the farm. Subsequently, each milk sample was assessed for total solids, pH, and OS content and relative abundance. Oligosaccharide diversity and abundance within and between samples was transformed through principal component analysis to reduce data complexity. Factors from principal component analysis were used to create similarity clusters, which were subsequently used in a multivariate logistic regression. In total, 30 OS were identified in early-lactation cow milk, including 21 distinct OS and 9 isomers with unique retention times. The majority of OS detected in the milk samples were present in all individual samples regardless of production type. Two clusters described distribution patterns of OS for the study sample; when median OS abundance was compared between the 2 clusters, we found that overall OS relative abundance was consistently greater in the cluster dominated by beef cows. For several of the structures, including those with known prebiotic effect, the difference in abundance was 2- to 4-fold greater in the beef-dominated cluster. Assuming that beef OS content in milk is the gold standard for cattle, it is likely that preweaning dairy

The demands of lactation promote differential regulation of lipid stores in fasting elephant seals.

PubMed

Fowler, Melinda A; Debier, Cathy; Champagne, Cory D; Crocker, Daniel E; Costa, Daniel P

2016-01-01

Fasting animals must ration stored reserves appropriately for metabolic demands. Animals that experience fasting concomitant with other metabolically demanding activities are presented with conflicting demands of energy conservation and expenditure. Our objective was to understand how fasting northern elephant seals regulate the mobilization of lipid reserves and subsequently milk lipid content during lactation. We sampled 36 females early and 39 at the end of lactation. To determine the separate influences of lactation from fasting, we also sampled fasting but non-lactating females early and late (8 and 6 seals, respectively) in their molting fasting period. Mass and adiposity were measured, as well as circulating non-esterified fatty acid (NEFA), triacylglycerol (TAG), cortisol, insulin and growth hormone levels. Milk was collected from lactating females. Milk lipid content increased from 31% in early to 51% in late lactation. In lactating females plasma NEFA was positively related to cortisol and negatively related to insulin, but in molting seals, only variation in cortisol was related to NEFA. Milk lipid content varied with mass, adiposity, NEFA, TAG, cortisol and insulin. Surprisingly, growth hormone concentration was not related to lipid metabolites or milk lipid. Suppression of insulin release appears to be the differential regulator of lipolysis in lactating versus molting seals, facilitating mobilization of stored lipids and maintenance of high NEFA concentrations for milk synthesis. Milk lipid was strongly impacted by the supply of substrate to the mammary gland, indicating regulation at the level of mobilization of lipid reserves. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-01-01

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

Comparative Transcriptome Analysis Reveals Different Molecular Mechanisms of Bacillus coagulans 2-6 Response to Sodium Lactate and Calcium Lactate during Lactic Acid Production

PubMed Central

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

2015-01-01

Lactate production is enhanced by adding calcium carbonate or sodium hydroxide during fermentation. However, Bacillus coagulans 2-6 can produce more than 180 g/L L-lactic acid when calcium lactate is accumulated, but less than 120 g/L L-lactic acid when sodium lactate is formed. The molecular mechanisms by which B. coagulans responds to calcium lactate and sodium lactate remain unclear. In this study, comparative transcriptomic methods based on high-throughput RNA sequencing were applied to study gene expression changes in B. coagulans 2-6 cultured in non-stress, sodium lactate stress and calcium lactate stress conditions. Gene expression profiling identified 712 and 1213 significantly regulated genes in response to calcium lactate stress and sodium lactate stress, respectively. Gene ontology assignments of the differentially expressed genes were performed. KEGG pathway enrichment analysis revealed that ‘ATP-binding cassette transporters’ were significantly affected by calcium lactate stress, and ‘amino sugar and nucleotide sugar metabolism’ was significantly affected by sodium lactate stress. It was also found that lactate fermentation was less affected by calcium lactate stress than by sodium lactate stress. Sodium lactate stress had negative effect on the expression of ‘glycolysis/gluconeogenesis’ genes but positive effect on the expression of ‘citrate cycle (TCA cycle)’ genes. However, calcium lactate stress had positive influence on the expression of ‘glycolysis/gluconeogenesis’ genes and had minor influence on ‘citrate cycle (TCA cycle)’ genes. Thus, our findings offer new insights into the responses of B. coagulans to different lactate stresses. Notably, our RNA-seq dataset constitute a robust database for investigating the functions of genes induced by lactate stress in the future and identify potential targets for genetic engineering to further improve L-lactic acid production by B. coagulans. PMID:25875592

Identification of potential markers in blood for the development of subclinical and clinical mastitis in dairy cattle at parturition and during early lactation.

PubMed

Moyes, K M; Larsen, T; Friggens, N C; Drackley, J K; Ingvartsen, K L

2009-11-01

Our objective was to identify specific blood markers as risk factors for the development of mastitis during early lactation. We used a subset of cows from a larger experiment that consisted of a total of 634 lactations from 317 cows. Cows were of 3 breeds and ranged from parity 1 to 4. Blood samples were collected weekly from 56 d before expected calving date through 90 d in milk (DIM). Blood was analyzed for several hormones, metabolites, and enzymes, and energy intake and energy balance were calculated. Veterinary treatment records and daily composite milk somatic cell counts were analyzed and used to determine incidence and severity of mastitis in early lactation. Cows were separated into 2 groups: 1) WK0, consisting of cows that developed clinical mastitis (CM), cows that developed subclinical mastitis (SM), or cows that were healthy (H) during the first 7 DIM; and 2) EL, consisting of CM, SM, or H cows during wk 2 through 13 of lactation. Data were adjusted for numerous fixed effects (e.g., parity, breed, season, and DIM) before statistical analysis. The time of mastitis (TOM) was recorded as the DIM in which the first rise in somatic cell count was observed and was recorded as TOM = 0. The time before and after TOM was distinguished as +/- n wk relative to TOM = 0. Healthy cows were paired with either a SM or CM cow and the TOM for each H cow was equal to the TOM for its paired SM or CM cow. Data from wk -1 and -2 relative to TOM were analyzed for group WK0 and EL, respectively. For all parameters, SM cows did not differ from H cows from either group. The CM cows had higher nonesterified fatty acid levels and a tendency toward higher beta-hydroxybutyrate levels than H cows before mastitis for both groups. For group WK0, glucose was higher -1 wk relative to calving in CM than H cows. For group EL, aspartate aminotransferase was higher -2 wk relative to mastitis in CM than H cows during 8 to 90 DIM. All other variables were similar among CM, SM, and H cows for

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

PubMed

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.

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

PubMed

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

2016-12-01

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

Genetic parameter estimation for milk β-hydroxybutyrate and acetone in early lactation and its association with fat to protein ratio and energy balance in Korean Holstein cattle.

PubMed

Ranaraja, Umanthi; Cho, KwangHyun; Park, MiNa; Kim, SiDong; Lee, SeokHyun; Do, ChangHee

2018-06-01

The objective of this study was to estimate the genetic parameters for milk β-hydroxybutyrate (BHBA), acetone (Ac), fat protein ratio (FPR), and energy balance (EB) using milk test day records and investigate the effect of early lactation FPR and EB on milk ketone body concentrations. Total 262,940 test-day records collected from Korea Animal Improvement Association during the period of 2012 to 2016 were used in this study. BHBA and Ac concentrations in milk were measured by Fourier transform infrared spectroscopy (FTIR). FPR values were obtained using test day records of fat and protein percentage. EB was calculated using previously developed equation based on parity, lactation week, and milk composition data. Genetic parameters were estimated by restricted maximum likelihood procedure based on repeatability model using Wombat program. Elevated milk BHBA and Ac concentrations were observed during the early lactation under the negative energy balance. Milk FPR tends to decrease with the decreasing ketone body concentrations. Heritability estimates for milk BHBA, Ac, EB, and FPR ranged from 0.09 to 0.14, 0.23 to 0.31, 0.19 to 0.52, and 0.16 to 0.42 respectively at parity 1, 2, 3, and 4. The overall heritability for BHBA, Ac, EB and FPR were 0.29, 0.32, 0.58, and 0.38 respectively. A common pattern was observed in heritability of EB and FPR along with parities. FPR and EB can be suggested as potential predictors for risk of hyperketonemia. The heritability estimates of milk BHBA, Ac, EB, and FPR indicate that the selective breeding may contribute to maintaining the milk ketone bodies at optimum level during early lactation.

Lactate as a marker of energy failure in critically ill patients: hypothesis.

PubMed

Valenza, Franco; Aletti, Gabriele; Fossali, Tommaso; Chevallard, Giorgio; Sacconi, Francesca; Irace, Manuela; Gattinoni, Luciano

2005-01-01

Lactate measurement in the critically ill has been traditionally used to stratify patients with poor outcome. However, plasma lactate levels are the result of a finely tuned interplay of factors that affect the balance between its production and its clearance. When the oxygen supply does not match its consumption, organisms such as man who are forced to produce ATP for their integrity adapt in many different ways up to the point when energy failure occurs. Lactate, being part of the adaptive response, may then be used to assess the severity of the supply/demand imbalance. In such a scenario, the time to intervention becomes relevant: early and effective treatment may allow the cell to revert to a normal state, as long as the oxygen machinery (i.e. mitochondria) is intact. Conversely, once the mitochondria are deranged, energy failure occurs even in the presence of normoxia. The lactate increase in critically ill patients may therefore be viewed as an early marker of a potentially reversible state.

Effects of supplementation and stage of lactation on performance of grazing dairy ewes.

PubMed

Mikolayunas, C M; Thomas, D L; Albrecht, K A; Combs, D K; Berger, Y M; Eckerman, S R

2008-04-01

The majority of dairy sheep in the world are fed pasture and supplemental grain during lactation; however, no trials have reported the effects of supplementation of dairy ewes grazing improved pastures in North America. In trial 1, 56 three-year-old grazing dairy ewes in early [21 +/- 10 d in milk (DIM)] or late (136 +/- 9 DIM) lactation were fed 0 or 0.82 kg of dry matter/d per ewe of supplement (16.5% crude protein mixture of corn and a soybean meal-based high-protein pellet) in a 2 x 2 factorial arrangement of treatments. There were no significant interactions between stage of lactation and supplementation treatments. Average test-day milk production was higher in early-lactation ewes than in late-lactation ewes (1.74 vs. 1.21 kg/d, respectively). Although test-day milk protein percentage was higher in late-lactation ewes than in early-lactation ewes (5.02 vs. 4.86%, respectively), there was no difference in milk fat percentage between stages of lactation. Supplemented ewes had higher milk production (1.59 vs. 1.36 kg/d, respectively), lower milk fat percentage (5.75 vs. 6.00%, respectively), and lower milk protein percentage (4.84 vs. 5.04%, respectively) than unsupplemented ewes. Milk urea N levels were similar between the 2 stages of lactation and between the 2 supplementation treatments and were above recommended levels for dairy sheep, indicating an excess intake or inefficient utilization of protein for both supplementation treatments. In trial 2, 96 two-, three-, and four-year-old grazing dairy ewes in midlactation (112 +/- 21 DIM) were randomly assigned to 4 treatments of 0, 0.41, 0.82, or 1.24 kg of dry matter/d per ewe of whole corn. Average test-day milk production increased linearly and milk fat percentage decreased quadratically with increasing amounts of corn supplementation. Milk protein yield increased linearly, and milk urea N levels decreased quadratically with increasing amounts of corn supplementation, suggesting an improvement in the

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

PubMed

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

2016-08-01

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.

Use of residual feed intake in Holsteins during early lactation shows potential to improve feed efficiency through genetic selection.

PubMed

Connor, E E; Hutchison, J L; Norman, H D; Olson, K M; Van Tassell, C P; Leith, J M; Baldwin, R L

2013-08-01

Improved feed efficiency is a primary goal in dairy production to reduce feed costs and negative impacts of production on the environment. Estimates for efficiency of feed conversion to milk production based on residual feed intake (RFI) in dairy cattle are limited, primarily due to a lack of individual feed intake measurements for lactating cows. Feed intake was measured in Holstein cows during the first 90 d of lactation to estimate the heritability and repeatability of RFI, minimum test duration for evaluating RFI in early lactation, and its association with other production traits. Data were obtained from 453 lactations (214 heifers and 239 multiparous cows) from 292 individual cows from September 2007 to December 2011. Cows were housed in a free-stall barn and monitored for individual daily feed consumption using the GrowSafe 4000 System (GrowSafe Systems, Ltd., Airdrie, AB, Canada). Animals were fed a total mixed ration 3 times daily, milked twice daily, and weighed every 10 to 14 d. Milk yield was measured at each milking. Feed DM percentage was measured daily, and nutrient composition was analyzed from a weekly composite. Milk composition was analyzed weekly, alternating between morning and evening milking periods. Estimates of RFI were determined as the difference between actual energy intake and predicted intake based on a linear model with fixed effects of parity (1, 2, ≥ 3) and regressions on metabolic BW, ADG, and energy-corrected milk yield. Heritability was estimated to be moderate (0.36 ± 0.06), and repeatability was estimated at 0.56 across lactations. A test period through 53 d in milk (DIM) explained 81% of the variation provided by a test through 90 DIM. Multiple regression analysis indicated that high efficiency was associated with less time feeding per day and slower feeding rate, which may contribute to differences in RFI among cows. The heritability and repeatability of RFI suggest an opportunity to improve feed efficiency through genetic

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

PubMed

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.

Pharmacokinetics of Metoprolol During Pregnancy and Lactation

PubMed Central

Ryu, Rachel J.; Eyal, Sara; Easterling, Thomas R.; Caritis, Steve N.; Venkataraman, Raman; Hankins, Gary; Rytting, Erik; Thummel, Kenneth; Kelly, Edward J.; Risler, Linda; Phillips, Brian; Honaker, Matthew T.; Shen, Danny D.; Hebert, Mary F.

2017-01-01

The objective of this study was to evaluate the steady-state pharmacokinetics of metoprolol during pregnancy and lactation. Serial plasma, urine, and breast milk concentrations of metoprolol and its metabolite, α-hydroxymetoprolol, were measured over 1 dosing interval in women treated with metoprolol (25–750 mg/day) during early pregnancy (n = 4), mid-pregnancy (n = 14), and late pregnancy (n = 15), as well as postpartum (n = 9) with (n = 4) and without (n = 5) lactation. Subjects were genotyped for CYP2D6 loss-of-function allelic variants. Using paired analysis, mean metoprolol apparent oral clearance was significantly higher in mid-pregnancy (361 ± 223 L/h, n = 5, P < .05) and late pregnancy (568 ± 273 L/h, n = 8, P < .05) compared with ≥3 months postpartum (200 ± 131 and 192 ± 98 L/h, respectively). When the comparison was limited to extensive metabolizers (EMs), metoprolol apparent oral clearance was significantly higher during both mid- and late pregnancy (P < .05). Relative infant exposure to metoprolol through breast milk was <1.0% of maternal weight-adjusted dose (n = 3). Because of the large, pregnancy-induced changes in metoprolol pharmacokinetics, if inadequate clinical responses are encountered, clinicians who prescribe metoprolol during pregnancy should be prepared to make aggressive changes in dosage (dose and frequency) or consider using an alternate beta-blocker. PMID:26461463

Lactate - A new frontier in the immunology and therapy of prostate cancer.

PubMed

Nenu, Iuliana; Gafencu, Grigore-Aristide; Popescu, Tiberiu; Kacso, Gabriel

2017-01-01

Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors. It was also demonstrated that hypoxia-inducible factor 1 (HIF1) induces the expression of TAM genes involved in prostate carcinogenesis. Furthermore, it should be noted that the stromal extracellular lactate, the result of tumoral glycolysis process is one of the HIF1 activators. In addition, lactate inhibits the differentiation of monocytes and dendritic cells and also induces the inactivation of the cytotoxic T-lymphocytes. Through an analysis of recent studies, we conclude that lactate is a vital component of several ways of modulating the immune response at the stromal prostatic adenocarcinoma including TAM activation and cytotoxic T lymphocytes immunosuppression. Our review focuses on the impact of lactate on prostatic adenocarcinoma progression in terms of its immunology, and how this influences the therapy of this condition and the clinical outcome.

Exposure to mother's pregnancy and lactation in infancy is associated with sexual attraction to pregnancy and lactation in adulthood.

PubMed

Enquist, Magnus; Aronsson, Hanna; Ghirlanda, Stefano; Jansson, Liselotte; Jannini, Emmanuele A

2011-01-01

Several theories, including psychodynamic theories, sexual imprinting and early conditioning have been formulated to explain sexual development. Empirical data, however, remain insufficient for a thorough evaluation of these theories. In this study, we test the hypothesis that a critical period exists for the acquisition of sexual preferences, as suggested by empirical findings in birds and mammals (sexual imprinting). An Internet questionnaire was used. We gather data from individuals with a sexual preference for pregnant and/or lactating women, under the hypothesis that pregnancy or lactation may become sexually attractive in adulthood following an exposure to pregnant or lactating women in infancy. We find that these preferences are more common in older siblings, i.e., in individuals who have been exposed to more maternal pregnancy and lactation. This result is independent of respondent and sibling sex. In addition, only maternal pregnancies and lactations experienced between 1.5 and 5 years of age are associated with the preferences. We discuss our findings in relation to theories of sexual development and to earlier reports of birth order effects on sexual behavior. We suggest that this age range may constitute a sensitive period for the acquisition of sexual preferences. © 2010 International Society for Sexual Medicine.

Effects of dry period length and dietary energy source on metabolic status and hepatic gene expression of dairy cows in early lactation.

PubMed

Chen, J; Gross, J J; van Dorland, H A; Remmelink, G J; Bruckmaier, R M; Kemp, B; van Knegsel, A T M

2015-02-01

In a prior study, we observed that cows with a 0-d dry period had greater energy balance and lower milk production compared with cows with a 30- or 60-d dry period in early lactation. The objective of the current study was to evaluate the influence of dry period length on metabolic status and hepatic gene expression in cows fed a lipogenic or glucogenic diet in early lactation. Holstein-Friesian dairy cows (n=167) were assigned randomly to 3×2 factorial design with 3 dry period lengths (n=56, 55, and 56 for 0-, 30-, and 60-d dry, respectively) and 2 early lactation diets (n=84 and 83 for glucogenic and lipogenic diet, respectively). Cows were fed a glucogenic or lipogenic diet from 10d before the expected calving date and onward. The main ingredient for a glucogenic concentrate was corn, and the main ingredients for a lipogenic concentrate were sugar beet pulp, palm kernel, and rumen-protected palm oil. Blood was sampled weekly from 95 cows from wk 3 precalving to wk 8 postcalving. Liver samples were collected from 76 cows in wk -2, 2, and 4 relative to calving. Liver samples were analyzed for triacylglycerol concentrations and mRNA expression of 12 candidate genes. Precalving, cows with a 0-d dry period had greater plasma β-hydroxybutyrate, urea, and insulin concentrations compared with cows with a 30- or 60-d dry period. Postcalving, cows with a 0-d dry period had lower liver triacylglycerol and plasma nonesterified fatty acids concentrations (0.20, 0.32, and 0.36mmol/L for 0-, 30-, and 60-d dry period, respectively), greater plasma glucose, insulin-like growth factor-I, and insulin (24.38, 14.02, and 11.08µIU/mL for 0-, 30-, and 60-d dry period, respectively) concentrations, and lower hepatic mRNA expression of pyruvate carboxylase, compared with cows with a 30- or 60-d dry period. Plasma urea and β-hydroxybutyrate concentrations were greater in cows fed a lipogenic diet compared with cows fed a glucogenic diet. In conclusion, cows with a 0-d dry period had

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

PubMed

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

2012-12-01

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

Comparative composition, diversity, and abundance of oligosaccharides in early lactation milk from commercial dairy and beef cows.

PubMed

Sischo, William M; Short, Diana M; Geissler, Mareen; Bunyatratchata, Apichaya; Barile, Daniela

2017-05-01

Prebiotics are nondigestible dietary ingredients, usually oligosaccharides (OS), that provide a health benefit to the host by directly modulating the gut microbiota. Although there is some information describing OS content in dairy-source milk, no information is available to describe the OS content of beef-source milk. Given the different trait emphasis between dairy and beef for milk production and calf survivability, it is plausible that OS composition, diversity, and abundance differ between production types. The goal of this study was to compare OS in milk from commercial dairy and beef cows in early lactation. Early-lactation multiparous cows (5-12 d in milk) from 5 commercial Holstein dairy herds and 5 Angus or Angus hybrid beef herds were sampled once. Milk was obtained from each enrolled cow and frozen on the farm. Subsequently, each milk sample was assessed for total solids, pH, and OS content and relative abundance. Oligosaccharide diversity and abundance within and between samples was transformed through principal component analysis to reduce data complexity. Factors from principal component analysis were used to create similarity clusters, which were subsequently used in a multivariate logistic regression. In total, 30 OS were identified in early-lactation cow milk, including 21 distinct OS and 9 isomers with unique retention times. The majority of OS detected in the milk samples were present in all individual samples regardless of production type. Two clusters described distribution patterns of OS for the study sample; when median OS abundance was compared between the 2 clusters, we found that overall OS relative abundance was consistently greater in the cluster dominated by beef cows. For several of the structures, including those with known prebiotic effect, the difference in abundance was 2- to 4-fold greater in the beef-dominated cluster. Assuming that beef OS content in milk is the gold standard for cattle, it is likely that preweaning dairy

Effect of physical effectiveness on digestibility of ration for cows in early lactation.

PubMed

Stojanovic, B; Grubic, G; Djordjevic, N; Bozickovic, A; Ivetic, A; Davidovic, V

2014-08-01

A study was conducted to investigate the effects of a diet particle size on nutrient digestibility in cows in early lactation. Treatments were diets with forage to concentrate ratio 43:57% in diet dry matter, with four different physically effective fibres (peNDF) content based on different cut length of corn silage and alfalfa haylage. The physical effectiveness factors (pef) and peNDF content of TMRs (total mixed ration) were determined using Penn State Particle Separator (PSPS) with two (pef8.0 , peNDF8.0) or three (pef1.18, peNDF1.18) sieves. The reducing of cut length of forages and particle size of diets did not affect on dry matter intake, while decreased peNDF intake by 16.34 and 8.83%, for peNDF8.0 and peNDF1.18 respectively. Apparent total tract digestibility of the nutrients was measured using two indicators: acid insoluble ash (AIA) and acid detergent insoluble lignin (ADL). Decreasing of forages cut length significantly increased apparent total tract digestibility of neutral detergent fibre (NDF) from 48.39% to 53.84% and from 53.9% to 58.66%, of crude protein from 73.96% to 79.24% and from 71.56% to 77.90%, with contemporary decreasing of non-fibre carbohydrate from 90.89% to 84.81% and from 91.99% to 86.80%, with AIA or ADL as indicator respectively. Dietary value of net energy for lactation (NEL) and energy intake was not affected by the peNDF content of the diet. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

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

PubMed Central

Omlin, Teye; Langevin, Karolanne

2014-01-01

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

Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and Early Lactation.

PubMed

Hambidge, K Michael; Miller, Leland V; Mazariegos, Manolo; Westcott, Jamie; Solomons, Noel W; Raboy, Victor; Kemp, Jennifer F; Das, Abhik; Goco, Norman; Hartwell, Ty; Wright, Linda; Krebs, Nancy F

2017-06-01

Background: Estimated physiologic requirements (PRs) for zinc increase in late pregnancy and early lactation, but the effect on dietary zinc requirements is uncertain. Objective: The aim of this study was to determine changes in daily fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of differing phytate contents in relation to physiologic zinc requirements during pregnancy and lactation. Methods: This was a prospective observational study of zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3) and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of childbearing age whose major food staple was maize and who had been randomly assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined from duplicate diets and fractional absorption (FAZ) by dual isotope ratio technique (TAZ = TDZ × FAZ). All variables were examined longitudinally and by group and compared with PRs. TAZ values at later phases were compared with phase 1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating (NPNL) women. Results: TAZ was greater in the LP group than in the C group at all phases. All variables increased from phase 1 to phases 2 and 3 and declined at phase 4. TAZ increased by 1.25 mg/d ( P = 0.045) in the C group and by 0.81 mg/d ( P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d ( P = 0.002) in the C group and 2.28 mg/d ( P = 0.0004) in the LP group, compared with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values in phases 2-4. Conclusions: Upregulation of zinc absorption in late pregnancy and early lactation matches increases in PRs of pregnant and lactating women, regardless of dietary phytate, which has implications for dietary zinc requirements of

Inhibition of Lactate Transport Erases Drug Memory and Prevents Drug Relapse.

PubMed

Zhang, Yan; Xue, Yanxue; Meng, Shiqiu; Luo, Yixiao; Liang, Jie; Li, Jiali; Ai, Sizhi; Sun, Chengyu; Shen, Haowei; Zhu, Weili; Wu, Ping; Lu, Lin; Shi, Jie

2016-06-01

Drug memories that associate drug-paired stimuli with the effects of abused drugs contribute to relapse. Exposure to drug-associated contexts causes consolidated drug memories to be in a labile state, during which manipulations can be given to impair drug memories. Although substantial evidence demonstrates the crucial role of neuronal signaling in addiction, little is known about the contribution of astrocyte-neuron communication. Rats were trained for cocaine-induced conditioned place preference (CPP) or self-administration and microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol into the basolateral amygdala (BLA) immediately after retrieval. The concentration of lactate was measured immediately after retrieval via microdialysis, and the CPP score and number of nosepokes were recorded 24 hours later. Furthermore, we used antisense oligodeoxynucleotides to disrupt the expression of astrocytic lactate transporters (monocarboxylate transporters 1 and 2) in the BLA after retrieval, tested the expression of CPP 1 day later, and injected L-lactate into the BLA 15 minutes before retrieval to rescue the effects of the oligodeoxynucleotides. Injection of 1,4-dideoxy-1,4-imino-D-arabinitol into the BLA immediately after retrieval prevented the subsequent expression of cocaine-induced CPP, decreased the concentration of lactate in the BLA, and reduced the number of nosepokes for cocaine self-administration. Disrupting the expression of monocarboxylate transporters 1 and 2 in the BLA also caused subsequent deficits in the expression of cocaine-induced CPP, which was rescued by pretreatment with L-lactate. Our results suggest that astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation of cocaine memory. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-04-01

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

Lactate dehydrogenase activity drives hair follicle stem cell activation

PubMed Central

Aimee, Flores; John, Schell; Abby, Krall; David, Jelinek; Matilde, Miranda; Melina, Grigorian; Daniel, Braas; White Andrew, C; Jessica, Zhou; Nick, Graham; Thomas, Graeber; Pankaj, Seth; Denis, Evseenko; Hilary, Coller; Jared, Rutter; Heather, Christofk; Lowry William, E

2017-01-01

Summary While normally dormant, Hair Follicle Stem Cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allow them to remain dormant and yet quickly respond to appropriate proliferative stimuli. PMID:28812580

Incremental amounts of Ascophyllum nodosum meal do not improve animal performance but increase milk iodine output in early lactation dairy cows fed high-forage diets

USDA-ARS?s Scientific Manuscript database

The objective of this study was to investigate the effects of incremental amounts of Ascophyllum nodosum meal (ANOD) on milk production, milk composition including fatty acids and I, blood metabolites, and nutrient intake and digestibility in early lactation dairy cows fed high-forage diets. Twelve ...

Upregulation of zinc absorption matches increases in physiological requirements for zinc in women consuming high-or-moderate-phytate diets during late pregnancy and early lactation

USDA-ARS?s Scientific Manuscript database

Objectives: To determine the roles of host and dietary factors in matching increases in physiological requirements for zinc (Zn) during late pregnancy and early lactation in women whose major dietary staple is maize with and without phytate reduction. Methods: Subjects were 22 indigenous Guatemalan ...

Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats.

PubMed

Crossland, Hannah; Constantin-Teodosiu, Dumitru; Gardiner, Sheila M; Greenhaff, Paul L

2017-07-01

The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5 ± 0.1 mg·kg -1 ·day -1 ) for 2 weeks before and during 24 h continuous intravenous infusion of LPS (15 μg·kg -1 ·h -1 ) or saline. Rosi blunted LPS-induced increases in muscle tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA by 70% ( P <0.05) and 64% ( P <0.01) respectively. Furthermore, Rosi suppressed the LPS-induced reduction in phosphorylated AKT and phosphorylated Forkhead box O (FOXO) 1 protein, as well as the up-regulation of muscle RING finger 1 (MuRF1; P <0.01) mRNA and the LPS-induced increase in 20S proteasome activity ( P <0.05). Accordingly, LPS reduced the muscle protein:DNA ratio (∼30%, P <0.001), which Rosi offset. Increased muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA ( P <0.001) and muscle lactate accumulation ( P <0.001) during endotoxaemia were suppressed by Rosi. Thus, pre-treatment with Rosi reduced muscle cytokine accumulation and blunted muscle protein loss and lactate accumulation during endotoxaemia, and at least in part by reducing activation of molecular events known to increase muscle protein breakdown and mitochondrial pyruvate use. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Lactation and reproduction*

PubMed Central

Thomson, A. M.; Hytten, F. E.; Black, A. E.

1975-01-01

The authors review the literature on the effect of lactation on fertility in the absence of contraception and on the effects of contraceptive measures on lactation. They examine data from several countries on the intervals between births and on the return of menstruation and ovulation after childbirth, comparing lactating with nonlactating women. They conclude that lactation is an inefficient contraceptive for the individual, but that in populations sustained lactation is associated with reduced fertility. Possible physiological mechanisms causing lactation amenorrhoea are discussed. Though much of the literature on the effect of contraceptives on lactation is inadequate, there is general agreement that the estrogen component of hormonal preparations has an adverse effect on lactation, but that progestins alone do not. Many questions remain. Is this effect seen in established lactation, or only in the puerperal period? Is it a direct pharmacological effect, or are pill-users the mothers least motivated to maintain breast-feeding? Does a close relationship exist between hormones given and lactation performance? The authors comment on some of the technical deficiencies of previous studies in this field and discuss practical possibilities of, and limitations to, obtaining adequate scientific information in the future. PMID:1084804

Tocopherols and tocotrienols in serum and liver of dairy cows receiving conjugated linoleic acids or a control fat supplement during early lactation.

PubMed

Sadri, H; Dänicke, S; Meyer, Ulrich; Rehage, J; Frank, J; Sauerwein, H

2015-10-01

The fat-soluble vitamin E comprises the 8 structurally related compounds (congeners) α-, β-, γ-, and δ-tocopherol (with a saturated side chain) and α-, β-, γ-, and δ-tocotrienol (with a 3-fold unsaturated side chain). Little is known regarding the blood and liver concentrations of the 8 vitamin E congeners during the transition from pregnancy to lactation in dairy cows. We thus quantified tocopherols (T) and tocotrienols (T3) in serum and liver and hepatic expression of genes involved in vitamin E metabolism in pluriparous German Holstein cows during late gestation and early lactation and investigated whether dietary supplementation (from d 1 in milk) with conjugated linoleic acids (CLA; 100g/d; each 12% of trans-10,cis-12 and cis-9,trans-11 CLA; n=11) altered these compared with control-fat supplemented cows (CTR; n=10). Blood samples and liver biopsies were collected on d -21, 1, 21, 70, and 105 (liver only) relative to calving. In both groups, the serum concentrations of αT, γT, βT3, and δT3 increased from d -21 to d 21 and remained unchanged between d 21 and 70, but were unaffected by CLA. The concentrations of the different congeners of vitamin E in liver did not differ between the CTR and the CLA groups. In both groups, the concentrations of the vitamin E forms in liver changed during the course of the study. The hepatic mRNA abundance of genes controlling vitamin E status did not differ between groups, but α-tocopherol transfer protein and tocopherol-associated protein mRNA increased with time of lactation in both. In conclusion, the concentrations of vitamin E congeners and the expression of genes related to vitamin E status follow characteristic time-related changes during the transition from late gestation to early lactation but are unaffected by CLA supplementation at the dosage used. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Lactate shuttles in nature.

PubMed

Brooks, G A

2002-04-01

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

Combination of Acute Physiology and Chronic Health Evaluation II score, early lactate area, and N-terminal prohormone of brain natriuretic peptide levels as a predictor of mortality in geriatric patients with septic shock.

PubMed

Wang, Hao; Li, Zhong; Yin, Mei; Chen, Xiao-Mei; Ding, Shi-Fang; Li, Chen; Zhai, Qian; Li, Yuan; Liu, Han; Wu, Da-Wei

2015-04-01

Given the high mortality rates in elderly patients with septic shock, the early recognition of patients at greatest risk of death is crucial for the implementation of early intervention strategies. Serum lactate and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels are often elevated in elderly patients with septic shock and are therefore important biomarkers of metabolic and cardiac dysfunction. We hypothesized that a risk stratification system that incorporates the Acute Physiology and Chronic Health Evaluation (APACHE) II score and lactate and NT-proBNP biomarkers would better predict mortality in geriatric patients with septic shock than the APACHE II score alone. A single-center prospective study was conducted from January 2012 to December 2013 in a 30-bed intensive care unit of a triservice hospital. The lactate area score was defined as the sum of the area under the curve of serial lactate levels measured during the 24 hours following admission divided by 24. The NT-proBNP score was assigned based on NT-proBNP levels measured at admission. The combined score was calculated by adding the lactate area and NT-proBNP scores to the APACHE II score. Multivariate logistic regression analyses and receiver operating characteristic curves were used to evaluate which variables and scoring systems served as the best predictors of mortality in elderly septic patients. A total of 115 patients with septic shock were included in the study. The overall 28-day mortality rate was 67.0%. When compared to survivors, nonsurvivors had significantly higher lactate area scores, NT-proBNP scores, APACHE II scores, and combined scores. In the multivariate regression model, the combined score, lactate area score, and mechanical ventilation were independent risk factors associated with death. Receiver operating characteristic curves indicated that the combined score had significantly greater predictive power when compared to the APACHE II score or the NT-proBNP score

Identifying poor metabolic adaptation during early lactation in dairy cows using cluster analysis.

PubMed

Tremblay, M; Kammer, M; Lange, H; Plattner, S; Baumgartner, C; Stegeman, J A; Duda, J; Mansfeld, R; Döpfer, D

2018-05-02

Currently, cows with poor metabolic adaptation during early lactation, or poor metabolic adaptation syndrome (PMAS), are often identified based on detection of hyperketonemia. Unfortunately, elevated blood ketones do not manifest consistently with indications of PMAS. Expected indicators of PMAS include elevated liver enzymes and bilirubin, decreased rumen fill, reduced rumen contractions, and a decrease in milk production. Cows with PMAS typically are higher producing, older cows that are earlier in lactation and have greater body condition score at the start of lactation. It was our aim to evaluate commonly used measures of metabolic health (input variables) that were available [i.e., blood β-hydroxybutyrate acid, milk fat:protein ratio, blood nonesterified fatty acids (NEFA)] to characterize PMAS. Bavarian farms (n = 26) with robotic milking systems were enrolled for weekly visits for an average of 6.7 wk. Physical examinations of the cows (5-50 d in milk) were performed by veterinarians during each visit, and blood and milk samples were collected. Resulting data included 790 observations from 312 cows (309 Simmental, 1 Red Holstein, 2 Holstein). Principal component analysis was conducted on the 3 input variables, followed by K-means cluster analysis of the first 2 orthogonal components. The 5 resulting clusters were then ascribed to low, intermediate, or high PMAS classes based on their degree of agreement with expected PMAS indicators and characteristics in comparison with other clusters. Results revealed that PMAS classes were most significantly associated with blood NEFA levels. Next, we evaluated NEFA values that classify observations into appropriate PMAS classes in this data set, which we called separation values. Our resulting NEFA separation values [<0.39 mmol/L (95% confidence limits = 0.360-0.410) to identify low PMAS observations and ≥0.7 mmol/L (95% confidence limits = 0.650-0.775) to identify high PMAS observations] were similar to values

Inhibition of lactation.

