WorldWideScience

Sample records for chemosensitivity targeting lactate

  1. Targeting the Mitochondrial Respiratory Chain of Cryptococcus through Antifungal Chemosensitization: A Model for Control of Non-Fermentative Pathogens

    Directory of Open Access Journals (Sweden)

    Kathleen L. Chan

    2013-07-01

    Full Text Available Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain (MRC inhibition compared to species of Candida. This higher sensitivity results from the inability of Cryptococcus to generate cellular energy through fermentation. To heighten disruption of cellular MRC, octyl gallate (OG or 2,3-dihydroxybenzaldehyde (2,3-DHBA, phenolic compounds inhibiting mitochondrial functions, were selected as chemosensitizers to pyraclostrobin (PCS; an inhibitor of complex III of MRC. The cryptococci were more susceptible to the chemosensitization (i.e., PCS + OG or 2,3-DHBA than the Candida with all Cryptococcus strains tested being sensitive to this chemosensitization. Alternatively, only few of the Candida strains showed sensitivity. OG possessed higher chemosensitizing potency than 2,3-DHBA, where the concentration of OG required with the drug to achieve chemosensitizing synergism was much lower than that required of 2,3-DHBA. Bioassays with gene deletion mutants of the model yeast Saccharomyces cerevisiae showed that OG or 2,3-DHBA affect different cellular targets. These assays revealed mitochondrial superoxide dismutase or glutathione homeostasis plays a relatively greater role in fungal tolerance to 2,3-DHBA or OG, respectively. These findings show that application of chemosensitizing compounds that augment MRC debilitation is a promising strategy to antifungal control against yeast pathogens.

  2. Chemosensitization of cancer cells by siRNA using targeted nanogel delivery

    International Nuclear Information System (INIS)

    Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics. We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated. Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05). This study suggests that targeted delivery of siRNAs by nanogels may be a promising strategy to increase the efficacy of chemotherapy drugs for the treatment of ovarian cancer. In addition, EphA2 is a viable target for therapeutic delivery, and the siRNAs are effectively protected by the nanogel carrier, overcoming the poor stability and uptake that has hindered clinical advancement of therapeutic siRNAs

  3. Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Hui; Xie, Jing [Medical College, Qingdao University, Qingdao, Shandong 266071 (China); Peng, Jianjun, E-mail: jianjunpeng@126.com [College of Life Sciences, Chongqing Normal University, Chongqing 401331 (China); Han, Yantao, E-mail: hanyt19@126.com [Medical College, Qingdao University, Qingdao, Shandong 266071 (China); Jiang, Qixiao; Han, Mei; Wang, Chunbo [Medical College, Qingdao University, Qingdao, Shandong 266071 (China)

    2015-03-15

    Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment. - Highlights: • Hispidulin inhibits proliferation of gallbladder cancer cells by targeting HIF-1α. • Hispidulin regulates HIF-1α via activating AMPK signaling. • Hispidulin sensitized the GBC cells to chemotherapeutics by down-regulating P-gp.

  4. Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α

    International Nuclear Information System (INIS)

    Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment. - Highlights: • Hispidulin inhibits proliferation of gallbladder cancer cells by targeting HIF-1α. • Hispidulin regulates HIF-1α via activating AMPK signaling. • Hispidulin sensitized the GBC cells to chemotherapeutics by down-regulating P-gp

  5. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity.

    Directory of Open Access Journals (Sweden)

    Julia P Brandt

    Full Text Available Many animals possess neurons specialized for the detection of carbon dioxide (CO(2, which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2. The ETS-5 transcription factor is necessary for the specification of CO(2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO(2-detection and transforms neurons into CO(2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2-sensing neurons in other phyla.

  6. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity

    DEFF Research Database (Denmark)

    Brandt, Julia P; Aziz-Zaman, Sonya; Juozaityte, Vaida;

    2012-01-01

    . We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2). The ETS-5 transcription factor is necessary for the specification of CO(2)-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient......Many animals possess neurons specialized for the detection of carbon dioxide (CO(2)), which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2) is poorly understood...... to bypass a requirement for ets-5 in CO(2)-detection and transforms neurons into CO(2)-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2)-sensing neurons in other phyla....

  7. MiR-92b regulates the cell growth, cisplatin chemosensitivity of A549 non small cell lung cancer cell line and target PTEN.

    Science.gov (United States)

    Li, Yan; Li, Li; Guan, Yan; Liu, Xiuju; Meng, Qingyong; Guo, Qisen

    2013-11-01

    MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance of human cancer. Fewer studies were explored the roles of miR-92b on human lung cancer cell growth and resistance to cisplatin (CDDP). In this paper, we utilized real-time PCR to verify miR-92b was significantly up-regulated in non-small cell lung cancer (NSCLC) tissues compared to matched adjacent normal tissues. In vitro assay demonstrated that knock-down of miR-92b inhabits cell growth and sensitized the A549/CDDP cells to CDDP. Furthermore, we found miR-92b could directly target PTEN, a unique tumor suppressor gene, which was downregulated in lung cancer tissues compared to the matched adjacent normal tissues. These data indicate that the miR-92b play an oncogene roles by regulates cell growth, cisplatin chemosensitivity phenotype, and could serve as a novel potential maker for NSCLC therapy. PMID:24099768

  8. An illegitimate microRNA target site within the 3' UTR of MDM4 affects ovarian cancer progression and chemosensitivity

    DEFF Research Database (Denmark)

    Wynendaele, Jessika; Böhnke, Anja; Leucci, Eleonora;

    2010-01-01

    Overexpression of MDM4 (also known as MDMX or HDMX) is thought to promote tumorigenesis by decreasing p53 tumor suppressor function. Even modest decrease in Mdm4 levels affects tumorigenesis in mice, suggesting that genetic variants of MDM4 might have similar effects in humans. We sequenced the MDM...... interval (CI) = 1.2-13.5; P = 0.02] increased risk of recurrence and 5.5-fold (95% CI = 1.5-20.5; P = 0.01) increased risk of tumor-related death. Unexpectedly, the frequency of p53 mutations was not significantly lower in A/A patients. We conclude that acquisition of an illegitimate miR-191 target site...... causes downregulation of MDM4 expression, thereby significantly delaying ovarian carcinoma progression and tumor-related death. Importantly, these effects appear to be, at least partly, independent of p53....

  9. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    Pierre Sonveaux

    Full Text Available Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1 pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1 that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2 and basic fibroblast growth factor (bFGF expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities.

  10. ERRα Regulated Lactate Metabolism Contributes to Resistance to Targeted Therapies in Breast Cancer

    Science.gov (United States)

    Park, Sunghee; Chang, Ching-yi; Safi, Rachid; Liu, Xiaojing; Baldi, Robert; Jasper, Jeff S.; Anderson, Grace R.; Liu, Tingyu; Rathmell, Jeffrey C.; Dewhirst, Mark W.; Wood, Kris C.; Locasale, Jason W.; McDonnell, Donald P.

    2016-01-01

    Summary Imaging studies in animals and in humans have indicated that the oxygenation and nutritional status of solid tumors is dynamic. Further, the extremely low level of glucose within tumors, while reflecting its rapid uptake and metabolism, also suggests that cancer cells must rely on other energy sources in some circumstances. Here we find that some breast cancer cells can switch to utilizing lactate as a primary source of energy, allowing them to survive glucose deprivation for extended periods, and that this activity confers resistance to PI3K/mTOR inhibitors. The nuclear receptor, estrogen-related receptor alpha (ERRα), was shown to regulate the expression of genes required for lactate utilization and isotopomer analysis revealed that genetic or pharmacological inhibition of ERRα activity compromised lactate oxidation. Importantly, ERRα antagonists increased the in vitro and in vivo efficacy of PI3K/mTOR inhibitors, highlighting the potential clinical utility of this drug combination. PMID:27050525

  11. ERRα-Regulated Lactate Metabolism Contributes to Resistance to Targeted Therapies in Breast Cancer.

    Science.gov (United States)

    Park, Sunghee; Chang, Ching-Yi; Safi, Rachid; Liu, Xiaojing; Baldi, Robert; Jasper, Jeff S; Anderson, Grace R; Liu, Tingyu; Rathmell, Jeffrey C; Dewhirst, Mark W; Wood, Kris C; Locasale, Jason W; McDonnell, Donald P

    2016-04-12

    Imaging studies in animals and in humans have indicated that the oxygenation and nutritional status of solid tumors is dynamic. Furthermore, the extremely low level of glucose within tumors, while reflecting its rapid uptake and metabolism, also suggests that cancer cells must rely on other energy sources in some circumstances. Here, we find that some breast cancer cells can switch to utilizing lactate as a primary source of energy, allowing them to survive glucose deprivation for extended periods, and that this activity confers resistance to PI3K/mTOR inhibitors. The nuclear receptor, estrogen-related receptor alpha (ERRα), was shown to regulate the expression of genes required for lactate utilization, and isotopomer analysis revealed that genetic or pharmacological inhibition of ERRα activity compromised lactate oxidation. Importantly, ERRα antagonists increased the in vitro and in vivo efficacy of PI3K/mTOR inhibitors, highlighting the potential clinical utility of this drug combination. PMID:27050525

  12. AKT–THE MAMMALIAN TARGET OF RAPAMYCIN (MTOR PATHWAY INHIBITION INCREASES CERVICAL CANCER CELL CHEMOSENSITIVITY TO ACTIVE FORM OF IRINOTECAN (SN-38

    Directory of Open Access Journals (Sweden)

    Leri Septiani

    2015-07-01

    Full Text Available Objective: To investigate the molecular pathway of the cytotoxic effect of SN-38 in human cervical cancer cell lines. Methods: Two human cervical cancer cell lines were treated with various concentrations of irinotecan for 24–72 hours and the sensitivity was analysed using the MTT assay. Apoptosis was further observed through microscopic examinations. The protein expression was determined using Western blot analysis. Results: CaSki cells demonstrated the highest sensitivity to SN-38, whereas HeLa cells showed the lowest. In cervical cancer cells, SN-38 induced apoptosis through an intrinsic- and extrinsic-pathways. In addition, we showed that SN-38 downregulated the phosphorylation of Akt-mTOR pathways in CaSki cells, but not in HeLa cells. Interestingly, in HeLa cells, which were more suggestive of a resistant phenotype, pre-treatment with LY294002 and rapamycin inhibited activation of Akt-mTOR signaling and significantly enhanced the sensitivity of HeLa cells to SN-38. Conclusions: Irinotecan exerts its anti-neoplastic effects on cervical cancer cells by inducing apoptosis through caspase-cascade. Inhibition of Akt-mTOR, LY294002 and rapamycin, which is targeted to Akt-mTOR pathways, may sensitize irinotecan-resistant cervical cancer cells.

  13. Metabolic Targeting of Lactate Efflux by Malignant Glioma Inhibits Invasiveness and Induces Necrosis: An In Vivo Study

    Directory of Open Access Journals (Sweden)

    Chaim B Colen

    2011-07-01

    Full Text Available Glioblastoma multiforme (GBM are the most malignant among brain tumors. They are frequently refractory to chemotherapy and radiotherapy with mean patient survival of approximately 6 months, despite surgical intervention. The highly glycolytic nature of glioblastomas describes their propensity to metabolize glucose to lactic acid at an elevated rate. To survive, GBMs efflux lactic acid to the tumor microenvironment through transmembrane transporters denoted monocarboxylate transporters (MCTs. We hypothesized that inhibition of MCT function would impair the glycolytic metabolism and affect both glioma invasiveness and survival. We examined the effect on invasiveness with α-cyano-4-hydroxy-cinnamic acid (ACCA, 4CIN, CHCA, a small-molecule inhibitor of lactate transport, through Matrigel-based and organotypic (brain slice culture invasive assays using U87-MG and U251-MG glioma cells. We then conducted studies in immunodeficient rats by stereotaxic intracranial implantation of the glioma cells followed by programmed orthotopic application of ACCA through osmotic pumps. Effect on the implanted tumor was monitored by small-animal magnetic resonance imaging. Our assays indicated that glioma invasion was markedly impaired when lactate efflux was inhibited. Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion. Most importantly, control animals did not display any adverse neurologic effects during orthotopic administration of ACCA to brain through programmed delivery. These results indicate the clinical potential of targeting lactate efflux in glioma through delivery of small-molecule inhibitors of MCTs either to the tumor bed or to the postsurgical resection cavity.

  14. Heterogeneity of chemosensitivity in esophagealcancer using ATP-tumor chemosensitivity assay

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang LING; Zhi-xing YANG; Jian YIN; Wei-min MAO; Chun-jian QI; Xiao-xiao LU; Li-juan QIAN; Lin-hui GU; Zhi-guo ZHENG; Qiang ZHAO; Shi WANG; Xian-hua FANG

    2012-01-01

    Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials,which fails to take into account the known heterogeneity of chemosensitivity between patients.This study was aimed to demonstrate the degree of heterogeneity of chemosensitivity in esophageal cancers.Methods:A total of 42 esophageal cancer specimens were collected.The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA).Results:Thirty eight specimens produced evaluable results (90.5%).The most active single agent tested was nedaplatin,to which 28.9% of samples were sensitive.Combinations of chemotherapy agents exhibited much higher sensitivity:cisplatin+paclitaxel was sensitive in 16 of 38 (42.1%) of samples,while nedaplatin+paclitaxel was more effective,which was sensitive in 20 of 38 cases (52.6%).Conclusion:There was a marked heterogeneity of chemosensitivity in esophageal cancer.Chemosensitivity testing may provide apractical method for testing new regimens before clinical trials in esophageal cancer patients.

  15. Accessing chemosensitivity and ventilatory stability from transient stimuli.

    Science.gov (United States)

    Bruce, E N

    1996-12-01

    The degree of ventilatory stability of human subjects is inferred from the presence or absence of oscillations in ventilation in response to a brief CO2 disturbance using the method of pseudorandom stimulation. Simultaneously, chemosensitivity is measured. Stability and chemosensitivity are compared in hyperoxia between wakefulness and stage 2 non-rapid eye movement (NREM) sleep and between normoxia and hyperoxia awake. Stability is unchanged between wakefulness and sleep but chemosensitivity decreases in sleep. In contrast, stability is reduced in normoxia whereas chemosensitivity is larger than in hyperoxia. It is concluded that chemosensitivity and ventilatory stability may change independently, implying that chemosensitivity alone is not an adequate indicator of the likelihood of a subject to exhibit periodic breathing. PMID:9085498

  16. Expression of target genes of nuclear factor E2-related factor 2 in the liver of dairy cows in the transition period and at different stages of lactation.

    Science.gov (United States)

    Gessner, D K; Schlegel, G; Keller, J; Schwarz, F J; Ringseis, R; Eder, K

    2013-02-01

    In the liver of dairy cows, the production of cytokines is enhanced during the periparturient phase, which in turn leads to inflammation and an impairment of hepatic function. Nuclear factor E2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that controls the transcription of genes encoding various antioxidative and cytoprotective proteins. In the present study, we investigated the hypothesis that Nrf2 is activated in the liver of dairy cows during the periparturient phase to protect the liver against the deleterious effects of cytokines and reactive oxygen species. Therefore, we determined relative mRNA abundances of TNF (encoding tumor necrosis factor-α), various acute phase proteins and several Nrf2 target genes in liver biopsy samples of 20 dairy cows at each time point from 3 wk antepartum to 1, 5, and 14 wk postpartum. We observed an increase in mRNA abundances of TNF and acute-phase proteins [serum amyloid A 3 (SAA3), haptoglobin (HP), and C-reactive protein (CRP)] from 3 wk antepartum to 1 wk postpartum, indicative of a proinflammatory condition. Messenger RNA abundances of various Nrf2 target genes with antioxidative or cytoprotective functions [glutathione peroxidase 3 (GPX3); microsomal glutathione S-transferase 3 (MGST3); superoxide dismutase (SOD1); catalase (CAT); metallothioneins 1A, 1E, and 2A (MT1A, MT1E, and MT2A, respectively); NAD(P)H dehydrogenase, quinone 1 (NQO1); heme oxygenase 2 (HMOX2); and UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)] were also greatly increased from 3 wk antepartum to 1 wk postpartum. From 1 wk postpartum to later lactation, mRNA abundances of all the Nrf2-target genes considered declined but remained at levels that were higher than those in 3 wk antepartum. No correlations were found, however, between plasma concentrations of nonesterified fatty acids or β-hydroxybutyrate and mRNA abundances of Nrf2 target genes, indicating that a negative energy balance might not have been the main

  17. N-methylformamide: cytotoxic, radiosensitizer, or chemosensitizer

    International Nuclear Information System (INIS)