PubMed

Llewellyn-Jones, D

1975-01-01

The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

Hypothyroxinemia induced by maternal mild iodine deficiency impairs hippocampal myelinated growth in lactational rats.

PubMed

Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

2015-11-01

Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring. © 2014 Wiley Periodicals, Inc.

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

PubMed Central

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

Perinatal Dietary Choline Deficiency in Sows Influences Concentrations of Choline Metabolites, Fatty Acids, and Amino Acids in Milk throughout Lactation.

PubMed

Mudd, Austin T; Alexander, Lindsey S; Johnson, Stacey K; Getty, Caitlyn M; Malysheva, Olga V; Caudill, Marie A; Dilger, Ryan N

2016-11-01

Choline is essential for synthesis of phospholipids, neurodevelopment, and DNA methylation. It is unknown whether dietary perinatal choline deficiency affects maternal milk composition. We examined whether perinatal maternal dietary choline deficiency influences porcine-milk composition. Yorkshire sows were fed choline-deficient (CD) or choline-sufficient (CS) gestation diets [544 or 1887 mg choline/kg dry matter (DM), respectively] from 65 d before to 48 h after parturition and then fed lactation diets (517 or 1591 mg choline/kg DM, respectively) through day 19 of lactation. Milk was collected from 7 sows fed each diet at days 0 (colostrum), 7-9 (mature milk), and 17-19 (preweaning) of lactation. Sow plasma was collected 65 d before and 19 d after parturition. Milk was analyzed for choline metabolite, fatty acid (FA), and amino acid composition. All outcomes were analyzed to assess main and interactive effects of choline intake and time. Plasma choline metabolites did not differ before treatment, but free choline, betaine, and dimethylglycine concentrations were lower in CD-fed than in CS-fed sows at day 19 of lactation (interaction; P < 0.05). Milk betaine concentrations responded similarly, with no differences due to choline intake at day 0 of lactation, but lower concentrations in CD-fed than in CS-fed sows at day 18 of lactation (interaction; P < 0.001). Certain milk long-chain FAs also exhibited no differences at day 0 of lactation but higher concentrations in CD-fed than in CS-fed sows at day 18 of lactation (P < 0.05). These data indicate that, in pigs, dietary choline deficiency induces alterations in plasma choline metabolites that are evident at the end of lactation. Betaine and select FAs in milk are sensitive to maternal dietary choline deficiency and day of lactation. Alterations in concentrations of these nutrients may affect early-life neonatal development. © 2016 American Society for Nutrition.

Brain activity-induced neuronal glucose uptake/glycolysis: Is the lactate shuttle not required?

PubMed

Tang, Bor Luen

2018-03-01

The astrocyte-neuron lactate shuttle (ANLS) hypothesis posits that during neuronal activation, astrocytic glycolysis consumes glucose and generates lactate, with the latter then imported by neurons as a preferred fuel. The hypothesis has been controversial, with multiple theoretical postulates for and against, and with empirical evidence that were either supportive or otherwise. Recent findings using direct in vivo imaging of lactate and glucose uptake as well as associated metabolic changes in neurons have now placed important constraints on the hypothesis. Here, I review these recent findings and discuss their implications on neuronal energetics. Copyright © 2017 Elsevier Inc. All rights reserved.

Breast abscess, an early indicator for diabetes mellitus in non-lactating women: a retrospective study from rural India.

PubMed

Verghese, Basil George; Ravikanth, R

2012-05-01

Breast abscess is commonly seen in lactating and non-lactating women. Diabetes mellitus (DM) frequently predisposes to soft tissue infections and has many different presentations. But DM presenting in the form of breast abscess is yet to be studied, and we believe our study is the first to explore this connection. We collected 30 cases of breast abscess in women who presented to our hospital from May 2010 to June 2011 retrospectively. They were classified into lactating and non-lactating women, and their glycemic status was evaluated, together with length of hospital stay, management, recurrence, and follow-up status after 6 months. We found that of the 30 patients in our study, 20% had high blood sugar levels. And 37.5% of the non-lactating women were diagnosed newly with DM. This study shows that DM can present as breast abscess in non-lactating women. Therefore, non-lactating women with a breast abscess should be evaluated for DM.

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

PubMed

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

2007-11-27

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

Rise in plasma lactate concentrations with psychosocial stress: a possible sign of cerebral energy demand.

PubMed

Kubera, Britta; Hubold, Christian; Otte, Saskia; Lindenberg, Ann-Sophie; Zeiss, Irena; Krause, Regina; Steinkamp, Mirja; Klement, Johanna; Entringer, Sonja; Pellerin, Luc; Peters, Achim

2012-01-01

It is known that exogenous lactate given as an i.v. energy infusion is able to counteract a neuroglycopenic state that developed during psychosocial stress. It is unknown, however, whether the brain under stressful conditions can induce a rise in plasma lactate to satisfy its increased needs during stress. Since lactate is i) an alternative cerebral energy substrate to glucose and ii) its plasmatic concentration is influenced by the sympathetic nervous system, the present study aimed at investigating whether plasma lactate concentrations increase with psychosocial stress in humans. 30 healthy young men participated in two sessions (stress induced by the Trier Social Stress Test and a non-stress control session). Blood samples were frequently taken to assess plasma lactate concentrations and stress hormone profiles. Plasma lactate increased 47% during psychosocial stress (from 0.9 ± 0.05 to 1.4 ± 0.1 mmol/l; interaction time × stress intervention: F = 19.7, p < 0.001). This increase in lactate concentrations during stress was associated with an increase in epinephrine (R(2) = 0.221, p = 0.02) and ACTH concentrations (R(2) = 0.460, p < 0.001). Plasma lactate concentrations increase during acute psychosocial stress in humans. This finding suggests the existence of a demand mechanism that functions to allocate an additional source of energy from the body towards the brain, which we refer to as 'cerebral lactate demand'.

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

PubMed

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

2017-09-01

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

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

PubMed

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

2017-01-01

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

Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice

PubMed Central

Dinger, Katharina; Kasper, Philipp; Hucklenbruch-Rother, Eva; Vohlen, Christina; Jobst, Eva; Janoschek, Ruth; Bae-Gartz, Inga; van Koningsbruggen-Rietschel, Silke; Plank, Christian; Dötsch, Jörg; Alejandre Alcázar, Miguel Angel

2016-01-01

Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma. PMID:27087690

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

PubMed

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

2015-12-01

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

Pregnancy development from day 28 to 42 of gestation in postpartum Holstein cows that were either milked (lactating) or not milked (not lactating) after calving.

PubMed

Green, Jacob C; Meyer, Joseph P; Williams, Amanda M; Newsom, Emily M; Keisler, Duane H; Lucy, Matthew C

2012-05-01

The objective was to determine if lactation affects fetal and placental development from day 28 to 42 of gestation. Bos taurus Holstein cows were assigned to one of the two treatments immediately after parturition (lactating (n=23) or nonlactating (dried off immediately after calving; n=20)). Cows were inseminated at ~60 days postpartum with semen from a single ejaculate. Pregnant cows were slaughtered at 1 of 3 days of gestation (day 28, 35, or 42) and tissues were collected. The interval to first insemination, services per conception, and days to pregnancy were similar for lactating and nonlactating cows. Lactating cows had greater plasma GH and nonesterified fatty acids. Nonlactating cows had greater plasma glucose, insulin, and IGF1. There was no effect of lactation on plasma progesterone or estradiol concentrations. Lactation had a negative effect on the weight of the fetus and placenta (weights were less in lactating cows). Fetuses collected from cows that became pregnant after first insemination were heavier than fetuses collected from cows that became pregnant after second or third insemination. Pregnancy after first insemination was associated with greater blood glucose and IGF1 during the first 30 days postpartum. The conclusions were that lactation negatively affects the growth of fetal and placental tissues perhaps through a mechanism that involves hormones and metabolites that are affected by lactation. Fetal growth within cows conceiving at first insemination compared to second or third insemination was more rapid and was associated with greater blood glucose and IGF1 early postpartum (before day 30).

Regional analyses of CNS microdialysate glucose and lactate in seizure patients.

PubMed

Cornford, Eain M; Shamsa, Kamran; Zeitzer, Jamie M; Enriquez, Cathleen M; Wilson, Charles L; Behnke, Eric J; Fried, Itzhak; Engel, Jerome

2002-11-01

To correlate glucose (and lactate) results obtained from microdialysate to recent studies suggesting that glucose transporter activity may be significantly altered in seizures. We used a fluorometric technique to quantify glucose and lactate levels in microdialysates collected from two to four depth electrodes implanted per patient in the temporal and frontal lobes of a series of four patients. Hour-by-hour and day-to-day changes in brain glucose and lactate levels at the same site were recorded. Additionally we compared regional variations in lactate/glucose ratios around the predicted epileptogenic region. Lactate/glucose ratios in the range of 1-2:1 were the most commonly seen. When the lactate/glucose ratio was <1:1, we typically observed a relative increase in local glucose concentration (rather than decreased lactate), suggesting increased transport, perhaps without increased glycolysis. In some sites, lactate/glucose ratios of 3:1-15:1 were seen, suggesting that a circumscribed zone of inhibition of tricarboxylic acid cycle activity may have been locally induced. In these dialysates, collected from probes closer to the epileptogenic region, the large increase in lactate/glucose ratios was a result of both increased lactate and reduced glucose levels. We conclude that regional variations in brain extracellular glucose concentrations may be of greater magnitude than previously believed and become even more accentuated in partial seizure patients. Data from concomitant assays of microdialysate lactate and glucose may aid in understanding cerebral metabolism.

myo-Inositol metabolism during lactation and development in the rat. The prevention of lactation-induced fatty liver by dietary myo-inositol.

PubMed

Burton, L E; Wells, W W

1976-11-01

Effects of dietary myo-inositol deprivation were examined during prenatal and postnatal development and during lactation in the rat. The deficient diet contained no detectable myo-inositol while the supplemented diet contained 0.5% (w/w) myo-inositol while the supplemented diet ct contained 0.5% (w/w) myo-inositol at the expense of sucrose. Both diets contained 25% casein, adequate amounts of all known vitamins, choline, and essential fatty acids as well as 0.5% (w/w) phthalylsulfathiazole to depress myo-inositol contribution to the diet by microorganisms. Pregnant rats of the Holtzman strain were fed the respective diets during gestation and lactation, and pups were fed the corresponding diet after weaning until 3 months of age. There were no significant differen-es in body weight between experimental groups. Supplementation of the diet with myo-inositol significanly increased the levels of myo-inositol in plasma, liver, kidney, and intestine of pups at all ages examined, and significantly increased the levels of myo-inositol in the milk and mammary tissue during lactation. During lactation, the myo-inositol deprived dams developed severe fatty livers (31% w/w) characterized by diminished phosphatidyl-inositol (50%) and total phospholipid phosphorus (57%) levels as compared with controls. After weaning, the liver lipid content of the myo-inositol deprived dams returned to normal (4.5%). The data suggest that a possible threshold level of free myo-inositol (approximately 0.15 mumoles/g lipid-free tissue) was required to prevent fatty liver in lactating dams under these dietary conditions. Effects of the deficient diet on fertility were also examined. Based on sperm count and production of offspring, there were no differnences between the experimental and control males. Females of both groups showed equal ability to produce offspring.

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

PubMed

Dai, Min; Yang, Yue; Shi, Xiaorui

2011-10-01

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

Effects of high and low blood lactate concentrations on sweat lactate response.

PubMed

Green, J M; Bishop, P A; Muir, I H; McLester, J R; Heath, H E

2000-11-01

Sweat lactate results from eccrine gland metabolism, however, the possible clearance of blood lactate through sweat has not been resolved. On separate days in an environmental chamber (32 +/- 1 C) 12 subjects completed a constant load (CON) (30 min at 40% VO2 max) and an interval cycling trial (INT) (15 one-min intervals at 80% VO2 max, each separated by one min rest) each designed to elicit different blood lactate responses. Each 30 min cycling trial was preceded by 15 min warm-up (30 watts) and followed by 15 min passive rest. Sweat and blood were analyzed for lactate concentration at 15, 25, 35, 45, and 60 min during CON and INT. Total body water loss was used to calculate sweat rate (ml/hr). Blood lactate was significantly greater (p < or = 0.05) at 25, 35, 45, and 60 min during INT compared to CON (approximately 5 mmol/L vs 1.5 mmol/L). Sweat lactate was not significantly different (p>0.05) between trials at any time (approximately 10 mmol/L). Sweat rates (approximately 600ml/hr) and estimated total lactate secretion were not significantly different (CON vs. INT) (p > 0.05). Elevated blood lactate was not associated with changes in sweat lactate concentration. Sweat lactate seems to originate in eccrine glands independent of blood lactate.

Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation.

PubMed

Jury, Nicholas J; McCormick, Betsy A; Horseman, Nelson D; Benoit, Stephen C; Gregerson, Karen A

2015-01-01

The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD) is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT) systems and related affective behaviors. Brain sections from lactating (day 10 postpartum) and age-matched nulliparous (non-pregnant) C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST) and marble burying task (MBT). Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day) or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although recent evidence

Enhanced Responsiveness to Selective Serotonin Reuptake Inhibitors during Lactation

PubMed Central

Jury, Nicholas J.; McCormick, Betsy A.; Horseman, Nelson D.; Benoit, Stephen C.; Gregerson, Karen A.

2015-01-01

The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD) is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT) systems and related affective behaviors. Brain sections from lactating (day 10 postpartum) and age-matched nulliparous (non-pregnant) C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST) and marble burying task (MBT). Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day) or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although recent evidence

Successful induction of lactation in a barren Thoroughbred mare: growth of a foal raised on induced lactation and the corresponding maternal hormone profiles.

PubMed

Korosue, Kenji; Murase, Harutaka; Sato, Fumio; Ishimaru, Mutsuki; Harada, Takehiro; Watanabe, Gen; Taya, Kazuyoshi; Nambo, Yasuo

2012-08-01

The purpose of this study was to demonstrate that a barren parous Thoroughbred mare with lactation induced by hormonal treatment can be introduced to an orphan foal at the same farm and that the mare can become pregnant after the end of the hormonal treatment. An additional purpose was to investigate the changes in the plasma concentrations of prolactin, estradiol-17β, progesterone, follicle-stimulating hormone, and luteinizing hormone before, during, and after hormonal treatment. The difference in body weight between the adopted foal and the control foals, which were at the same farm and raised by their natural mothers, was 17 kg at 24 weeks old, when the foals were weaned. However, the adopted foal and the control foals had almost the same weight at 35 weeks old and later. The first ovulation after hormonal treatment was confirmed 10 days after the end of hormonal treatment and then the normal estrous cycle resumed. Furthermore, the changes in plasma progesterone, estradiol-17β, follicle-stimulating hormone, and luteinizing hormone showed regular patterns after the first ovulation. Conception was confirmed in the fifth ovulation. Meanwhile, another study demonstrated that conception was confirmed in the first ovulation after hormonal treatment. The present study is the first to demonstrate the hormonal profiles during and after induction of lactation in a Thoroughbred mare. This approach is useful for solving the economic and epidemic problems of introducing a nurse mare to an orphan foal.

Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early-weaned rats at adulthood.

PubMed

Peixoto-Silva, Nayara; Moura, Egberto G; Carvalho, Janaine C; Nobre, Jéssica L; Quitete, Fernanda T; Pinheiro, Cintia R; Santos-Silva, Ana Paula; de Oliveira, Elaine; Lisboa, Patricia C

2017-04-01

Non-pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. Lactating rats were divided into two groups: dams with an adhesive bandage around the body to prevent breastfeeding on the last 3 days of lactation and dams whose pups had free suckling (C). Offspring from both groups were subdivided into two groups: pups treated with BRO (intraperitoneal (i.p.) 4 mg/kg per day) on the last 3 days of lactation (NPEW/BRO and C/BRO) or pups treated with the vehicle (NPEW and C). At PN120, offspring were challenged with a high fat diet (HFD), and food intake was recorded after 30 minutes and 12 hours. Rats were killed at PN120 and PN200. At PN120, adipocyte size was greater in the NPEW group but was normal in the NPEW/BRO group. At PN200, the NPEW group presented hyperphagia, higher adiposity, adipocyte hypertrophy, hyperleptinaemia, glucose intolerance and increased hepatic triglycerides. These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities. © 2017 John Wiley & Sons Australia, Ltd.

Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain.

PubMed

Imran, Imran; Hillert, Markus H; Klein, Jochen

2015-12-01

The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five-fold increase in lactate during seizures. Lactate release was because of neuronal activation as it was strongly reduced by infusion of tetrodotoxin, administration of atropine or when seizures were terminated by diazepam or ketamine. In ex vivo assays, mitochondrial function as measured by respirometry was not affected by 90 min of seizures. Extracellular levels of choline, however, increased two-fold and glycerol levels 10-fold, which indicate cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold and formation of isoprostanes 20-fold, revealing significant oxidative stress in hippocampal tissue. Increases in lactate, glycerol and isoprostanes were abrogated, and increases in choline were completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases in extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains intact for at least 90 min. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. Status epilepticus (SE) was induced in rats by

[The nutrition status of lactating women in China].

PubMed

Dong, C X; Yin, S A

2016-12-06

Nutritional status of lactating women is considered to be a quantitative indicator reflecting the status of reproductive health. To improve nutrition status of lactating women and promote breastfeeding through targeted intervention measures, their dietary and nutritional situations, and related problems, should be fully understood. Generally, energy and macronutrient intake of lactating women can reach or exceed recommended levels, especially during the first month postpartum. However, the intake of some micronutrients is difficult to meet the requirement. These include vitamin D and vitamin B 12 , iron and zinc, and calcium, if milk and dairy product consumption is very low, suggesting that extra supplementation should be considered. The percentage of obesity or postpartum weight retention showed an increasing trend in urban and rural areas and was related to decreased or delayed breastfeeding or early weaning. Common micronutrient deficiencies included in vitamin D, vitamin B 12 , iron and zinc. In this paper, we reviewed various characteristics of the lactating women, including nutritional status, postpartum weight retention and micronutrient deficiencies. We suggest that improved suggestions be developed for China, based on data from National Nutrition Survey, Chinese National Nutrition and Health Surveillance and related studies conducted over the past 10 years.

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.

PubMed

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.

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.

PubMed

Leelarungrayub, Donrawee; Khansuwan, Raphiphat; Pothongsunun, Prapas; Klaphajone, Jakkrit

2011-01-01

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 (VO(2max)), 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 VO(2max). 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 VO(2max) 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, VO(2max), maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

Do Lactation-Induced Changes in Ghrelin, Glucagon-Like Peptide-1, and Peptide YY Influence Appetite and Body Weight Regulation during the First Postpartum Year?

PubMed Central

Larson-Meyer, D. Enette; Schueler, Jessica; Kyle, Erin; Austin, Kathleen J.; Hart, Ann Marie; Alexander, Brenda M.

2016-01-01

To determine whether fasting and meal-induced appetite-regulating hormones are altered during lactation and associated with body weight retention after childbearing, we studied 24 exclusively breastfeeding women (BMI = 25.2 ± 3.6 kg/m2) at 4-5 weeks postpartum and 20 never-pregnant controls (BMI = 24.0 ± 3.1 kg/m2). Ghrelin, PYY, GLP-1, and appetite ratings were measured before/and 150 minutes after a standardized breakfast and 60 minutes after an ad libitum lunch. Body weight/composition were measured at 6 and 12 months. Fasting and area under-the-curve responses for appetite-regulating hormones did not differ between lactating and control groups; ghrelinacyl, however, tended to track higher after the standardized breakfast in lactating women and was higher (p < 0.05) after the ad libitum lunch despite a 24% higher energy intake (p < 0.05). By 12 months, lactating women lost 5.3 ± 2.2 kg (n = 18), whereas control women (n = 15) remained weight stable (p = 0.019); fifteen of the lactating women returned to within ±2.0 kg of prepregnancy weight but three retained >6.0 kg. The retainers had greater (p < 0.05) postmeal ghrelin rebound responses following breakfast. Overall these studies do not support the hypothesis that appetite-regulating hormones are altered during lactation and associated with postpartum weight retention. Altered ghrelin responses, however, deserve further exploration. PMID:27313876

Effects of low dietary cation-anion difference induced by ruminal ammonium chloride infusion on performance, serum, and urine metabolites of lactating dairy cows.

PubMed

Wang, Kun; Nan, Xuemei; Zhao, Puyi; Liu, Wei; Drackley, James K; Liu, Shijie; Zhang, Kaizhan; Bu, Dengpan

2018-05-01

The objective of the present study was to determine ammonium chloride tolerance of lactating dairy cows, by examining effects of negative dietary cation anion difference (DCAD) induced by ruminal ammonium chloride infusion on performance, serum and urine minerals, serum metabolites and enzymes of lactating dairy cows. Four primiparous lactating Chinese Holstein cows fitted with ruminal cannulas were infused with increasing amounts (0, 150, 300, or 450 g/d) of ammonium chloride in a crossover design. The DCAD of the base diet was 279 mEq/kg dry matter (DM) using the DCAD formula (Na + K - Cl - S)/kg of DM. Ammonium chloride infusion added the equivalent of 0, 128, 330, and 536 mEq/kg DM of Cl in treatments. According to the different dry matter intakes (DMI), the resulting actual DCAD of the four treatments was 279, 151, -51, and -257 mEq/kg DM, respectively. DMI decreased linearly as DCAD decreased. Yields of milk, 4% fat-corrected milk, energy-corrected milk, milk fat, and milk protein decreased linearly as DCAD decreased. Concentrations of milk protein and milk urea nitrogen increased linearly with decreasing DCAD. Concentration of Cl- in serum increased linearly and concentration of PO43- in serum increased quadratically as DCAD decreased. Urine pH decreased linearly and calculated urine volume increased linearly with decreasing DCAD. Linear increases in daily urinary excretion of Cl - , Ca 2+ , PO 4 3- , urea N, and ammonium were observed as DCAD decreased. Activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase in serum and urea N concentration in serum increased linearly as DCAD decreased. In conclusion, negative DCAD induced by ruminal ammonium chloride infusion resulted in a metabolic acidosis, had a negative influence on performance, and increased serum enzymes indicating potential liver and kidney damage in lactating dairy cows. Daily ammonium chloride intake by lactating dairy cows should not exceed 300 g, and 150

Increased Ventricular Cerebrospinal Fluid Lactate in Depressed Adolescents

PubMed Central

Bradley, Kailyn A. L.; Mao, Xiangling; Case, Julia A. C.; Kang, Guoxin; Shungu, Dikoma C.; Gabbay, Vilma

2016-01-01

Background Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. Methods Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. Results Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1, 41) = 6.98, p = .01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. Conclusions Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function. PMID:26802978

The Norwegian Healthier Goats program--modeling lactation curves using a multilevel cubic spline regression model.

PubMed

Nagel-Alne, G E; Krontveit, R; Bohlin, J; Valle, P S; Skjerve, E; Sølverød, L S

2014-07-01

In 2001, the Norwegian Goat Health Service initiated the Healthier Goats program (HG), with the aim of eradicating caprine arthritis encephalitis, caseous lymphadenitis, and Johne's disease (caprine paratuberculosis) in Norwegian goat herds. The aim of the present study was to explore how control and eradication of the above-mentioned diseases by enrolling in HG affected milk yield by comparison with herds not enrolled in HG. Lactation curves were modeled using a multilevel cubic spline regression model where farm, goat, and lactation were included as random effect parameters. The data material contained 135,446 registrations of daily milk yield from 28,829 lactations in 43 herds. The multilevel cubic spline regression model was applied to 4 categories of data: enrolled early, control early, enrolled late, and control late. For enrolled herds, the early and late notations refer to the situation before and after enrolling in HG; for nonenrolled herds (controls), they refer to development over time, independent of HG. Total milk yield increased in the enrolled herds after eradication: the total milk yields in the fourth lactation were 634.2 and 873.3 kg in enrolled early and enrolled late herds, respectively, and 613.2 and 701.4 kg in the control early and control late herds, respectively. Day of peak yield differed between enrolled and control herds. The day of peak yield came on d 6 of lactation for the control early category for parities 2, 3, and 4, indicating an inability of the goats to further increase their milk yield from the initial level. For enrolled herds, on the other hand, peak yield came between d 49 and 56, indicating a gradual increase in milk yield after kidding. Our results indicate that enrollment in the HG disease eradication program improved the milk yield of dairy goats considerably, and that the multilevel cubic spline regression was a suitable model for exploring effects of disease control and eradication on milk yield. Copyright © 2014

Effects of nutrition on pregnant and lactating sows.

PubMed

Einarsson, S; Rojkittikhun, T

1993-01-01

It has been suggested that the long-term reproduction of the sow is best served by minimizing weight and fat loss in lactation. Such a strategy would require only a minimal restoration of weight in the following pregnancy, which would be beneficial, since the greater feed intake and weight gain in pregnancy, the greater the weight loss in lactation. Feeding ad libitum should be practised during lactation while gestation feed intake must be held low. A relationship between feed intake and embryo survival has been demonstrated in several studies, but the data are sometimes difficult to interpret. High energy feeding during the premating period and during early pregnancy, however, are often associated with increased embryo mortality. A short-term starvation in lactation decreased prolactin to post-weaning concentrations, and insulin and glucose to very low concentrations. Prolactin increased very rapidly after refeeding indicating that a neural mechanism might be involved. The increasing levels of cholecystokinin after refeeding and the neural reflex triggered might be related to this increase in prolactin. No changes in LH release were observed during the periods of starvation or refeeding. The catabolic rate during the first week of lactation is higher in sows with higher backfat thickness than in late gestation. As lactation progresses a more balanced metabolism is achieved regardless of backfat thickness before parturition. High-weight-loss primiparous sows need a longer recovery period from their negative energy balance during lactation than do low-weight-loss primiparous sows or multiparous sows. Several investigations have demonstrated that sows losing excessive amounts of body weight have extended weaning to oestrous intervals and an increase in anoestrus. Sows with low body-weight loss during lactation have higher plasma insulin and lower cortisol around weaning than do sows with high body-weight loss. What remains undefined is the degree of weight or

Pharmacokinetics of metoprolol during pregnancy and lactation.

PubMed

Ryu, Rachel J; Eyal, Sara; Easterling, Thomas R; Caritis, Steve N; Venkataraman, Raman; Hankins, Gary; Rytting, Erik; Thummel, Kenneth; Kelly, Edward J; Risler, Linda; Phillips, Brian; Honaker, Matthew T; Shen, Danny D; Hebert, Mary F

2016-05-01

The objective of this study was to evaluate the steady-state pharmacokinetics of metoprolol during pregnancy and lactation. Serial plasma, urine, and breast milk concentrations of metoprolol and its metabolite, α-hydroxymetoprolol, were measured over 1 dosing interval in women treated with metoprolol (25-750 mg/day) during early pregnancy (n = 4), mid-pregnancy (n = 14), and late pregnancy (n = 15), as well as postpartum (n = 9) with (n = 4) and without (n = 5) lactation. Subjects were genotyped for CYP2D6 loss-of-function allelic variants. Using paired analysis, mean metoprolol apparent oral clearance was significantly higher in mid-pregnancy (361 ± 223 L/h, n = 5, P < .05) and late pregnancy (568 ± 273 L/h, n = 8, P < .05) compared with ≥3 months postpartum (200 ± 131 and 192 ± 98 L/h, respectively). When the comparison was limited to extensive metabolizers (EMs), metoprolol apparent oral clearance was significantly higher during both mid- and late pregnancy (P < .05). Relative infant exposure to metoprolol through breast milk was <1.0% of maternal weight-adjusted dose (n = 3). Because of the large, pregnancy-induced changes in metoprolol pharmacokinetics, if inadequate clinical responses are encountered, clinicians who prescribe metoprolol during pregnancy should be prepared to make aggressive changes in dosage (dose and frequency) or consider using an alternate beta-blocker. © 2015, The American College of Clinical Pharmacology.

Training-induced elevations in extracellular lactate in hippocampus and striatum: Dissociations by cognitive strategy and type of reward.

PubMed

Newman, Lori A; Scavuzzo, Claire J; Gold, Paul E; Korol, Donna L

2017-01-01

Recent evidence suggests that astrocytes convert glucose to lactate, which is released from the astrocytes and supports learning and memory. This report takes a multiple memory perspective to test the role of astrocytes in cognition using real-time lactate measurements during learning and memory. Extracellular lactate levels in the hippocampus or striatum were determined with lactate biosensors while rats were learning place (hippocampus-sensitive) or response (striatum-sensitive) versions of T-mazes. In the first experiment, rats were trained on the place and response tasks to locate a food reward. Extracellular lactate levels in the hippocampus increased beyond those of feeding controls during place training but not during response training. However, striatal lactate levels did not increase beyond those of controls when rats were trained on either the place or the response version of the maze. Because food ingestion itself increased blood glucose and brain lactate levels, the contribution of feeding may have confounded the brain lactate measures. Therefore, we conducted a second similar experiment using water as the reward. A very different pattern of lactate responses to training emerged when water was used as the task reward. First, provision of water itself did not result in large increases in either brain or blood lactate levels. Moreover, extracellular lactate levels increased in the striatum during response but not place learning, whereas extracellular lactate levels in the hippocampus did not differ across tasks. The findings from the two experiments suggest that the relative engagement of the hippocampus and striatum dissociates not only by task but also by reward type. The divergent lactate responses of the hippocampus and striatum in place and response tasks under different reward conditions may reflect ethological constraints tied to foraging for food and water. Copyright © 2016 Elsevier Inc. All rights reserved.

Atherogenicity index and health-related fatty acids in different stages of lactation from Friesian, Jersey and Friesian×Jersey cross cow milk under a pasture-based dairy system.

PubMed

Nantapo, C T W; Muchenje, V; Hugo, A

2014-03-01

The objective of the study was to investigate the effect of stage of lactation on the fatty acid profiles of milk from Friesian, Jersey and Friesian×Jersey cows. Linoleic acid in pastures was highest in the second phase which coincided with mid-lactation days (p<0.05). Highest milk moisture content and lowest fat free dry matter content was seen in early lactation (p<0.05). Higher fat content was observed in late lactation than early lactation. Highest butyric, caproic, linoleic, omega-6 and polyunsaturated fatty acids were observed for milk from Friesian cows. Highest conjugated fatty acids, α-linolenic acid, linoleic acid, saturated fatty acids, polyunsaturated fatty acids, omega-6, and omega-3 were observed in early lactation. Atherogenicity index and desaturase activity indices were highest in late lactation. In conclusion, stage of lactation and genotype affected milk health-related fatty acid profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lactate shuttling and lactate use as fuel after traumatic brain injury: metabolic considerations

PubMed Central

Dienel, Gerald A

2014-01-01

Lactate is proposed to be generated by astrocytes during glutamatergic neurotransmission and shuttled to neurons as ‘preferred' oxidative fuel. However, a large body of evidence demonstrates that metabolic changes during activation of living brain disprove essential components of the astrocyte–neuron lactate shuttle model. For example, some glutamate is oxidized to generate ATP after its uptake into astrocytes and neuronal glucose phosphorylation rises during activation and provides pyruvate for oxidation. Extension of the notion that lactate is a preferential fuel into the traumatic brain injury (TBI) field has important clinical implications, and the concept must, therefore, be carefully evaluated before implementation into patient care. Microdialysis studies in TBI patients demonstrate that lactate and pyruvate levels and lactate/pyruvate ratios, along with other data, have important diagnostic value to distinguish between ischemia and mitochondrial dysfunction. Results show that lactate release from human brain to blood predominates over its uptake after TBI, and strong evidence for lactate metabolism is lacking; mitochondrial dysfunction may inhibit lactate oxidation. Claims that exogenous lactate infusion is energetically beneficial for TBI patients are not based on metabolic assays and data are incorrectly interpreted. PMID:25204393

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

PubMed

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

2014-05-01

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

Effects of feeding fatty acid calcium and the interaction of forage quality on production performance and biochemical indexes in early lactation cow.

PubMed

Hu, Z Y; Yin, Z Y; Lin, X Y; Yan, Z G; Wang, Z H

2015-10-01

Multiparous early lactation Holstein cows (n = 16) were used in a randomized complete block design to determine the effects of feeding fatty acid calcium and the interaction of forage quality on production performance and biochemical indexes in early lactation cow. Treatments were as follows: (i) feeding low-quality forage without supplying fatty acid calcium (Diet A), (ii) feeding low-quality forage with supplying 400 g fatty acid calcium (Diet B), (iii) feeding high-quality forage without supplying fatty acid calcium (Diet C) and (iv) feeding high-quality forage with supplying 400 g fatty acid calcium. This experiment consisted 30 days. The milk and blood samples were collected in the last day of the trail. Intakes were recorded in the last 2 days of the trail. Supplementation of fatty acid calcium decreased significantly dry matter intake (DMI) (p < 0.01). Addition fatty acid calcium decreased milk protein percentage (p < 0.01) and milk SNF percentage (p < 0.01), but increased MUN (p < 0.05). Supplemented fatty acid decreased concentration of blood BHBA (p < 0.05), but increased TG, NEFA, glucagon, GLP-1, CCK, leptin, ApoA-IV, serotonin and MSH concentration in blood, the CCK concentration and feed intake showed a significant negative correlation (p < 0.05). Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats.

PubMed

Rehni, Ashish K; Shukla, Vibha; Perez-Pinzon, Miguel A; Dave, Kunjan R

2018-03-15

Cerebral ischemia is a serious possible manifestation of diabetic vascular disease. Recurrent hypoglycemia (RH) enhances ischemic brain injury in insulin-treated diabetic (ITD) rats. In the present study, we determined the role of ischemic acidosis in enhanced ischemic brain damage in RH-exposed ITD rats. Diabetic rats were treated with insulin and mild/moderate RH was induced for 5 days. Three sets of experiments were performed. The first set evaluated the effects of RH exposure on global cerebral ischemia-induced acidosis in ITD rats. The second set evaluated the effect of an alkalizing agent (Tris-(hydroxymethyl)-aminomethane: THAM) on ischemic acidosis-induced brain injury in RH-exposed ITD rats. The third experiment evaluated the effect of the glucose transporter (GLUT) inhibitor on ischemic acidosis-induced brain injury in RH-exposed ITD rats. Hippocampal pH and lactate were measured during ischemia and early reperfusion for all three experiments. Neuronal survival in Cornu Ammonis 1 (CA1) hippocampus served as a measure of ischemic brain injury. Prior RH exposure increases lactate concentration and decreases pH during ischemia and early reperfusion when compared to controls. THAM and GLUT inhibitor treatments attenuated RH-induced increase in ischemic acidosis. GLUT inhibitor treatment reduced the RH-induced increase in lactate levels. Both THAM and GLUT inhibitor treatments significantly decreased ischemic damage in RH-exposed ITD rats. Ischemia causes increased acidosis in RH-exposed ITD rats via a GLUT-sensitive mechanism. Exploring downstream pathways may help understand mechanisms by which prior exposure to RH increases cerebral ischemic damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Feeding a High Concentrate Diet Down-Regulates Expression of ACACA, LPL and SCD and Modifies Milk Composition in Lactating Goats

PubMed Central

Tao, Hui; Chang, Guangjun; Xu, Tianle; Zhao, Huajian; Zhang, Kai; Shen, Xiangzhen

2015-01-01

High concentrate diets are fed to early and mid-lactation stages dairy ruminants to meet the energy demands for high milk production in modern milk industry. The present study evaluated the effects of a high concentrate diet on milk fat and milk composition, especially, cis-9, trans-11 CLA content in milk and gene expression of lactating goats. Eight mid-lactating goats with rumen fistula were randomly assigned into a high concentrate diet (HCD) group and low concentrate diet (LCD) group. High concentrate diet feeding significantly increased lipopolysaccharides (LPS) in plasma and decreased milk fat content, vaccenic acid (VA) and cis-9, trans-11 CLA in milk of the lactating goats. The mRNA expression levels of sterol regulatory element binding protein B 1c (SREBP1c), lipoprotein lipase (LPL), fatty acid synthetase (FASN) and acetyl-CoA carboxylase α (ACACA, ACCα) involving in lipid metabolism were analyzed, and ACACA and LPL all decreased in their expression level in the mammary glands of goats fed a high concentrate diet. DNA methylation rate of stearoyl-CoA desaturase (SCD) was elevated and decreased, and SCD mRNA and protein expression was reduced significantly in the mammary glands of goats fed a high concentrate diet. In conclusion, feeding a high concentrate diet to lactating goats decreases milk fat and reduced expression of SCD in the mammary gland, which finally induced cis-9, trans-11 CLA content in milk. PMID:26086219

Effects of glucose, lactate and basic FGF as limiting factors on the expansion of human induced pluripotent stem cells.

PubMed

Horiguchi, Ikki; Urabe, Yusuke; Kimura, Keiichi; Sakai, Yasuyuki

2018-01-01

Pluripotent stem cells (PSCs) are one of the promising cell sources for tissue engineering and drug screening. However, mass production of induced pluripotent stem cells (iPSCs) is still developing. Especially, a huge amount of culture medium usage causes expensive cost in the mass production process. In this report, we reduced culture medium usage by extending interval of changing culture medium. In parallel, we also increased glucose concentration and supplied heparan sulfate to avoid depletion of glucose and bFGF, respectively. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses showed that reducing medium change frequency increased differentiation marker expressions but high glucose concentration downregulated these expressions. In contrast, heparan sulfate did not prevent differentiation marker expressions. According to analyses of growth rate, cell growth with extended medium change interval was decreased in later stage of log growth phase despite the existence of high glucose concentration and heparan sulfate. This result and culturing iPSCs with lactate showed that the accumulation of excreted lactate decreased the growth rate regardless of pH control. Conclusively, these experiments show that adding glucose and removing lactate are important to expand iPSCs with reduced culture medium usage. This knowledge should be useful to design economical iPSC mass production and differentiation system. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

PubMed

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

2018-02-01

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

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

PubMed Central

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

2018-01-01

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

Dopamine-regulated adrenocorticotropic hormone secretion in lactating rats: functional plasticity of melanotropes.

PubMed

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is

Dopamine-Regulated Adrenocorticotropic Hormone Secretion in Lactating Rats: Functional Plasticity of Melanotropes

PubMed Central

Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E.; Nagy, György M.; Vecsernyés, Miklós

2009-01-01

Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and β-lipotropin in corticotropes of the anterior lobe, and to α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence α-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in α-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by α-methyl-p-tyrosine (αMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma α-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both αMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. PMID

Plasma ceramides are elevated in overweight Holstein dairy cows experiencing greater lipolysis and insulin resistance during the transition from late pregnancy to early lactation.

PubMed

Rico, J E; Bandaru, V V R; Dorskind, J M; Haughey, N J; McFadden, J W

2015-11-01

Insulin resistance is a homeorhetic adaptation to parturition in dairy cows transitioning from late pregnancy to early lactation. An increase in prepartum adiposity can predispose periparturient cows to greater lipolysis and insulin resistance, thus increasing the risk for metabolic disease. Mechanisms mediating the development of insulin resistance in overweight peripartal dairy cows may depend on ceramide metabolism. The sphingolipid ceramide accumulates in plasma and tissues of overweight monogastric animals, and facilitates saturated fatty acid-induced insulin resistance. Considering this evidence, we hypothesized that plasma ceramides would be elevated in periparturient dairy cattle and that these sphingolipids would correlate with the magnitude of lipolysis and insulin resistance. To test our central hypothesis, multiparous Holstein cows were allocated into 2 groups according to their body condition score (BCS) at d -30 prepartum: lean (BCS <3.0; n=10) or overweight (BCS >4.0; n=11). Blood samples were collected at d -45, -30, -15, and -7, relative to expected parturition, and at d 4 postpartum. Plasma glucose, insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate (BHBA) concentrations were measured, and insulin sensitivity was estimated. The concentrations of individual plasma ceramide and glycosylated ceramide were determined using liquid chromatography-based mass spectrometry. Results demonstrated that greater adiposity was associated with a greater loss in body condition during late pregnancy. Overweight cows had greater circulating concentrations of glucose, insulin, and NEFA, and lower insulin sensitivity relative to lean cows. We detected 30 different sphingolipids across 6 lipid classes with acyl chains ranging from 16 to 26 carbons. The most abundant plasma sphingolipids detected were C24:0-ceramide, C24:0-monohexosylceramide, and C16:0-lactosylceramide. Plasma concentrations of total ceramide and monohexosylceramide increased as

Oxygen-Inducible Conversion of Lactate to Acetate in Heterofermentative Lactobacillus brevis ATCC 367.

PubMed

Guo, Tingting; Zhang, Li; Xin, Yongping; Xu, ZhenShang; He, Huiying; Kong, Jian

2017-11-01

Lactobacillus brevis is an obligatory heterofermentative lactic acid bacterium that produces high levels of acetate, which improve the aerobic stability of silages against deterioration caused by yeasts and molds. However, the mechanism involved in acetate accumulation has yet to be elucidated. Here, experimental evidence indicated that aerobiosis resulted in the conversion of lactate to acetate after glucose exhaustion in L. brevis ATCC 367 (GenBank accession number NC_008497). To elucidate the conversion pathway, in silico analysis showed that lactate was first converted to pyruvate by the reverse catalytic reaction of lactate dehydrogenase (LDH); subsequently, pyruvate conversion to acetate might be mediated by pyruvate dehydrogenase (PDH) or pyruvate oxidase (POX). Transcriptional analysis indicated that the pdh and pox genes of L. brevis ATCC 367 were upregulated 37.92- and 18.32-fold, respectively, by oxygen and glucose exhaustion, corresponding to 5.32- and 2.35-fold increases in the respective enzyme activities. Compared with the wild-type strain, the transcription and enzymatic activity of PDH remained stable in the Δ pox mutant, while those of POX increased significantly in the Δ pdh mutant. More lactate but less acetate was produced in the Δ pdh mutant than in the wild-type and Δ pox mutant strains, and more H 2 O 2 (a product of the POX pathway) was produced in the Δ pdh mutant. We speculated that the high levels of aerobic acetate accumulation in L. brevis ATCC 367 originated mainly from the reuse of lactate to produce pyruvate, which was further converted to acetate by the predominant and secondary functions of PDH and POX, respectively. IMPORTANCE PDH and POX are two possible key enzymes involved in aerobic acetate accumulation in lactic acid bacteria (LAB). It is currently thought that POX plays the major role in aerobic growth in homofermentative LAB and some heterofermentative LAB, while the impact of PDH remains unclear. In this study, we

Oxygen-Inducible Conversion of Lactate to Acetate in Heterofermentative Lactobacillus brevis ATCC 367

PubMed Central

Guo, Tingting; Zhang, Li; Xin, Yongping; Xu, ZhenShang; He, Huiying

2017-01-01

ABSTRACT Lactobacillus brevis is an obligatory heterofermentative lactic acid bacterium that produces high levels of acetate, which improve the aerobic stability of silages against deterioration caused by yeasts and molds. However, the mechanism involved in acetate accumulation has yet to be elucidated. Here, experimental evidence indicated that aerobiosis resulted in the conversion of lactate to acetate after glucose exhaustion in L. brevis ATCC 367 (GenBank accession number NC_008497). To elucidate the conversion pathway, in silico analysis showed that lactate was first converted to pyruvate by the reverse catalytic reaction of lactate dehydrogenase (LDH); subsequently, pyruvate conversion to acetate might be mediated by pyruvate dehydrogenase (PDH) or pyruvate oxidase (POX). Transcriptional analysis indicated that the pdh and pox genes of L. brevis ATCC 367 were upregulated 37.92- and 18.32-fold, respectively, by oxygen and glucose exhaustion, corresponding to 5.32- and 2.35-fold increases in the respective enzyme activities. Compared with the wild-type strain, the transcription and enzymatic activity of PDH remained stable in the Δpox mutant, while those of POX increased significantly in the Δpdh mutant. More lactate but less acetate was produced in the Δpdh mutant than in the wild-type and Δpox mutant strains, and more H2O2 (a product of the POX pathway) was produced in the Δpdh mutant. We speculated that the high levels of aerobic acetate accumulation in L. brevis ATCC 367 originated mainly from the reuse of lactate to produce pyruvate, which was further converted to acetate by the predominant and secondary functions of PDH and POX, respectively. IMPORTANCE PDH and POX are two possible key enzymes involved in aerobic acetate accumulation in lactic acid bacteria (LAB). It is currently thought that POX plays the major role in aerobic growth in homofermentative LAB and some heterofermentative LAB, while the impact of PDH remains unclear. In this study, we

Comparison of surrogate indices for insulin sensitivity with parameters of the intravenous glucose tolerance test in early lactation dairy cattle.

PubMed

Alves-Nores, V; Castillo, C; Hernandez, J; Abuelo, A

2017-10-01

The aim of this study was to investigate the correlation between different surrogate indices and parameters of the intravenous glucose tolerance test (IVGTT) in dairy cows at the start of their lactation. Ten dairy cows underwent IVGTT on Days 3 to 7 after calving. Areas under the curve during the 90 min after infusion, peak and nadir concentrations, elimination rates, and times to reach half-maximal and basal concentrations for glucose, insulin, nonesterified fatty acids, and β-hydroxybutyrate were calculated. Surrogate indices were computed using the average of the IVGTT basal samples, and their correlation with the IVGTT parameters studied through the Spearman's rank test. No statistically significant or strong correlation coefficients (P > 0.05; |ρ| < 0.50) were observed between the insulin sensitivity measures derived from the IVGTT and any of the surrogate indices. Therefore, these results support that the assessment of insulin sensitivity in early lactation cattle cannot rely on the calculation of surrogate indices in just a blood sample, and the more laborious tests (ie, hyperinsulinemic euglycemic clamp test or IVGTT) should be employed to predict the sensitivity of the peripheral tissues to insulin accurately. Copyright © 2017 Elsevier Inc. All rights reserved.

Lactate Utilization Is Regulated by the FadR-Type Regulator LldR in Pseudomonas aeruginosa

PubMed Central

Gao, Chao; Hu, Chunhui; Zheng, Zhaojuan; Jiang, Tianyi; Dou, Peipei; Zhang, Wen; Che, Bin; Wang, Yujiao; Lv, Min

2012-01-01

NAD-independent l-lactate dehydrogenase (l-iLDH) and NAD-independent d-lactate dehydrogenase (d-iLDH) activities are induced coordinately by either enantiomer of lactate in Pseudomonas strains. Inspection of the genomic sequences of different Pseudomonas strains revealed that the lldPDE operon comprises 3 genes, lldP (encoding a lactate permease), lldD (encoding an l-iLDH), and lldE (encoding a d-iLDH). Cotranscription of lldP, lldD, and lldE in Pseudomonas aeruginosa strain XMG starts with the base, C, that is located 138 bp upstream of the lldP ATG start codon. The lldPDE operon is located adjacent to lldR (encoding an FadR-type regulator, LldR). The gel mobility shift assays revealed that the purified His-tagged LldR binds to the upstream region of lldP. An XMG mutant strain that constitutively expresses d-iLDH and l-iLDH was found to contain a mutation in lldR that leads to an Ile23-to-serine substitution in the LldR protein. The mutated protein, LldRM, lost its DNA-binding activity. A motif with a hyphenated dyad symmetry (TGGTCTTACCA) was identified as essential for the binding of LldR to the upstream region of lldP by using site-directed mutagenesis. l-Lactate and d-lactate interfered with the DNA-binding activity of LldR. Thus, l-iLDH and d-iLDH were expressed when the operon was induced in the presence of l-lactate or d-lactate. PMID:22408166

Identification of conserved microRNAs in peripheral blood from giant panda: expression of mammary gland-related microRNAs during late pregnancy and early lactation.

PubMed

Wang, C D; Long, K; Jin, L; Huang, S; Li, D H; Ma, X P; Wei, M; Gu, Y; Ma, J D; Zhang, H

2015-11-13

The giant panda (Ailuropoda melanoleuca) is one of the world's most endangered mammals, and it has evolved several unusual biological and behavioral traits. During puberty, pregnancy, lactation, and involution, the mammary gland undergoes profound morphological and functional changes. A large number of microRNAs (miRNAs) have been identified to be involved in mammary gland development and lactation. In this study, we identified 202 conserved mature miRNAs, corresponding to 147 pre-miRNAs, in giant panda peripheral blood using a small RNA-sequencing approach. In addition, 27 miRNA families and 29 miRNA clusters were identified. We analyzed the arm selection preference of pre-miRNAs and found that: 1) most giant panda pre-miRNAs generated one-strand miRNAs, and the 5p-arm only miRNAs have a higher expression level than 3p-arm only miRNAs; 2) there were more 5p-arm dominant miRNAs than 3p-arm dominant miRNAs; and 3) 5p-arm dominant miRNAs have a larger fold change within miRNA pairs than 3p-arm dominant miRNAs. Expression of 12 lactation-related miRNAs was detected across late pregnancy and early lactation stages by qPCR, and seven miRNAs were identified as clustered in one significant model. Most of these clustered miRNAs exhibited inhibitory roles in proliferation and differentiation of mammary epithelial cells. Functional analysis highlighted important roles of the seven as signed miRNAs in mammary development and metabolic changes, including blood vessel morphogenesis, macromolecule biosynthesis, cell cycle regulation, and protein transport.

The work patterns of lactating women in Madura.

PubMed

Launer, L J

1993-08-01

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

Effects of nutritional plane and selenium supply during gestation on visceral organ mass and indices of intestinal growth and vascularity in primiparous ewes at parturition and during early lactation.

USDA-ARS?s Scientific Manuscript database

Objectives were to investigate effects of nutritional plane and Se supply during gestation on visceral organ mass and intestinal growth and vascularization in ewes at parturition and during early lactation. Primiparous Rambouillet ewes (n = 84) were allocated to 2 × 3 × 2 factorial arrangement of tr...

Effect of Lactation on myocardial vulnerability to ischemic insult in rats.

PubMed

Askari, Sahar; Imani, Alireza; Sadeghipour, Hamidreza; Faghihi, Mahdieh; Edalatyzadeh, Zohreh; Choopani, Samira; Karimi, Nasser; Fatima, Sulail

2017-05-01

Cardiovascular diseases are the leading cause of mortality and long-term disability worldwide. Various studies have suggested a protective effect of lactation in reducing the risk of cardiovascular diseases. This study was designed to assess the effects of pregnancy and lactation on the vulnerability of the myocardium to an ischemic insult. Eighteen female rats were randomly divided into three groups: ischemia-reperfusion (IR), in which the hearts of virgin rats underwent IR (n = 6); lactating, in which the rats nursed their pups for 3 weeks and the maternal hearts were then submitted to IR (n = 6); and non-lactating, in which the pups were separated after birth and the maternal hearts were submitted to IR (n = 6). Outcome measures included heart rate (HR), left ventricular developed pressure (LVDP), rate pressure product (RPP), ratio of the infarct size to the area at risk (IS/AAR %), and ventricular arrhythmias - premature ventricular contraction (PVC) and ventricular tachycardia (VT). The IS/AAR was markedly decreased in the lactating group when compared with the non-lactating group (13.2 ± 2.5 versus 39.7 ± 3.5, p < 0.001) and the IR group (13.2 ± 2.5 versus 34.0 ± 4.7, p < 0.05). The evaluation of IR-induced ventricular arrhythmias indicated that the number of compound PVCs during ischemia, and the number and duration of VTs during ischemia and in the first 5 minutes of reperfusion in the non-lactating group were significantly (p < 0.05) higher than those in the lactating and IR groups. Lactation induced early-onset cardioprotective effects, while rats that were not allowed to nurse their pups were more susceptible to myocardial IR injury. As doenças cardiovasculares são a principal causa de mortalidade e invalidez a longo prazo a nível mundial. Diversos estudos têm sugerido um efeito protetor da lactação na redução do risco para doenças cardiovasculares. Este estudo foi desenvolvido para avaliar os efeitos da gestação e da lactação sobre a

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

PubMed

Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.

Differential changes of fat-soluble vitamins and pollutants during lactation in northern elephant seal mother-pup pairs.

PubMed

Debier, Cathy; Crocker, Daniel E; Houser, Dorian S; Vanden Berghe, Marie; Fowler, Melinda; Mignolet, Eric; de Tillesse, Tanguy; Rees, Jean-François; Thomé, Jean-Pierre; Larondelle, Yvan

2012-08-01

We investigated the changes of vitamins A and E as well as PCBs and DDTs during lactation in northern elephant seal (Mirounga angustirostris) mother-pup pairs. On average, milk vitamin A concentrations were 6 times higher during late lactation than during early lactation, a pattern that differs dramatically from terrestrial mammals. Vitamin A concentrations also significantly increased in the inner blubber throughout lactation, whereas they remained constant in the outer blubber. Similar dynamics were observed for PCBs and DDTs in maternal blubber and milk. Blubber appears to be an important storage site for vitamin A and organochlorines in seals and a direct transfer of those molecules to the mammary gland may occur. The dynamics of vitamin A, PCBs and DDTs differed from those of vitamin E. There was a significant drop in milk vitamin E concentrations between early and late lactation, which is the usual pattern observed in terrestrial mammals. The dynamics of vitamin E in the blubber layers also differed from those of vitamin A, suggesting different mechanisms of mobilization and transfer into the milk. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

Mahrt, A; Burfeind, O; Heuwieser, W

2015-05-01

The objectives of this study were to describe the onset of hyperketonemia, the number of positive hyperketonemia test results, and the duration of the longest hyperketonemic period during the first 42 d in milk (DIM) in dairy cows. Furthermore, we set out to evaluate test characteristics of single and repeated measurements of β-hydroxybutyric acid (BHBA) during this period to diagnose hyperketonemia. Using an electronic handheld meter, 252 cows from 3 farms were tested twice weekly for hyperketonemia (blood BHBA ≥1.2 mmol/L) during the first 42 DIM, resulting in 12 test results per cow (i.e., in lactation wk 0.5 to 6). Prevalence and incidence of hyperketonemia were calculated for the 12 examination days and the 42-d period, respectively. Test characteristics for the diagnosis of hyperketonemia were calculated for 4 different testing scenarios (testing all cows 1, 2, 3, or 6 times during the first 42 DIM) and 2 different gold-standard definitions (BHBA ≥1.2 mmol/L at least once during the observation period or BHBA ≥1.2 mmol/L at least twice during the observation period). Mean prevalence of hyperketonemia was 11.8%, ranging from 9.6% in lactation wk 0.5 and 2.0 to 14.6% in lactation wk 5.5. In total, 134 cows (53.2%) had at least 1 positive hyperketonemia test result during the whole 42-d period. Of these cows, 46.3% had only 1 positive result. The median first positive hyperketonemia test result was in lactation wk 2.0 [interquartile range (IQR) 1.0-3.5]. Median frequency of positive test results in cows affected by hyperketonemia was 2 positive test results (IQR 1-3). Median duration of the longest hyperketonemic period per cow affected was 1 examination interval (3-4 d; IQR 1-2). Considering a minimum of 1 positive hyperketonemia test result during the first 42 DIM as the gold standard, sensitivity of a single BHBA measurement during this period to diagnose hyperketonemia was 21%. A weekly testing protocol had a sensitivity of 72%. Specificity was 100

Hepatic gene expression involved in glucose and lipid metabolism in transition cows: effects of fat mobilization during early lactation in relation to milk performance and metabolic changes.

PubMed

Weber, C; Hametner, C; Tuchscherer, A; Losand, B; Kanitz, E; Otten, W; Sauerwein, H; Bruckmaier, R M; Becker, F; Kanitz, W; Hammon, H M

2013-09-01

Insufficient feed intake during early lactation results in elevated body fat mobilization to meet energy demands for milk production. Hepatic energy metabolism is involved by increasing endogenous glucose production and hepatic glucose output for milk synthesis and by adaptation of postcalving fuel oxidation. Given that cows differ in their degree of fat mobilization around parturition, indicated by variable total liver fat concentration (LFC), the study investigated the influence of peripartum fat mobilization on hepatic gene expression involved in gluconeogenesis, fatty acid oxidation, ketogenesis, and cholesterol synthesis, as well as transcriptional factors referring to energy metabolism. German Holstein cows were grouped according to mean total LFC on d 1, 14, and 28 after parturition as low [<200mg of total fat/g of dry matter (DM); n=10], medium (200-300 mg of total fat/g of DM; n=10), and high (>300 mg of total fat/g of DM; n=7), indicating fat mobilization during early lactation. Cows were fed total mixed rations ad libitum and held under equal conditions. Liver biopsies were taken at d 56 and 15 before and d 1, 14, 28, and 49 after parturition to measure mRNA abundances of pyruvate carboxylase (PC); phosphoenolpyruvate carboxykinase; glucose-6-phosphatase; propionyl-coenzyme A (CoA) carboxylase α; carnitine palmitoyl-transferase 1A (CPT1A); acyl-CoA synthetase, long chain 1 (ASCL1); acyl-CoA dehydrogenase, very long chain; 3-hydroxy-3-methylglutaryl-CoA synthase 1 and 2; sterol regulatory element-binding factor 1; and peroxisome proliferator-activated factor α. Total LFC postpartum differed greatly among cows, and the mRNA abundance of most enzymes and transcription factors changed with time during the experimental period. Abundance of PC mRNA increased at parturition to a greater extent in high- and medium-LFC groups than in the low-LFC group. Significant LFC × time interactions for ACSL1 and CPT1A during the experimental period indicated variable

[Secondary osteoporosis UPDATE. Bone metabolic change and osteoporosis during pregnancy and lactation].

PubMed

Kurabayashi, Takumi; Tamura, Ryo; Hata, Yuki; Nishijima, Shota; Tsuneki, Ikunosuke; Tamura, Masaki; Yanase, Toru

2010-05-01

Calcium transfer from the mother to the infant during pregnancy and lactation plays an extremely important role in the bone health of the mother and neonate. Calcium aids in bone health through all ages but is especially crucial during pregnancy and lactation. Changes in the structure and metabolism of bone during pregnancy and the early stage of postpartum are evaluated by investigating bone mineral density (BMD), bone histomorphometry and bone markers of human or animal models. The bone resorption increased at the end of pregnancy and lactation, and the bone formation increases and the bone structure is almost recovered after cessation of lactating in postpartum. Puerperal BMD remained static over the subsequent 5-10 years. If the women have a low BMD at this stage of their reproductive life, it tends not to improve over this time. Perhaps identification of this at-risk group may lead to effective interventions to reduce fracture risk in later life.

Effects of nutritional plane and selenium supply during gestation on visceral organ mass and indices of intestinal growth and vascularity in primiparous ewes at parturition and during early lactation.

PubMed

Meyer, A M; Reed, J J; Neville, T L; Taylor, J B; Reynolds, L P; Redmer, D A; Vonnahme, K A; Caton, J S

2012-08-01

Objectives were to investigate effects of nutritional plane and Se supply during gestation on visceral organ mass and intestinal growth and vascularization in ewes at parturition and during early lactation. Primiparous Rambouillet ewes (n = 84) were allocated to 2 × 3 × 2 factorial arrangement of treatments. Factors included dietary Se [adequate Se (ASe, 11.5 μg/kg BW) or high Se (HSe, 77.0 μg/kg BW)], nutritional plane [60% (restricted; RES), 100% (control; CON), or 140% (high; HIH)], and physiological stage at necropsy (parturition or d 20 of lactation). At parturition, lambs were removed and 42 ewes (7 per treatment) were necropsied. Remaining ewes were transitioned to a common diet which met lactation requirements and mechanically milked for 20 d. In the absence of interactions (P > 0.10), main effects are reported. At parturition, stomach complex and liver masses were greatest for HIH, intermediate for CON, and least for RES (P < 0.02). Small intestinal mass was greater (P ≤ 0.002) for HIH than RES and CON, and greater (P < 0.01) for ASe than HSe. During early lactation, RES and CON gastrointestinal masses increased disproportionally to BW (P < 0.05). At parturition, jejunal mucosal density was less (P ≤ 0.01) for RES than CON and HIH, whereas CON had greater (P < 0.003) jejunal mucosal RNA concentration and RNA:DNA than RES and HIH. Although there were no differences (P > 0.17) at parturition, jejunal cell percent proliferation was greatest in RES, intermediate in CON, and least in HIH (P ≤ 0.09) at d 20 lactation. At both stages, RES had less (P = 0.01) jejunal capillary area density than HIH and less (P ≤ 0.03) capillary surface density than CON and HIH. During lactation, jejunal capillary size was greater (P = 0.04) for ewes previously fed HSe compared with ASe. At parturition, ASe-HIH had greater (P < 0.02) jejunal mucosal endothelial nitric oxide synthase 3 mRNA than all other treatments and greater (P = 0.10) vascular endothelial growth

Dinosaur lactation?

PubMed

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.

Metabolic and productive response to ruminal protein degradability in early lactation cows fed untreated or xylose-treated soybean meal-based diets.

PubMed

Jahani-Moghadam, M; Amanlou, H; Nikkhah, A

2009-12-01

Effects of different dietary rumen undegradable (RUP) to degradable (RDP) protein ratios on ruminal nutrient degradation, feed intake, blood metabolites and milk production were determined in early lactation cows. Four multiparous (43 ± 5 days in milk) and four primiparous (40 ± 6 days in milk) tie-stall-housed Holstein cows were used in a duplicated 4 × 4 Latin square design with four 21-day periods. Each period had 14-day of adaptation and 7-day of sampling. Diets contained on a dry matter (DM) basis, 23.3% alfalfa hay, 20% corn silage and 56.7% concentrate. Cows were first offered alfalfa hay at 7:00, 15:00 and 23:00 hours, and 30 min after each alfalfa hay delivery were offered a mixture of corn silage and concentrate. Treatments were diets with RUP:RDP ratios of (i) 5.2:11.6 (control), (ii) 6.1:10.6, (iii) 7.1:9.5 and (iv) 8.1:8.5, on a dietary DM% basis. Different RUP:RDP ratios were obtained by partial and total replacement of untreated soybean meal (SBM) with xylose-treated SBM (XSBM). In situ study using three rumen-cannulated non-lactating cows showed that DM and crude protein (CP) of SBM had greater rapidly degradable fractions. The potentially degradable fractions were degraded more slowly in XSBM. Treatment cows produced greater milk, protein, lactose, solids-non-fat and total solids than control cows. Increasing RUP:RDP reduced blood urea linearly. Feed costs dropped at RUP:RDP ratios of 6.1:10.6 and 7.1:9.5, but not at 8.1:8.5, compared with the 5.2:11.6 ratio. Intake of DM and CP, rumen pH, blood glucose, albumin and total protein, faecal and urine pH, changes in body weight and body condition score, and milk lactose and solids-non-fat percentages did not differ among treatments. Results provide evidence that increasing dietary RUP:RDP ratio from 5.2:11.6 to 7.1:9.5 optimizes nitrogen metabolism and milk production and reduces feed costs in early lactation cows. Reduced blood urea suggests reprodutive benefits.

Lactate threshold responses to a season of professional British youth soccer

PubMed Central

McMillan, K; Helgerud, J; Grant, S; Newell, J; Wilson, J; Macdonald, R; Hoff, J

2005-01-01

Objective: To examine the changes in aerobic endurance performance of professional youth soccer players throughout the soccer season. Methods: Nine youth soccer players were tested at six different time points throughout the soccer season by sub-maximal blood lactate assessment, using an incremental treadmill protocol. Whole blood lactate concentration and heart frequency (Hf) were determined at each exercise stage. Running velocities at the first lactate inflection point (v-Tlac) and at a blood lactate concentration of 4 mmol l–1 (v-4mM) were determined. Results: Running velocity at the two lactate thresholds increased from the start of pre-season training to the early weeks of the competitive season, from 11.67 (0.29) to 12.96 (0.28) km h–1 for v-Tlac, and from 13.62 (0.25) to 14.67 (0.24) km h–1 for v-4mM (p<0.001). However, v-Tlac and v-4mM when expressed relative to maximum heart frequency (Hfmax) remained unchanged. The Hf to blood lactate concentration relationship was unchanged after the pre-season training period. The two expressions of lactate threshold did not reveal differences between each other. Conclusion: Running velocity at v-Tlac and v-4mM increased significantly over the pre-season period, but v-Tlac and v-4mM were unchanged when expressed relative to Hfmax. This finding may indicate that increased endurance performance may be mainly attributable to alterations in Vo2max. Although lactate assessment of soccer players is useful for determining endurance training adaptations in soccer players, additional assessment of the other two determinants of endurance performance (Vo2max and running economy) may provide more useful information for determining physiological adaptations resulting from soccer training and training interventions. PMID:15976165

Genetic analysis of milk β-hydroxybutyrate and its association with fat-to-protein ratio, body condition score, clinical ketosis, and displaced abomasum in early first lactation of Canadian Holsteins.

PubMed

Koeck, A; Jamrozik, J; Schenkel, F S; Moore, R K; Lefebvre, D M; Kelton, D F; Miglior, F

2014-11-01

The aim of this study was to estimate genetic parameters for milk β-hydroxybutyrate (BHBA) in early first lactation of Canadian Holstein cows and to examine its genetic association with indicators of energy balance (fat-to-protein ratio and body condition score) and metabolic diseases (clinical ketosis and displaced abomasum). Data for milk BHBA recorded between 5 and 100 d in milk was obtained from Valacta (Sainte-Anne-de-Bellevue, Québec, Canada), the Canadian Dairy Herd Improvement organization responsible for Québec and Atlantic provinces. Test-day milk samples were analyzed by mid-infrared spectrometry using previously developed calibration equations for milk BHBA. Test-day records of fat-to-protein ratio were obtained from the routine milk recording scheme. Body condition score records were available from the routine type classification system. Data on clinical ketosis and displaced abomasum recorded by producers were available from the national dairy cattle health system in Canada. Data were analyzed using linear animal models. Heritability estimates for milk BHBA at different stages of early lactation were between 0.14 and 0.29. Genetic correlations between milk BHBA were higher between adjacent lactation intervals and decreased as intervals were further apart. Correlations between breeding values for milk BHBA and routinely evaluated traits revealed that selection for lower milk BHBA in early lactation would lead to an improvement of several health and fertility traits, including SCS, calving to first service, number of services, first service to conception, and days open. Also, lower milk BHBA was associated with a longer herd life, better conformation, and better feet and legs. A higher genetic merit for milk yield was associated with higher milk BHBA, and, therefore, a greater susceptibility to hyperketonemia. Milk BHBA at the first test-day was moderately genetically correlated with fat-to-protein ratio (0.49), body condition score (-0.35), and

Acquisition of Maternal Antibodies both from the Placenta and by Lactation Protects Mouse Offspring from Yersinia pestis Challenge

PubMed Central

Qi, Zhizhen; Zhao, Haihong; Zhang, Qingwen; Bi, Yujing; Ren, Lingling; Zhang, Xuecan; Yang, Hanqing; Yang, Xiaoyan; Wang, Qiong; Li, Cunxiang; Zhou, Jiyuan; Xin, Youquan; Yang, Yonghai; Yang, Huiying; Du, Zongmin; Tan, Yafang; Han, Yanping; Song, Yajun; Zhou, Lei; Zhang, Pingping; Cui, Yujun; Yan, Yanfeng; Zhou, Dongsheng

2012-01-01

Artificially passive immunization has been demonstrated to be effective against Yersinia pestis infection in animals. However, maternal antibodies' protective efficacy against plague has not yet been demonstrated. Here, we evaluated the kinetics, protective efficacy, and transmission modes of maternal antibodies, using mice immunized with plague subunit vaccine SV1 (20 μg of F1 and 10 μg of rV270). The results showed that the rV270- and F1-specific antibodies could be detected in the sera of newborn mice (NM) until 10 and 14 weeks of age, respectively. There was no antibody titer difference between the parturient mice immunized with SV1 (PM-S) and the caesarean-section newborns (CSN) from the PM-S or between the lactating mice immunized by SV1 (LM-S) and the cross-fostered mice (CFM) during 3 weeks of lactation. The NM had a 72% protection against 4,800 CFU Y. pestis strain 141 challenge at 6 weeks of age, whereas at 14 weeks of age, NM all succumbed to 5,700 CFU of Y. pestis challenge. After 7 weeks of age, CFM had an 84% protection against 5,000 CFU of Y. pestis challenge. These results indicated that maternal antibodies induced by the plague subunit vaccine in mother mice can be transferred to NM by both placenta and lactation. Passive antibodies from the immunized mothers could persist for 3 months and provide early protection for NM. The degree of early protection is dependent on levels of the passively acquired antibody. The results indicate that passive immunization should be an effective countermeasure against plague during its epidemics. PMID:22933398

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

PubMed

Liesegang, A; Risteli, J; Wanner, M

2006-06-01

The goal of the present study was to compare mobilization rate of calcium (Ca) from bone in pregnant and lactating goats and sheep. Blood samples were collected from goats and sheep monthly during pregnancy and at 1, 2, and 4 weeks postpartum (pp) and monthly during lactation until 6 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography at the same intervals as the blood was taken. Bone resorption was assessed by immunoassays quantitating two epitopes of the carboxyterminal telopeptide of type I collagen (ICTP, CTX). Bone formation was estimated by quantifying serum osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25-dihydroxy vitamin D (1,25-VITD) concentrations were determined in serum. Mean ICTP and CTX concentrations of both animal species increased the first week after parturition. By the second week pp, the concentrations of both markers had decreased toward early gestation levels. In contrast, mean OC concentrations continually decreased until the 1st week pp. By the 2nd week pp, the mean concentrations of OC started to increase again. Mean bAP activities decreased during gestation and reached a nadir in the first week pp in goats and 4 weeks pp in sheep. Afterwards, mean bAP activities increased again in goats and sheep. 1,25-VITD concentrations peaked the first week pp and returned to early gestation values thereafter. Total BMC and BMD decreased from the 4th month of pregnancy until the 1st week pp in both species. Afterwards, BMC increased throughout the first month pp in goats and the first 3 months pp in sheep. BMD levels of sheep and goats returned to prepartum levels during lactation. The resorptive phase of bone remodeling is accelerated at parturition and in early lactation and is uncoupled from the process of bone formation. This allows the animal to achieve Ca homeostasis at the expense of bone. Increased

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

PubMed

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

2012-12-01

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

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

PubMed

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.