    N-methylformamide (NMF), a polar solvent, is currently being evaluated by the National Cancer Institute (NCI) as an antineoplastic agent because of its activity against colon, mammary, and lung tumor xenografts. Results from preclinical studies suggest that it has radiosensitizing, chemosensitizing, and differentiating activity. Its mechanism of action remains unknown, but may involve cellular depletion of glutathione, cell membrane changes, or modulation of proto-oncogene expression. Preclinical toxicology studies conducted in mice, rats, and beagle dogs showed reversible hepatotoxicity to be dose-limiting. Clinically, NMF is administered both orally and by intravenous (IV) injection. The bioavailability with oral administration is 90% to 95%. The highest reported plasma concentration of NMF is approximately 4 mmol/L in a patient who received a dose of 2,000 mg/m2 of IV NMF. Biphasic elimination with IV NMF is seen on both the daily for five days and weekly for 3 weeks schedule. Approximately 5% to 7% of the total administered IV dose is excreted in the urine. In phase I studies, dose-limiting toxicities included reversible hepatotoxicity, a generalized malaise syndrome, and nausea and vomiting. One partial response has been reported in the 111 patients treated on phase II trials in colorectal, head and neck, and renal carcinomas. Suggestions for the future development of this drug are presented. 82 references

  18. CO2 chemosensitivity during immersion in humans.

    Science.gov (United States)

    Chang, L P; Lundgren, C E

    1995-01-01

    Hypercapnic ventilatory response was compared in 9 seated subjects during head-out immersion in 35 degrees C (thermoneutral) water and during non-immersion in 28 degrees C (thermoneutral) room air. Using Read's CO2-rebreathing technique, minute ventilation (VE) and end-tidal (ET) PCO2 were sampled continuously for 4-5 min with a spirometer and a mass spectrometer, while the subject rebreathed a 6 L gas mixture initially containing 7% CO2 and 93% O2 in a bag-in-box system. The slope of the hypercapnic ventilatory response curve, expressed as delta VE/delta PETCO2, ranged from 0.76 to 2.49 L/min/mmHg. Immersion affected neither the slope nor the position of the hypercapnic ventilatory response curve. The rate of rise of PETCO2 during immersed CO2-rebreathing was significantly reduced (4.47 +/- 0.19 [SE] mmHg/min), as compared to the control value (5.67 +/- 0.24). It was concluded that the CO2 chemosensitivity during immersion in humans did not change and that the capacity to store CO2 in tissue might have been increased. PMID:8549236

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

    Science.gov (United States)

    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...

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

    Directory of Open Access Journals (Sweden)

    Lam Mary K

    2011-06-01

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

  1. Chemosensitization of plant pathogenic fungi to agricultural fungicides

    Science.gov (United States)

    Continual use of fungicides in agriculture often results in development of resistance in pathogens. A new strategy to aid in overcoming or minimizing this problem is enhancement of pathogen sensitivity to fungicides by chemosensitization. This involves combining fungicides with certain non-fungicida...

  2. Lactate Transport and Receptor Actions in Retina

    DEFF Research Database (Denmark)

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L;

    2016-01-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also...... excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies...... reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect...

  3. Overexpression of miR-100 inhibits cell proliferation, migration, and chemosensitivity in human glioblastoma through FGFR3

    Directory of Open Access Journals (Sweden)

    Luan YX

    2015-11-01

    Full Text Available Yongxin Luan,1 Shuyan Zhang,1 Ling Zuo,2 Lixiang Zhou1 1Department of Neurosurgery, First Bethune Hospital of Jilin University, 2Department of Ophthalmology, Second Bethune Hospital of Jilin University, Changchun, People’s Republic of China Background: Glioblastoma multiforme is one of the most deadly forms of brain cancer. We investigated the regulatory effects of microRNA-100 (miR-100 on cell proliferation, migration, and chemosensitivity in human glioblastoma. Methods: miR-100 expression was assessed by quantitative real-time polymerase chain reaction in both glioblastoma cells and human tumors. Lentiviruses of miR-100 mimics and inhibitors were transfected into U251 and T98G cells. The regulatory effects of either overexpressing or downregulating miR-100 on glioblastoma were evaluated by a viability assay, growth assay, migration assay, chemosensitivity assay, and an in vivo tumor transplantation assay. Expression of fibroblast growth factor receptor 3 (FGFR3, the bioinformatically predicted target of miR-100, was examined by Western blot in glioblastoma. FGFR3 was then ectopically overexpressed in U251 and T98G cells, and its effects on miR-100-mediated cancer regulation were evaluated by growth, migration, and chemosensitivity assays. Results: MiR-100 was markedly downregulated in both glioblastoma cell lines and human tumors. Overexpressing miR-100 through lentiviral transfection in U251 and T98G cells significantly inhibited cancer growth (both in vitro and in vivo and migration and increased chemosensitivity to cisplatin and 1, 3-bis (2-chloroethyl-l-nitrosourea, whereas downregulation of miR-100 had no effects on development of cancer. FGFR3 was directly regulated by miR-100 in glioblastoma. Ectopically overexpressing FGFR3 was able to ameliorate the anticancer effects of upregulation of miR-100 on glioblastoma growth, migration, and chemosensitivity. Conclusion: MiR-100 was generally downregulated in glioblastoma. Overexpressing mi

  4. MicroRNA-mediated Silencing of RhoC Inhibits Tumor Invasion and Increases Chemosensitivity to Paclitaxel in SKOV3 Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    PAN Ying; DU Zhen-wu; LENG Wei-chun; ZHOU Jia-wen; WANG Ying-jian; SHENG Min-jia; WANG Jun-rong; ZHANG Gui-zhen

    2011-01-01

    RhoC is a member of the Ras-homologous family of genes which are implicated in tumorigenesis and tumor progression. Up-regulation of RhoC is associated with tumor progression in ovarian carcinoma and RhoC is significantly correlated with the invasive capability of ovarian cancer cell lines in vitro. We developed a system that blocks RhoC in the human ovarian cancer SKOV3 cells using specific MicroRNA(miRNA) interference. By transfecting SKOV3 cells with the plasmid vector to express specific MiRNA that targets human RhoC, we were able to establish a stable clone in which RhoC expression was significantly downregnlated. This resulted in the decreased invasive potential of SKOV3 cells as well as increased chemosensitivity to paclitaxel. RhoC involves in invasion and chemosensitivity of SKOV3, indicating that RhoC may be a promising therapeutic target for ovarian cancer.

  5. RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro

    Directory of Open Access Journals (Sweden)

    Zhu Chan

    2010-06-01

    Full Text Available Abstract Background CD147 is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. CD147 has been implicated in numerous physiological and pathological activities. Enriched on the surface of many tumor cells, CD147 promotes tumor growth, invasion, metastasis and angiogenesis and confers resistance to some chemotherapeutic drugs. In this study, we investigated the possible role of CD147 in the progression of gastric cancer. Methods Short hairpin RNA (shRNA expressing vectors targeting CD147 were constructed and transfected into human gastric cancer cells SGC7901 and CD147 expression was monitored by quantitative realtime RT-PCR and Western blot. Cell proliferation, the activities of MMP-2 and MMP-9, the invasive potential and chemosensitivity to cisplatin of SGC7901 cells were determined by MTT, gelatin zymography, Transwell invasion assay and MTT, respectively. Results Down-regulation of CD147 by RNAi approach led to decreased cell proliferation, MMP-2 and MMP-9 activities and invasive potential of SGC7901 cells as well as increased chemosensitivity to cisplatin. Conclusion CD147 involves in proliferation, invasion and chemosensitivity of human gastric cancer cell line SGC7901, indicating that CD147 may be a promising therapeutic target for gastric cancer.

  6. Lactational Infertility- A Review

    OpenAIRE

    Ramachandran Prema

    1987-01-01

    Studies undertaken by the National Institute of Nutrition during the last 10 years indicate that prolonged breast-feeding is still the rule among rural and urban low income group population in Hyderabad. Lactation induced hyperprolactinaemia prolongs postpartum amenorrhea and inter pregnancy interval by about 6 months. Duration of lactational amenorrhea infants results in a fall of plasma prolactin levels and rapid return of menstruation and fertility. Lactational amenorrhea lasts longer in u...

  7. In vitro chemosensitivity of head and neck cancer cell lines

    Directory of Open Access Journals (Sweden)

    Schuler PJ

    2010-08-01

    Full Text Available Abstract Background Systemic treatment of head and neck squamous cell carcinoma (HNSCC includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance. Methods Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations. Results All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin. Conclusion Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.

  8. Lactic acid and lactates

    NARCIS (Netherlands)

    Schreurs, V.V.A.M.

    2010-01-01

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

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

    KAUST Repository

    Sotelo-Hitschfeld, T.

    2015-03-11

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

  10. Association of telomerase activity with radio- and chemosensitivity of neuroblastomas

    International Nuclear Information System (INIS)

    Telomerase activity compensates shortening of telomeres during cell division and enables cancer cells to escape senescent processes. It is also supposed, that telomerase is associated with radio- and chemoresistance. In the here described study we systematically investigated the influence of telomerase activity (TA) and telomere length on the outcome of radio- and chemotherapy in neuroblastoma. We studied the effects on dominant negative (DN) mutant, wild type (WT) of the telomerase catalytic unit (hTERT) using neuroblastoma cell lines. The cells were irradiated with 60Co and treated with doxorubicin, etoposide, cisplatin and ifosfamide, respectively. Viability was determined by MTS/MTT-test and the GI50 was calculated. Telomere length was measured by southernblot analysis and TA by Trap-Assay. Compared to the hTERT expressing cells the dominant negative cells showed increased radiosensitivity with decreased telomere length. Independent of telomere length, telomerase negative cells are significantly more sensitive to irradiation. The effect of TA knock-down or overexpression on chemosensitivity were dependent on TA, the anticancer drug, and the chemosensitivity of the maternal cell line. Our results supported the concept of telomerase inhibition as an antiproliferative treatment approach in neuroblastomas. Telomerase inhibition increases the outcome of radiotherapy while in combination with chemotherapy the outcome depends on drug- and cell line and can be additive/synergistic or antagonistic. High telomerase activity is one distinct cancer stem cell feature and the here described cellular constructs in combination with stem cell markers like CD133, Aldehyddehydrogenase-1 (ALDH-1) or Side population (SP) may help to investigate the impact of telomerase activity on cancer stem cell survival under therapy

  11. Lactational Infertility- A Review

    Directory of Open Access Journals (Sweden)

    Ramachandran Prema

    1987-01-01

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

  12. Research on Molybdenum Target Positioning Biopsy of Breast Lesions in Lactational Patient and Clinical Nursing%哺乳期钼靶定位乳腺病变的穿刺活检及临床护理研究

    Institute of Scientific and Technical Information of China (English)

    姜娥先; 魏本和; 司凯; 王军帅

    2014-01-01

    目的:探析哺乳期钼靶定位乳腺病变穿刺活检临床应用及护理干预。方法收集我院2012年1月至2014年1月140例进行钼靶定位乳腺病变穿刺活检术患者病例资料,并对该资料进行分析。结果钼靶提示存在单侧微钙化灶患者中,发现非典型增生5例,乳腺癌17例(检出率达12.14%),导管原位癌8例,浸润性导管癌9例;84例簇状分布微钙化中检出13例乳腺癌,56例非簇状分布微钙化中检出3例乳腺癌,微钙化呈簇状分布对比其他分布发生乳腺癌的概率相对较高。结论通过钼靶定位乳腺病变穿刺活检可以发现早期乳腺病变,尤其是乳腺癌,操作安全,从而能够早期诊断和早期治疗是提高乳腺癌患者生存质量的关键。%Objective To analyze the clinical application and nursing intervention of molybdenum target positioning biopsy of breast lesions in lactational patients.Method To Collect molybdenum target positioning biopsy of breast lesions in 140 lactational patients from January 2012 to January 2014 ,and analyze the data.Results In the patients: 5 cases of atypical hyperplasia , 17 cases of breast cancer rate(12.14%), 8 cases of ductal carcinoma in situ, 9 cases of infiltrating ductal carcinoma; 13 cases of breast cancer in 84 cases of microcalcification clusters of distribution, 56 cases of microcalcification clusters of distribution in 3 cases of breast cancer detection, it reveals that microcalcification clusters has relatively high incidence of breast cancer compared with other distribution.Conclusion To find early breast lesions, especially breast cancer by molybdenum target positioning biopsy breast lesions which handle without risk, can attain treatment early, it is the key to improve the quality of life of breast cancer patients.

  13. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    International Nuclear Information System (INIS)

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: • We used different technologies to prove our conclusion. • DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. • DUSP4 is a potential target for combating drug resistance in breast cancer. • DUSP4 is a potential target for regulating the EMT in breast cancer

  14. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu; Du, Feiya; Chen, Wei; Yao, Minya; Lv, Kezhen; Fu, Peifen, E-mail: fupeifendoczju@163.com

    2013-12-10

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: • We used different technologies to prove our conclusion. • DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. • DUSP4 is a potential target for combating drug resistance in breast cancer. • DUSP4 is a potential target for regulating the EMT in breast cancer.

  15. Suppression of bcl-2 Gene by RNA Interference Increases Chemosensitivity to Cisplatin in Nasopharyngeal Carcinoma Cell Line CNE1

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua YIN; Cai-Ping REN; Feng LI; Xu-Yu YANG; Hui LI; Ming ZHAO; Kai-Tai YAO

    2004-01-01

    To explore the effect of suppressing BCL-2 expression using RNA interference (RNAi) technique in nasopharyngeal carcinoma cell line CNE1. CNE1 cell lines stably expressing shRNAs targeted bcl-2 and GL3 gene were established and gene expression inhibition was assessed by Western blotting analysis. The effect of suppressing bcl-2 by RNAi on cell growth was studied, the apoptosis induction and the sensitization of CNE 1 cells to cisplatin were quantified by MTT assay and flow cytometry. The results showed that: stable transfection of CNE 1 cells with vectors expressing shRNAs against bcl-2 decreased the expression of BCL-2 protein; suppression of BCL-2 expression did not affect cell proliferation but could increase the chemosensitivity to cisplatin in CNE1 cells. This will help physicians to make some clinical trials of gene therapy on nasopharyngeal carcinoma by RNAi.

  16. Rapid in vitro chemosensitivity analysis of human colon tumor cell lines

    International Nuclear Information System (INIS)

    In oncology, diagnostic assays have the potential to individualize treatment. Due to a large number of chemotherapeutic agents available, a chemosensitivity assay would be of great value for patients receiving chemotherapy. However, no broadly accepted test exists to date. Our work aims at establishing a chemosensitivity test using a microphysiometer, a device that measures the extracellular acidification rate of cells. The test assesses chemosensitivity by comparing the acidification rate of cells treated with cytostatic agents with that of nontreated cells. We performed experiments with two human colon tumor cell lines, HCT 116 and SW620, and cytostatic agents commonly used in therapy of colon carcinoma. We showed that a chemosensitivity test can be reproducibly performed using a microphysiometer. Suitable media and conditions for the assay were found. Test results were further correlated with the crystal violet assay and a tetrazolium salt assay. In comparison, cytostatic effects were rapidly and most clearly displayed with the microphysiometer. Our results suggest that microphysiometry is a promising platform for chemosensitivity testing

  17. RASSF1A expression inhibits cell growth and enhances cell chemosensitivity to mitomycin in BEL-7402 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    GUAN Hong-geng; XUE Wan-jiang; QIAN Hai-xin; ZHOU Xiao-jun; QIN Lei; LAN Jing

    2009-01-01

    Background The antitumor role of Ras association domain family 1A (RASSFIA) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSFIA in hepatoceliular carcinoma, and study the mechanisms of cell apoptosis induced by RASSFIA.Methods After stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Westem blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.Results Wild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatJn treatment.Conclusion Wild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.

  18. In Vitro Chemosensitivity Testing of Primary and Recurrent Breast Carcinomas and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    Zhi LI; Haiping SONG; Wenshan HE; Yuan TIAN; Tao HUANG

    2008-01-01

    In this study, in vitro chemosensitivity testing was conducted on primary cultured breast cancer cells from 96 patients with breast cancer, and the results showed that the cells from a few patients with primary breast cancer developed multidrug resistance (MDR) prior to the first chemotherapy exposure. All the cells from the recurrent cancer patients had MDR. The findings suggested that patients having MDR would benefit from high-dose chemotherapy (HDC) regimens. In vitro chemosensitivity screening, which was aimed at improving the therapeutic efficacy and minimizing side effects, helps in choosing individualized treatment for breast cancer.

  19. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kasamatsu, Atsushi, E-mail: kasamatsua@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Uzawa, Katsuhiro, E-mail: uzawak@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Endo-Sakamoto, Yosuke; Ogawara, Katsunori [Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Shiiba, Masashi; Takiguchi, Yuichi [Medical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Tanzawa, Hideki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan)

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  20. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    International Nuclear Information System (INIS)

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  1. Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells

    Directory of Open Access Journals (Sweden)

    He Fan

    2010-12-01

    Full Text Available Abstract Background Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. Methods Two cervical cancer cell lines, HeLa and Siha, an ovarian cancer cell line, SKOV3, and a non-small cell lung cancer cell line, A549, were treated with saikosaponins or cisplatin individually or in combination. Cell death was quantitatively detected by the release of lactate dehydrogenase (LDH using a cytotoxicity detection kit. Cellular ROS was analyzed by flow cytometry. Apoptosis was evaluated by AO/EB staining, flow cytometry after Anexin V and PI staining, and Western blot for caspase activation. ROS scavengers and caspase inhibitor were used to determine the roles of ROS and apoptosis in the effects of saikosaponins on cisplatin-induced cell death. Results Both saikosaponin-a and -d sensitized cancer cells to cisplatin-induced cell death in a dose-dependent manner, which was accompanied with induction of reactive oxygen species (ROS accumulation. The dead cells showed typical apoptotic morphologies. Both early apoptotic and late apoptotic cells detected by flow cytometry were increased in saikosaponins and cisplatin cotreated cells, accompanied by activation of the caspase pathway. The pan-caspase inhibitor z-VAD and ROS scanvengers butylated hydroxyanisole (BHA and N-acetyl-L-cysteine (NAC dramatically suppressed the potentiated cytotoxicity achieved by combination of saikosaponin-a or -d and cisplatin. Conclusions These results suggest that saikosaponins sensitize cancer cells to cisplatin through ROS-mediated apoptosis, and the combination of saikosaponins with cisplatin could be an effective therapeutic strategy.