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

PubMed Central

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

2016-01-01

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

Do pregnancy, postpartum period and lactation predispose to recurrent toxoplasmic retinochoroiditis?

PubMed

Brydak-Godowska, Joanna; Borkowski, Piotr Karol; Rabczenko, Daniel; Moneta-Wielgoś, Joanna; Kęcik, Dariusz

2015-02-23

The aim of the study was a statistical analysis of the possible effects of pregnancy, postpartum period, and lactation on increased risk for reactivation of toxoplasmic retinochoroiditis. A retrospective study was undertaken of the clinical records of 661 patients referred with the diagnosis of acute toxoplasmic retinochoroiditis to the Department of Zoonoses and Tropical Diseases, Medical University of Warsaw and to the Department of Ophthalmology, Medical University of Warsaw in the years 1994-2014. This group of inpatients consisted of 213 women of child-bearing age (18 to 40 years). Reactivation of toxoplasmic retinochoroiditis was observed in 24 women aged 15 to 39 years who were pregnant, in the postpartum period, or lactating. To compare the rate of the relapses in pregnant/lactating patients vs. non-pregnant/non-lactating patients, the Fisher exact test was used. Calculations were performed with WinPepi software (Abramson JH (2004) WINPEPI (PEPI-for-Windows) for epidemiologists. Epidemiologic Perspectives & Innovations, 2005, 1: 6). A total of 28 reactivations of toxoplasmic retinochoroiditis were observed (16 episodes in pregnancy, 4 in the postpartum period, and 8 during lactation) in 24 women aged 15 to 39 years. In 3 women, multiple episodes were reported (in early pregnancy and the postpartum period in 2 women, and during 2 pregnancies and lactation in 1 woman). Statistical analysis showed that the risk of an episode of toxoplasmic retinochoroiditis is 7.4-fold higher in pregnancy compared to the non-pregnant/non-lactating women (p<0.0001). Women of childbearing age with toxoplasma ocular lesions should be informed by their doctors about possible active recurrences during pregnancy and should be followed carefully by an ophthalmologist when pregnant.

The control of short-term feed intake by metabolic oxidation in late-pregnant and early lactating dairy cows exposed to high ambient temperatures.

PubMed

Eslamizad, Mehdi; Lamp, Ole; Derno, Michael; Kuhla, Björn

2015-06-01

The objective of the present study was to integrate the dynamics of feed intake and metabolic oxidation in late pregnant and early lactating Holstein cows under heat stress conditions. On day 21 before parturition and again on day 20 after parturition, seven Holstein cows were kept for 7days at thermoneutral (TN) conditions (15°C; temperature-humidity-index (THI)=60) followed by a 7day heat stress (HS) period at 28°C (THI=76). On the last day of each temperature condition, gas exchange, feed intake and water intake were recorded every 6min in a respiration chamber. Pre- and post-partum cows responded to HS by decreasing feed intake. The reduction in feed intake in pre-partum cows was achieved through decreased meal size, meal duration, eating rate and daily eating time with no change in meal frequency, while post-partum cows kept under HS conditions showed variable responses in feeding behavior. In both pre- and post-partum cows exposed to heat stress, daily and resting metabolic heat production decreased while the periprandial respiratory quotient (RQ) increased. The prolonged time between meal and the postprandial minimum in fat oxidation and the postprandial RQ maximum, respectively, revealed that HS as compared to TN early-lactating cows have slower postprandial fat oxidation, longer feed digestion, and thereby showing a shift from fat to glucose utilization. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

Hernandez, L L

2018-04-25

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

The relationship between exsanguination blood lactate concentration and carcass quality in slaughter pigs.

PubMed

Edwards, L N; Engle, T E; Correa, J A; Paradis, M A; Grandin, T; Anderson, D B

2010-07-01

A group of 128 cross-bred barrows were used to determine the relationship between exsanguination blood lactate concentration ([LAC]) and carcass quality following commercial marketing conditions. After 10h of feed withdrawal, pigs were loaded on a truck with a hydraulically lifted second deck and transported approximately 1h to the slaughter facility. Pigs were rested for 8h and stunned with carbon dioxide. Blood lactate concentration was measured on exsanguination blood. Fourteen pork quality measurements were obtained following normal post-mortem processing. Pearson correlations were used to determine the relationships between [LAC] and the meat quality parameters. Exsanguination blood lactate concentration ranged from 4 to 19.7 mM. Higher lactate was associated with lower 60 min pH (P=0.0004) and higher drip loss (P=0.02). These results suggest that under low-stress loading and standard marketing conditions, exsanguination [LAC] is predictive of the rate of early post-mortem metabolism. Copyright 2010 Elsevier Ltd. All rights reserved.

A Review of Worksite Lactation Accommodations.

PubMed

Hilliard, Elizabeth Dianne

2017-01-01

The purpose of this review was to examine workplace lactation accommodations, and their association with breastfeeding duration, and identify strategies occupational health professionals can use to promote lactation improvements. This study included literature published from 1985 through 2015 and listed in PubMed and CINAHL. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 articles were identified for review. Presence of a corporate lactation program, on-site child care, and return to work/telephone lactation consultation were consistently associated with breastfeeding at 6 months. Other breastfeeding accommodations (i.e., lactation spaces, lactation breaks, worksite lactation policies, and supervisor/coworker support) were not consistently associated with breastfeeding duration. Occupational health professionals can play key roles in improving the effectiveness of lactation accommodations. Assuring adequate implementation of accommodations, increasing communication and marketing of accommodations, and promoting supervisor and coworker support are areas that occupational health professionals should explore for improving lactation duration.

Bicarbonate, NBCe1, NHE, and Carbonic Anhydrase Activity Enhance Lactate-H+ Transport in Bovine Corneal Endothelium

PubMed Central

Nguyen, Tracy T.

2011-01-01

Purpose. To identify and localize the monocarboxylate transporters (MCTs) expressed in bovine corneal endothelial cells (BCEC) and to test the hypothesis that buffering contributed by HCO3−, sodium bicarbonate cotransporter (NBCe1), sodium hydrogen exchanger (NHE), and carbonic anhydrase (CA) activity facilitates lactate flux. Methods. MCT1–4 expression was screened by RT-PCR, Western blot analysis, and immunofluorescence. Endogenous lactate efflux and/or pHi were measured in BCEC in HCO3−-free or HCO3−-rich Ringer, with and without niflumic acid (MCT inhibitor), acetazolamide (ACTZ, a CA inhibitor), 5-(N-Ethyl-N-isopropyl)amiloride (EIPA) (Na+/H+ exchange blocker), disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS; anion transport inhibitor), or with NBCe1-specific small interfering (si) RNA-treated cells. Results. MCT1, 2, and 4 are expressed in BCEC. MCT1 was localized to the lateral membrane, MCT2 was lateral and apical, while MCT4 was apical. pHi measurements showed significant lactate-induced cell acidification (LIA) in response to 20-second pulses of lactate. Incubation with niflumic acid significantly reduced the rate of pHi change (dpHi/dt) and lactate-induced cell acidification. EIPA inhibited alkalinization after lactate removal. Lactate-dependent proton flux was significantly greater in the presence of HCO3− but was reduced by ACTZ. Efflux of endogenously produced lactate was significantly faster in the presence of HCO3−, was greater on the apical surface, was reduced on the apical side by ACTZ, as well as on the apical and basolateral side by NBCe1-specific siRNA, DIDS, or EIPA. Conclusions. MCT1, 2, and 4 are expressed in BCEC on both the apical and basolateral membrane (BL) surfaces consistent with niflumic acid-sensitive lactate-H+ transport. Lactate dependent proton flux can activate Na+/H+ exchange and be facilitated by maximizing intracellular buffering capacity through the presence of HCO3−, HCO3− transport, NHE

Identification of diagnostic biomarkers and metabolic pathway shifts of heat-stressed lactating dairy cows.

PubMed

Tian, He; Wang, Weiyu; Zheng, Nan; Cheng, Jianbo; Li, Songli; Zhang, Yangdong; Wang, Jiaqi

2015-07-01

Controlling heat stress (HS) is a global challenge for the dairy industry. However, simple and reliable biomarkers that aid the diagnoses of HS-induced metabolic disorders have not yet been identified. In this work, an integrated metabolomic and lipidomic approach using (1)H nuclear magnetic resonance and ultra-fast LC-MS was employed to investigate the discrimination of plasma metabolic profiles between HS-free and HS lactating dairy cows. Targeted detection using LC-MS in multiple reaction monitoring mode was used to verify the reliability of the metabolites as biomarker candidates. Overall, 41 metabolites were identified as candidates for lactating dairy cows exposed to HS, among which 13 metabolites, including trimethylamine, glucose, lactate, betaine, creatine, pyruvate, acetoacetate, acetone, β-hydroxybutyrate, C16 sphinganine, lysophosphatidylcholine (18:0), phosphatidylcholine (16:0/14:0), and arachidonic acid, had high sensitivity and specificity in diagnosing HS status, and are likely to be the potential biomarkers of HS dairy cows. All of these potentially diagnostic biomarkers were involved in carbohydrate, amino acid, lipid, or gut microbiome-derived metabolism, indicating that HS affected the metabolic pathways in lactating dairy cows. Further research is warranted to evaluate these biomarkers in practical applications and to elucidate the physiological mechanisms of HS-induced metabolic disorders. Heat stress (HS) annually causes huge losses to global dairy industry, including animal performance decrease, metabolic disorder and health problem. So far, physiological mechanisms underlying HS of dairy cows still remain elusive. To our best knowledge, this is the first attempt to elucidate the HS-induced metabolic disorders of dairy cows using integrated (1)H NMR and LC-MS-based metabolic study. The results not only provided potential diagnostic biomarkers for HS lactating dairy cows, but also significantly explored the related physiological mechanisms

Risk factors for postpartum ovarian cysts and their spontaneous recovery or persistence in lactating dairy cows.

PubMed

López-Gatius, F; Santolaria, P; Yániz, J; Fenech, M; López-Béjar, M

2002-11-01

Cystic ovarian disease is a major cause of reproductive failure and economic loss for the dairy industry. Many cysts that develop during the early postpartum period regress spontaneously. However, it is difficult to decide at what point it would be more cost effective to treat ovarian cysts than to wait for spontaneous recovery. The objective of this study was to analyze risk factors for the development of the ovarian cystic condition during early and late postpartum, and for its persistence or recovery during the pre-service period in lactating dairy cows. Using multiple logistic regression, we analyzed data derived from 873 lactating dairy cows from a single herd. An ovarian cyst was diagnosed if it was possible to observe a single follicular structure with an antrum diameter > or = 25 mm in the absence of a corpus luteum in three sonograms performed at 7-day intervals. The cystic condition was denoted as early if the cyst was diagnosed 43-49 days postpartum, and late if detected 57-63-day postpartum. Spontaneous cyst regression before 60-day postpartum was regarded as early cystic recovery. For the early cystic group, there were no significant effects of lactation number, body condition score on prepartum Day 60, at parturition or on postpartum Day 30, or of body condition loss from parturition to 30-day postpartum. Cows calving in summer were 2.6 times more likely to develop ovarian cysts than those giving birth in winter. The risk of having a cyst was 1.9 times higher in cows with an abnormal puerperium. A 1-kg increase in milk yield raised the risk of cysts by a factor of 1.05. A 1-unit increase in body condition score (scale from 1 to 5) from prepartum Day 60 to parturition increased the risk of cyst development 8.4 times. Milk production and lactation number were negatively correlated with spontaneous early cyst recovery. A 1-kg decrease in milk production increased the probability of cyst recovery by a factor of 1.06, and a 1-unit drop in lactation number

An evaluation of the effect of altering nutrition and nutritional strategies in early lactation on reproductive performance and estrous behavior of high-yielding Holstein-Friesian dairy cows.

PubMed

Gilmore, H S; Young, F J; Patterson, D C; Wylie, A R G; Law, R A; Kilpatrick, D J; Elliott, C T; Mayne, C S

2011-07-01

Reproductive performance in the high-yielding dairy cow has severely decreased in the last 40 yr. The aim of this study was to compare the effectiveness of 4 nutritional strategies in improving the reproductive performance of high-yielding dairy cows. It was hypothesized that offering cows a high-starch ration in early lactation would enhance the onset of luteal activity, and that decreasing the severity of negative energy balance in the early postcalving period would improve reproductive parameters. Nutritional regimens aimed at improving fertility were applied to 96 Holstein-Friesian dairy animals. Upon calving, animals were allocated in a balanced manner to one of 4 dietary treatments. Primiparous animals were balanced according to live weight, body condition score and calving date. Multiparous animals were balanced according to parity, previous lactation milk yield, liveweight, body condition score and calving date. Treatment 1 was based on an industry best practice diet (control) to contain 170 g of crude protein/kg of dry matter. Treatment 2 was an individual cow feeding strategy, whereby the energy balance (EB) of individual animals was managed so as to achieve a predetermined target daily EB profile (±10 MJ/d). Treatment 3 was a high-starch/high-fat combination treatment, whereby an insulinogenic (high-starch) diet was offered in early lactation to encourage cyclicity and followed by a lipogenic (low-starch, high-fat) diet to promote embryo development. Treatment 4 was a low-protein diet, containing 140 g of crude protein/kg of dry matter, supplemented with protected methionine at an inclusion level of 40 g per animal per day. The nutritional strategies implemented in this study had no statistically significant effects on cow fertility measures, which included the onset of luteal activity, conception rate, in-calf rate, and the incidence of atypical cycles. The individual cow feeding strategy improved EB in early lactation but had no benefit on conception

Incidence of double ovulation during the early postpartum period in lactating dairy cows.

PubMed

Kusaka, Hiromi; Miura, Hiroshi; Kikuchi, Motohiro; Sakaguchi, Minoru

2017-03-15

In lactating cattle, the incidence of twin calving has many negative impacts on production and reproduction in dairy farming. In almost all cases, natural twinning in dairy cattle is the result of double ovulation. It has been suggested that the milk production level of cows influences the number of ovulatory follicles. The objective of the present study was to investigate the incidence of double ovulations during the early postpartum period in relation to the productive and reproductive performance of dairy cows. The ovaries of 43 Holstein cows (26 primiparous and 17 multiparous) were ultrasonographically scanned throughout the three postpartum ovulation sequences. The incidence of double ovulation in the unilateral ovaries was 66.7%, with a higher incidence in the right ovary than in the left, whereas that in bilateral ovaries was 33.3%. When double ovulations were counted dividing into each side ovary in which ovulations occurred, the total frequency of ovulations deviated from a 1:1 ratio (60.3% in the right side and 39.7% in the left side, P < 0.05). In multiparous cows, double ovulation occurred more frequently than in primiparous cows (58.8% vs. 11.5% per cow and 30.0% vs. 3.8% per ovulation, respectively P < 0.01). The double ovulators experienced more anovulatory repeated waves of follicles before their first ovulations than the single ovulators, which resulted in an extension of the period from parturition to third ovulation (81.5 days vs. 64.2 days, P < 0.05). In the multiparous cows, the double ovulators exhibited higher peak milk yield (P < 0.01) with lower milk lactose concentration (P < 0.05), indicating the prevalence of a more severe negative energy balance during the postpartum 3-month compared to the multiparous single ovulators. Our results showed that, regardless of their parity, double ovulation had no impact on the reproductive performance of the cows. Two multiparous cows that experienced double ovulation during the early

Circulating blood metabolites in early-lactation dairy cows fed canola or soybean meals

USDA-ARS?s Scientific Manuscript database

A successful transition from pregnancy to lactation is imperative for dairy cows to maximize milk production potential. Altering the dietary protein source can change the availability of energy to the cow. The objective of this experiment was to evaluate the effect of crude protein (CP) source canol...

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

PubMed Central

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

2012-01-01

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. PMID:22385215

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

PubMed

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

2016-07-01

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

Differences in the ribosomes prepared from lactating and non-lactating bovine mammary gland

PubMed Central

Herrington, M. D.; Hawtrey, A. O.

1971-01-01

1. Ribosomes prepared from bovine lactating mammary gland are able to synthesize protein, whereas similar preparations from non-lactating glands are not. Washing the ribosome suspensions through a medium containing 0.5m-ammonium chloride enhanced their ability to incorporate phenylalanine into polyphenylalanine. 2. Ribosomes isolated from non-lactating bovine mammary gland, in contrast with those from rat liver and lactating mammary gland, contained significant amounts of extraneous nucleases. These enzymes could be removed by washing with a medium A buffer containing 0.5m-ammonium chloride. 3. Only those ribosomes from functionally active tissues were able to bind polyuridylic acid and phenylalanyl-tRNA. PMID:5165653

Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer's Disease Biomarkers Changes.

PubMed

Liguori, Claudio; Mercuri, Nicola Biagio; Izzi, Francesca; Romigi, Andrea; Cordella, Alberto; Sancesario, Giuseppe; Placidi, Fabio

2017-05-01

Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer's Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid42, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP). We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis. OSA patients showed lower CSF Aβ42 concentrations, higher CSF lactate levels, and higher t-tau/Aβ42 ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ42 levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients. We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ42 levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Treatment of field cases of East Coast fever with halofuginone lactate.

PubMed

Njau, B C; Mkonyi, P A; Mleche, W C; Kitaly, J I; Maiseli, N C

1985-11-01

In a series of field trials 48 (55%) of 88 field cases of East Coast fever treated with halofuginone lactate recovered and survived and 40 (45%) died while 31 (86%) of 36 untreated control animals died of East Coast fever and five (14%) recovered. For cases diagnosed and treated early a 100% recovery rate was achieved. A single dose at 1.2 mg/kg body weight per os was adequate. Recovery rate was only 36% for cases diagnosed and treated at an advanced stage. Such cases required two doses at 1.2 mg/kg or a combination of 1.2 and 2.4 mg/kg body weight given at about two days interval. The temperature dropped to normal levels within 48 h of treatment and schizonts started degenerating as early as 24 h after treatment and had disappeared by 48 to 72 h. Piroplasms were not affected by the drug. Recovered animals remained free of East Coast fever for periods up to 12 months of observation despite continuous tick challenge. It was concluded that, with early detection and treatment augmented with proper tick control, outbreaks of East Coast fever can be effectively controlled with halofuginone lactate.

A Lactate Kinetics Method for Assessing the Maximal Lactate Steady State Workload

PubMed Central

Hering, Gernot O.; Hennig, Ewald M.; Riehle, Hartmut J.; Stepan, Jens

2018-01-01

During a continuously increasing exercise workload (WL) a point will be reached at which arterial lactate accumulates rapidly. This so-called lactate threshold (LT) is associated with the maximal lactate steady state workload (MLSSW), the highest WL, at which arterial lactate concentration [LA] does not change. However, the physiological range in which the LT and the MLSSW occur has not been demonstrated directly. We used minor WL variations in the MLSSW range to assess arterial lactate kinetics in 278 treadmill and 148 bicycle ergometer exercise tests. At a certain workload, minimal further increment of running speed (0.1–0.15 m/s) or cycling power (7–10 W) caused a steep elevation of [LA] (0.9 ± 0.43 mM, maximum increase 2.4 mM), indicating LT achievement. This sharp [LA] increase was more pronounced when higher WL increments were used (0.1 vs. 0.30 m/s, P = 0.02; 0.15 vs. 0.30 m/s, P < 0.001; 7 vs. 15 W, P = 0.002; 10 vs. 15 W, P = 0.001). A subsequent workload reduction (0.1 m/s/7 W) stopped the [LA] increase indicating MLSSW realization. LT based determination of running speed (MLSSW) was highly reproducible on a day-to-day basis (r = 0.996, P < 0.001), valid in a 10 km constant velocity setting (r = 0.981, P < 0.001) and a half marathon race (r = 0.969, P < 0.001). These results demonstrate a fine-tuned regulation of exercise-related lactate metabolism, which can be reliably captured by assessing lactate kinetics at the MLSSW. PMID:29651253

Genetic analysis of fat-to-protein ratio, milk yield and somatic cell score of Holstein cows in Japan in the first three lactations by using a random regression model.

PubMed

Nishiura, Akiko; Sasaki, Osamu; Aihara, Mitsuo; Takeda, Hisato; Satoh, Masahiro

2015-12-01

We estimated the genetic parameters of fat-to-protein ratio (FPR) and the genetic correlations between FPR and milk yield or somatic cell score in the first three lactations in dairy cows. Data included 3,079,517 test-day records of 201,138 Holstein cows in Japan from 2006 to 2011. Genetic parameters were estimated with a multiple-trait random regression model in which the records within and between parities were treated as separate traits. The phenotypic values of FPR increased soon after parturition and peaked at 10 to 20 days in milk, then decreased slowly in mid- and late lactation. Heritability estimates for FPR yielded moderate values. Genetic correlations of FPR among parities were low in early lactation. Genetic correlations between FPR and milk yield were positive and low in early lactation, but only in the first lactation. Genetic correlations between FPR and somatic cell score were positive in early lactation and decreased to become negative in mid- to late lactation. By using these results for genetic evaluation it should be possible to improve energy balance in dairy cows. © 2015 Japanese Society of Animal Science.

Influence of lactation and pregnancy + lactation on mechanical properties and mineral content of the rat femur.

PubMed

Peng, T C; Kusy, R P; Garner, S C; Hirsch, P F; De Blanco, M C

1987-06-01

The quality of bone was assessed from femurs of rats both during lactation and after pregnancy + lactation. Mechanical properties of stiffness, strength, toughness, and ductility were measured, along with standard measurements of dry weight, ash weight, and total bone mineral. No changes occurred during the first week of lactation. During the second and third weeks of lactation all bone parameters except ductility decreased significantly. These data are consistent with bone losing mineral in order to supplement the dietary calcium intake necessary for milk production. In other experiments, femurs were collected from nulliparous rats and from rats that had previously undergone 1-3 pregnancy + lactations. The largest changes in bone mineral and mechanical properties occurred after a single pregnancy + lactation period, although significant further decreases in stiffness and strength occurred after the second pregnancy + lactation. No additional losses occurred following the third pregnancy + lactation. Even 5 months after only one pregnancy + lactation period, the bone quality was still impaired as all bone properties were lower than in nulliparous controls. Because the changes, especially stiffness and strength, were relatively larger than the changes in dry and ash weights of bone, measurements of these mechanical properties provide a more sensitive method to evaluate the quality of bone.

Elevated lactate during psychogenic hyperventilation.

PubMed

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

2011-04-01

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 visited the emergency department (ED) with psychogenic hyperventilation. Over a 5-month period, all the patients who visited the ED of a university hospital with presumed psychogenic hyperventilation were evaluated. Psychogenic hyperventilation was presumed to be present when an increased respiratory rate (>20 min) was documented at or before the ED visit and when somatic causes explaining the hyperventilation were absent. Arterial blood gas and lactate levels (reference values 0.5-1.5 mmol/l) were immediately measured by a point-of-care analyser that was managed and calibrated by the central laboratory. During the study period, 46 patients were diagnosed as having psychogenic hyperventilation. The median (range) Pco(2) for this group was 4.3 (2.0-5.5) kPa, the pH was 7.47 (7.40-7.68) and the lactate level was 1.2 (0.5-4.4) mmol/l. 14 participants (30%) had a lactate level above the reference value of 1.5 mmol/l. Pco(2) was the most important predictor of lactate in multivariate analysis. None of the participants underwent any medical treatment other than observation at the ED or had been hospitalised after their ED visit. In patients with psychogenic hyperventilation, lactate levels are frequently elevated. Whereas high lactates are usually associated with acidosis and an increased risk of poor outcome, in patients with psychogenic hyperventilation, high lactates are associated with hypocapnia and alkalosis. In this context, elevated arterial lactate levels should not be regarded as an adverse sign.

Biological underpinnings of breastfeeding challenges: the role of genetics, diet, and environment on lactation physiology

PubMed Central

Lee, Sooyeon

2016-01-01

Lactation is a dynamic process that has evolved to produce a complex biological fluid that provides nutritive and nonnutritive factors to the nursing offspring. It has long been assumed that once lactation is successfully initiated, the primary factor regulating milk production is infant demand. Thus, most interventions have focused on improving breastfeeding education and early lactation support. However, in addition to infant demand, increasing evidence from studies conducted in experimental animal models, production animals, and breastfeeding women suggests that a diverse array of maternal factors may also affect milk production and composition. In this review, we provide an overview of our current understanding of the role of maternal genetics and modifiable factors, such as diet and environmental exposures, on reproductive endocrinology, lactation physiology, and the ability to successfully produce milk. To identify factors that may affect lactation in women, we highlight some information gleaned from studies in experimental animal models and production animals. Finally, we highlight the gaps in current knowledge and provide commentary on future research opportunities aimed at improving lactation outcomes in breastfeeding women to improve the health of mothers and their infants. PMID:27354238

Oxygen control of breathing by an olfactory receptor activated by lactate

PubMed Central

Chang, Andy J.; Ortega, Fabian E.; Riegler, Johannes; Madison, Daniel V.; Krasnow, Mark A.

2015-01-01

Summary Animals have evolved homeostatic responses to changes in oxygen availability that act on different time scales. Although the hypoxia-inducible factor (HIF) transcriptional pathway that controls long term responses to low oxygen (hypoxia) has been established1, the pathway that mediates acute responses to hypoxia in mammals is not well understood. Here we show that the olfactory receptor Olfr78 is highly and selectively expressed in oxygen-sensitive glomus cells of the carotid body, a chemosensory organ at the carotid artery bifurcation that monitors blood oxygen and stimulates breathing within seconds when oxygen declines2. Olfr78 mutants fail to increase ventilation in hypoxia but respond normally to hypercapnia. Glomus cells are present in normal numbers and appear structurally intact, but hypoxia-induced carotid body activity is diminished. Lactate, a metabolite that rapidly accumulates in hypoxia and induces hyperventilation3–6, activates Olfr78 in heterologous expression experiments, induces calcium transients in glomus cells, and stimulates carotid sinus nerve activity through Olfr78. We propose that in addition to its role in olfaction, Olfr78 acts as a hypoxia sensor in the breathing circuit by sensing lactate produced when oxygen levels decline. PMID:26560302

Lactate: link between glycolytic and oxidative metabolism.

PubMed

Brooks, George A

2007-01-01

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilised continuously under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of cell-cell shuttles include lactate exchanges (i) between white-glycolytic and red-oxidative fibres within a working muscle bed; (ii) between working skeletal muscle and heart; and (iii) between tissues of net lactate release and gluconeogenesis. Lactate shuttles exist in diverse tissues including in the brain, where a shuttle between astrocytes and neurons is linked to glutamatergic signalling. Because lactate, the product of glycogenolysis and glycolysis, is disposed of by oxidative metabolism, lactate shuttling unites the two major processes of cellular energy transduction. Lactate disposal is mainly through oxidation, especially during exercise when oxidation accounts for 70-75% of removal and gluconeogenesis the remainder. Lactate flux occurs down proton and concentration gradients that are established by the mitochondrial lactate oxidation complex. Marathon running is a power activity requiring high glycolytic and oxidative fluxes; such activities require lactate shuttling. Knowledge of the lactate shuttle is yet to be imparted to the sport.

Loss of body fat and associated decrease in leptin in early lactation are related to shorter duration of postpartum anovulation in healthy US women.

PubMed

Domer, Mary Colleen; Beerman, Kathy A; Ahmadzadeh, Amin; Dasgupta, Nairanjana; Williams, Janet E; McGuire, Mark A; McGuire, Michelle K

2015-05-01

The mechanisms regulating postpartum anovulation (PPA) are not well understood, although poor nutritional status and "intense" breastfeeding behaviors are associated with longer durations. This study was designed primarily to investigate the hypothesis that higher body fat and leptin concentrations are related to shorter PPA in healthy, lactating US women. Nutrient intake, breastfeeding behaviors, prolactin, and insulin levels were also evaluated. Fasting serum was collected during the third trimester of pregnancy, at 2 and 4 weeks postpartum, and every 4 weeks until the occurrence of the first postpartum menses. Body composition and breastfeeding behaviors were assessed at the same times postpartum. Women (n = 13) were categorized based on initial percentage body fat and timing of first postpartum menses. There were no consistent relationships between body composition, leptin, or breastfeeding behaviors and duration of PPA. However, there was an interaction (P = .005) between ovulation group and time on adiposity; earlier ovulating women had less percentage body fat in early lactation than did later ovulating women. There was also an interaction (P = .1) between ovulation group and time postpartum on leptin, such that leptin concentrations tended to be greater in later than earlier ovulating groups beginning at 12 weeks postpartum. In summary, although baseline percentage body fat and leptin were not related to duration of PPA, fertility returned earlier in women who lost greater percentage body fat during the early postpartum period. © The Author(s) 2015.

Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother.

PubMed

Alzamendi, Ana; Castrogiovanni, Daniel; Gaillard, Rolf C; Spinedi, Eduardo; Giovambattista, Andrés

2010-09-01

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.

Effect of water-based recovery on blood lactate removal after high-intensity exercise.

PubMed

Lucertini, Francesco; Gervasi, Marco; D'Amen, Giancarlo; Sisti, Davide; Rocchi, Marco Bruno Luigi; Stocchi, Vilberto; Benelli, Piero

2017-01-01

This study assessed the effectiveness of water immersion to the shoulders in enhancing blood lactate removal during active and passive recovery after short-duration high-intensity exercise. Seventeen cyclists underwent active water- and land-based recoveries and passive water and land-based recoveries. The recovery conditions lasted 31 minutes each and started after the identification of each cyclist's blood lactate accumulation peak, induced by a 30-second all-out sprint on a cycle ergometer. Active recoveries were performed on a cycle ergometer at 70% of the oxygen consumption corresponding to the lactate threshold (the control for the intensity was oxygen consumption), while passive recoveries were performed with subjects at rest and seated on the cycle ergometer. Blood lactate concentration was measured 8 times during each recovery condition and lactate clearance was modeled over a negative exponential function using non-linear regression. Actual active recovery intensity was compared to the target intensity (one sample t-test) and passive recovery intensities were compared between environments (paired sample t-tests). Non-linear regression parameters (coefficients of the exponential decay of lactate; predicted resting lactates; predicted delta decreases in lactate) were compared between environments (linear mixed model analyses for repeated measures) separately for the active and passive recovery modes. Active recovery intensities did not differ significantly from the target oxygen consumption, whereas passive recovery resulted in a slightly lower oxygen consumption when performed while immersed in water rather than on land. The exponential decay of blood lactate was not significantly different in water- or land-based recoveries in either active or passive recovery conditions. In conclusion, water immersion at 29°C would not appear to be an effective practice for improving post-exercise lactate removal in either the active or passive recovery modes.

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

PubMed

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

2014-05-01

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

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

PubMed

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

2016-08-01

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

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

PubMed

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

2012-01-01

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

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

PubMed

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

2014-09-01

Breeding values for dry matter intake (DMI) are important to optimize dairy cattle breeding goals for feed efficiency. However, generally, only small data sets are available for feed intake, due to the cost and difficulty of measuring DMI, which makes understanding the genetic associations between traits across lactation difficult, let alone the possibility for selection of breeding animals. However, estimating national breeding values through cheaper and more easily measured correlated traits, such as milk yield and liveweight (LW), could be a first step to predict DMI. Combining DMI data across historical nutritional experiments might help to expand the data sets. Therefore, the objective was to estimate genetic parameters for DMI, fat- and protein-corrected milk (FPCM) yield, and LW across the entire first lactation using a relatively large data set combining experimental data across the Netherlands. A total of 30,483 weekly records for DMI, 49,977 for FPCM yield, and 31,956 for LW were available from 2,283 Dutch Holstein-Friesian first-parity cows between 1990 and 2011. Heritabilities, covariance components, and genetic correlations were estimated using a multivariate random regression model. The model included an effect for year-season of calving, and polynomials for age of cow at calving and days in milk (DIM). The random effects were experimental treatment, year-month of measurement, and the additive genetic, permanent environmental, and residual term. Additive genetic and permanent environmental effects were modeled using a third-order orthogonal polynomial. Estimated heritabilities ranged from 0.21 to 0.40 for DMI, from 0.20 to 0.43 for FPCM yield, and from 0.25 to 0.48 for LW across DIM. Genetic correlations between DMI at different DIM were relatively low during early and late lactation, compared with mid lactation. The genetic correlations between DMI and FPCM yield varied across DIM. This correlation was negative (up to -0.5) between FPCM yield in

Cross-fostering reduces obesity induced by early exposure to monosodium glutamate in male rats.

PubMed

Miranda, Rosiane Aparecida; da Silva Franco, Claudinéia Conationi; de Oliveira, Júlio Cezar; Barella, Luiz Felipe; Tófolo, Laize Peron; Ribeiro, Tatiane Aparecida; Pavanello, Audrei; da Conceição, Ellen Paula Santos; Torrezan, Rosana; Armitage, James; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar; de Freitas Mathias, Paulo Cezar; Vieira, Elaine

2017-01-01

Maternal obesity programmes a range of metabolic disturbances for the offspring later in life. Moreover, environmental changes during the suckling period can influence offspring development. Because both periods significantly affect long-term metabolism, we aimed to study whether cross-fostering during the lactation period was sufficient to rescue a programmed obese phenotype in offspring induced by maternal obesity following monosodium L-glutamate (MSG) treatment. Obesity was induced in female Wistar rats by administering subcutaneous MSG (4 mg/g body weight) for the first 5 days of postnatal life. Control and obese female rats were mated in adulthood. The resultant pups were divided into control second generation (F 2 ) (CTLF 2 ), MSG-treated second generation (F 2 ) (MSGF 2 ), which suckled from their CTL and MSG biological dams, respectively, or CTLF 2 -CR, control offspring suckled by MSG dams and MSGF 2 -CR, MSG offspring suckled by CTL dams. At 120 days of age, fat tissue accumulation, lipid profile, hypothalamic leptin signalling, glucose tolerance, glucose-induced, and adrenergic inhibition of insulin secretion in isolated pancreatic islets were analysed. Maternal MSG-induced obesity led to an obese phenotype in male offspring, characterized by hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, dyslipidaemia, and impaired leptin signalling, suggesting central leptin resistance, glucose intolerance, impaired glucose-stimulated, and adrenergic inhibition of insulin secretion. Cross-fostering normalized body weight, food intake, leptin signalling, lipid profiles, and insulinaemia, but not glucose homeostasis or insulin secretion from isolated pancreatic islets. Our findings suggest that alterations during the lactation period can mitigate the development of obesity and prevent the programming of adult diseases.

Lactation is associated with altered metabolomic signatures in women with gestational diabetes.

PubMed

Much, Daniela; Beyerlein, Andreas; Kindt, Alida; Krumsiek, Jan; Stückler, Ferdinand; Rossbauer, Michaela; Hofelich, Anna; Wiesenäcker, David; Hivner, Susanne; Herbst, Melanie; Römisch-Margl, Werner; Prehn, Cornelia; Adamski, Jerzy; Kastenmüller, Gabi; Theis, Fabian; Ziegler, Anette-G; Hummel, Sandra

2016-10-01

Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures postpartum. We enrolled 197 women with gestational diabetes at a median of 3.6 years (interquartile range 0.7-6.5 years) after delivery. Targeted metabolomics profiles (including 156 metabolites) were obtained during a glucose challenge test. Comparisons of metabolite concentrations and ratios between women who lactated for >3 months and women who lactated for ≤3 months or not at all were performed using linear regression with adjustment for age and BMI at the postpartum visit, time since delivery, and maternal education level, and correction for multiple testing. Gaussian graphical modelling was used to generate metabolite networks. Lactation for >3 months was associated with a higher total lysophosphatidylcholine/total phosphatidylcholine ratio; in women with short-term follow-up, it was also associated with lower leucine concentrations and a lower total branched-chain amino acid concentration. Gaussian graphical modelling identified subgroups of closely linked metabolites within phosphatidylcholines and branched-chain amino acids that were affected by lactation for >3 months and have been linked to the pathophysiology of type 2 diabetes in previous studies. Lactation for >3 months in women with gestational diabetes is associated with changes in the metabolomics profile that have been linked to the early pathogenesis of type 2 diabetes.