  2. Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Amer Khalid

    2009-08-01

    Full Text Available Abstract Background NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.

  3. Lactate as a fuel for mitochondrial respiration

    DEFF Research Database (Denmark)

    Van Hall, Gerrit

    2000-01-01

    and also in other tissues. Studies using lactate isotopes have shown that skeletal muscle extracts lactate from the circulation despite a substantial net lactate release, and that skeletal muscle has a large capacity for lactate oxidation; these processes being enhanced with exercise. Lactate...... muscle lactate metabolism presented is in essence based on a synthesis of old and more recent studies on skeletal muscle lactate transport, uptake, release, oxidation, and the role of LDH at rest and during exercise....

  4. Systematically characterizing and prioritizing chemosensitivity related gene based on Gene Ontology and protein interaction network

    Directory of Open Access Journals (Sweden)

    Chen Xin

    2012-10-01

    Full Text Available Abstract Background The identification of genes that predict in vitro cellular chemosensitivity of cancer cells is of great importance. Chemosensitivity related genes (CRGs have been widely utilized to guide clinical and cancer chemotherapy decisions. In addition, CRGs potentially share functional characteristics and network features in protein interaction networks (PPIN. Methods In this study, we proposed a method to identify CRGs based on Gene Ontology (GO and PPIN. Firstly, we documented 150 pairs of drug-CCRG (curated chemosensitivity related gene from 492 published papers. Secondly, we characterized CCRGs from the perspective of GO and PPIN. Thirdly, we prioritized CRGs based on CCRGs’ GO and network characteristics. Lastly, we evaluated the performance of the proposed method. Results We found that CCRG enriched GO terms were most often related to chemosensitivity and exhibited higher similarity scores compared to randomly selected genes. Moreover, CCRGs played key roles in maintaining the connectivity and controlling the information flow of PPINs. We then prioritized CRGs using CCRG enriched GO terms and CCRG network characteristics in order to obtain a database of predicted drug-CRGs that included 53 CRGs, 32 of which have been reported to affect susceptibility to drugs. Our proposed method identifies a greater number of drug-CCRGs, and drug-CCRGs are much more significantly enriched in predicted drug-CRGs, compared to a method based on the correlation of gene expression and drug activity. The mean area under ROC curve (AUC for our method is 65.2%, whereas that for the traditional method is 55.2%. Conclusions Our method not only identifies CRGs with expression patterns strongly correlated with drug activity, but also identifies CRGs in which expression is weakly correlated with drug activity. This study provides the framework for the identification of signatures that predict in vitro cellular chemosensitivity and offers a valuable

  5. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

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

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated...

  6. Safety assessment of lactate esters

    NARCIS (Netherlands)

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

    1998-01-01

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

  7. Mixed glucose and lactate uptake by Corynebacterium glutamicum through metabolic engineering.

    Science.gov (United States)

    Neuner, Andreas; Heinzle, Elmar

    2011-03-01

    The Corynebacterium glutamicum ATCC 13032 lysC(fbr) strain was engineered to grow fast on racemic mixtures of lactate and to secrete lysine during growth on lactate as well as on mixtures of lactate and glucose. The wild-type C. glutamicum only grows well on L-lactate. Overexpression of D-lactate dehydrogenase (dld) achieved by exchanging the native promoter of the dld gene for the stronger promoter of the sod gene encoding superoxide dismutase in C. glutamicum resulted in a duplication of biomass yield and faster growth without any secretion of lysine. Elementary mode analysis was applied to identify potential targets for lysine production from lactate as well as from mixtures of lactate and glucose. Two targets for overexpression were pyruvate carboxylase and malic enzyme. The overexpression of these genes using again the sod promoter resulted in growth-associated production of lysine with lactate as sole carbon source with a carbon yield of 9% and a yield of 15% during growth on a lactate-glucose mixture. Both substrates were taken up simultaneously with a slight preference for lactate. As surmised from the elementary mode analysis, deletion of glucose-6-phosphate isomerase resulted in a decreased production of lysine on the mixed substrate. Elementary mode analysis together with suitable objective functions has been found a very useful tool guiding the design of strains producing lysine on mixed substrates. PMID:21370474

  8. Extended lactation in dairy cows

    DEFF Research Database (Denmark)

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

    2008-01-01

    of the lactation, protein and fat percentages increasing and lactose percentage decreasing, irrespective of treatment. The quality of the milk for processing into cheese, fermented products, heat-treated products and cream liqueurs was assessed by calculation of casein number (casein protein as a...... supplementary concentrate from week 9 of lactation onwards. Commencing at the same time, half of the udder of each cow was subjected to increased milking frequency (thrice daily rather than twice daily). Lactation persistency (and hence total milk yield) was significantly increased by frequent milking. Winter...... calving cows and supplemented cows also exhibited better persistency, but this was only evident up until the point of re-breeding, at around lactation week 33. Milk composition was measured in the spring-calving cows in both their first and second extended lactations. Composition altered during the course...

  9. Targeted Therapies in Epithelial Ovarian Cancer

    OpenAIRE

    Jurjees Hasan; Loaie El-Helw; Emma Dean

    2010-01-01

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the a...

  10. Azathioprine treatment during lactation

    DEFF Research Database (Denmark)

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

    2008-01-01

    BACKGROUND: Thiopurines are widely used to maintain remission in inflammatory bowel disease. Treatment during pregnancy is generally recommended to improve the chance of a normal birth outcome, but advice concerning breastfeeding is conflicting. Aim To estimate the exposure of breastfed infants to...... 6-mercaptopurine, as a metabolite of azathioprine, from maternal milk. METHODS: Eight lactating women with inflammatory bowel disease receiving maintenance therapy with azathioprine 75-200 mg daily were studied. Milk and plasma samples were obtained 30 and 60 min after drug administration and hourly...... maternal milk. After 6 h an average of 10% of the peak values were measured. CONCLUSIONS: The major part of 6-mercaptopurine in breast milk is excreted within the first 4 h after drug intake. On the basis of maximum concentration measured, the infant ingests mercaptopurine of <0.008 mg/kg bodyweight/24 h...

  11. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal

    Directory of Open Access Journals (Sweden)

    Choi Cheol-Hee

    2005-10-01

    Full Text Available Abstract One of the major problems related with anticancer chemotherapy is resistance against anticancer drugs. The ATP-binding cassette (ABC transporters are a family of transporter proteins that are responsible for drug resistance and a low bioavailability of drugs by pumping a variety of drugs out cells at the expense of ATP hydrolysis. One strategy for reversal of the resistance of tumor cells expressing ABC transporters is combined use of anticancer drugs with chemosensitizers. In this review, the physiological functions and structures of ABC transporters, and the development of chemosensitizers are described focusing on well-known proteins including P-glycoprotein, multidrug resistance associated protein, and breast cancer resistance protein.

  12. 20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

    Science.gov (United States)

    Liu, Junhua; Wang, Xu; Liu, Peng; Deng, Rongxin; Lei, Min; Chen, Wantao; Hu, Lihong

    2013-07-15

    Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells. PMID:23683834

  13. CD80 antigen expression as a predictor of ex vivo chemosensitivity in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kivekäs, Ilkka; Hulkkonen, Janne; Hurme, Mikko; Vilpo, Leena; Vilpo, Juhani

    2002-05-01

    We investigated the correlation between expression of 31 surface membrane antigens and chemosensitivity of peripheral blood mononuclear cells from 36 patients with CLL. The sensitivity of CLL cells to nine drugs (2'-chlorodeoxyadenosine, cisplatin, chlorambucil, cyclosporin A, doxorubicin, fludarabine, prednisolone, verapamil and vincristine) and two types of irradiation (gamma and UV-irradiation) was determined from dose-response curves of 4-day cultures ex vivo. The results indicated that the CLL cases responding to purine analogs (2'-chlorodeoxyadenosine and fludarabine) can be identified according to CD80 expression: all resistant cases had low or negative CD80 expression. No other correlations were revealed. CD80 may be a surrogate chemosensitivity marker for purine analogs. PMID:11916516

  14. Respiratory control in the newborn : Central chemosensitivity, neuropeptides and nicotinic effects

    OpenAIRE

    Wickström, Ronny

    2002-01-01

    Breathing is regulated by a complex network of neurons located mainly in the brainstem. For the newborn, it is critical for survival that a continuous respiration is established after birth. However, the regulation of respiration also undergoes maturation in the postnatal period. This thesis focuses on some of the systems modulating respiration that may be of great importance for the newborn: central (C02) chemosensitivity and the neuropeptides substance P (SP) and galanin ...

  15. EFFECTS OF SIMULATED MICROGRAVITY ON PROLIFERATION AND CHEMOSENSITIVITY IN MALIGNANT GLIOMA CELLS

    OpenAIRE

    Kurisu, Kaoru; Takeda, Masaaki; Okazaki, Takahito; Kawahara, Yumi; Yuge, Lous

    2014-01-01

    BACKGROUND: Everything on the earth can be affected by gravity of the earth. So, microgravity, as small as 10 minus 3 times G, can make some effects to the growth or maturation of cells. Under this hypothesis we examined cell proliferation and chemosensitivity after exposure to simulated microgravity using the malignant glioma cell lines. We exposed cells to simulated microgravity using a 3D-clinostat which is a type of rotating culture system that has two independent axes of rotation to disp...

  16. Aurora A反义寡核苷酸对肺癌细胞A549的作用和对紫杉醇化疗敏感性的影响%The effect of antisense oligodeoxynucleotides targeting Aurora A kinase on cell proliferation and chemosensitivity to paclitaxel in human lung cancer cell line A549

    Institute of Scientific and Technical Information of China (English)

    Rui Meng; Gang Wu; Jing Cheng; Tao Wang

    2007-01-01

    Objective:Aurora A kinase representing a family of evolutionarily conserved mitotic serine/threonine kinases has been found elevated in human lung adenocarcinoma cell line A549.It is suggested that the overexpression of Aurora A contributes to the carcinogenesis,chromosomal instability (CIN),and de-differentiation of lung cancers.To address its possibility as a therapeutic target for lung cancer,we employed the antisense oligodeoxynucleotide (ASODN) technique to inhibi Aurora A expression and investigate its effects on tumor growth and cell cycle of A549.as well as the chemosensitivilty to paclitaxel.Methods:Aurora A ASODN was synthesized and transfected into A549 cells by lipofectAMINE 2000.Aurora A mRNA and protein expression were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.Cell cycle distribution was observed by flow cytometer.MTT assay was used to evaluate cell inhibition ratio before and after transfection.Results:The proliferation of the A549 cell swas inhibited by Aurora AASODN dose and time dependently.It was also observed thal the IC50 of A549 cells after 48 hours'treatmenl of ASODN was about 300 nmol/L and under such circumstances,the Aurora A mRNA and protein expression significantly decreased(P<0.05),along with the induction of accumulation of cells in S phase and the G2-M transition.Furlhermore.cell inhibition ratio of the combination of Aurora AASODN and paclitaxel was higher significantly than paclitaxel(P<0.05)or Aurora AASODN alone (P<0.05).Conclusion:Inhibition of Aurora A expression can result in the suppression of cell growth and chemosensilizina activity to paclitaxel in human lung cancer cell line A549.

  17. Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Xie Li

    2009-02-01

    Full Text Available Abstract Background Astrocyte elevated gene-1 (AEG-1 was originally characterized as a HIV-1-inducible gene in primary human fetal astrocyte. Recent studies highlight a potential role of AEG-1 in promoting tumor progression and metastasis. The aim of this study was to investigate if AEG-1 serves as a potential therapeutic target of human neuroblastoma. Methods We employed RNA interference to reduce AEG-1 expression in human neuroblastoma cell lines and analyzed their phenotypic changes. Results We found that the knockdown of AEG-1 expression in human neuroblastoma cells significantly inhibited cell proliferation and apoptosis. The specific downregulation induced cell arrest in the G0/G1 phase of cell cycle. In the present study, we also observed a significant enhancement of chemo-sensitivity to cisplatin and doxorubicin by knockdown of AEG-1. Conclusion Our study suggests that overexpressed AEG-1 enhance the tumorogenic properties of neuroblastoma cells. The inhibition of AEG-1 expression could be a new adjuvant therapy for neuroblastoma.

  18. Increased leucine-rich repeats and immunoglobulin- like domains 1 expression enhances chemosensitivity in glioma

    Institute of Scientific and Technical Information of China (English)

    Baohui Liu; Shenqi Zhang; Dong Ruan; Xiaonan Zhu; Zhentao Guo; Huimin Dong; Mingmin Yan; Qianxue Chen; Daofeng Tian; Liquan Wu; Junmin Wang; Qiang Cai; Heng Shen; Baowei Ji; Long Wang

    2011-01-01

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is an anti-oncogene.LRIG1 is correlated with Bcl-2 in ependymomas.Decreased Bcl-2 and manganese superoxide dismutase expression can improve the chemosensitivity of glioma.In the present study, a tissue microarray of human brain astrocytomas was constructed.To investigate the relationship of LRIG1 with Bcl-2 and manganese superoxide dismutase, LRIG1, Bcl-2 and manganese superoxide dismutase expression in our tissue microarray was determined using immunohistochemistry.In addition, we constructed the LRIG1-U251 cell line, and its responses to doxorubicin and temozolomide were detected using the MTT assay.Results showed that LRIG1 expression was significantly negatively correlated with Bcl-2 and manganese superoxide dismutase expression in glioma.Also, proliferation of LRIG1-U251 cells exposed to doxorubicin or temozolomide was significantly inhibited, i.e.in the LRIG1-U251 cell line, the chemosensitivity to doxorubicin and temozolomide was increased.This indicates that increased LRIG1 expression produces a chemosensitivity in glioma.

  19. Lactate levels with glioblastoma multiforme.

    Science.gov (United States)

    Kahlon, Arunpreet Singh; Alexander, Mariam; Kahlon, Arundeep; Wright, Jonathan

    2016-07-01

    A 37-year-old woman with known glioblastoma multiforme was admitted for treatment of new deep vein thrombosis. Anion gap and plasma lactate levels were found to be elevated. Magnetic resonance imaging of the brain showed a stable, advanced glioblastoma multiforme. All causes of lactic acidosis, including infections and medications, were ruled out. Aggressive tumors have been shown to produce lactate levels in minute quantities in their microenvironment, which helps them metastasize and evade immune response and even radiation. PMID:27365883

  20. Lactate levels with glioblastoma multiforme

    OpenAIRE

    Kahlon, Arunpreet Singh; Alexander, Mariam; Kahlon, Arundeep; Wright, Jonathan

    2016-01-01

    A 37-year-old woman with known glioblastoma multiforme was admitted for treatment of new deep vein thrombosis. Anion gap and plasma lactate levels were found to be elevated. Magnetic resonance imaging of the brain showed a stable, advanced glioblastoma multiforme. All causes of lactic acidosis, including infections and medications, were ruled out. Aggressive tumors have been shown to produce lactate levels in minute quantities in their microenvironment, which helps them metastasize and evade ...

  1. Lactating Adenoma of the Breast.

    Science.gov (United States)

    Barco Nebreda, Israel; Vidal, M Carmen; Fraile, Manel; Canales, Lydia; González, Clarisa; Giménez, Nuria; García-Fernández, Antonio

    2016-08-01

    Lactating adenoma is an uncommon breast palpable lesion occurring in pregnancy or lactation. Although it is a benign condition, it often requires core biopsy or even surgery to exclude malignancy. As with other solid lesions in pregnancy and lactation, lactating adenoma needs an accurate evaluation in order to ensure its benign nature. Work-up must include both imaging and histologic findings. Ultrasound evaluation remains the first step in assessing the features of the lesion. Some authors consider magnetic resonance imaging as a useful tool in cases of inconclusive evaluation after ultrasound and histologic exam in an attempt to avoid surgery. Most lactating adenomas resolve spontaneously, whereas others persist or even increase in size and must be removed. The authors present a case of a 35-year-old woman at 6 months postpartum with a lactating adenoma in her right breast. After surgical removal, breastfeeding was perfectly continued within the next 24 hours, which highlights the fact that breast surgery is most often compatible with breastfeeding. PMID:27197575

  2. Targeting the oxidative stress response system of fungi with safe, redox-potent chemosensitizing agents

    Science.gov (United States)

    One mode of action of the antimycotics amphotericin B (AMB) or itraconazole (ITZ) against filamentous fungi involves cellular oxidative stress response. Aspergillus fumigatus sakA', a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidation system, was more sensitive to AMB ...