Changes in central sodium and not osmolarity or lactate induce panic-like responses in a model of panic disorder.

PubMed

Molosh, Andre I; Johnson, Philip L; Fitz, Stephanie D; Dimicco, Joseph A; Herman, James P; Shekhar, Anantha

2010-05-01

Panic disorder is a severe anxiety disorder characterized by recurrent panic attacks that can be consistently provoked with intravenous (i.v.) infusions of hypertonic (0.5 M) sodium lactate (NaLac), yet the mechanism/CNS site by which this stimulus triggers panic attacks is unclear. Chronic inhibition of GABAergic synthesis in the dorsomedial hypothalamus/perifornical region (DMH/PeF) of rats induces a vulnerability to panic-like responses after i.v. infusion of 0.5 M NaLac, providing an animal model of panic disorder. Using this panic model, we previously showed that inhibiting the anterior third ventricle region (A3Vr; containing the organum vasculosum lamina terminalis, the median preoptic nucleus, and anteroventral periventricular nucleus) attenuates cardiorespiratory and behavioral responses elicited by i.v. infusions of NaLac. In this study, we show that i.v. infusions of 0.5 M NaLac or sodium chloride, but not iso-osmolar D-mannitol, increased 'anxiety' (decreased social interaction) behaviors, heart rate, and blood pressure responses. Using whole-cell patch-clamp preparations, we also show that bath applications of NaLac (positive control), but not lactic acid (lactate stimulus) or D-mannitol (osmolar stimulus), increases the firing rates of neurons in the A3Vr, which are retrogradely labeled from the DMH/PeF and which are most likely glutamatergic based on a separate study using retrograde tracing from the DMH/PeF in combination with in situ hybridization for vesicular glutamate transporter 2. These data show that hypertonic sodium, but not hyper-osmolarity or changes in lactate, is the key stimulus that provokes panic attacks in panic disorder, and is consistent with human studies.

Diminution in energy expenditure during lactation.

PubMed Central

Illingworth, P J; Jung, R T; Howie, P W; Leslie, P; Isles, T E

1986-01-01

Energy expenditure at rest and in response to a meal and to an infusion of noradrenaline was measured in 12 lactating women and compared with that in seven bottle feeding women and seven non-pregnant, non-lactating controls. The energy response of the lactating women was remeasured after lactation stopped. During lactation the resting metabolic rate was unaltered but there was a reduced response to infusion of noradrenaline and to a meal, which increased to normal control values after lactation stopped. Such reductions in expenditure were not found in women who had been bottle feeding and were tested at a similar six to eight weeks post partum. These findings suggest that metabolic efficiency is enhanced in lactating women, who may not need to increase energy intake to the extent suggested by current recommended dietary allowances. PMID:3081114

Early Detection of Ventilation-Induced Brain Injury Using Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: An In Vivo Study in Preterm Lambs

PubMed Central

Skiöld, Béatrice; Wu, Qizhu; Hooper, Stuart B.; Davis, Peter G.; McIntyre, Richard; Tolcos, Mary; Pearson, James; Vreys, Ruth; Egan, Gary F.; Barton, Samantha K.; Cheong, Jeanie L. Y.; Polglase, Graeme R.

2014-01-01

Background and Aim High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs. Methods Newborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations. Results No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups. Conclusion Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is

The extracellular matrix locally regulates asynchronous concurrent lactation in tammar wallaby (Macropus eugenii).

PubMed

Wanyonyi, Stephen S; Lefevre, Christophe; Sharp, Julie A; Nicholas, Kevin R

2013-08-08

Asynchronous concurrent lactation (ACL) is an extreme lactation strategy in macropod marsupials including the tammar wallaby, that may hold the key to understanding local control of mammary epithelial cell function. Marsupials have a short gestation and a long lactation consisting of three phases; P2A, P2B and P3, representing early, mid and late lactation respectively and characterised by profound changes in milk composition. A lactating tammar is able to concurrently produce phase 2A and 3 milk from adjacent glands in order to feed a young newborn and an older sibling at heel. Physiological effectors of ACL remain unknown and in this study the extracellular matrix (ECM) is investigated for its role in switching mammary phenotypes between phases of tammar wallaby lactation. Using the level of expression of the genes for the phase specific markers tELP, tWAP, and tLLP-B representing phases 2A, 2B and 3 respectively we show for the first time that tammar wallaby mammary epithelial cells (WallMECs) extracted from P2B acquire P3 phenotype when cultured on P3 ECM. Similarly P2A cells acquire P2B phenotype when cultured on P2B ECM. We further demonstrate that changes in phase phenotype correlate with phase-specific changes in ECM composition. This study shows that progressive changes in ECM composition in individual mammary glands provide a local regulatory mechanism for milk protein gene expression thereby enabling the mammary glands to lactate independently. Copyright © 2013. Published by Elsevier B.V.

Ruminal bacterial community composition in dairy cows is dynamic over the course of two lactations and correlates with feed efficiency

USDA-ARS?s Scientific Manuscript database

A group of 14 Holstein cows of similar age were followed through the course of their first two lactation cycles. During each lactation cycle, ruminal solids and liquids, milk samples and production data, and feed consumption data were collected for each cow during Early (76-82 days in milk, DIM), Mi...

CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.

PubMed

Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Naïken, Tanesha; Ilc, Karine; Ilk, Karine; Murray, Clare M; Critchlow, Susan E; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

2011-10-04

Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H(+)/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res(-)) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res(-) cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H(+) symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basigin(high) cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy.

CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors

PubMed Central

Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Ilc, Karine; Murray, Clare M.; Critchlow, Susan E.; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

2011-01-01

Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H+/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res−) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res− cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H+ symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basiginhigh cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy. PMID:21930917

Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function.

PubMed

Jamali, Somayeh; Klier, Michael; Ames, Samantha; Barros, L Felipe; McKenna, Robert; Deitmer, Joachim W; Becker, Holger M

2015-09-04

The most aggressive tumour cells, which often reside in hypoxic environments, rely on glycolysis for energy production. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms of regulated lactate transport in MCF-7 human breast cancer cells. Under hypoxia, expression of MCT1 and MCT4 remained unchanged, while expression of carbonic anhydrase IX (CAIX) was greatly enhanced. Our results show that CAIX augments MCT1 transport activity by a non-catalytic interaction. Mutation studies in Xenopus oocytes indicate that CAIX, via its intramolecular H(+)-shuttle His200, functions as a "proton-collecting/distributing antenna" to facilitate rapid lactate flux via MCT1. Knockdown of CAIX significantly reduced proliferation of cancer cells, suggesting that rapid efflux of lactate and H(+), as enhanced by CAIX, contributes to cancer cell survival under hypoxic conditions.

Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function

PubMed Central

Jamali, Somayeh; Klier, Michael; Ames, Samantha; Felipe Barros, L.; McKenna, Robert; Deitmer, Joachim W.; Becker, Holger M.

2015-01-01

The most aggressive tumour cells, which often reside in hypoxic environments, rely on glycolysis for energy production. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms of regulated lactate transport in MCF-7 human breast cancer cells. Under hypoxia, expression of MCT1 and MCT4 remained unchanged, while expression of carbonic anhydrase IX (CAIX) was greatly enhanced. Our results show that CAIX augments MCT1 transport activity by a non-catalytic interaction. Mutation studies in Xenopus oocytes indicate that CAIX, via its intramolecular H+-shuttle His200, functions as a “proton-collecting/distributing antenna” to facilitate rapid lactate flux via MCT1. Knockdown of CAIX significantly reduced proliferation of cancer cells, suggesting that rapid efflux of lactate and H+, as enhanced by CAIX, contributes to cancer cell survival under hypoxic conditions. PMID:26337752

Peak energy turnover in lactating European hares: the role of fat reserves

PubMed Central

Valencak, T. G.; Tataruch, F.; Ruf, T.

2010-01-01

SUMMARY European hares (Lepus europaeus) in central Europe have high energetic costs of reproduction, mainly due to precocial, rapidly growing young that rely largely on energy rich milk. Thus, hares in this climate build up large fat stores during winter which are then gradually depleted during the spring to autumn breeding season. We hypothesized that diminishing fat stores of females over the breeding season may affect resource allocation, peak energy assimilation during lactation, or the total investment in offspring. Therefore, we measured energy intake, milk quality and milk production throughout lactation in spring, summer and autumn, in females raising (size-manipulated) litters with three young each, under natural photoperiod but at buffered ambient temperatures inside our facility. Over the course of the breeding season the amount of milk production remained constant but fat content of the milk decreased. Hence, total energy transfer to young decreased significantly in autumn. By using undecanoic acid as a tracer of body fat mobilization we were able to show that milk fat partially originated from maternal fat stores particularly in spring. Peak sustained energy assimilation rates of lactating females were significantly higher in autumn, due to increased rates of food intake. We conclude that fat stores allow female hares to downregulate energy intake and expenditure early in the breeding season whereas late breeding forces them to reach peak energy intake levels. Accordingly, we suggest that in hares, peak energy turnover during lactation varies with the availability of fat reserves. Limits to sustained metabolic rate serve as variable constraints on reproductive investment. There may be a trade-off in energetic costs to mothers rearing early vs. late litters in the year. PMID:19112142

Salivary lactate dehydrogenase levels can provide early diagnosis of hypoxic-ischaemic encephalopathy in neonates with birth asphyxia.

PubMed

Mehta, Akshay; Chawla, Deepak; Kaur, Jasbinder; Mahajan, Vidushi; Guglani, Vishal

2015-06-01

Timely detection of hypoxic-ischaemic encephalopathy (HIE) is crucial for selecting neonates who are likely to benefit from neuroprotective therapy. This study evaluated the efficacy of salivary lactate dehydrogenase (LDH) in the early diagnosis of HIE among neonates with perinatal asphyxia. We prospectively enrolled 30 neonates who needed resuscitation at birth or had a history of delayed cry into the HIE group if they developed HIE within 12 h of birth. The control group comprised 30 neonates who had no evidence of HIE, but had intrapartum foetal distress or needed resuscitation at birth. LDH was measured using saliva samples collected within 12 h of birth. Salivary LDH was significantly higher in the HIE group, with a median of 2578 and an interquartile range (IQR) of 1379-3408 international units per litre (IU/L), than in the control group (median 558.5, IQR: 348-924 IU/L, p < 0.001). The test demonstrated excellent discriminating ability: the area under the curve was 0.92 and the levels of 893 IU/L showed a sensitivity of 90% and a specificity of 73.3%. Measuring salivary LDH among neonates with birth asphyxia provided an early and accurate diagnosis of HIE and could be used as a triage tool. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron filings, reaction of ferrous chloride with sodium lactate, or reaction of ferrous sulfate...

Transport of pyruvate and lactate in yeast mitochondria.

PubMed

Briquet, M

1977-02-07

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

Lactation stage-dependent expression of transporters in rat whole mammary gland and primary mammary epithelial organoids.

PubMed

Gilchrist, Samuel E; Alcorn, Jane

2010-04-01

Since solute carrier (SLC) and ATP-binding cassette (ABC) transporters play pivotal roles in the transport of both nutrients and drugs into breast milk, drug-nutrient transport interactions at the lactating mammary gland are possible. Our purpose was to characterize lactation stage-dependent changes in transporter expression in rat mammary gland and isolated mammary epithelial organoids (MEO) to provide additional insight for the safe use of maternal medications during breastfeeding. We used quantitative reverse transcription-polymerase chain reaction to assess the temporal expression patterns of SLC and ABC transporters in rat mammary gland and isolated MEO at different stages of lactation. In whole mammary gland five distinct patterns of expression emerged relative to late gestation: (i) decreasing throughout lactation (Mdr1a, Mdr1b, Mrp1, Octn2, Ent2, Ent3, Ncbt2, Mtx1); (ii) prominent increase in early lactation, which may remain elevated or decline with advancing lactation (Octn1, Cnt2, Cnt3, Ent1, Pept1, Pept2); (iii) constant but decreasing later in lactation (Octn3, Dmt1); (iv) increasing until mid-to-late lactation (Oct1, Cnt1); and (v) prominent increase late in lactation (Ncbt1). In isolated MEO (an enriched source of mammary epithelial cells) major differences in expression patterns were noted for Octn3, Ncbt1, and Mtx1, but otherwise were reasonably similar with the whole mammary gland. In conclusion our study augments existing data on transporter expression in the lactating mammary gland. These data should facilitate investigations into lactation-stage dependent changes in drug or nutrient milk-to-serum concentration ratios, the potential for drug- or disease-transporter interactions, and mechanistic studies of transporter function in the lactating mammary gland.

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

PubMed Central

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

2011-01-01

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

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... It is prepared by reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron filings, reaction of ferrous chloride with sodium lactate, or reaction of ferrous...

Lactating Mother and Psychotropic Drugs

PubMed Central

Tripathi, B. M.; Majumder, Pradipta

2010-01-01

Usage of psychotropics during pregnancy and lactation has always been a topic of debate and controversy. The debate stems from the potential adverse effects on the growing fetus or infants due to the transfer of psychotropic drugs through placenta or breast milk of mothers receiving them; and the problem of discontinuing psychotropics in lactating mother considering chances of relapse. However, most of the psychotropics are found to be relatively safe when used cautiously during the lactation phase. This article describes available data on the use of psychotropics in lactating mothers, in particular, in relation to the safety profile of infants. PMID:21327172

Maternal Visceral Adiposity by Consistency of Lactation

PubMed Central

Catov, Janet; Ness, Roberta; Schwarz, Eleanor Bimla

2013-01-01

The purpose of this study was to examine the assocation between lactation and maternal visceral adiposity among US women who were on average 7 years postpartum. This cross-sectional analysis included 89 women who gave birth between 1997 and 2002, who did not have preeclampsia, prepregnancy hypertension or prepregnancy diabetes, and enrolled in The Women and Infant Study of Healthy Hearts (WISH). Computed tomography was used to assess abdominal adiposity. History of lactation was self-reported. Visceral adiposity was greater by 36.96 cm2 (95% CI: 20.92,53.01) among mothers who never breastfed than mothers who breastfed for ≥3 months after every birth, even after adjustment for age, parity, years since last birth, site, socioeconomic, lifestyle, psychological, and family history variables, early adult BMI, and current BMI. Similarly, in fully adjusted models, mothers who breastfed any of their children for less than 3 months had 20.38 cm2 (95% CI: 2.70, 38.06) greater visceral adiposity than mothers who consistently breastfed all their children for 3 or more months. This study found that 7 years postpartum visceral fat depots are significantly greater among mothers who lactated for less than 3 months after the birth of each of their children. These results provide a potential physiologic basis for prior findings that women who do not consistently breastfeed are at an increased risk of diabetes, cardiovascular disease, and the metabolic syndrome. PMID:21404071

Short communication: infrared thermography and visual examination of hooves of dairy cows in two stages of lactation.

PubMed

Nikkhah, A; Plaizier, J C; Einarson, M S; Berry, R J; Scott, S L; Kennedy, A D

2005-08-01

Hooves of 16 lactating Holstein cows were examined twice for sole hemorrhages and underrun heels. Images of hooves were taken using infrared thermography to determine the temperatures of the coronary band and that of a control area above the coronary band. To adjust for skin (control) temperature, the difference (DeltaT) between the coronary band and the control area was calculated. Effects of stage of lactation, that is, 200 DIM, on temperature of the coronary band, DeltaT, and visual abnormalities were determined. Temperatures of the coronary bands of cows were greater for cows lactation (25.5 +/- 1.3 vs. 21.0 degrees C). The DeltaT was also greater for cows 200 DIM (6.1 +/- 0.8 vs. 3.3 +/- 0.9 degrees C). The DeltaT was greater for lateral claws than for medial claws (5.2 +/- 0.6 vs. 4.2 +/- 0.6 degrees C). Chi-square analysis revealed that the frequency of sole hemorrhages in hind lateral claws was significantly higher for cows lactation. In contrast, underrun heel was more frequently observed among cows >200 DIM. Increased temperatures of the coronary band and DeltaT in early/midlactation coincided with increased incidence of sole hemorrhages, but not to incidences of underrun heels. Because higher hoof temperatures occurred in cows lactation, measurement of hoof temperatures among cows in early lactation may be useful in monitoring hoof health.

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

PubMed Central

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

2016-01-01

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+, Ca2+, 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 KATP 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 Po2 were decreased, while FAD fluorescence increased likely due to a reduced conversion of FAD into FADH2. These data suggest that lactate shuttle contributes to regulation of ion homeostatsis and synaptic signaling even in the presence of ample glucose. PMID:27559140

Blocking Lactate Export by Inhibiting the Myc Target MCT1 Disables Glycolysis and Glutathione Synthesis

PubMed Central

Doherty, Joanne R.; Yang, Chunying; Scott, Kristen E. N.; Cameron, Michael D.; Fallahi, Mohammad; Li, Weimin; Hall, Mark A.; Amelio, Antonio L.; Mishra, Jitendra K.; Li, Fangzheng; Tortosa, Mariola; Genau, Heide Marika; Rounbehler, Robert J.; Lu, Yunqi; Dang, Chi. V.; Kumar, K. Ganesh; Butler, Andrew A.; Bannister, Thomas D.; Hooper, Andrea T.; Unsal-Kacmaz, Keziban; Roush, William R.; Cleveland, John L.

2014-01-01

Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1, and that elevated MCT1 levels are manifest in premalignant and neoplastic Eμ-Myc transgenic B cells and in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1 function leads to an accumulation of intracellular lactate that rapidly disables tumor cell growth and glycolysis, provoking marked alterations in glycolytic intermediates, and reductions in glucose transport, and in levels of ATP, NADPH and glutathione. Reductions in glutathione then lead to increases in hydrogen peroxide, mitochondrial damage and, ultimately, cell death. Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies. PMID:24285728

Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis.

PubMed

Doherty, Joanne R; Yang, Chunying; Scott, Kristen E N; Cameron, Michael D; Fallahi, Mohammad; Li, Weimin; Hall, Mark A; Amelio, Antonio L; Mishra, Jitendra K; Li, Fangzheng; Tortosa, Mariola; Genau, Heide Marika; Rounbehler, Robert J; Lu, Yunqi; Dang, Chi V; Kumar, K Ganesh; Butler, Andrew A; Bannister, Thomas D; Hooper, Andrea T; Unsal-Kacmaz, Keziban; Roush, William R; Cleveland, John L

2014-02-01

Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here, we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1 and that elevated MCT1 levels are manifest in premalignant and neoplastic Eμ-Myc transgenic B cells and in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1 function leads to an accumulation of intracellular lactate that rapidly disables tumor cell growth and glycolysis, provoking marked alterations in glycolytic intermediates, reductions in glucose transport, and in levels of ATP, NADPH, and ultimately, glutathione (GSH). Reductions in GSH then lead to increases in hydrogen peroxide, mitochondrial damage, and ultimately, cell death. Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies.

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

PubMed

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

2014-09-01

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

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

PubMed

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

2007-05-01

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

Cumulative lactate and hospital mortality in ICU patients

PubMed Central

2013-01-01

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

Reliability of the Lactate Scout point-of-care instrument for the determination of blood L-lactate concentration in sheep.

PubMed

Kaynar, Ozgur; Karapinar, Tolga; Hayirli, Armagan; Baydar, Ersoy

2015-12-01

Data on accuracy and precision of the Lactate Scout point-of-care (POC) analyzer in ovine medicine are lacking. The purpose of the study was to assess the reliability of the Lactate Scout in sheep. Fifty-seven sheep at varying ages with various diseases were included. Blood lactate concentration in samples collected from the jugular vein was measured immediately on the Lactate Scout. Plasma L-lactate concentration was measured by the Cobas autoanalyzer as the reference method. Data were subjected to Student's t-test, Passing-Bablok regression, and Bland-Altman plot analyses for comparison and assessment of accuracy, precision, and reliability. Plasma l-lactate concentration was consistently lower than blood L-lactate concentration (3.06 ± 0.24 vs 3.3 ± 0.3 mmol/L, P < .0001). There was a positive correlation between plasma and blood L-lactate concentrations (r = .98, P < .0001). The Lactate Scout had 99% accuracy and 98% precision with the reference method. Blood (Y) and plasma (X) L-lactate concentrations were fitted to Y = 0.28 + 1.00 · X, with a residual standard deviation of 0.31 and a negligible deviation from the identity line (P = .93). The bias was fitted to Y = 0.10 + 0.05 · X, with Sy.x of 0.44 (P < .07). The Lactate Scout has high accuracy and precision, with a negligible bias. It is a reliable POC analyzer to assess L-lactate concentration in ovine medicine. © 2015 American Society for Veterinary Clinical Pathology.

Extending lactation in pasture-based dairy cows. II: Effect of genetic strain and diet on plasma hormone and metabolite concentrations.

PubMed

Kay, J K; Phyn, C V C; Roche, J R; Kolver, E S

2009-08-01

Fifty-six genetically divergent New Zealand and North American Holstein-Friesian (HF) cows grazed pasture, and were offered 0, 3, or 6 kg of concentrate DM/cow per day for an extended lactation (605 +/- 8.3 d in milk; mean +/- standard error of the mean). Weekly blood samples collected from individual cows from wk 1 to 10 postpartum (early lactation), and from wk 47 to 63 postpartum (extended lactation) were analyzed for nonesterified fatty acids (NEFA), glucose, insulin, leptin, growth hormone (GH), insulin-like growth factor-I (IGF-I), calcium, and urea. During early lactation, NEFA and GH concentrations were greater and IGF-I concentrations were less, and increased at a slower rate in North American HF. During this 10-wk period, there were no strain effects on plasma glucose, leptin, insulin, or calcium. During the extended lactation period, North American HF had greater NEFA and GH concentrations; there were strain x diet interactions for insulin and leptin, and a tendency for a strain x diet interaction for glucose. These interactions were primarily due to greater plasma insulin, leptin, and glucose concentrations in the New Zealand HF fed 6 kg of concentrate DM/cow per day, a result of excessive body condition in this treatment. In this period, there was no strain effect on plasma IGF-I, calcium, or urea concentration. During early lactation, there was a linear increase in glucose and IGF-I, and a linear decrease in GH and urea with increasing concentrate in the diet. However, plasma calcium, NEFA, insulin, and leptin remained unchanged. During the extended lactation period, there was an effect of feed supplementation on GH and urea, which decreased linearly with increasing concentrate in the diet. There was, however, no supplementation effect on NEFA, calcium, or IGF-I. These data indicate potential strain differences in recoupling of the somatotropic axis, insulin resistance, and energy partitioning, and may help explain the physiology behind the previously

Improved biocompatibility of bicarbonate/lactate-buffered PDF is not related to pH.

PubMed

Zareie, Mohammad; Keuning, Eelco D; ter Wee, Piet M; Schalkwijk, Casper G; Beelen, Robert H J; van den Born, Jacob

2006-01-01

Chronic exposure to conventional peritoneal dialysis fluid (PDF) is associated with functional and structural alterations of the peritoneal membrane. The bioincompatibility of conventional PDF can be due to hypertonicity, high glucose concentration, lactate buffering system, presence of glucose degradation products (GDPs) and/or acidic pH. Although various investigators have studied the sole effects of hyperosmolarity, high glucose, GDPs and lactate buffer in experimental PD, less attention has been paid to the chronic impact of low pH in vivo. Rats received daily 10 ml of either conventional lactate-buffered PDF (pH 5.2; n=7), a standard bicarbonate/lactate-buffered PDF with physiological pH (n=8), bicarbonate/lactate-buffered PDF with acidic pH (adjusted to pH 5.2 with 1 N hydrochloride, n=5), or bicarbonate/lactate buffer, without glucose, pH 7.4 (n=7). Fluids were instilled via peritoneal catheters connected to implanted subcutaneous mini vascular access ports for 8 weeks. Control animals with or without peritoneal catheters served as control groups (n=8/group). Various functional (2 h PET) and morphological/cellular parameters were analyzed. Compared with control groups and the buffer group, conventional lactate-buffered PDF induced a number of morphological/cellular changes, including angiogenesis and fibrosis in various peritoneal tissues (all parameters P<0.05), accompanied by increased glucose absorption and reduced ultrafiltration capacity. Daily exposure to standard or acidified bicarbonate/lactate-buffered PDF improved the performance of the peritoneal membrane, evidenced by reduced new vessel formation in omentum (P<0.02) and parietal peritoneum (P<0.008), reduced fibrosis (P<0.02) and improved ultrafiltration capacity. No significant differences were found between standard and acidified bicarbonate/lactate-buffered PDF. During PET, acidic PDF was neutralized within 15 to 20 min. The bicarbonate/lactate-buffered PDF, acidity per se did not contribute

Characterization of plasma metabolites at late gestation and lactation in early parity sows on production and post-weaning reproductive performance

USDA-ARS?s Scientific Manuscript database

Lactation is a very energy demanding period for sows. The current study provides a better understanding of the biochemical response of first- (n = 246) or second-parity (n = 127) sows during late gestation through lactation and assesses relationships with piglet production and dam reproductive perfo...

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

PubMed Central

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

Effects of Dietary Supplementation of Oregano Essential Oil to Sows on Oxidative Stress Status, Lactation Feed Intake of Sows, and Piglet Performance

PubMed Central

Tan, Chengquan; Sun, Haiqing; Ao, Jiangtao; Long, Guang; Jiang, Siwen; Peng, Jian

2015-01-01

Fifty-four multiparous large white sows were used to determine the effects of supplementing oregano essential oil (OEO) to the gestation and lactation diets on oxidative stress status, lactation feed intake, and their piglet performance. Two groups were fed diets with (OEO; n = 28) or without (Control; n = 26) supplemental 15 mg/kg OEO during gestation and lactation. The serum levels of reactive oxygen species (ROS) (P < 0.05), 8-hydroxy-deoxyguanosine (8-OHdG) (P < 0.05), and thiobarbituric acid reactive substances (TBARS) (P < 0.05) were higher during gestation (days 90 and 109) and lactation (days 1 and 3) than in early gestation (day 10). Compared with the control group, the OEO diet significantly reduced sows' serum concentrations of 8-OHdG (P < 0.05) and TBARS (P < 0.01) on day 1 of lactation. The OEO diet increased the sows' counts of faecal lactobacillus (P < 0.001) while reducing Escherichia coli (P < 0.001) and Enterococcus (P < 0.001). In the third week of lactation the treatment tended to increase sow's feed intake (P = 0.07), which resulted in higher average daily gain (P < 0.01) of piglets. Our results demonstrated that there is an increased systemic oxidative stress during late gestation and early lactation of sows. The OEO supplementation to sows' diet improved performance of their piglets, which may be attributed to the reduced oxidative stress. PMID:26539506

Long-term microfluidic glucose and lactate monitoring in hepatic cell culture

PubMed Central

Prill, Sebastian; Jaeger, Magnus S.; Duschl, Claus

2014-01-01

Monitoring cellular bioenergetic pathways provides the basis for a detailed understanding of the physiological state of a cell culture. Therefore, it is widely used as a tool amongst others in the field of in vitro toxicology. The resulting metabolic information allows for performing in vitro toxicology assays for assessing drug-induced toxicity. In this study, we demonstrate the value of a microsystem for the fully automated detection of drug-induced changes in cellular viability by continuous monitoring of the metabolic activity over several days. To this end, glucose consumption and lactate secretion of a hepatic tumor cell line were continuously measured using microfluidically addressed electrochemical sensors. Adapting enzyme-based electrochemical flat-plate sensors, originally designed for human whole-blood samples, to their use with cell culture medium supersedes the common manual and laborious colorimetric assays and off-line operated external measurement systems. The cells were exposed to different concentrations of the mitochondrial inhibitor rotenone and the cellular response was analyzed by detecting changes in the rates of the glucose and lactate metabolism. Thus, the system provides real-time information on drug-induced liver injury in vitro. PMID:24926387

A rare cause of metabolic acidosis: ketoacidosis in a non-diabetic lactating woman

PubMed Central

Ali, Amjad; Webster, Jonathan

2017-01-01

Ketoacidosis occurring during lactation has been described infrequently. The condition is incompletely understood, but it appears to be associated with a combination of increased metabolic demands during lactation, reduction in carbohydrate intake and acute illness. We present a case of a 27-year-old woman, 8 weeks post-partum, who was exclusively breastfeeding her child whilst following a low carbohydrate diet. She developed gastroenteritis and was unable to tolerate an oral diet for several days. She presented with severe metabolic acidosis on admission with a blood 3-hydroxybutyrate of 5.4 mmol/L. She was treated with intravenous dextrose and intravenous sodium bicarbonate, and given dietary advice to increase her carbohydrate intake. She made a rapid and full recovery. We provide a summary of the common causes of ketoacidosis and compare our case with other presentations of lactation ketoacidosis. Learning points: Ketoacidosis in the lactating woman is a rare cause of raised anion gap metabolic acidosis. Low carbohydrate intake, starvation, intercurrent illness or a combination of these factors could put breastfeeding women at risk of ketoacidosis. Ketoacidosis in the lactating woman has been shown to resolve rapidly with sufficient carbohydrate intake and intravenous dextrose. Early diagnosis and prompt treatment are essential because the condition is reported to be reversible with a low chance of recurrence with appropriate dietary advice. PMID:28924478

The effect of body condition at calving and supplementation with Saccharomyces cerevisiae on energy status and some reproductive parameters in early lactation dairy cows.

PubMed

AlIbrahim, R M; Crowe, M A; Duffy, P; O'Grady, L; Beltman, M E; Mulligan, F J

2010-08-01

Improving the energy status of dairy cows during the early post-partum (PP) period by adding a safe dietary supplement such as live yeast culture (YS) may have a positive effect on reproductive function. The objective was to examine potential benefits of YS supplementation on PP energy status and fertility indices of dairy cows managed to have low or high body condition score (BCS, 1-5 scale) at calving. Forty (10 primiparous and 30 multiparous) Holstein/Friesian dairy cows were blocked by yield, parity, BCS, and predicted calving date. Within each block, cows were randomly allocated to a 2 x 2 factorial arrangement of treatments which were: BCS at calving (low < or =3.5 or high > or =3.75; n=20) and YS supplementation (2.5g/cow/day for pre-calving and 10g/cow/day for post-calving x 10(8) CFU of Saccharomyces cerevisiae/g) (supplemented or control; n=20). Daily milk yield was recorded and weekly milk composition, BCS and BW were assessed from calving to week 10 PP. Forage (100% grass silage pre-calving; 50% grass silage, 50% maize silage post-calving; ad libitum) intake was recorded individually. Concentrate (2kg of pre-calver nuts+/-YS for pre-calving and 8 kg of lactating nuts+/-YS for post-calving) feeding was controlled individually. Estimated energy balance PP was calculated on a weekly basis individually as the difference between the net energy (NE) intake and the sum of NE for maintenance and milk production. Insulin and IGF-I concentrations were determined on days 14 and 7 pre-calving and 1, 5, 15, 25 and 35 post-calving. Daily ovarian ultrasonography was performed from day 10 PP to monitor the size and development of the first dominant follicle (>10mm in diameter with absence of other large growing follicles), first ovulatory follicle and days to first ovulation PP. Pre-ovulatory peak of serum oestradiol concentration was determined during the 2 days before ovulation day. Cows with high BCS (over-conditioned) at calving ingested less NE, produced more milk

A randomized controlled trial on the effect of incomplete milking during early lactation on ketonemia and body condition loss in Holstein dairy cows.

PubMed

Morin, P-A; Krug, C; Chorfi, Y; Dubuc, J; Lacasse, P; Roy, J-P; Santschi, D E; Dufour, S

2018-05-01

Limiting milk production for a short period of time in early lactation could be a relevant strategy to prevent hyperketonemia (HYK). From December 2013 to March 2015, 838 multiparous Holstein cows from 13 herds were enrolled in a randomized controlled trial evaluating the effect of incomplete milking in early lactation on ketonemia and its effect on body condition score (BCS) loss. Cows were randomly assigned 4 wk before expected calving date to 1 of 2 treatment groups, (1) a conventional milking protocol (CON) for which cows were completely milked or (2) an incomplete milking protocol (INC) for which a maximum of 10 to 14 kg of milk/d were withdrawn during the first 5 d in milk (DIM). β-Hydroxybutyrate (BHB) concentrations were measured from blood samples collected on each cow 3 times at weekly intervals. Hyperketonemia was defined as BHB ≥1.4 mmol/L. Body condition score variation in the postcalving period was calculated by subtracting BCS assessed at wk 7 from BCS assessed at first week after calving. Effect of treatment on ketonemia and prevalence of HYK were evaluated for 4 specific time periods: 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM. Effect of treatment on ketonemia was investigated using linear mixed models with natural logarithm of BHB measurements as outcome and treatment groups as fixed effect. Generalized linear mixed models with HYK as outcome, using logit link, and treatment groups as fixed effect were used to investigate effect of treatment on odds of HYK. A logistic regression model with BCS loss (<0.75 or ≥0.75) as outcome and treatment groups and herd as fixed effects was used to study effect of INC on odds of having BCS loss ≥0.75. A total of 813 lactations had complete data and were used for statistical analysis of ketonemia and HYK. A total of 709 lactations had complete data and were used for analysis of BCS loss. Geometric means of blood BHB concentrations during the 1 to 3, 4 to 7, 8 to 17, and 18 to 26 DIM periods were

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

PubMed

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.

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

PubMed

Brooks, G A

1999-01-01

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

A selective, non-peptide CRF receptor 1 antagonist prevents sodium lactate-induced acute panic-like responses.

PubMed

Shekhar, Anantha; Johnson, Philip L; Fitz, Stephanie D; Nakazato, Atsuro; Chaki, Shigeyuki; Steckler, Thomas; Schmidt, Mark

2011-04-01

Corticotropin releasing factor (CRF) is implicated in a variety of stress-related disorders such as depression and anxiety, and blocking CRF receptors is a putative strategy for treating such disorders. Using a well-studied animal model of panic, we tested the efficacy of JNJ19567470/CRA5626, a selective, non-peptidergic CRF type 1 receptor (CRF1) antagonist (3, 10 and 40 mg/kg intraperitoneal injection), in preventing the sodium lactate (NaLac)-induced panic-like behavioural and cardiovascular responses. Adult male rats with chronic reduction of GABA levels (by inhibition of GABA synthesis with l-allyglycine, a glutamic acid decarboxylase inhibitor) in the dorsomedial/perifornical hypothalamus are highly anxious and exhibit physiological and behavioural responses to intravenous NaLac infusions similar to patients with panic disorder. These 'panic-prone' rats pre-treated with vehicle injections displayed NaLac-induced increases in autonomic responses (i.e. tachycardia and hypertensive responses), anxiety-like behaviour in the social interaction test, and flight-like increases in locomotor activity. However, systemically injecting such panic-prone rats with the highest dose of CRF1 receptor antagonist prior to NaLac infusions blocked all NaLac-induced behaviour and cardiovascular responses. These data suggest that selective CRF1 receptor antagonists could be a novel target for developing anti-panic drugs that are as effective as benzodiazepines in acute treatment of a panic attack without the deleterious side-effects (e.g. sedation and cognitive impairment) associated with benzodiazepines.