  3. Lactate clearance in cardiorespiratory emergency

    Directory of Open Access Journals (Sweden)

    Serena Greco

    2007-08-01

    Full Text Available Early goal directed therapy has been found to improve prognosis in septic patients, if the therapeutic goal is achieved within the first six hours. The aim of our study is to demonstrate that in patients with acute cardiorespiratory failure, rapid (within 2 hours lactate clearance can help define patients’ prognosis. 67 consecutive patients, admitted to our 16-bed Emergency Medicine ward for acute cardiorespiratory failure (age 75,9 ± 9,8 (APACHE II score 19,0 ± 4,1, were included in the study. Blood lactate concentration was read at admission and after 2, 6 and 24 hours. We evaluated mortality at seven days and the use of orotracheal intubation (patients with negative outcome vs. discharge or transfer to a non-emergency ward with subsequent discharge (patients with negative outcome. Lactate concentration at admission was 4,6 ± 2,5 mmol/l; lactate clearance (% at 2 hours was 40,4 ± 32,1 in patients with a positive outcome and –8,3 ± 5,0 in patients with a negative outcome (p < 0,05. Lactate clearance at 2 hours < 25% is correlated to a negative outcome with an 84,2% sensitivity and a 79,2% specificity. The positive predictive value was 61,5% and the negative predictive value was 92,2%. Systematic lactate clearance monitoring can be used in cases of acute cardiorespiratory insufficiency to identify patients with a high risk of negative outcome. In our study, low clearance at two hours was associated with an increase in mortality and/or the need for orotracheal intubation. Conversely, a clearance at two hours of > 25% in most cases confirms the therapeutic strategy undertaken. Serial evaluation of blood lactate concentration may therefore be useful in guiding treatment strategies.

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    This study tested the hypothesis that a 3-week oral lactate supplementation affects postexercise blood lactate disappearance in untrained male subjects. Fifteen men were randomly assigned to either a lactate supplementation (n = 8) or a placebo (n = 7) treatment. During the treatment period they...... drank an oral lactate or a maltodextrin (placebo) supplement twice a day. The lactate drink contained 10 g of lactate as calcium, sodium, and potassium salts. Blood lactate concentrations were studied before, during, and immediately after three exercise tests, both pre- and posttreatment. Peak lactate...... during the long (30- to 45-min) recovery periods amounted to / 10 mmol/L. Blood lactate changes were highly reproducible. However, a 3-week oral lactate supplementation did not result in differences in lactate disappearance. This study does not support the hypothesis that regular oral lactate intake at...

  5. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

    2013-11-15

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  6. Deregulation of MicroRNA-375 inhibits cancer proliferation migration and chemosensitivity in pancreatic cancer through the association of HOXB3

    Science.gov (United States)

    Yang, Dejun; Yan, Ronglin; Zhang, Xin; Zhu, Zhenxin; Wang, Changming; Liang, Chao; Zhang, Xin

    2016-01-01

    Background: The expression pattern and regulatory effect of microRNA-375 (miR-375) in human pancreatic cancer was explored. Methods: Gene expression of miR-375 was compared between pancreatic tumors and non-tumorous pancreatic tissues, as well as pancreatic cancer cell lines and normal epithelial cells. MiR-375 was downregulated in pancreatic cancer cell lines, Capan-1 and PANC-1 cells, to assess possible tumor suppressive effects on cancer proliferation, migration, cisplatin chemosensitivity and in vivo growth of tumor explant. The regulation of miR-375 on its target gene, homeobox B3 (HOXB3) gene, was assessed though luciferase activity assay and qRT-PCR. HOXB3 was also downregulated in Capan-1 and PANC-1 cells to assess its functional correlation with miR-375 on cancer regulation. Results: MiR-375 was upregulated in pancreatic tumors and pancreatic cancer cell lines. MiR-375 downregulation had tumor suppressive effects in Capan-1 and PANC-1 cells by reducing cancer proliferation & migration, increasing cisplatin sensitivity and inhibiting in vivo tumor explant growth. HOXB3 was directly bound by miR-375, and was negatively regulated by miR-375 in pancreatic cancer cells. Subsequent HOXB3 downregulation reversed the suppression of miR-375 downregulation on cancer proliferation, migration and cisplatin chemosensitivity in pancreatic cancer. Conclusion: MiR-375 is an oncogene in pancreatic cancer. Deregulation of miR-375 is inhibitory to the development of pancreatic cancer, and reversely regulated by HOXB3. PMID:27186281

  7. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    International Nuclear Information System (INIS)

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  8. Noscapine chemosensitization enhances docetaxel anticancer activity and nanocarrier uptake in triple negative breast cancer.

    Science.gov (United States)

    Doddapaneni, Ravi; Patel, Ketan; Chowdhury, Nusrat; Singh, Mandip

    2016-08-01

    Chemosensitization and enhanced delivery to solid tumor are widely explored strategies to augment the anticancer efficacy of existing chemotherapeutics agents. The aim of current research was to investigate the role of low dose Noscapine (Nos) in potentiating docetaxel cytotoxicity and enhancing tumor penetration of nanocarriers. The objectives are; (1) To evaluate the chemo-sensitizing effect of Nos in combination with docetaxel (DTX), and to elucidate the possible mechanism (2) To investigate the effect of low dose Nos on tumor stroma and enhancing nanocarrier uptake in triple negative breast cancer (TNBC) bearing nude mice. Cytotoxicity and flow cytometry analysis of DTX in Nos (4µM) pre-treated MDA-MB-231 cells showed 3.0-fold increase in cell killing and 30% increase in number of late apoptotic cells, respectively. Stress transducer p38 phosphorylation was significantly upregulated with Nos exposure. DTX showed remarkable downregulation in expression of bcl-2, survivin and pAKT in Nos pre-treated MDA-MB-231 cells. Nos pre-sensitization significantly (p<0.02) enhanced the anti-migration effect of DTX. In vivo studies in orthotopic TNBC tumor bearing mice showed marked reduction in tumor collagen-I levels and significantly (p<0.03) higher intra-tumoral uptake of coumarin-6 loaded PEGylated liposomes (7-fold) in Nos treated group. Chemo-sensitization and anti-fibrotic effect of Nos could be a promising approach to increase anticancer efficacy of DTX which can be used for other nanomedicinal products. PMID:27177833

  9. Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas

    International Nuclear Information System (INIS)

    Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed. To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-κB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation. The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-κB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes. Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects

  10. Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Woo, Seon Rang [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Juhn, Kyoung-Mi; Ju, Yeun-Jin; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun Ran; Park, In-chul; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Jung-Kee [Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735 (Korea, Republic of); Kim, Hae Kwon [Department of Biotechnology, Seoul Woman' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-74-2 (Korea, Republic of); Park, Gil Hong [Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2011-01-14

    Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, and eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.

  11. Cerebral and muscle deoxygenation, hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness during incremental exercise.

    Science.gov (United States)

    Peltonen, Juha E; Paterson, Donald H; Shoemaker, J Kevin; Delorey, Darren S; Dumanoir, Gregory R; Petrella, Robert J; Kowalchuk, John M

    2009-10-31

    To examine if cerebral (frontal cortex) and skeletal muscle (m. vastus lateralis) deoxygenation and cerebral blood flow velocity (V(mean)) in the middle cerebral artery differentiated between normoxic and hypoxic (end-tidal P(O)(2) 71 mmHg) conditions, and if they were associated with hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness, 8 men performed incremental cycling trials (30W/min ramp) under normoxic (T1-N) and hypoxic (T1-H) conditions until volitional fatigue, or until arterial O2 saturation decreased below 80%. The tests were repeated (T2-N; T2-H) on another day with supplemental O2 (Sup-O2) at the end of exercise. The V(mean) response was similar in normoxia and hypoxia. In hypoxia compared to normoxia, cerebral deoxygenation ( upward arrow deoxyhemoglobin concentration (Delta[HHb]) and downward arrow tissue oxygenation index (TOI)) was greater at a given work rate. A strong hypoxic ventilatory chemosensitivity was associated with a rapid reduction of cerebral TOI (r=0.94, PMuscle deoxygenation was similar in normoxia and hypoxia suggesting greater muscle blood flow in hypoxia compared to normoxia and thus the existence of control features that match muscle perfusion and O2 delivery tightly with O2 demand during exercise. Sup-O2 reduced both cerebral and muscle deoxygenation, at least transiently. PMID:19729079

  12. A case of advanced intrahepatic cholangiocarcinoma successfully treated with chemosensitivity test-guided systemic chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Kazumichi Abe; Takeru Wakatsuki; Fumiko Katsushima; Kyoko Monoe; Yukiko Kanno; Atsushi Takahashi; Junko Yokokawa; Hiromasa Ohira

    2009-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment Ⅷ of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion.After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

  13. Inducing Lactation: Breastfeeding for Adoptive Moms

    Science.gov (United States)

    ... Español Text Size Email Print Share Inducing Lactation: Breastfeeding for Adoptive Moms Page Content Article Body A growing number of adoptive mothers are interested in breastfeeding their babies through induced lactation. Prescription Medications No ...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Lactate is shuttled between organs, as demonstrated in the Cori cycle. Although the brain releases lactate at rest, during physical exercise there is a cerebral uptake of lactate. Here, we evaluated the cerebral lactate uptake and release in hypoxia, during exercise and when the two interventions...