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2010 CFR

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...

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

PubMed Central

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

2014-01-01

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

Pulque intake during pregnancy and lactation in rural Mexico: alcohol and child growth from 1 to 57 months.

PubMed

Backstrand, J R; Goodman, A H; Allen, L H; Pelto, G H

2004-12-01

To examine maternal intake of a mildly alcoholic beverage (pulque) during pregnancy and lactation, and its potential effect on postpartum child growth and attained size. A prospective cohort study that followed mothers (during pregnancy and lactation) and their offspring (from birth to approximately 57 months of age). Six villages in rural, central Mexico. Subjects are 58 mother-child pairs. Pulque intake was measured as part of a dietary assessment that was conducted for 2days/month during pregnancy and early lactation. Most mothers consumed pulque during pregnancy (69.0%) and lactation (72.4%). Among pulque drinkers, the average ethanol intake was 125.1 g/week during pregnancy and 113.8 g/week during lactation. Greater pulque intake during lactation, independent of intake during pregnancy, was associated with slower weight and linear growth from 1 to 57 months, and smaller attained size at 57 months. Low-to-moderate pulque intake during pregnancy, in comparison to either nonconsumption or heavy intake, was also associated with greater stature at 57 months. Pulque intake during lactation may have adversely influenced postnatal growth in this population. Public health interventions are urgently needed in Mexico to reduce heavy intake of pulque by pregnant and lactating women, and to replace intake with foods that provide the vitamins and minerals present in the traditional alcoholic beverage.

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

PubMed

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

2016-06-01

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

Lactation and changes in maternal metabolic risk factors.

PubMed

Gunderson, Erica P; Lewis, Cora E; Wei, Gina S; Whitmer, Rachel A; Quesenberry, Charles P; Sidney, Steve

2007-03-01

To examine the relationship between duration of lactation and changes in maternal metabolic risk factors. This 3-year prospective study examined changes in metabolic risk factors among lactating women from preconception to postweaning and among nonlactating women from preconception to postdelivery, in comparison with nongravid women. Of 1,051 (490 black, 561 white) women who attended two consecutive study visits in years 7 (1992-1993) and 10 (1995-1996), 942 were nongravid and 109 had one interim birth. Of parous women, 48 (45%) did not lactate, and 61 (55%) lactated and weaned before year 10. The lactated and weaned women were subdivided by duration of lactation into less than 3 months and 3 months or more. Multiple linear regression models estimated mean 3-year changes in metabolic risk factors adjusted for age, race, parity, education, and behavioral covariates. Both parous women who did not lactate and parous women who lactated and weaned gained more weight (+5.6, +4.4 kg) and waist girth (+5.3, +4.9 cm) than nongravid women over the 3-year interval; P<.001. Low-density lipoprotein cholesterol (+6.7 mg/dL, P<.05) and fasting insulin (+2.6 microunits, P=.06) increased more for parous women who did not lactate than for nongravid and parous women who lactated and weaned. High-density lipoprotein cholesterol decrements for both parous women who did not lactate and parous women who lactated and weaned were 4.0 mg/dL greater than for nongravid women (P<.001). Among parous, lactated and weaned women, lactation for 3 months or longer was associated with a smaller decrement in high-density lipoprotein cholesterol (-1.3 mg/dL versus -7.3 mg/dL for less than 3 months; P<.01). Lactation may attenuate unfavorable metabolic risk factor changes that occur with pregnancy, with effects apparent after weaning. As a modifiable behavior, lactation may affect women's future risk of cardiovascular and metabolic diseases. II.

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

PubMed

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.

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

PubMed

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

Higher Accuracy of the Lactate Minimum Test Compared to Established Threshold Concepts to Determine Maximal Lactate Steady State in Running.

PubMed

Wahl, Patrick; Zwingmann, Lukas; Manunzio, Christian; Wolf, Jacob; Bloch, Wilhelm

2018-05-18

This study evaluated the accuracy of the lactate minimum test, in comparison to a graded-exercise test and established threshold concepts (OBLA and mDmax) to determine running speed at maximal lactate steady state. Eighteen subjects performed a lactate minimum test, a graded-exercise test (2.4 m·s -1 start,+0.4 m·s -1 every 5 min) and 2 or more constant-speed tests of 30 min to determine running speed at maximal lactate steady state. The lactate minimum test consisted of an initial lactate priming segment, followed by a short recovery phase. Afterwards, the initial load of the subsequent incremental segment was individually determined and was increased by 0.1 m·s -1 every 120 s. Lactate minimum was determined by the lowest measured value (LM abs ) and by a third-order polynomial (LM pol ). The mean difference to maximal lactate steady state was+0.01±0.14 m·s -1 (LM abs ), 0.04±0.15 m·s -1 (LM pol ), -0.06±0.31 m·s 1 (OBLA) and -0.08±0.21 m·s 1 (mDmax). The intraclass correlation coefficient (ICC) between running velocity at maximal lactate steady state and LM abs was highest (ICC=0.964), followed by LM pol (ICC=0.956), mDmax (ICC=0.916) and OBLA (ICC=0.885). Due to the higher accuracy of the lactate minimum test to determine maximal lactate steady state compared to OBLA and mDmax, we suggest the lactate minimum test as a valid and meaningful concept to estimate running velocity at maximal lactate steady state in a single session for moderately up to well-trained athletes. © Georg Thieme Verlag KG Stuttgart · New York.

Adiposity and Fat Metabolism in Lactating and Fasting Northern Elephant Seals12

PubMed Central

Crocker, Daniel E.; Champagne, Cory D.; Fowler, Melinda A.; Houser, Dorian S.

2014-01-01

Several taxa of animals fast completely from food and water during energy-intensive periods such as lactation, breeding, and development. In elephant seals, these behaviors are sustained by high adiposity, high rates of fat mobilization, and reduced oxidation of carbohydrates and proteins. Adiposity and the regulation of lipolysis directly affect lactation energetics, milk composition, and mating success. Long-term fasting induces changes in regulation of lipolysis and lipid metabolism that influence fatty acid (FA) availability and the onset of insulin resistance. Hypoinsulinemia and elevated circulating FAs are also associated with several unique features of carbohydrate metabolism, including elevated plasma glucose, gluconeogenesis, and Cori cycle activity as well as high rates of pyruvate and tricarboxylic acid cycling. Glucose-lactate pools and triacylglycerol-FA cycles may be linked via glyceroneogenesis and this may be an important pathway influencing both fat and carbohydrate metabolism. Together, these features allow a sustained, high intensity, fat-based metabolism without substantial accumulation of ketoacids. PMID:24425723

Partial reconstruction of in vitro gluconeogenesis arising from mitochondrial l-lactate uptake/metabolism and oxaloacetate export via novel L-lactate translocators.

PubMed

De Bari, Lidia; Atlante, Anna; Valenti, Daniela; Passarella, Salvatore

2004-05-15

In the light of the occurrence of L-lactate dehydrogenase inside the mitochondrial matrix, we looked at whether isolated rat liver mitochondria can take up and metabolize L-lactate, and provide oxaloacetate outside mitochondria, thus contributing to a partial reconstruction of gluconeogenesis in vitro. We found that: (1) L-lactate (10 mM), added to mitochondria in the presence of a cocktail of glycolysis/gluconeogenesis enzymes and cofactors, can lead to synthesis of glyceraldehyde-3-phosphate at a rate of about 7 nmol/min per mg mitochondrial protein. (2) Three novel translocators exist to mediate L-lactate traffic across the inner mitochondrial membrane. An L-lactate/H+ symporter was identified by measuring fluorimetrically the rate of endogenous pyridine nucleotide reduction. Consistently, L-lactate oxidation was found to occur with P/O ratio=3 (where P/O ratio is the ratio of mol of ATP synthesized to mol of oxygen atoms reduced to water during oxidative phosphorylation) and with generation of membrane potential. Proton uptake, which occurred as a result of addition of L-lactate to RLM together with electron flow inhibitors, and mitochondrial swelling in ammonium L-lactate solutions were also monitored. L-Lactate/oxaloacetate and L-lactate/pyruvate anti-porters were identified by monitoring photometrically the appearance of L-lactate counter-anions outside mitochondria. These L-lactate translocators, which are distinct from the monocarboxylate carrier, were found to differ from each other in V(max) values and in inhibition and pH profiles, and proved to regulate mitochondrial L-lactate metabolism in vitro. The role of lactate/mitochondria interactions in gluconeogenesis is discussed.

Short communication: Associations between blood glucose concentration, onset of hyperketonemia, and milk production in early lactation dairy cows.

PubMed

Ruoff, J; Borchardt, S; Heuwieser, W

2017-07-01

The objectives of this study were to describe the associations between hypoglycemia and the onset of hyperketonemia (HYK) within the first 6 wk of lactation, to evaluate the effects of body condition score at calving on glucose concentration, and to study the effects of hypoglycemia on milk production. A total of 621 dairy cows from 6 commercial dairy farms in Germany were enrolled between 1 and 4 d in milk (DIM). Cows were tested twice weekly using an electronic handheld meter for glucose and β-hydroxybutyrate (BHB), respectively, for a period of 42 d. Hypoglycemia was defined as glucose concentration ≤2.2 mmol/L. Hyperketonemia was defined as a BHB concentration ≥1.2 mmol/L. The onset of HYK was described as early onset (first HYK event within the first 2 wk postpartum) and late onset (first HYK event in wk 3 to 6 postpartum). The effect of ketosis status on blood glucose within 42 DIM was evaluated using a generalized linear mixed model. No effect was observed of HYK on glucose concentration in primiparous cows. Multiparous cows with early-onset HYK had a lower glucose concentration (-0.21 mmol/L) compared with nonketotic cows. Overall, primiparous cows had a lower prevalence and incidence of hypoglycemia than multiparous cows. Hypoglycemia in multiparous cows was associated with higher first test-day milk production and 100 DIM milk production. In conclusion, hypoglycemia mainly occurred in multiparous cows with early-onset HYK, whereas primiparous cows were at a lower risk for hypoglycemia. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Metabolomics Reveals Aryl Hydrocarbon Receptor Activation Induces Liver and Mammary Gland Metabolic Dysfunction in Lactating Mice.

PubMed

Belton, Kerry R; Tian, Yuan; Zhang, Limin; Anitha, Mallappa; Smith, Philip B; Perdew, Gary H; Patterson, Andrew D

2018-04-06

The liver and the mammary gland have complementary metabolic roles during lactation. Substrates synthesized by the liver are released into the circulation and are taken up by the mammary gland for milk production. The aryl hydrocarbon receptor (AHR) has been identified as a lactation regulator in mice, and its activation has been associated with myriad morphological, molecular, and functional defects such as stunted gland development, decreased milk production, and changes in gene expression. In this study, we identified adverse metabolic changes in the lactation network (mammary, liver, and serum) associated with AHR activation using 1 H nuclear magnetic resonance (NMR)-based metabolomics. Pregnant mice expressing Ahr d (low affinity) or Ahr b (high affinity) were fed diets containing beta naphthoflavone (BNF), a potent AHR agonist. Mammary, serum, and liver metabolomics analysis identified significant changes in lipid and TCA cycle intermediates in the Ahr b mice. We observed decreased amino acid and glucose levels in the mammary gland extracts of Ahr b mice fed BNF. The serum of BNF fed Ahr b mice had significant changes in LDL/VLDL (increased) and HDL, PC, and GPC (decreased). Quantitative PCR analysis revealed ∼50% reduction in the expression of key lactogenesis mammary genes including whey acid protein, α-lactalbumin, and β-casein. We also observed morphologic and developmental disruptions in the mammary gland that are consistent with previous reports. Our observations support that AHR activity contributes to metabolism regulation in the lactation network.

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

PubMed

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

2018-05-01

Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission. Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic transmission through a reduction in the number of functional synaptic vesicle release sites and a slowing of vesicle pool replenishment, without a consistent change in release probability. Metabolic function is compromised in many pathological conditions (e.g. stroke, traumatic brain injury and neurodegeneration). Knowledge of how synaptic transmission is constrained by metabolic stress, especially during intense brain activity, will provide insights to improve cognition following pathological insults. The synapse has high energy demands, which increase during intense activity. Presynaptic ATP production depends on substrate availability and usage will increase during activity, which in turn could influence transmitter release and information transmission. We investigated transmitter release at the mouse calyx of Held synapse using glucose or lactate (10, 1 or 0 mm) as the extracellular substrates while inducing metabolic stress. High-frequency stimulation (HFS) and recovery paradigms evoked trains of EPSCs monitored under voltage-clamp. Whilst postsynaptic intracellular ATP was stabilised by diffusion from the patch pipette, depletion of glucose increased EPSC depression during HFS and impaired subsequent recovery. Computational modelling of these data demonstrated a reduction in the number of functional release sites and slowed vesicle pool replenishment during metabolic stress, with little change in release probability. Directly depleting presynaptic terminal ATP impaired transmitter release in an analogous manner to glucose depletion. In the absence of glucose, presynaptic terminal metabolism could utilise lactate from the aCSF and this was blocked by

Torpor use during gestation and lactation in a primate

NASA Astrophysics Data System (ADS)

Canale, Cindy I.; Perret, Martine; Henry, Pierre-Yves

2012-02-01

Torpor is an energy-saving mechanism that allows endotherms to overcome energetic challenges. Torpor should be avoided during reproduction because of potential incompatibility with offspring growth. To test if torpor can be used during gestation and lactation to compensate for food shortage, we exposed reproductive female grey mouse lemurs ( Microcebus murinus), a heterothermic primate, to different levels of food availability. Torpor use was characterised by daily skin temperature profiles, and its energetic outcome was assessed from changes in body mass. Food shortage triggered torpor during the end of the gestation period ( n = 1), ranging from shallow in response to 40% food restriction to deep daily torpor in response to 80% restriction. During the early period of lactation, females fed ad libitum ( n = 2) or exposed to a 40% restriction ( n = 4) remained normothermic; but 80% food restricted females ( n = 5) gave priority to energy saving, increasing the frequency and depth of torpor bouts. The use of torpor was insufficient to compensate for 80% energetic shortage during lactation resulting in loss of mass from the mother and delayed growth in the pups. This study provides the first evidence that a heterothermic primate can use torpor to compensate for food shortages even during reproduction. This physiological flexibility likely evolved as a response to climate-driven fluctuations in food availability in Madagascar.

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio

PubMed Central

Ross, Jaime M.; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J.; Olson, Lars

2010-01-01

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes. PMID:21041631

High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio.

PubMed

Ross, Jaime M; Öberg, Johanna; Brené, Stefan; Coppotelli, Giuseppe; Terzioglu, Mügen; Pernold, Karin; Goiny, Michel; Sitnikov, Rouslan; Kehr, Jan; Trifunovic, Aleksandra; Larsson, Nils-Göran; Hoffer, Barry J; Olson, Lars

2010-11-16

At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate → lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes.

Lactation and appetite-regulating hormones: increased maternal plasma peptide YY concentrations 3-6 months postpartum.

PubMed

Vila, Greisa; Hopfgartner, Judith; Grimm, Gabriele; Baumgartner-Parzer, Sabina M; Kautzky-Willer, Alexandra; Clodi, Martin; Luger, Anton

2015-10-28

Breast-feeding is associated with maternal hormonal and metabolic changes ensuring adequate milk production. In this study, we investigate the impact of breast-feeding on the profile of changes in maternal appetite-regulating hormones 3-6 months postpartum. Study participants were age- and BMI-matched lactating mothers (n 10), non-lactating mothers (n 9) and women without any history of pregnancy or breast-feeding in the previous 12 months (control group, n 10). During study sessions, young mothers breast-fed or bottle-fed their babies, and maternal blood samples were collected at five time points during 90 min: before, during and after feeding the babies. Outcome parameters were plasma concentrations of ghrelin, peptide YY (PYY), leptin, adiponectin, prolactin, cortisol, insulin, glucose and lipid values. At baseline, circulating PYY concentrations were significantly increased in lactating mothers (100·3 (se 6·7) pg/ml) v. non-lactating mothers (73·6 (se 4·9) pg/ml, P=0·008) and v. the control group (70·2 (se 9) pg/ml, P=0·021). We found no differences in ghrelin, leptin and adiponectin values. Baseline prolactin concentrations were over 4-fold higher in lactating mothers (P<0·001). Lactating women had reduced TAG levels and LDL-cholesterol:HDL-cholesterol ratio, but increased waist circumference, when compared with non-lactating women. Breast-feeding sessions further elevated circulating prolactin (P<0·001), but induced no acute effects on appetite-regulating hormones. In summary, one single breast-feeding session did not acutely modulate circulating appetite-regulating hormones, but increased baseline PYY concentrations are associated with prolonged lactation. PYY might play a role in the coordination of energy balance during lactation, increasing fat mobilisation from maternal depots and ensuring adequate milk production for the demands of the growing infant.

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

PubMed Central

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

2014-01-01

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

21 CFR 862.1440 - Lactate dehydrogenase test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Systems § 862.1440 Lactate dehydrogenase test system. (a) Identification. A lactate dehydrogenase test system is a device intended to measure the activity of the enzyme lactate dehydrogenase in serum. Lactate... hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction...

Brain lactate metabolism: the discoveries and the controversies

PubMed Central

Dienel, Gerald A

2012-01-01

Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an ‘opportunistic', glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain. PMID:22186669

Effect of limestone reactivity and percent on production by dairy cows in early lactation.

PubMed

Nocek, J E; Braund, D G; English, J E

1983-12-01

Seventy-two Holstein cows (16 first lactation) were assigned to four treatments: A) normal-grind limestone (800 to 1000 mu) added to provide .77% calcium (total ration dry basis); B) fine-grind limestone (less than 150 mu) at .77% calcium; C) normal-grind at 1.15% calcium; and D) fine-grind limestone at 1.15% calcium. Cows fed diets containing .77% calcium had higher percent milk fat and fat yield than those fed 1.15% calcium diets, and cows fed fine-grind limestone had greater percent fat and fat yield than those fed normal-grind limestone. Four percent fat-corrected milk was higher for cows fed .77% calcium diets. Trends were similar for heifers in first lactation. Dry matter intake was higher for cows fed .77% calcium diets, and nutrient efficiency for milk synthesis favored cows fed fine-grind 1.15% calcium. Fecal pH was higher during wk 4 on treatment for cows fed high calcium diets; however, 8 wk were not different. Fecal starch and calcium and phosphorus in plasma were not different between treatments: however, heifers fed fine-grind 1.15% calcium showed a decrease of fecal starch with time.

Lactate-H+ Transport Is a Significant Component of the In Vivo Corneal Endothelial Pump

PubMed Central

Nguyen, Tracy T.; Bonanno, Joseph A.

2012-01-01

Purpose. To confirm the expression of monocarboxylate transporters (MCT) 1, 2, and 4 in rabbit CE and to test the hypothesis that cellular buffering contributed by HCO3−, NBCe1, and carbonic anhydrase (CA) activity facilitates lactate-H+ efflux thereby controlling corneal hydration in vivo. Methods. MCT1–4 expression of rabbit endothelium was examined by Western blotting and immunofluorescence staining. Lactate-induced acidification (LIA) was measured in perfused CE in the presence and absence of HCO3− and acetazolamide (ACTZ) using tissue treated with siRNA specific to MCT1, 2, and 4. Corneal thickness and lactate concentration were measured in New Zealand White rabbits treated with the topical CA inhibitor Azopt, and from eyes that were injected intracamerally with ouabain, disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS), and shRNA specific to the 1Na+:2HCO3− cotransporter NBCe1. Results. MCT1 and MCT4 are localized to the lateral membrane, while MCT2 is apical. Cell pH measurements showed LIA in response to 40 mM lactate in bicarbonate free (BF) Ringer's that was inhibited by niflumic acid and by MCT siRNA knockdown, and significantly reduced in the presence of HCO3−. Lactate-dependent proton flux in vitro was not significantly greater in the presence of HCO3− or reduced by ACTZ. However, when active transport, NBCe1, or CA activity was disrupted in vivo, corneal edema ensued and was associated with significant corneal lactate accumulation. Conclusions. MCT1, 2, and 4 are expressed in rabbit CE on both the apical and basolateral surfaces and function to transport lactate-H+. Lactate-H+ flux is facilitated by active transport, HCO3− transport and CA activity, disruption of which causes corneal edema in vivo and indicates that facilitation of lactate efflux is a component of the endothelial pump. PMID:22410572

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

PubMed

Dienel, Gerald A

2017-01-10

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

D-Lactate transport and metabolism in rat liver mitochondria.

PubMed

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

2002-07-15

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

Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations.

PubMed

Oliveira, Vitor Antunes; Favero, Gaia; Stacchiotti, Alessandra; Giugno, Lorena; Buffoli, Barbara; de Oliveira, Claudia Sirlene; Lavazza, Antonio; Albanese, Massimo; Rodella, Luigi Fabrizio; Pereira, Maria Ester; Rezzani, Rita

2017-05-01

This work investigated the effects of mercury chloride (HgCl 2 ) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18 th gestation day) and lactating (7 th lactation day) were injected once with HgCl 2 (5 mg/kg) or saline (controls). We observed that HgCl 2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl 2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl 2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl 2 -exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl 2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500-1512, 2017. © 2016 Wiley Periodicals, Inc.

Lactate Injection by Electric Currents for Bioremediation of Tetrachloroethylene in Clay

PubMed Central

Wu, Xingzhi; Gent, David B.; Davis, Jeffrey L.; Alshawabkeh, Akram N.

2012-01-01

Biological transformation of tetrachloroethylene (PCE) in silty clay samples by ionic injection of lactate under electric fields is evaluated. To prepare contaminated samples, a silty clay slurry was mixed with PCE, inoculated with KB-1® dechlorinators and was consolidated in a 40 cm long cell. A current density between 5.3 and 13.3 A m−2 was applied across treated soil samples while circulating electrolytes containing 10 mg L−1 lactate concentration between the anode and cathode compartments to maintain neutral pH and chemically reducing boundary conditions. The total adsorbed and aqueous PCE was degraded in the soil to trichloroethylene (TCE), cis-1,2-dichloroethene (cis-DCE), vinyl chloride (VC) and ethene in 120 d, which is about double the time expected for transformation. Lactate was delivered into the soil by a reactive transport rate of 3.7 cm2 d−1 V−1. PCE degradation in the clay samples followed zero order transformation rates ranging from 1.5 to 5 mg L−1 d−1 without any significant formation of TCE. cis-DCE transformation followed first order transformation rates of 0.06 to 0.10 per day. A control experiment conducted with KB-1 and lactate, but without electricity did not show any significant lactate buildup or cis-DCE transformation because the soil was practically impermeable (hydraulic conductivity of 2×10−7 cm s−1). It is concluded that ionic migration will deliver organic additives and induce biological activity and complete PCE transformation in clay, even though the transformation occurs under slower rates compared to ideal conditions. PMID:23264697

Measurement of cardiac troponin I in healthy lactating dairy cows using a point of care analyzer (i-STAT-1).

PubMed

Labonté, Josiane; Roy, Jean-Philippe; Dubuc, Jocelyn; Buczinski, Sébastien

2015-06-01

Cardiac troponin I (cTnI) has been shown to be an accurate predictor of myocardial injury in cattle. The point-of-care i-STAT 1 immunoassay can be used to quantify blood cTnI in cattle. However, the cTnI reference interval in whole blood of healthy early lactating dairy cows remains unknown. To determine a blood cTnI reference interval in healthy early lactating Holstein dairy cows using the analyzer i-STAT 1. Forty healthy lactating dairy Holstein cows (0-60 days in milk) were conveniently selected from four commercial dairy farms. Each selected cow was examined by a veterinarian and transthoracic echocardiography was performed. A cow-side blood cTnI dosage was measured at the same time. A bootstrap statistical analysis method using unrestricted resampling was used to determine a reference interval for blood cTnI values. Forty healthy cows were recruited in the study. Median blood cTnI was 0.02 ng/mL (minimum: 0.00, maximum: 0.05). Based on the bootstrap analysis method with 40 cases, the 95th percentile of cTnI values in healthy cows was 0.036 ng/mL (90% CI: 0.02-0.05 ng/mL). A reference interval for blood cTnI values in healthy lactating cows was determined. Further research is needed to determine whether cTnI blood values could be used to diagnose and provide a prognosis for cardiac and noncardiac diseases in lactating dairy cows. Copyright © 2015 Elsevier B.V. All rights reserved.

Safety and efficacy of blue cohosh (Caulophyllum thalictroides) during pregnancy and lactation.

PubMed

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

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 herbal medicines in pregnancy and lactation. This is one article in a series that systematically reviews the evidence for commonly used herbs during pregnancy and lactation. To systematically review the literature for evidence on the use, safety and pharmacology of blue cohosh, focusing on issues pertaining to pregnancy and lactation. We searched 7 electronic databases and compiled data according to the grade of evidence found. According to a survey of midwives in the United States, approximately 64% of midwives reported using blue cohosh as a labour-inducing aid. There are three case reports in the scientific literature that blue cohosh taken at the time of delivery may cause; 1) perinatal stroke, 2) acute myocardial infarction, profound congestive heart failure and shock and 3) severe multi-organ hypoxic injury. There is one case report that blue cohosh possesses abortifacient properties. There is in vitro evidence that blue cohosh may have teratogenic, embryotoxic and oxytoxic effects. In lactation, the safety of blue cohosh is unknown. Based on the available scientific information, blue cohosh should; 1) be used with extreme caution during pregnancy, 2) be used only under medical professional supervision and 3) not be available to the public as an over-the-counter product. There is an urgent need to conduct a retrospective or prospective cohort study of midwifes using blue cohosh in order to determine its safety. Key words: Blue cohosh, caulophyllum thalictroides, pregnancy, lactation, breastfeeding, systematic review.

Resveratrol Intake During Pregnancy and Lactation Modulates the Early Metabolic Effects of Maternal Nutrition Differently in Male and Female Offspring.

PubMed

Ros, Purificación; Díaz, Francisca; Freire-Regatillo, Alejandra; Argente-Arizón, Pilar; Barrios, Vicente; Argente, Jesús; Chowen, Julie A

2018-02-01

Poor maternal nutrition can have detrimental long-term consequences on energy homeostasis in the offspring. Resveratrol exerts antioxidant and antiobesity actions, but its impact during development remains largely unknown. We hypothesized that resveratrol intake during pregnancy and lactation could improve the effects of poor maternal nutrition on offspring metabolism. Wistar rats received a low-fat diet (LFD; 10.2% kcal from fat) or high-fat diet (HFD; 61.6% kcal from fat), with half of each group receiving resveratrol in their drinking water (50 mg/L) during pregnancy and lactation. Body weight (BW) of dams was measured at treatment onset and weaning [postnatal day (PND) 21] and of pups at birth and PND21, at which time dams and pups were euthanized. Although HFD dams consumed more energy, their BW at the end of lactation was unaffected. Mean litter size was not modified by maternal diet or resveratrol. At birth, male offspring from HFD and resveratrol (HFD + R) dams weighed less than those from LFD and resveratrol (LFD + R) dams. On PND21, pups of both sexes from HFD dams weighed more, had more visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT), and had higher serum leptin levels than those from LFD dams. Resveratrol reduced BW, leptin, VAT, and SCAT, with females being more affected, but increased glycemia. Neuropeptide levels were unaffected by resveratrol. In conclusion, resveratrol intake during pregnancy and lactation decreased BW and adipose tissue content in offspring of dams on an HFD but did not affect offspring from LFD-fed dams, suggesting that the potential protective effects of resveratrol during gestation/lactation are diet dependent. Copyright © 2018 Endocrine Society.

Exercise prevents the increased anxiety-like behavior in lactational di-(2-ethylhexyl) phthalate-exposed female rats in late adolescence by improving the regulation of hypothalamus-pituitary-adrenal axis.

PubMed

Wang, Dean-Chuan; Chen, Tsan-Ju; Lin, Ming-Lu; Jhong, Yue-Cih; Chen, Shih-Chieh

2014-09-01

Both the detrimental effects of early life adversity and the beneficial effects of exercise on the hypothalamic-pituitary-adrenal (HPA) axis have been reported. Early life exposure to di-(2-ethylhexyl)-phthalate (DEHP) may impair the development of endocrine system. In this study, we investigated the effects of lactational DEHP exposure on stress responses in late adolescent female rats and examined the protective role of treadmill running. Sprague-Dawley dams were fed with DEHP (10mg/kg per day) or vehicle during lactation. After weaning, the female offspring rats were trained to exercise on a treadmill for 5 weeks and then stressed by exploring on an elevated plus maze. The activities of HPA axis were evaluated by measuring the plasma levels of ACTH and corticosterone, the expressions of adrenal enzymes cholesterol side-chain cleavage enzyme (CYP11A1) and cytochrome P-450 11β-hydroxylase (CYP11B1), and the expression of hypothalamic glucocorticoid receptors (GR). The results demonstrate that DEHP-exposed rats exhibited enhanced anxiety-like behaviors. Increased hypothalamic GR and plasma ACTH levels, but decreased adrenal CYP11A1 and corticosterone levels, were observed in DEHP-exposed animals under stressed condition. Importantly, in DEHP-exposed animals, exercise during childhood-adolescence reduced anxiety-like behaviors by normalizing stress-induced alterations in ACTH level and adrenal CYP11A1 expression. The findings of this study suggest that treadmill running may provide beneficial effects on ameliorating the dysregulation of HPA axis in lactational DEHP-exposed adolescent female rats. Copyright © 2014 Elsevier Inc. All rights reserved.

In utero and lactational β-carotene supplementation attenuates D-galactose-induced hearing loss in newborn rats.

PubMed

Yu, Fei; Hao, Shuai; Zhao, Yue; Yang, Hui; Fan, Xiao-Lan; Yang, Jun

2011-08-01

D-Galactose could give rise to free radical damage by disturbing the some maternal antioxidants. The oxidative stress induced by D-galactose is a potent inducer of apoptosis, which is accompanied by the activation of protein-splitting enzymes called caspases. Apoptosis is a crucial physiological determinant of embryonic and neonatal development, and play an essential role in the development of the inner ear structures. Recently the increasing of D-galactose exposure is due to high consumption of dairy foods or reduced galactose metabolism. An overwhelming presence of D-galactose is known to become highly ototoxicity to humans. The purpose of this study was to investigate whether supplementation of pregnant and lactational mothers with β-carotene could attenuate cochlear function damage and hair cells apoptosis induced by d-galactose in newborn rats. Pregnant rats were supplemented with D-galactose, or D-galactose and β-carotene from gestational day (GD) 7 until postnatal day (PND) 21. On PND 22, offspring were examined in the distortion product otoacoustic emission (DPOAE) task, cochleae were then harvested for assessment of apoptosis by immunohistochemical stain for cysteine-aspartic acid proteases 3 (caspase-3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Maternal and offspring blood samples were then collected by direct cardiac puncture in heparin tubes, blood levels of D-galactose and β-carotene were measured, plasma was separated for malondialdehyde (MDA) analysis, erythrocytes were left for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH). D-Galactose could significantly disturb the balance between maternal antioxidants and free radicals, and induce hearing loss in the offspring and cochlear hair cell apoptosis. In contrast, β-carotene supplementation, coincidentally with D-galactose exposure, ameliorated these changes. Our data offer a conceptual framework for designing

Alcohol consumption decreases lactate clearance in acutely injured patients☆

PubMed Central

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

2017-01-01

Introduction Alcohol, a common risk factor for injury, has direct toxic effects on the liver. The use of lactate clearance has been well described as an indicator of the adequacy of resuscitation in injured patients. We investigated whether acutely injured patients with positive blood alcohol content (+BAC) had less lactate clearance than sober patients. Methods We conducted a retrospective cohort study of acutely injured patients treated at an urban Level 1 trauma centre between January 2010 and December 2012. Blood alcohol and venous lactate levels were measured on all patients at the time of arrival. Study subjects were patients transported directly from the scene of injury, who had an elevated lactate concentration on arrival (≥3.0 mmol/L) and at least one subsequent lactate measurement within 24 h after admission. Lactate clearance ([Lactate1 − Lactate2]/Lactate1) was calculated for all patients. Chi-squared tests were used to compare values from sober and intoxicated subjects. Lactate clearance was plotted against alcohol levels and stratified by age and Injury Severity Score (ISS). Results Serial lactate concentration measurements were obtained in 3910 patients; 1674 of them had +BAC. Patients with +BAC were younger (mean age: 36.6 [SD 14.7] vs 41.0 [SD 19.9] years [p = 0.0001]), were more often male (83.4% vs 75.9% [p = 0.0001]), had more minor injuries (ISS < 9) (33.8% vs 27.1% [p = 0.0001]), had a lower in-hospital mortality rate (1.4% vs 3.9% [p = 0.0001]), but also had lower average lactate clearance (37.8% vs 47.6% [p = 0.0001]). The lactate clearance of the sober patients (47.6 [SD 33.5]) was twice that of those with +BAC >400 (23.5 [SD 6.5]). Lactate clearance decreased with increasing BAC irrespective of age and ISS. Conclusions In a large group of acutely injured patients, a dose-dependent decrease in lactate clearance was seen in those with elevated BAC. This relationship will cause a falsely elevated lactate reading or prolong lactate

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

PubMed Central

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

Workplace lactation support by New Jersey employers following US Reasonable Break Time for Nursing Mothers law.

PubMed

Bai, Yeon K; Gaits, Susan I; Wunderlich, Shahla M

2015-02-01

Returning to an unsupportive work environment has been identified as a major reason for avoidance or early abandonment of breastfeeding among working mothers. This study aimed to examine the nature and extent of accommodations offered to breastfeeding employees among New Jersey employers since the US federal Reasonable Break Time for Nursing Mothers law enactment. A cross-sectional survey was conducted to measure current lactation support in the workplace in New Jersey. Using convenience sampling, the survey was sent to managerial personnel in hospitals and nonhospitals. The level of support was assessed on company policy, lactation room, and room amenity. A composite lactation amenity score was calculated based on responses about lactation room amenities. Respondents (N = 51) completed a 22-item online questionnaire during fall 2011. The support level was compared by type of organization: hospital (n = 37) versus nonhospital (n = 14). The amenity score of hospitals was significantly higher than nonhospitals (1.44 vs 0.45, P = .002). The mean amenity score (score = 0.95) for all employers was far below comprehensive (score = 3.0). Compared to nonhospitals, hospitals were more likely to offer lactation rooms (81% vs 36%, P = .003), have their own breastfeeding policy (35.1% vs 7.1%, P = .01), and provide additional breastfeeding support (eg, education classes, resources; P < .05). Employers, regardless of the type of organization, need to improve their current practices and create equity of lactation support in the workplace. © The Author(s) 2014.

Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury.

PubMed

Reinert, Michael; Schaller, Benoit; Widmer, Hans Rudolf; Seiler, Rolf; Bullock, Ross

2004-08-01

Severe traumatic brain injury (TBI) imposes a huge metabolic load on brain tissue, which can be summarized initially as a state of hypermetabolism and hyperglycolysis. In experiments O2 consumption has been shown to increase early after trauma, especially in the presence of high lactate levels and forced O2 availability. In recent clinical studies the effect of increasing O2 availability on brain metabolism has been analyzed. By their nature, however, clinical trauma models suffer from a heterogeneous injury distribution. The aim of this study was to analyze, in a standardized diffuse brain injury model, the effect of increasing the fraction of inspired O2 on brain glucose and lactate levels, and to compare this effect with the metabolism of the noninjured sham-operated brain. A diffuse severe TBI model developed by Foda and Maramarou, et al., in which a 420-g weight is dropped from a height of 2 m was used in this study. Forty-one male Wistar rats each weighing approximately 300 g were included. Anesthesized rats were monitored by placing a femoral arterial line for blood pressure and blood was drawn for a blood gas analysis. Two time periods were defined: Period A was defined as preinjury and Period B as postinjury. During Period B two levels of fraction of inspired oxygen (FiO2) were studied: air (FiO2 0.21) and oxygen (FiO2 1). Four groups were studied including sham-operated animals: air-air-sham (AAS); air-O2-sham (AOS); air-air-trauma (AAT); and air-O2-trauma (AOT). In six rats the effect of increasing the FiO2 on serum glucose and lactate was analyzed. During Period B lactate values in the brain determined using microdialysis were significantly lower (p < 0.05) in the AOT group than in the AAT group and glucose values in the brain determined using microdialysis were significantly higher (p < 0.04). No differences were demonstrated in the other groups. Increasing the FiO2 had no significant effect on the serum levels of glucose and lactate. Increasing the Fi

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.5311 - Ferrous lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5311 Ferrous lactate. (a) Product. Ferrous lactate. (b) Conditions of use. This substance...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice. ...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice. ...

21 CFR 582.1207 - Calcium lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Additives § 582.1207 Calcium lactate. (a) Product. Calcium lactate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or feeding practice. ...

The agreement between abnormal venous lactate and arterial lactate in the ED: a retrospective chart review.

PubMed

Bloom, B; Pott, J; Freund, Y; Grundlingh, J; Harris, T

2014-06-01

The evidence for prognostication using lactate is often based on arterial lactate (AL). Arterial sampling is painful and difficult, and carries risks. Studies comparing peripheral venous lactate (PVL) with AL showed little difference but predominantly included patients with normal lactate. The objective of this study was to measure agreement between PVL and AL in patients with elevated venous lactate. This is a retrospective cross-sectional study. ED patients age≥16, attending from October 2010 to June 2011 inclusive, with PVL≥2.0 mmol/L and AL taken within 1 hour. intravenous fluid prior to or between initial venous and arterial sampling. Primary endpoint: agreement between PVL and AL defined as mean difference±95% limits of agreement (LOA). The misclassification rate was assessed. N=232. VL median 3.50 mmol/L, range 2.00 to 15.00 mmol/L. AL median 2.45 mmol/L, range 1.0 to 13.2 mmol/L. The mean difference±SD between PVL and AL for all patients was 1.06±1.30 mmol/L (95%LOA -1.53 to 3.66 mmol/L). Using a cut-off of 2 mmol/L and 4 mmol/L, 36.2% and 17.9% of patients respectively were incorrectly classified as having elevated lactate. We report greater bias between VL and AL with broader LOA than previously documented. This may partly be due to the fact that we studied only patients with abnormal venous values, for whom close agreement would confer greatest clinical significance. The agreement between abnormal PVL and AL is poor and the high rate of misclassification may suggest that PVL is not a good substitute for AL if the venous lactate is abnormal. Copyright © 2014 Elsevier Inc. All rights reserved.

Mild zinc deficiency in male and female rats: early postnatal alterations in renal nitric oxide system and morphology.

PubMed

Tomat, Analia Lorena; Veiras, Luciana Cecilia; Aguirre, Sofía; Fasoli, Héctor; Elesgaray, Rosana; Caniffi, Carolina; Costa, María Ángeles; Arranz, Cristina Teresa

2013-03-01

Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of lactate concentrations in canine synovial fluid.

PubMed

Proot, J L J; de Vicente, F; Sheahan, D E

2015-01-01

To report synovial fluid lactate concentrations in normal and pathological canine joints. Controlled, prospective study. Lactate was measured in synovial fluid using a hand-held meter and the rest of the fluid was sent to a commercial laboratory for analysis. Samples were divided into four groups; group 1: control, group 2: osteoarthritis, group 3: immune-mediated inflammatory arthritis, and group 4: septic arthritis. Statistical analysis was performed to compare lactate concentrations between the four groups and to examine the predictive value of lactate in the diagnosis of septic arthritis. A correlation was sought between synovial fluid lactate and synovial fluid total nucleated cell count and total protein. Seventy-four samples were investigated from 55 dogs. Statistical analysis found that lactate concentrations were significantly higher in the septic arthritis group than in each of the other three groups. No significant correlation could be found between synovial fluid lactate concentrations and synovial fluid total nucleated cell count or synovial fluid total protein. Lactate concentration was found to be a useful predictor of septic arthritis, with a low concentration pointing towards exclusion rather than a high concentration to the diagnosis of septic arthritis. Synovial fluid lactate concentration is not a good marker for osteoarthritis or immune-mediated inflammatory arthritis, but it is significantly increased in septic arthritis and could help the clinician in ruling out this condition in a quick and cost-effective way.

Restraint stress in lactating mice alters the levels of sulfur-containing amino acids in milk.

PubMed

Nishigawa, Takuma; Nagamachi, Satsuki; Ikeda, Hiromi; Chowdhury, Vishwajit S; Furuse, Mitsuhiro

2018-03-30

It is well known that maternal stress during the gestation and lactation periods induces abnormal behavior in the offspring and causes a lowering of the offspring's body weight. Various causes of maternal stress during the lactation period, relating to, for example, maternal nutritional status and reduced maternal care, have been considered. However, little is known about the effects on milk of maternal stress during the lactation period. The current study aimed to determine whether free amino acids, with special reference to sulfur-containing amino acids in milk, are altered by restraint stress in lactating mice. The dams in the stress group were restrained for 30 min at postnatal days 2, 4, 6, 8, 10 and 12. Restraint stress caused a reduction in the body weight of lactating mice. The concentration of taurine and cystathionine in milk was significantly higher in the stress group, though stress did not alter their concentration in maternal plasma. The ratio of taurine concentration in milk to its concentration in maternal plasma was significantly higher in the stress group, suggesting that stress promoted taurine transportation into milk. Furthermore, taurine concentration in milk was positively correlated with corticosterone levels in plasma. In conclusion, restraint stress in lactating mice caused the changes in the metabolism and in the transportation of sulfur-containing amino acids and resulted in higher taurine concentration in milk. Taurine concentration in milk could also be a good parameter for determining stress status in dams.

Randomized clinical trial of a calcium supplement for improvement of health in dairy cows in early lactation.

PubMed

Miltenburg, Cynthia L; Duffield, Todd F; Bienzle, Dorothee; Scholtz, Elizabeth L; LeBlanc, Stephen J

2016-08-01

Prophylactic Ca supplementation immediately after calving is a common strategy to prevent clinical and subclinical hypocalcemia in parturient dairy cows. The objective of this study was to evaluate the effect of prophylactic administration of an injected Ca supplement on blood Ca concentration at 24 and 48h after treatment, incidence risk of clinical disease and culling, milk production in early lactation, and probability of pregnancy at first insemination. Cows without signs of visible milk fever (n=984) from 7 farms were blocked by parity and randomly assigned to receive either Ca gluconate (35% wt/vol) in combination with Ca glucoheptonate (10% wt/vol; TheraCalcium, Vétoquinol Canada Inc., Lavaltrie, Quebec) or a placebo (medication vehicle solution with no Ca) at first contact with each cow after calving and again 12 to 24h later. Each dose was 120mL injected subcutaneously over 2 sites. Total serum Ca concentration (tCa) was measured from coccygeal blood samples before (time 0) and 24 and 48h after first treatment in a subsample of cows (n=129). Blood β-hydroxybutyrate concentrations were measured from all cows twice between 3 and 16d in milk at weekly visits and cows were evaluated for vaginal discharge once between 28 and 42d in milk. Disease events, production data from the first 3 Dairy Herd Improvement milk tests, reproduction, and culling data were collected from each herd. For cows that had received 1 injection of Ca before the blood sample at 24h (n=95), tCa was significantly higher in the treated cows: mean ± standard error, 2.03±0.03 versus 1.90±0.03mmol/L, accounting for tCa at time of enrollment and a treatment by tCa at enrollment interaction. At 48h, no significant difference was found in tCa between treatment and control (mean ± SE, 2.12±0.02 and 2.10±0.03mmol/L, respectively). Cows treated with the Ca product were significantly less likely to have received intravenous, subcutaneous, or oral supplemental Ca for exhibiting clinical signs

Effect of dietary protein content on animal production and blood metabolites of dairy cows during lactation.

PubMed

Law, R A; Young, F J; Patterson, D C; Kilpatrick, D J; Wylie, A R G; Mayne, C S

2009-03-01

Ninety autumn-calving Holstein dairy cows [45 primiparous and 45 multiparous (mean parity, 3.1)] were allocated to 1 of 3 dietary crude protein (CP) concentrations: 173, 144, or 114 g of CP/kg of DM, from calving until d 150 of lactation. On d 151, half of the animals in each treatment were allocated an alternative dietary protein concentration. Half of the animals receiving 114 g of CP/kg of DM went onto 144 g of CP/kg of DM; half of the animals receiving 144 g of CP/kg of DM went onto 173 g of CP/kg of DM; and half of the animals receiving 173 g of CP/kg of DM went onto 144 g of CP/kg of DM, with the remaining animals staying on their original treatment. This resulted in 6 treatments in the mid to late lactation period: 114/114, 144/144, 173/173, 114/144, 144/173, and 173/144 g of CP/kg of DM. An increase in dietary CP concentration significantly increased milk, fat, and protein yield in early lactation (d 1 to 150). Dry matter intake was also increased with increased dietary protein concentration; however, this was not significant between 144 and 173 g of CP/kg of DM. Increased dietary CP significantly increased plasma urea, albumin, and total protein concentrations but had no significant effect on NEFA, leptin, or IGF-1 concentrations. Decreasing the dietary CP concentration in mid-late lactation (d 151 to 305) from 173 to 144 g/kg of DM had no significant effect on milk yield, dry matter intake, or milk fat and protein yield, compared with animals that remained on 173 g of CP/kg of DM throughout lactation. Increasing dietary CP concentration from 144 to 173 g/kg of DM significantly increased dry matter intake compared with animals that remained on the 144 g of CP/kg of DM throughout lactation. There were no significant dietary treatment effects on live weight or body condition score change throughout the experiment. Results of this study indicate that high protein diets (up to 173 g of CP/kg of DM) improved feed intake and animal performance in early lactation

Lactate Test

MedlinePlus

... by cells as the body turns food into energy (cell metabolism). Depending on pH , it is sometimes ... level or when the primary way of producing energy in the body's cells is disrupted. Excess lactate ...

Bedside ABG, electrolytes, lactate and procalcitonin in emergency pediatrics

PubMed Central

Batra, Prerna; Dwivedi, Ajeet Kumar; Thakur, Neha

2014-01-01

Point of care testing, is the term commonly applied to the bedside tests performed in sick patients. Common clinical conditions encountered in pediatric emergency rooms are respiratory, gastro-intestinal, infections and cardiac. Emergencies at most of the places, especially developing countries are overburdened. Availability of tests like arterial blood gas, lactate, electrolytes and procalcitonin, bedside tests or point of care tests can help identify sick patients quickly. Abnormalities like acid-base disturbances and dyselectrolytemias can be dealt with instantly, thus improving the overall prognosis. Lactate levels in emergency give the earliest clue to cardiovascular compromise and poor tissue perfusion. Procalcitonin has recently gained significant importance as an acute phase reactant for early identification of sepsis. Decisions for initiating or withholding antibiotic therapy can also be taken based on procalcitonin levels in emergency. Bedside estimation of serum electrolytes, blood gas analysis and procalcitonin thus facilitate the clinical evaluation and management of critical patients. An extensive literature review of current status of these investigations as point of care tests is appraised here. PMID:25337488

l-Lactate metabolism in HEP G2 cell mitochondria due to the l-lactate dehydrogenase determines the occurrence of the lactate/pyruvate shuttle and the appearance of oxaloacetate, malate and citrate outside mitochondria.

PubMed

Pizzuto, Roberto; Paventi, Gianluca; Porcile, Carola; Sarnataro, Daniela; Daniele, Aurora; Passarella, Salvatore

2012-09-01

As part of an ongoing study of l-lactate metabolism both in normal and in cancer cells, we investigated whether and how l-lactate metabolism occurs in mitochondria of human hepatocellular carcinoma (Hep G2) cells. We found that Hep G2 cell mitochondria (Hep G2-M) possess an l-lactate dehydrogenase (ml-LDH) restricted to the inner mitochondrial compartments as shown by immunological analysis, confocal microscopy and by assaying ml-LDH activity in solubilized mitochondria. Cytosolic and mitochondrial l-LDHs were found to differ from one another in their saturation kinetics. Having shown that l-lactate itself can enter Hep G2 cells, we found that Hep G2-M swell in ammonium l-lactate, but not in ammonium pyruvate solutions, in a manner inhibited by mersalyl, this showing the occurrence of a carrier-mediated l-lactate transport in these mitochondria. Occurrence of the l-lactate/pyruvate shuttle and the appearance outside mitochondria of oxaloacetate, malate and citrate arising from l-lactate uptake and metabolism together with the low oxygen consumption and membrane potential generation are in favor of an anaplerotic role for l-LAC in Hep G2-M. Copyright © 2012 Elsevier B.V. All rights reserved.

Early colonization of functional groups of microbes in the infant gut.

PubMed

Pham, Van T; Lacroix, Christophe; Braegger, Christian P; Chassard, Christophe

2016-07-01

The colonization of the infant gut is crucial for early life development. Although the composition and diversity of the infant gut microbiota (GM) has been well described at a taxonomic level, functional aspects of this ecosystem remain unexplored. In the infant gut, lactate is produced by a number of bacteria and plays an important role in the trophic chain of the fermentation process. However, little is known about the lactate-utilizing bacteria (LUB) community in infants and their impact on gut health. By combining culture-based and molecular methods, we intensively studied LUB in fecal samples of 40 healthy infants on both taxonomic and functional levels. We demonstrated metabolic cross-feeding of lactate and identified keystone species specified for lactate utilization. The interactions of such species and their metabolic outcome could have direct impacts on infant health, either beneficial (production of short chain fatty acids) or detrimental (accumulation of hydrogen or hydrogen sulfide). We identified mode of delivery as a strong determinant for lactate-producing and -utilizing bacteria levels. These findings present the early establishment of GM with a novel perspective and emphasize the importance of lactate utilization in infancy. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Subcutaneous administration of monosodium glutamate to pregnant mice reduces weight gain in pups during lactation.

PubMed

Park, Ji-Hun; Choi, Tae-Saeng

2016-04-01

Administering monosodium glutamate (MSG) to neonatal rodents induces obesity and type 2 diabetes. In addition, several studies have shown that MSG administered to pregnant animals can cross the placenta and reach the foetus. The present study was performed to investigate the effects of administering MSG to pregnant ICR mice on dam and neonatal growth. Pregnant mice were treated with 60 or 120 mg MSG once daily from day 5 of pregnancy to one day before parturition by subcutaneous injection. In addition, the body weights of the neonates were determined until nine weeks of age. The birth weights of neonates were not different between the control and MSG-treated groups. However, MSG treatment resulted in a lower body weight gain of neonates during lactation. In addition, this underweight of the MSG-treated group at weaning returned to normal compared with the control group at five weeks of age. Cross-fostering experiments indicated that the lower body weight gain of neonates in the MSG-treated group during lactation was due to its effects on the dam. Serum prolactin levels and mammary gland development of the mice were examined next to determine the reasons for this lactation problem. Although there were no differences in prolactin levels, morphological analyses of the mammary glands revealed apparent differences, including low numbers and altered phenotype of alveoli, between the control and MSG-treated groups. Taken together, our results show that treating pregnant mice with excess MSG induced lower neonate body weight gain during lactation. © The Author(s) 2015.

Regulation of mammary gland sensitivity to thyroid hormones during the transition from pregnancy to lactation.

PubMed

Capuco, A V; Connor, E E; Wood, D L

2008-10-01

Thyroid hormones are galactopoietic and help to establish the mammary gland's metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I (DIO1), type II (DIO2) and type III (DIO3), thyroid hormone receptors alpha1 (TRalpha1), alpha2 (TRalpha2) and beta1 (TRbeta1), and retinoic acid receptors alpha (RXRalpha) and gamma (RXRgamma), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation (P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRbeta1 mRNA in mammary gland increased with onset of lactation, whereas TRalpha1 and TRalpha2 transcripts did not vary with physiological state. Conversely, quantity of RXRalpha mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRbeta1 and DIO2, and decreased RXRalpha, provide a mechanism to increase thyroid hormone activity within the mammary gland during

Lactate Profile During Greco-Roman Wrestling Matchx

PubMed Central

Karnincic, Hrvoje; Tocilj, Zoran; Uljevic, Ognjen; Erceg, Marko

2009-01-01

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. Key Points There were no significant differences in lactate concentrations at the end of the match between two proficiency levels of wrestlers. More proficient (elite) wrestlers raise lactates gradually through the wrestling match while less proficient (club) wrestlers raise it abruptly at the end of the first bout. Both groups of wrestlers are unable to sustain same level of activity through the match suggesting that they are utilizing too much energy from anaerobic glycolysis. PMID:24474881

The lactate paradox revisited in lowlanders during acclimatization to 4100 m and in high-altitude natives

PubMed Central

van Hall, G; Lundby, C; Araoz, M; Calbet, J A L; Sander, M; Saltin, B

2009-01-01

Chronic hypoxia has been proposed to induce a closer coupling in human skeletal muscle between ATP utilization and production in both lowlanders (LN) acclimatizing to high altitude and high-altitude natives (HAN), linked with an improved match between pyruvate availability and its use in mitochondrial respiration. This should result in less lactate being formed during exercise in spite of the hypoxaemia. To test this hypothesis six LN (22–31 years old) were studied during 15 min warm up followed by an incremental bicycle exercise to exhaustion at sea level, during acute hypoxia and after 2 and 8 weeks at 4100 m above sea level (El Alto, Bolivia). In addition, eight HAN (26–37 years old) were studied with a similar exercise protocol at altitude. The leg net lactate release, and the arterial and muscle lactate concentrations were elevated during the exercise in LN in acute hypoxia and remained at this higher level during the acclimatization period. HAN had similar high values; however, at the moment of exhaustion their muscle lactate, ADP and IMP content and Cr/PCr ratio were higher than in LN. In conclusion, sea-level residents in the course of acclimatization to high altitude did not exhibit a reduced capacity for the active muscle to produce lactate. Thus, the lactate paradox concept could not be demonstrated. High-altitude natives from the Andes actually exhibit a higher anaerobic energy production than lowlanders after 8 weeks of acclimatization reflected by an increased muscle lactate accumulation and enhanced adenine nucleotide breakdown. PMID:19139048

Lactate transport and receptor actions in cerebral malaria

PubMed Central

Mariga, Shelton T.; Kolko, Miriam; Gjedde, Albert; Bergersen, Linda H.

2014-01-01

Cerebral malaria (CM), caused by Plasmodium falciparum infection, is a prevalent neurological disorder in the tropics. Most of the patients are children, typically with intractable seizures and high mortality. Current treatment is unsatisfactory. Understanding the pathogenesis of CM is required 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, which serves to equalize lactate concentrations across cell membranes in the direction of the concentration gradient. The equalizing action of MCTs is the basis for lactate’s role as a volume transmitter of metabolic signals in the brain. Lactate binds to the lactate receptor GPR81, recently discovered on brain cells and cerebral blood vessels, causing inhibition of adenylyl cyclase. High levels of lactate delivered by the parasite at the vascular endothelium may damage the blood–brain barrier, disrupt lactate homeostasis in the brain, and imply MCTs and the lactate receptor as novel therapeutic targets in CM. PMID:24904266

Alkaline Phosphatase Protects Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

PubMed Central

Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C.

2015-01-01

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women. PMID:25910276

Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.

PubMed

Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C

2015-01-01

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.

Channel-mediated lactate release by K⁺-stimulated astrocytes.

PubMed

Sotelo-Hitschfeld, Tamara; Niemeyer, María I; Mächler, Philipp; Ruminot, Iván; Lerchundi, Rodrigo; Wyss, Matthias T; Stobart, Jillian; Fernández-Moncada, Ignacio; Valdebenito, Rocío; Garrido-Gerter, Pamela; Contreras-Baeza, Yasna; Schneider, Bernard L; Aebischer, Patrick; Lengacher, Sylvain; San Martín, Alejandro; Le Douce, Juliette; Bonvento, Gilles; Magistretti, Pierre J; Sepúlveda, Francisco V; Weber, Bruno; Barros, L Felipe

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. Copyright © 2015 the authors 0270-6474/15/354168-11$15.00/0.

Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation.

PubMed

Sun, Bo; Liang, Nu-Chu; Ewald, Erin R; Purcell, Ryan H; Boersma, Gretha J; Yan, Jianqun; Moran, Timothy H; Tamashiro, Kellie L K

2013-11-01

Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype of the offspring. Here, we determined the effects of postweaning exercise in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and lactation. All pups were weaned onto chow diet on postnatal day (PND) 21. At 4 wk of age, male pups were given free access to running wheels (RW) or remained sedentary (SED) for 3 wk, after which all rats remained sedentary, resulting in four groups: CHOW-SED, CHOW-RW, HF-SED, and HF-RW. Male HF offspring gained more body weight by PND7 compared with CHOW pups and maintained this weight difference through the entire experiment. Three weeks of postweaning exercise did not affect body weight gain in either CHOW or HF offspring, but reduced adiposity in HF offspring. Plasma leptin was decreased at the end of the 3-wk running period in HF-RW rats but was not different from HF-SED 9 wk after the exercise period ended. At 14 wk of age, intracerebroventricular injection of leptin suppressed food intake in CHOW-SED, CHOW-RW, and HF-RW, while it did not affect food intake in HF-SED group. At death, HF-RW rats also had higher leptin-induced phospho-STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA expression in adult offspring. Our data suggest that postweaning exercise improves central leptin sensitivity and signaling in this model.

Mangiferin induces cell death against rhabdomyosarcoma through sustained oxidative stress.

PubMed

Padma, Vishwanadha Vijaya; Kalaiselvi, Palanisamy; Yuvaraj, Rangasamy; Rabeeth, M

2015-06-01

Embryonic rhabdomyosarcoma (RD) is the most prevalent type of cancer among children. The present study aimed to investigate cell death induced by mangiferin in RD cells. The Inhibitory concentration (IC 50 ) value of mangiferin was determined by an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Cell death induced by mangiferin against RD cells was determined through lactate dehydrogenase and nitric oxide release, intracellular calcium levels, reactive oxygen species generation, antioxidant status, mitochondrial calcium level, and mitochondrial membrane potential. Furthermore, acridine orange/ethidium bromide staining was performed to determine early/late apoptotic event. Mangiferin induced cell death in RD cells with an IC 50 value of 70 μM. The cytotoxic effect was reflected in a dose-dependent increase in lactate dehydrogenase leakage and nitric oxide release during mangiferin treatment. Mangiferin caused dose dependent increase in reactive oxygen species generation, intracellular calcium levels with subsequent decrease in antioxidant status (catalase, superoxide dismutase, glutathione-S-transferase, and glutathione) and loss of mitochondrial membrane potential in RD cells. Further data from fluorescence microscopy suggest that mangiferin caused cell shrinkage and nuclear condensation along with the occurrence of a late event of apoptosis. Results of the present study shows that mangiferin can act as a promising chemopreventive agent against RD by inducing sustained oxidative stress.

Effect of zinc supplementation on lipid peroxidation and lactate levels in rats with diabetes induced by streptozotocin and subjected to acute swimming exercise.

PubMed

Bicer, M; Gunay, M; Baltaci, A K; Uney, K; Mogulkoc, R; Akil, M

2012-01-01

The present study aims to explore the effect of zinc supplementation on lipid peroxidation and lactate levels in rats having diabetes induced by streptozotocin and subjected to acute swimming exercise. A total of 80 adult male rats of Sprague-Dawley type were equally allocated to 8 groups: Group 1, general control. Group 2, zinc-supplemented group. Group 3, zinc-supplemented, diabetic group. Group 4, swimming control group. Group 5, zinc-supplemented swimming group. Group 6, zinc-supplemented diabetic swimming group. Group 7, diabetic swimming group. Group 8, diabetic group. At the end of the 4-week study, blood samples were collected to determine MDA, GSH, GPx, SOD, lactate and zinc levels. The highest MDA values were found in group 7 and 8 (p<0.001). GSH values in groups 5 and 6 were higher (p<0.001). The highest GPx values were established in groups 2, 5 and 6 (p<0.001). SOD values were the highest in groups 5 and 6 (p<0.001) and lowest in groups 2, 3 and 8 (p<0.001). The highest plasma lactate levels were found in group 7 (p<0.001). The highest zinc levels were obtained in groups 1, 2 and 5 (p<0.001), and the lowest zinc levels were found in groups 7 and 8 (p<0.001). Results of the study reveal that zinc supplementation prevents the increase of free radical formation, suppression of antioxidant activity and muscle exhaustion, all of which result from diabetes and acute exercise. Zinc supplementation may contribute to health performance in diabetes and acute exercise (Tab. 2, Fig. 1 Ref. 47). Full Text in PDF www.elis.sk.

Imperfect asymmetry of life: earth microbial communities prefer D-lactate but can use L-lactate also.

PubMed

Moazeni, Faegheh; Zhang, Gaosen; Sun, Henry J

2010-05-01

Asymmetrical utilization of chiral compounds has been sought on Mars as evidence for biological activity. This method was recently validated in glucose. Earth organisms utilize D-glucose, not L-glucose, a perfect asymmetry. In this study, we tested the method in lactate and found utilization of both enantiomers. Soil-, sediment-, and lake-borne microbial communities prefer D-lactate but can consume L-lactate if given extra time to acclimate. This situation is termed imperfect asymmetry. Future life-detection mission investigators need to be aware of imperfect asymmetry so as not to miss relatively subtle signs of life.

Electrochemical lactate biosensor based upon chitosan/carbon nanotubes modified screen-printed graphite electrodes for the determination of lactate in embryonic cell cultures.

PubMed

Hernández-Ibáñez, Naiara; García-Cruz, Leticia; Montiel, Vicente; Foster, Christopher W; Banks, Craig E; Iniesta, Jesús

2016-03-15

l-lactate is an essential metabolite present in embryonic cell culture. Changes of this important metabolite during the growth of human embryo reflect the quality and viability of the embryo. In this study, we report a sensitive, stable, and easily manufactured electrochemical biosensor for the detection of lactate within embryonic cell cultures media. Screen-printed disposable electrodes are used as electrochemical sensing platforms for the miniaturization of the lactate biosensor. Chitosan/multi walled carbon nanotubes composite have been employed for the enzymatic immobilization of the lactate oxidase enzyme. This novel electrochemical lactate biosensor analytical efficacy is explored towards the sensing of lactate in model (buffer) solutions and is found to exhibit a linear response towards lactate over the concentration range of 30.4 and 243.9 µM in phosphate buffer solution, with a corresponding limit of detection (based on 3-sigma) of 22.6 µM and exhibits a sensitivity of 3417 ± 131 µAM(-1) according to the reproducibility study. These novel electrochemical lactate biosensors exhibit a high reproducibility, with a relative standard deviation of less than 3.8% and an enzymatic response over 82% after 5 months stored at 4 °C. Furthermore, high performance liquid chromatography technique has been utilized to independently validate the electrochemical lactate biosensor for the determination of lactate in a commercial embryonic cell culture medium providing excellent agreement between the two analytical protocols. Copyright © 2015 Elsevier B.V. All rights reserved.

21 CFR 184.1311 - Ferrous lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... reacting calcium lactate or sodium lactate with ferrous sulfate, direct reaction of lactic acid with iron... section 412(a)(2) of the act (21 U.S.C. 350a(a)(2)). (d) Prior sanctions for this ingredient different...

Feeding rumen-protected methionine pre- and postpartum increases milk protein content and yield in early lactation

USDA-ARS?s Scientific Manuscript database

Objectives were to evaluate the effects of feeding rumen-protected methionine (MET) from 23 d (±12) before calving until 98 days in milk (DIM) on lactation performance, dry matter intake (DMI), body condition score (BCS) and body weight (BW) change of dairy cows. Multiparous Holstein cows (n = 223) ...

Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats.

PubMed

Laporta, J; Peters, T L; Weaver, S R; Merriman, K E; Hernandez, L L

2013-05-01

An increasing demand for calcium during pregnancy and lactation can result in both clinical and subclinical hypocalcemia during the early lactation period in several mammalian species, in particular the dairy cow. Serotonin (5-HT) was recently identified as a regulator of lactation and bone turnover. The purpose of this study was to determine whether supplementation of the maternal diet with a 5-HT precursor would increase maternal bone turnover and calcium mobilization to maintain appropriate circulating maternal concentrations of ionized calcium during lactation. Female Sprague-Dawley rats (n = 30) were fed either a control diet (n = 15) or a diet supplemented with the 5-HT precursor 5-hydroxytryptophan (5-HTP, 0.2%; n = 15) from day 13 of pregnancy through day 9 of lactation. Maternal serum and plasma (day 1 and day 9 of lactation), milk and pup weight (daily), mammary gland and bone tissue (day 9 of lactation) were collected for analysis. The 5-HTP diet elevated circulating maternal concentrations of 5-HT on day 1 and day 9 of lactation and parathyroid hormone related-protein (PTHrP) on day 9 of lactation (P < 0.033). In addition, 5-HTP supplementation increased total serum calcium concentrations on day 1 of lactation and total milk calcium concentration on day 9 of lactation (P < 0.032). Supplemental 5-HTP did not alter milk yield, maternal body weight, mammary gland structure, or pup litter weights (P > 0.05). Supplemental 5-HTP also resulted in increased concentrations of mammary 5-HT and PTHrP, as well as increased mRNA expression of rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 1, and Pthrp mRNA on day 9 of lactation (P < 0.028). In addition, supplementation of 5-HTP resulted in increased mRNA expression of maternal mammary calcium transporters and resorption of bone in the femur, indicated by increase osteoclast number and diameter as well as mRNA expression of classical markers of bone resorption on day 9 of lactation (P < 0

Induced ovulation and conception in locating sows.

PubMed

Hausler, C L; Hodson, H H; Kuo, D C; Kinney, T J; Rauwolf, V A; Strack, L E

1980-05-01

Fifty lactating sows were injected with 1,500 IU pregnant mare serum gonadotrophin (PMSG) at an average of 25 days postpartum. Twenty-four of these sows received prostaglandin F2 alpha (PGF2 alpha) 24 hr prior to PMSG. Ninety-six hours after the PMSG injection, 1,000 IU of human chorionic gonadotrophin (HCG) were injected. Artificial insemination was performed at 24 and 36 to 42 hr post-HCG. The PMSG/HCG treatment resulted in pregnancy in 17 of 20 sows slaughtered from 34 to 43 days postbreeding and in 23 of 30 sows allowed to complete gestation. Mean numbers of corpora lutea (33) and viable embryos (15) were counted at slaughter. Litter sizes were averaged (11) for those sows allowed to farrow. Treatment with PGF2 alpha prior to PMSG injection had no effect on conception rates, number of corpora lutea, number of embryos or litter size in the lactating sows. In a second experiment, the same hormone treatments were administered to lactating sows beginning on day 5, 10, 15 or 20 postpartum. Pregnancy rates were 0/10, 2/10, 8/10 and 6/10, respectively (P less than .05, chi-square). At slaughter (30 to 40 days postbreeding), corpora lutea and embryo numbers recorded from pregnant sows were 23.0, 9.5; 31.5, 15.3, and 28.0, 18.8, respectively, for the sows in the day 10, day 15 and day 20 groups. In a third experiment, sows were given PMSG-HCG as previously described on either day 5 (five sows) or day 10 (14 sows) postpartum. Laparotomy of these sows 2 to 5 days postbreeding revealed minimal ovarian responsiveness at day 5, but 43% of the animals responded with multiple ovulations at day 10. The low pregnancy rate seen at day 10 in Exp. 2 may reflect embryonic mortality due to unfavorable uterine environment. We conclude that the PMSG/HCG treatment followed by timed artificial insemination of lactating sows will induce ovulation and coneption as early as 15 days postfarrowing. Pregnancy is thus concurrent with lactation, eliminating the need for early weaning and

Associations between Parity, Hair Hormone Profiles during Pregnancy and Lactation, and Infant Development in Rhesus Monkeys (Macaca mulatta)

PubMed Central

Dettmer, Amanda M.; Rosenberg, Kendra L.; Suomi, Stephen J.; Meyer, Jerrold S.; Novak, Melinda A.

2015-01-01

Studies examining hormones throughout pregnancy and lactation in women have been limited to single, or a few repeated, short-term measures of endocrine activity. Furthermore, potential differences in chronic hormonal changes across pregnancy/lactation between first-time and experienced mothers are not well understood, especially as they relate to infant development. Hormone concentrations in hair provide long-term assessments of hormone production, and studying these measures in non-human primates allows for repeated sampling under controlled conditions that are difficult to achieve in humans. We studied hormonal profiles in the hair of 26 female rhesus monkeys (Macaca mulatta, n=12 primiparous), to determine the influences of parity on chronic levels of cortisol (hair cortisol concentration, HCC) and progesterone (hair progesterone concentration, HPC) during early- to mid-pregnancy (PREG1), in late pregnancy/early lactation (PREG2/LACT1), and in peak lactation (LACT2). We also assessed infants’ neurobehavioral development across the first month of life. After controlling for age and stage of pregnancy at the first hair sampling period, we found that HCCs overall peaked in PREG2/LACT1 (p=0.02), but only in primiparous monkeys (p<0.001). HPCs declined across pregnancy and lactation for all monkeys (p<0.01), and primiparous monkeys had higher HPCs overall than multiparous monkeys (p=0.02). Infants of primiparous mothers had lower sensorimotor reflex scores (p=0.02) and tended to be more irritable (p=0.05) and less consolable (p=0.08) in the first month of life. Moreover, across all subjects, HCCs in PREG2/LACT1 were positively correlated with irritability (r(s)=0.43, p=0.03) and negatively correlated with sensorimotor scores (r(s)=-0.41, p=0.04). Together, the present results indicate that primiparity influences both chronic maternal hormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in

Blood lactate accumulation in top level swimmers following competition.

PubMed

Bonifazi, M; Martelli, G; Marugo, L; Sardella, F; Carli, G

1993-03-01

The purposes of this study were to evaluate the significance of blood lactate values after competitions and the blood lactate-swimming speed relationship to swimming performances. Auricular blood samples (N = 421) were collected in 203 top level Italian swimmers (116 males and 87 females) at the end of competitions performed in a 25 m swimming pool. The distribution of all lactate values differed between males and females. The lowest lactate values occurred in swimmers performing the longest distances both in males (1500 m) and females (800 m). In swimmers performing freestyle events a relationship between V-4 mM (swimming speed at 4 mmol/l blood lactate value) and competition velocities was observed, in males, at 200, 400 and 1500 m and, in females, at 400 and 800 m. The predicted velocity corresponding to the competition lactate value assessed by the individual blood lactate-swimming speed relationship was found to be highly related to the actual competition velocity. Results suggest that blood lactate values in swimmers are a useful indication of individual aptitudes.

Characteristics of feed efficiency within and across lactation in dairy cows and the effect of genetic selection.

PubMed

Hurley, A M; Lopez-Villalobos, N; McParland, S; Lewis, E; Kennedy, E; O'Donovan, M; Burke, J L; Berry, D P

2018-02-01

The objective of the present study was to investigate the phenotypic inter- and intra-relationships within and among alternative feed efficiency metrics across different stages of lactation and parities; the expected effect of genetic selection for feed efficiency on the resulting phenotypic lactation profiles was also quantified. A total of 8,199 net energy intake (NE I ) test-day records from 2,505 lactations on 1,290 cows were used. Derived efficiency traits were either ratio based or residual based; the latter were derived from least squares regression models. Residual energy intake (REI) was defined as NE I minus predicted energy requirements based on lactation performance; residual energy production (REP) was defined as net energy for lactation minus predicted energy requirements based on lactation performance. Energy conversion efficiency was defined as net energy for lactation divided by NE I . Pearson phenotypic correlations among traits were computed across lactation stages and parities, and the significance of the differences was determined using the Fisher r-to-z transformation. Sources of variation in the feed efficiency metrics were investigated using linear mixed models, which included the fixed effects of contemporary group, breed, parity, stage of lactation, and the 2-way interaction of parity by stage of lactation. With the exception of REI, parity was associated with all efficiency and production traits. Stage of lactation, as well as the 2-way interaction of parity by stage of lactation, were associated with all efficiency and production traits. Phenotypic correlations among the efficiency and production traits differed not only by stage of lactation but also by parity. For example, the strong phenotypic correlation between REI and energy balance (EB; 0.89) for cows in parity 3 or greater and early lactation was weaker for parity 1 cows at the same lactation stage (0.81), suggesting primiparous cows use the ingested energy for both milk

In utero and lactational exposure to BDE-47 promotes obesity development in mouse offspring fed a high-fat diet: impaired lipid metabolism and intestinal dysbiosis.

PubMed

Wang, Dezhen; Yan, Jin; Teng, Miaomiao; Yan, Sen; Zhou, Zhiqiang; Zhu, Wentao

2018-05-01

In this study, we investigated the effects of in utero and lactational exposure to BDE-47 on the progression of obesity and metabolic dysfunction in a diet-induced obesity model. Pregnant ICR mice were treated via oral gavage with low doses of BDE-47 (0, 0.002, and 0.2 mg/kg body weight) from gestational day 6 to postnatal day 21. After weaning, male offspring were fed an AIN93-based normal diet (ND) or high-fat diet (HFD: 60% calories from fat) for 14 weeks. We examined body weight, liver weight, histopathology, blood biochemistry, gene expression, and serum metabolic changes. A combination of 16S rRNA gene sequencing and 1 H NMR-based metabolomics was conducted to examine the effects of BDE-47 on the gut microbiome. Results showed that in utero and lactational exposure to BDE-47 caused a worsening of HFD-induced obesity, hepatic steatosis, and injury; impaired glucose homeostasis and metabolic dysfunction, and mRNA levels of genes involved in lipid metabolism were significantly altered in the BDE-47-treated HFD group. The gut microbiome were perturbed by BDE-47, causing diversity reduction, compositional alteration, and metabolic changes. These changes were more pronounced for BDE-47-treated HFD mice. All these results indicate that early life exposure to low doses of BDE-47 can promote obesity and the development of metabolic dysfunction.

Glymphatic clearance controls state-dependent changes in brain lactate concentration.

PubMed

Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2017-06-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

Glymphatic clearance controls state-dependent changes in brain lactate concentration

PubMed Central

Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2016-01-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep–wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport. PMID:27481936

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

PubMed

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.

Outcome of prolactinoma after pregnancy and lactation: a study on 73 patients.

PubMed

Domingue, Marie-Eve; Devuyst, France; Alexopoulou, Orsalia; Corvilain, Bernard; Maiter, Dominique

2014-05-01

Prolactinoma is the most frequent pituitary tumour among women of child-bearing age. Only a few studies have addressed the outcome of prolactinoma after pregnancy. To study remission, defined as prolactin normalization without medical treatment, after pregnancy and lactation in women with prolactinoma. A retrospective study conducted in 2 Belgian academic centres including 73 patients (54 microprolactinomas and 19 macroprolactinomas) with 104 pregnancies continuing beyond first trimester. Dopamine agonists were stopped in early pregnancy in all treated cases. Prolactin level and adenoma size at pituitary magnetic resonance imaging (MRI) were recorded before pregnancy and throughout follow-up. Thirty of 73 women (41%) were in remission after a median follow-up of 22 months after delivery or cessation of lactation. Adenoma size at diagnosis was smaller in women in remission (5 vs 8 mm). There was a nonsignificant higher rate of remission for microprolactinomas than for macroprolactinoma (46% vs 26%). The first pituitary MRI after pregnancy and lactation showed no tumour and a decreased adenoma size in 23% and 39% of women, respectively. MRI normalization was associated with remission. The number of pregnancies per woman as well as breastfeeding and its duration did not influence remission rate. More than 40% of women with previous diagnosis of prolactinoma have normal PRL level without medical treatment for a median follow-up of 22 months after pregnancy and lactation. The likelihood of remission is associated with a smaller initial adenoma size and normalization of pituitary MRI after pregnancy. © 2013 John Wiley & Sons Ltd.

In vitro effects of bicarbonate and bicarbonate-lactate buffered peritoneal dialysis solutions on mesothelial and neutrophil function.

PubMed

Topley, N; Kaur, D; Petersen, M M; Jörres, A; Williams, J D; Faict, D; Holmes, C J

1996-02-01

The inclusion of bicarbonate in the formulation of peritoneal dialysis solutions may avoid the in vitro impairment of certain cell functions seen with acidic lactate-based fluids. The supranormal physiological levels of HCO3- and PCO2 inherent in such formulations may, however, not be biocompatible. This study compared the in vitro biocompatibility of a pH 5.2 lactate-based formulation with formulations containing either 40 mM lactate at pH 7.4, 38 mM HCO3- at pH 6.8 (PCO2 at approximately 240 mm Hg) or 7.4 (PCO2 at approximately 60 mm Hg), and 25 mM HCO3- plus 15 mM lactate at pH 6.8 (PCO2 at approximately 160 mm Hg) or 7.4 (PCO2 at approximately 40 mm Hg). Significant release of lactate dehydrogenase or decreases in ATP content by human peritoneal mesothelial cells (HPMC) and human peripheral polymorphonuclear leukocytes (PMN) after a 30-min exposure to each test solution was only seen with the pH 5.2 lactate-based fluid. The ATP content of HPMC exposed to this fluid returned to control levels after 30 min of recovery in M199 control medium but showed a trend toward decreasing ATP content at 240 min. Similarly, interleukin (IL)-1 beta-induced IL-6 synthesis by HPMC was also only significantly reduced by the pH 5.2 lactate solution. PMN chemiluminescence was unaffected by 30-min exposure to all test solutions except for the pH 5.2 lactate formulation. Staphylococcus epidermidis phagocytosis was reduced to between 46 to 57% of control with all test solutions except the pH 5.2 lactate solution, which further suppressed the chemiluminescence response to 17% of control. These data suggest that short exposure to supranormal physiological levels of HCO3- and PCO2 does not impair HPMC or PMN viability and function. Furthermore, neutral pH lactate-containing solutions show equivalent biocompatibility to bicarbonate-based ones.

Normal lactate concentration range in the neonatal brain.

PubMed

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.

Lactate biosensors: current status and outlook.

PubMed

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.

Lactational mastitis caused by Streptococcus lactarius.

PubMed

Tena, Daniel; Fernández, Cristina; López-Garrido, Beatriz; Pérez-Balsalobre, Mercedes; Losa, Cristina; Medina-Pascual, María José; Sáez-Nieto, Juan Antonio

2016-08-01

Human infections caused by Streptococcus lactarius have not been previously reported. In the present report, we describe a lactational mastitis caused by this organism. The infection occurred in a 28-year-old breast-feeding female, with a 10-days history of moderate pain on the right breast. The patient was cured after antibiotic treatment with levofloxacin for 21 days. Our case shows that S. lactarius should be considered as a cause of lactational mastitis. The introduction of molecular microbiology techniques can be extremely useful for knowing the implication of streptococci in lactational mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

[Clinical study of induced abortion of early-early pregnancy: an analysis of 10, 404 cases].

PubMed

Kang, Jian; Wang, Xue-fen; Zhang, Li; Liu, Jian-hua

2012-01-03

To evaluate the advantages and disadvantages of early-early pregnancy induced abortion (EPIA). A total of 10 404 cases of EPIA performed at our hospital from January 1993 to December 2003 were retrospectively analyzed and compared with 9434 cases of common induced abortion (CIA). The amount of hemorrhage and operative duration, degree of pain, rate of induced-abortion syndrome, rate of incomplete abortion, menstrual changes and post-operative onset of Asherman's syndrome were observed and compared between 2 groups. The average age, ratio of parous cases, ratio of the cases of first-pregnancy induced abortion were not different between 2 groups (P > 0.05). The amount of hemorrhage bleeding ((4.9 ± 3.2) ml), operative duration ((90.3 ± 12.4) s), degree of pain, rate of induced-abortion syndrome, menstrual changes and the rate of Asherman's syndrome in the EPIA group were all significantly less than those in the CIA group (P < 0.05). However, the rate of incomplete abortion (0.44%) in the EPIA group was significantly higher than that (0.21%) in the CIA group (P < 0.05). EPIA has the advantages of lesser hemorrhage, less pain, shorter operative duration and fewer complications over CIA. Therefore the recovery of EPIA cases is earlier than that of CIA cases. While the risk of incomplete abortion stays high.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

PubMed

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

PubMed Central

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

Genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins.

PubMed

Koeck, A; Miglior, F; Jamrozik, J; Kelton, D F; Schenkel, F S

2013-07-01

The aim of this study was to investigate the genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins. Health data recorded by producers were available from the national dairy cattle health system in Canada. Test-day records of milk, fat, and protein yields were obtained from the routine milk recoding scheme. Ketosis and displaced abomasum were defined as binary traits (0 = healthy; 1 = sick) based on whether or not the cow had at least 1 case of the respective disease in the period from calving to 100 d after calving. Mean frequencies of ketosis and displaced abomasum were 4.1 and 2.7%, respectively. The following milk production traits were considered: milk yield, fat percentage (Fat%), protein percentage (Prot%), fat-to-protein (F:P) ratio, and F:P ratio >1.5. The trait F:P ratio >1.5 was scored as 1 or 0, based on whether or not the cow had an F:P ratio >1.5. For milk production traits, the first (5-30 d in milk) and the second (31-60 d in milk) test days were considered. Data were analyzed using bivariate linear animal models. Average heritabilities of 0.02 and 0.04 were obtained for ketosis and displaced abomasum, respectively. For milk production traits, the lowest heritabilities were obtained for F:P >1.5 (0.04 to 0.08), whereas the highest estimates were found for Prot% (0.27 to 0.38). Ketosis and displaced abomasum were genetically uncorrelated with milk yield in early lactation. Moderate favorable correlations were found between metabolic diseases and milk composition traits. Ketosis was significantly correlated with Fat% (0.33), F:P ratio (0.30), and F:P ratio >1.5 (0.35) at the first test day, whereas all genetic correlations with milk composition traits at the second test day were not significant and close to zero. Significant favorable genetic correlations were also found between displaced abomasum and F:P ratio (0.26), F:P ratio >1.5 (0.25) and Prot% (-0.19) at the first test

Blood lactate clearance after maximal exercise depends on active recovery intensity.

PubMed

Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

2014-06-01

High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05). Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

L-lactate production from biodiesel-derived crude glycerol by metabolically engineered Enterococcus faecalis: cytotoxic evaluation of biodiesel waste and development of a glycerol-inducible gene expression system.

PubMed

Doi, Yuki

2015-03-01

Biodiesel waste is a by-product of the biodiesel production process that contains a large amount of crude glycerol. To reuse the crude glycerol, a novel bioconversion process using Enterococcus faecalis was developed through physiological studies. The E. faecalis strain W11 could use biodiesel waste as a carbon source, although cell growth was significantly inhibited by the oil component in the biodiesel waste, which decreased the cellular NADH/NAD(+) ratio and then induced oxidative stress to cells. When W11 was cultured with glycerol, the maximum culture density (optical density at 600 nm [OD600]) under anaerobic conditions was decreased 8-fold by the oil component compared with that under aerobic conditions. Furthermore, W11 cultured with dihydroxyacetone (DHA) could show slight or no growth in the presence of the oil component with or without oxygen. These results indicated that the DHA kinase reaction in the glycerol metabolic pathway was sensitive to the oil component as an oxidant. The lactate dehydrogenase (Ldh) activity of W11 during anaerobic glycerol metabolism was 4.1-fold lower than that during aerobic glycerol metabolism, which was one of the causes of low l-lactate productivity. The E. faecalis pflB gene disruptant (Δpfl mutant) expressing the ldhL1LP gene produced 300 mM l-lactate from glycerol/crude glycerol with a yield of >99% within 48 h and reached a maximum productivity of 18 mM h(-1) (1.6 g liter(-1) h(-1)). Thus, our study demonstrates that metabolically engineered E. faecalis can convert crude glycerol to l-lactate at high conversion efficiency and provides critical information on the recycling process for biodiesel waste. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Lactate response to different volume patterns of power clean.

PubMed

Date, Anand S; Simonson, Shawn R; Ransdell, Lynda B; Gao, Yong

2013-03-01

The ability to metabolize or tolerate lactate and produce power simultaneously can be an important determinant of performance. Current training practices for improving lactate use include high-intensity aerobic activities or a combination of aerobic and resistance training. Excessive aerobic training may have undesired physiological adaptations (e.g., muscle loss, change in fiber types). The role of explosive power training in lactate production and use needs further clarification. We hypothesized that high-volume explosive power movements such as Olympic lifts can increase lactate production and overload lactate clearance. Hence, the purpose of this study was to assess lactate accumulation after the completion of 3 different volume patterns of power cleans. Ten male recreational athletes (age 24.22 ± 1.39 years) volunteered. Volume patterns consisted of 3 sets × 3 repetition maximum (3RM) (low volume [LV]), 3 sets × 6 reps at 80-85% of 3RM (midvolume [MV]), and 3 sets × 9 reps at 70-75% of 3RM (high volume [HV]). Rest period was identical at 2 minutes. Blood samples were collected immediately before and after each volume pattern. The HV resulted in the greatest lactate accumulation (7.43 ± 2.94 mmol·L) vs. (5.27 ± 2.48 and 4.03 ± 1.78 mmol·L in MV and LV, respectively). Mean relative increase in lactate was the highest in HV (356.34%). The findings indicate that lactate production in power cleans is largely associated with volume, determined by number of repetitions, load, and rest interval. High-volume explosive training may impose greater metabolic demands than low-volume explosive training and may improve ability to produce power in the presence of lactate. The role of explosive power training in overloading the lactate clearance mechanism should be examined further, especially for athletes of intermittent sport.

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

PubMed

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.

Cloning of D-lactate dehydrogenase genes of Lactobacillus delbrueckii subsp. bulgaricus and their roles in D-lactic acid production.

PubMed

Huang, Yanna; You, Chunping; Liu, Zhenmin

2017-07-01

Lactobacillus delbrueckii subsp. bulgaricus is a heterogenous lactic acid bacterium that converts pyruvate mainly to D-lactic acid using D-lactate dehydrogenases (D-LDHs), whose functional properties remain poorly characterized. Here, the D-LDHs genes (ldb0101, ldb0813, ldb1010, ldb1147 and ldb2021) were cloned and overexpressed in Escherichia coli JM109 from an inducible pUC18 vector, respectively, and the resulting strains were compared in terms of D-lactic acid production. The strain expressing ldb0101 and ldb1010 gene individually produced more D-lactate than other three strains. Further study revealed that Ldb0101 activity was down-regulated by the oxygen and, therefore, achieved a highest titer of D-lactate (1.94 g/L) under anaerobic condition, and introduction of ldb1010 gene enhanced D-lactate formation (0.94 and 0.85 g/L, respectively) both in aerobic and anaerobic conditions due to a relatively stable q d-lactate . Our results suggested that the enzyme Ldb0101 and Ldb1010 played a role of more importance in D-lactate formation. To the best of our knowledge, we demonstrate for the first time the roles of different D-LDH homologs from L. bulgaricus in D-lactic acid production.

Prediction of body lipid change in pregnancy and lactation.

PubMed

Friggens, N C; Ingvartsen, K L; Emmans, G C

2004-04-01

lipid change through lactation in a simple way that requires few parameters and inputs that can be derived in practice. It is expected that prediction of the cow's energy requirements can be substantially improved, particularly in early lactation, by incorporating a genetically driven body energy mobilization.

Heifers infected with coagulase-negative staphylococci in early lactation have fewer cases of clinical mastitis and higher milk production in their first lactation than noninfected heifers.

PubMed

Piepers, S; Opsomer, G; Barkema, H W; de Kruif, A; De Vliegher, S

2010-05-01

Intramammary infections (IMI) in recently calved dairy heifers are more common than was formerly believed but their relevance for future performance has been studied only rarely. In the present study, the association between the IMI status of fresh heifers and their subsequent udder health, milk production, and culling in first lactation was explored. Quarter milk samples were collected between 1 and 4 d in milk (DIM) and between 5 and 8 DIM from 191 dairy heifers in 20 dairy herds for bacteriological culturing and somatic cell count (SCC) analysis. Monthly milk recording data including composite milk SCC and test-day milk yield (MY) were obtained for the first 285 DIM or until culling. Farmer-recorded clinical mastitis cases were available. Data were analyzed using mixed models and survival analysis. Approximately 80% of the fresh heifers (79.8%) had at least one culture-positive quarter. Coagulase-negative staphylococci (CNS) were the most frequently isolated pathogens (72%), followed by esculin-positive streptococci (4.6%) and Staphylococcus aureus (3.5%). Overall geometric mean SCC at quarter level decreased between the first and second samplings from 348,000 to 116,000 cells/mL. Heifers infected with CNS had an intermediate average test-day SCC (84,000 cells/mL) during the first 285 DIM compared with noninfected heifers (53,000 cells/mL) and heifers infected with major pathogens (195,000 cells/mL). Heifers infected with major pathogens had a much lower average daily MY (18.3kg) during first lactation compared with noninfected animals (21.3kg). That CNS-infected heifers out-produced their noninfected counterparts could be at least partially explained by their significantly lower incidence of clinical mastitis (incidence risk 3.6 vs. 21.0%) during first lactation compared with noninfected heifers. We conclude that although CNS cause the majority of IMI in heifers around calving, they should not be a reason for serious concern. Copyright 2010 American Dairy

Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.

PubMed

Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I Kati; Watson, David G; Kennedy, Malcolm W

2015-01-01

Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1), days 7-20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth.

Genetic improvement of total milk yield and total lactation persistency of the first three lactations in dairy cattle.

PubMed

Togashi, K; Lin, C Y

2008-07-01

The objective of this study was to compare 6 selection criteria in terms of 3-parity total milk yield and 9 selection criteria in terms of total net merit (H) comprising 3-parity total milk yield and total lactation persistency. The 6 selection criteria compared were as follows: first-parity milk estimated breeding value (EBV; M1), first 2-parity milk EBV (M2), first 3-parity milk EBV (M3), first-parity eigen index (EI(1)), first 2-parity eigen index (EI(2)), and first 3-parity eigen index (EI(3)). The 9 selection criteria compared in terms of H were M1, M2, M3, EI(1), EI(2), EI(3), and first-parity, first 2-parity, and first 3-parity selection indices (I(1), I(2), and I(3), respectively). In terms of total milk yield, selection on M3 or EI(3) achieved the greatest genetic response, whereas selection on EI(1) produced the largest genetic progress per day. In terms of total net merit, selection on I(3) brought the largest response, whereas selection EI(1) yielded the greatest genetic progress per day. A multiple-lactation random regression test-day model simultaneously yields the EBV of the 3 lactations for all animals included in the analysis even though the younger animals do not have the opportunity to complete the first 3 lactations. It is important to use the first 3 lactation EBV for selection decision rather than only the first lactation EBV in spite of the fact that the first-parity selection criteria achieved a faster genetic progress per day than the 3-parity selection criteria. Under a multiple-lactation random regression animal model analysis, the use of the first 3 lactation EBV for selection decision does not prolong the generation interval as compared with the use of only the first lactation EBV. Thus, it is justified to compare genetic response on a lifetime basis rather than on a per-day basis. The results suggest the use of M3 or EI(3) for genetic improvement of total milk yield and the use of I(3) for genetic improvement of total net merit H

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

PubMed

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.

[NUCLEAR STRUCTURE IN THE SECRETORY CELLS OF MAMMARY GLANDS IN LACTATING AND NON-LACTATING RATS].

PubMed

Tyutina, K V; Skopichev, V G; Bogolyubov, D S; Bogolyubova, I O

2016-01-01

The features of structural and functional organization of the main nuclear compartments and distribution of their key molecular components (chromatin-remodeling protein ATRX, RNA polymerase I and II, and the splicing factor SC35) has been studied in the nuclei of mammary gland cells at different functional states. No significant differences between the nuclei of the cells in the lactating and non-lactating mammary glands have been revealed at the ultrastructural level. At the same time, photometric analysis has revealed higher intensity of nucleoplasmic immunofluorescent staining of mammary glands in the lactating animals when antibodies against the proteins ATRX and SC35 were used. Apparently, this observation reflects the changes of the structural and functional status of chromatin as well as the redistribution of splicing factors between the sites of their deposition and transcription.

Breastfeeding and Prolactin Levels in Lactating Women With a Family History of Alcoholism

PubMed Central

Mennella, Julie A.; Pepino, Marta Yanina

2010-01-01

OBJECTIVE Many motivated new mothers fail to reach public health goals for breastfeeding, highlighting the need to identify risk factors. Because having a family history of alcoholism is associated with blunted prolactin responses to an alcohol challenge in nonlactating individuals, this study aimed to identify associations in family history of alcoholism, prolactin, and breastfeeding behaviors in lactating women. METHODS This was a 2-day experimental study that used within-subject alcohol or control beverage consumption and between-subject family history of alcoholism factors. The participants were non–alcohol-dependent lactating women; 7 were family history–positive (FHP) for alcohol dependence, and 21 were family history–negative (FHN). Consumption of 0.4 g/kg alcohol or nonalcoholic beverage occurred in separate randomized sessions, followed by use of a breast pump. Basal and suckling-induced prolactin, blood alcohol concentrations, milk yield, self-reported drug effects, neophobia, and breastfeeding patterning were measured. RESULTS Although no group differences in alcohol pharmacokinetics were detected, FHP women exhibited blunted prolactin to breast stimulation after drinking the control and alcohol beverage and felt more of the stimulant-like effects of alcohol than did FHN women. FHP women reported more frequent daily breastfeeding than did FHN women. CONCLUSIONS This is the first evidence that family history of alcoholism is associated with a blunted magnitude, rapidity, and duration of the prolactin response to breast stimulation and an alcohol challenge in lactating women. More frequent breastfeeding by FHP women suggests behavioral compensation for perceived and/or actual poor lactation. Alcohol did not enhance lactational performance, further disputing the lore that alcohol is a galactagogue. PMID:20403941

On the analysis of Canadian Holstein dairy cow lactation curves using standard growth functions.

PubMed

López, S; France, J; Odongo, N E; McBride, R A; Kebreab, E; AlZahal, O; McBride, B W; Dijkstra, J

2015-04-01

Six classical growth functions (monomolecular, Schumacher, Gompertz, logistic, Richards, and Morgan) were fitted to individual and average (by parity) cumulative milk production curves of Canadian Holstein dairy cows. The data analyzed consisted of approximately 91,000 daily milk yield records corresponding to 122 first, 99 second, and 92 third parity individual lactation curves. The functions were fitted using nonlinear regression procedures, and their performance was assessed using goodness-of-fit statistics (coefficient of determination, residual mean squares, Akaike information criterion, and the correlation and concordance coefficients between observed and adjusted milk yields at several days in milk). Overall, all the growth functions evaluated showed an acceptable fit to the cumulative milk production curves, with the Richards equation ranking first (smallest Akaike information criterion) followed by the Morgan equation. Differences among the functions in their goodness-of-fit were enlarged when fitted to average curves by parity, where the sigmoidal functions with a variable point of inflection (Richards and Morgan) outperformed the other 4 equations. All the functions provided satisfactory predictions of milk yield (calculated from the first derivative of the functions) at different lactation stages, from early to late lactation. The Richards and Morgan equations provided the most accurate estimates of peak yield and total milk production per 305-d lactation, whereas the least accurate estimates were obtained with the logistic equation. In conclusion, classical growth functions (especially sigmoidal functions with a variable point of inflection) proved to be feasible alternatives to fit cumulative milk production curves of dairy cows, resulting in suitable statistical performance and accurate estimates of lactation traits. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A case series of pregnancy- and lactation-associated osteoporosis and a review of the literature

PubMed Central

Nakamura, Yukio; Kamimura, Mikio; Ikegami, Shota; Mukaiyama, Keijiro; Komatsu, Masatoshi; Uchiyama, Shigeharu; Kato, Hiroyuki

2015-01-01

The syndrome of pregnancy- and lactation-associated osteoporosis is a rare disorder whose precise etiology and treatment are largely unknown. We herein report two such cases occurring in the early postpartum period that led to multiple fragility compression fractures. Combination therapy of vitamin D and vitamin K enabled a marked gradual increase in bone mineral density. PMID:26379439

Analytical performance of three whole blood point-of-care lactate devices compared to plasma lactate comparison methods and a flow-injection mass spectrometry method.

PubMed

Tolan, Nicole V; Wockenfus, Amy M; Koch, Christopher D; Crews, Bridgit O; Dietzen, Dennis J; Karon, Brad S

2017-03-01

Point of care (POC) whole blood lactate testing may facilitate rapid detection of sepsis. We evaluated three POC methods against both plasma lactate comparison methods and a flow-injection mass spectrometric (MS) method. Nova StatStrip, Abbott i-STAT CG4+ and Radiometer ABL90 POC lactate methods were evaluated against the mean of Cobas Integra 400 and Vitros 350 plasma lactate. POC methods were also compared to a flow-injection mass spectrometric assay measuring lactate in ZnSO 4 -precipitated whole blood extracts. Intra- and inter-assay precision was determined using quality control material. Method comparison included specimens from normal donors at rest, after exertion, and after spiking with lactic acid. Intra- and inter-assay coefficient of variation was <5% for i-STAT and ABL90; but ranged from 3.1-8.2% on two StatStrip meters. Mean (±SD) bias between POC and plasma lactate ranged from -0.2±0.9 (i-STAT and ABL90) to -0.4±1.2 (StatStrip) mmol/L. At concentrations >6mmol/L, all POC methods showed proportional negative bias compared to plasma methods; but this bias was not observed when compared to the MS method. Despite proportional negative bias, all POC methods demonstrated acceptable concordance (94-100%) with plasma lactate within the reference interval (<2.3mmol/L) and >4mmol/L, commonly used clinical cut-offs for detection of sepsis. POC lactate methods demonstrate acceptable concordance with plasma lactate across commonly used clinical cut-offs for detection of sepsis. Due to systematic negative bias at higher lactate concentrations, POC and plasma lactate should not be used interchangeably to monitor patients with elevated lactate concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Commercial sheep flocks--fatty acid and fat-soluble antioxidant composition of milk and cheese related to changes in feeding management throughout lactation.

PubMed

Valdivielso, Izaskun; Bustamante, María Ángeles; Buccioni, Arianna; Franci, Oreste; Ruiz de Gordoa, Juan Carlos; de Renobales, Mertxe; Barron, Luis Javier R

2015-08-01

Fatty acids (FAs), tocopherols and retinoids were analysed in raw milk and cheese from six commercial sheep flocks monitored from early lactation in winter to late lactation in summer. In winter, animals received concentrate and forage indoors; in early spring, animals grazed part-time on cultivated or natural valley grasslands; and from mid spring on, animals were kept outdoors constantly on mountain natural pastures. Mountain grazing in late lactation significantly increased the amount of healthy desirable unsaturated FAs such as C18:1t11 (VA), C18:2c9t11 (RA), C18:2t11c13, C18:3c9c12c15 (ALA) and C20:5c5c8c11c14c17 (EPA), and those of α-tocopherol and α-tocotrienol of milk and cheese. Stepwise discriminant analysis was applied to classify cheese samples according to seasonal feeding management. The multivariate approach was able to discriminate beyond doubt mountain cheeses from those of indoor feeding and part-time valley grazing.

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

PubMed

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

2016-01-12

Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

Ketones and lactate increase cancer cell “stemness”, driving recurrence, metastasis and poor clinical outcome in breast cancer

PubMed Central

Tsirigos, Aristotelis; Lin, Zhao; Pavlides, Stephanos; Wang, Chengwang; Flomenberg, Neal; Knudsen, Erik S; Howell, Anthony; Pestell, Richard G

2011-01-01

Previously, we showed that high-energy metabolites (lactate and ketones) “fuel” tumor growth and experimental metastasis in an in vivo xenograft model, most likely by driving oxidative mitochondrial metabolism in breast cancer cells. To mechanistically understand how these metabolites affect tumor cell behavior, here we used genome-wide transcriptional profiling. Human breast cancer cells (MCF7) were cultured with lactate or ketones, and then subjected to transcriptional analysis (exon-array). Interestingly, our results show that treatment with these high-energy metabolites increases the transcriptional expression of gene profiles normally associated with “stemness”, including genes upregulated in embryonic stem (ES) cells. Similarly, we observe that lactate and ketones promote the growth of bonafide ES cells, providing functional validation. The lactate- and ketone-induced “gene signatures” were able to predict poor clinical outcome (including recurrence and metastasis) in human breast cancer patients. Taken together, our results are consistent with the idea that lactate and ketone utilization in cancer cells promotes the “cancer stem cell” phenotype, resulting in significant decreases in patient survival. One possible mechanism by which high-energy metabolites might induce stemness is by increasing the pool of Acetyl-CoA, leading to increased histone acetylation and elevated gene expression. Thus, our results mechanistically imply that clinical outcome in breast cancer could simply be determined by epigenetics and energy metabolism, rather than by the accumulation of specific “classical” gene mutations. We also suggest that high-risk cancer patients (identified by the lactate/ketone gene signatures) could be treated with new therapeutics that target oxidative mitochondrial metabolism, such as the anti-oxidant and “mitochondrial poison” metformin. Finally, we propose that this new approach to personalized cancer medicine be termed �

Flexible graphene bio-nanosensor for lactate.

PubMed

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.

Quantitative Analysis of the Human Milk Whey Proteome Reveals Developing Milk and Mammary-Gland Functions across the First Year of Lactation

PubMed Central

Zhang, Qiang; Cundiff, Judy K.; Maria, Sarah D.; McMahon, Robert J.; Woo, Jessica G.; Davidson, Barbara S.; Morrow, Ardythe L.

2013-01-01

In-depth understanding of the changing functions of human milk (HM) proteins and the corresponding physiological adaptions of the lactating mammary gland has been inhibited by incomplete knowledge of the HM proteome. We analyzed the HM whey proteome (n = 10 women with samples at 1 week and 1, 3, 6, 9 and 12 months) using a quantitative proteomic approach. One thousand three hundred and thirty three proteins were identified with 615 being quantified. Principal component analysis revealed a transition in the HM whey proteome-throughout the first year of lactation. Abundance changes in IgG, sIgA and sIgM display distinct features during the first year. Complement components and other acute-phase proteins are generally at higher levels in early lactation. Proteomic analysis further suggests that the sources of milk fatty acids (FA) shift from more direct blood influx to more de novo mammary synthesis over lactation. The abundances of the majority of glycoproteins decline over lactation, which is consistent with increased enzyme expression in glycoprotein degradation and decreased enzyme expression in glycoprotein synthesis. Cellular detoxification machinery may be transformed as well, thereby accommodating increased metabolic activities in late lactation. The multiple developing functions of HM proteins and the corresponding mammary adaption become more apparent from this study. PMID:28250401

Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract.

PubMed

Gessner, Denise K; Winkler, Anne; Koch, Christian; Dusel, Georg; Liebisch, Gerhard; Ringseis, Robert; Eder, Klaus

2017-03-23

transition period at 1 week postpartum indicates that polyphenol-rich feed components are able to inhibit ER stress-induced UPR and inflammatory processes, both of which are considered to contribute to liver-associated diseases and to impair milk performance in dairy cows, in the liver of dairy cows during early lactation.

Regulation of bone mineral loss during lactation

NASA Technical Reports Server (NTRS)

Brommage, R.; Deluca, H. F.

1985-01-01

The effects of varyng dietary calcium and phosphorous levels, vitamin D deficiency, oophorectomy, adrenalectomy, and simultaneous pregnancy on bone mineral loss during lactation in rats are studied. The experimental procedures and evaluations are described. The femur ash weight of lactating and nonlactating rats are calculated. The data reveals that a decrease in dietary calcium of 0.02 percent results in an increased loss of bone mineral, an increase in calcium to 1.4 percent does not lessen bone mineral loss, and bone mineral loss in vitamin D deficient rats is independent of calcium levels. It is observed that changes in dietary phosphorous level, oophorectomy, adrenalectomy, and simultaneous pragnancy do not reduce bone mineral loss during lactation. The analysis of various hormones to determine the mechanism that triggers bone mineral loss during lactation is presented.

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

21 CFR 73.165 - Ferrous lactate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Ferrous lactate. 73.165 Section 73.165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.165 Ferrous lactate. (a) Identity. The color additive ferrous...

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

PubMed

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

2007-04-01

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

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

PubMed

Herbst, Eric A F; George, Mitchell A J; Brebner, Karen; Holloway, Graham P; Kane, Daniel A

2018-05-01

The nature and existence of mitochondrial lactate oxidation is debated in the literature. Obscuring the issue are disparate findings in isolated mitochondria, as well as relatively low rates of lactate oxidation observed in permeabilized muscle fibres. However, respiration with lactate has yet to be directly assessed in brain tissue with the mitochondrial reticulum intact. To determine if lactate is oxidized in the matrix of brain mitochondria, oxygen consumption was measured in saponin-permeabilized mouse brain cortex samples, and rat prefrontal cortex and hippocampus (dorsal) subregions. While respiration in the presence of ADP and malate increased with the addition of lactate, respiration was maximized following the addition of exogenous NAD + , suggesting maximal lactate metabolism involves extra-matrix lactate dehydrogenase. This was further supported when NAD + -dependent lactate oxidation was significantly decreased with the addition of either low-concentration α-cyano-4-hydroxycinnamate or UK-5099, inhibitors of mitochondrial pyruvate transport. Mitochondrial respiration was comparable between glutamate, pyruvate, and NAD + -dependent lactate oxidation. Results from the current study demonstrate that permeabilized brain is a feasible model for assessing lactate oxidation, and support the interpretation that lactate oxidation occurs outside the mitochondrial matrix in rodent brain.

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