  15. Radionuclides and maternal lactation

    International Nuclear Information System (INIS)

    The increase in the number of nuclear medicine centers, both official and private in the country, as well as the increase in the number of patients, due to the effectiveness of their diagnostic and therapeutic procedures, brings out new situations that must be studied from the point of view of radioprotection. This work makes a revision in the medical literature about procedures with radioisotopes during the maternal nursing period. In general, it is recommended to stop nursing for 24 hours for 99mtc test, and to resume it after the draining of the milky content. This can be done in spite of the sensitivity of the target organ of the baby, because the dosage will be below permissible limits accepted by international agencies with respect to diagnostic test and I-131 treatment, and if continuing nursing is desired, it is recommended to use other diagnostic or therapeutic procedures before discontinuing the most important nutritional resource at this age

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

    Directory of Open Access Journals (Sweden)

    Pollard Katherine S

    2007-11-01

    Full Text Available Abstract Background The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood. Results 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. Conclusion 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.

  17. Aptamer–polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing

    Science.gov (United States)

    Shen, Qinglin; Peng, Caixia; Zhan, Yan; Fan, Liang; Wang, Mengyi; Zhou, Qing; Liu, Jue; Lv, Xiaojuan; Tang, Qiu; Li, Jun; Huang, Xiaodong; Xia, Jiahong

    2016-01-01

    Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs), which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer–poly (N-isopropylacrylamide) functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush), which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate–tumor chemosensitivity assay, and the results suggested that our method can determine which agent and what concentration have the best chemosensitivity for the culturing recovered CTCs. So, the novel method capable of a highly effective capture and recovery of high viability CTCs will pave the way for chemosensitivity testing. PMID:27274239

  18. Aptamer-polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing.

    Science.gov (United States)

    Shen, Qinglin; Peng, Caixia; Zhan, Yan; Fan, Liang; Wang, Mengyi; Zhou, Qing; Liu, Jue; Lv, Xiaojuan; Tang, Qiu; Li, Jun; Huang, Xiaodong; Xia, Jiahong

    2016-01-01

    Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs), which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer-poly (N-isopropylacrylamide) functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush), which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate-tumor chemosensitivity assay, and the results suggested that our method can determine which agent and what concentration have the best chemosensitivity for the culturing recovered CTCs. So, the novel method capable of a highly effective capture and recovery of high viability CTCs will pave the way for chemosensitivity testing. PMID:27274239

  19. In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Pathak K

    2007-01-01

    Full Text Available Context : Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s will achieve the maximum clinical response. Aims : To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. Settings and Design : Prospective study in a tertiary cancer care center. Methods and Material : We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA and correlated them to the clinical response to chemotherapy. Statistical Analysis Used : Chi Square test. Results : Biopsy samples were successfully histocultured in 52/57 (91% cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52% tumors were sensitive to cisplatin, 27 (52% to methotrexate, 24 (46% to 5-fluorouracil, 38 (73% to combination of cisplatin and methotrexate and 36 (69% to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03 between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. Conclusions : We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

  20. 200th anniversary of lactate research in muscle.

    Science.gov (United States)

    Gladden, L Bruce

    2008-07-01

    This year, 2008, marks the bicentennial of research into lactate metabolism in muscle. Berzelius linked lactate accumulation to exercise in 1807/1808 when he noted the presence of lactate in the muscles of "hunted stags." Today, the exact mechanism of intramuscular lactate oxidation and the relationship of lactate dehydrogenase to mitochondria remain unresolved as animated debate surrounds the intracellular lactate shuttle. PMID:18580290

  1. Milk Yield of Holstein Cows Induced into Lactation Twice Consecutively and Lactation Curve Models Fitted to Artiifcial Lactations

    Institute of Scientific and Technical Information of China (English)

    Jesus Mellado; Edgar Sepulveda; Jose E Garcia; Alvaro Rodriguez; Maria A De Santiago; Francisco G Veliz; Miguel Mellado

    2014-01-01

    Nineteen multiparous barren Holstein cows were subjected to an induction of lactation protocol for 21 d administering estradiol cypionate (2 mg kg-1 of body weight (BW) d-1, on day 1 to 14), progesterone (0.10 mg kg-1 of BW, on day 1 to 7), lfumethasone (0.03 mg kg-1 of BW, on day 18 to 20) and recombinant bovine somatotropin (rbST;500 mg per cow, on day 1, 6, 16 and 21). At the end of lactation and with a minimum of a 2-mon dry period, the same cows were again hormonally induced into lactation. Cows in both lactations were not artiifcially inseminated, they were milked 3 times daily and received rbST throughout lactation. Mean accumulated milk yield at 305 d in milk (DIM) did not differ between the ifrst and second induced lactations ((9 710 ±1 728) vs. (9 309±2 150) kg;mean±SD). Total milk yield ((12 707±3 406) vs. (12 306±4 218) kg;mean±SD) and lactation length ((405±100) vs. (410±91) d;mean±SD) were not different between the ifrst and second induced lactations. In a second study, 15 empirical models including exponential, power law, yield-density, sigmoidal and miscellaneous models were compared for their suitability by modeling 12-mon (n=334), 18-mon (n=164) and 29-mon (n=22) lactation cycles of Holsteins cows induced into lactation and treated with rbST throughout the lactation. Hoerl (Y=ab1/xxc), Wood (Y=axb exp(cx)) and Dhanoa (Y=ax(bc)exp(cx)) models were equally suitable to describe 12-mon lactations. An exponential model with ifve parameters (Y=exp(a+bx+cd2+e/x)) showed the best ift for milk yield for 18-mon lactations. The rational model (Y=a+bx/1+cx+dx2) was found to produce the closest ift for 29-mon lactations. It was concluded that, with the protocol used in the present study, multiparous cows respond favorably to a second cycle of induced lactation, with milk yield similar to that experienced during the ifrst cycle. Thus, dairy producers might be able to lengthen the productive life of infertile high producing cows with a renewal of

  2. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  3. Chemosensitivity of radioresistant cells in the multicellular spheroids of A549 lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Huang Gang

    2009-06-01

    Full Text Available Abstract Background The relapse of cancer after radiotherapy is a clinical knotty problem. Previous studies have demonstrated that the elevation of several factors is likely in some way to lead to the development of treatment tolerance, so it is necessary to further explore the problem of re-proliferated radioresistant cells to chemotherapeutic agents. In the present study, we aimed to investigate the chemosensitivity of radioresistant cells originated from the multicellular spheroids of A549 lung adenocarcinoma. Methods After irradiated with 25 Gy of 6 MV X-ray to A549 multicellular spheroids, whose 10th re-proliferated generations were employed as radioresistant cells, and the control groups were A549 parental cells and MCF7/VCR resistant cells. The chemo-sensitivity test was made by six kinds of chemotherapeutic drugs which were DDP, VDS, 5-Fu, HCP, MMC and ADM respectively, while verapamil (VPL was used as the reversal agent. Then the treatment effect was evaluated by MTT assay, and the multidrug resistant gene expressions of mdr1 and MRP were measured by RT-PCR. Results Both A549 parental cells and A549 derived radioresistant cells were resistant to DDP, but sensitive to VDS, 5-Fu, HCP, MMC and ADM. The inhibitory rates of VPL to these two types of cell were 98% and 25% respectively (P Mdr1/β2-MG and MRP/β2-MG of all A549 cells were about 0 and 0.7 respectively, and those of MCF7/VCR cells were 35 and 4.36. Conclusion The chemosensitivity of A549 radioresistant cells had not changed markedly, and the decreased sensitivity to VPL could not be explained by the gene expression of mdr1 and MRP. It is possible that the changes in the cell membrane and decreased proliferate ability might be attributed to the resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to radioresistant cells. Therefore, the new biological strategy needs to be developed to treat recurring radioresistant tumor in combination

  4. Continuous lactation in dairy cows

    DEFF Research Database (Denmark)

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

    2008-01-01

    milk yield higher than 45 kg/d were studied in 28 Holstein dairy cows managed without bovine somatotropin. Performance and metabolic parameters were followed in late gestation and in the following early lactation. Fourteen cows were milked continuously throughout late gestation, and another 14 dairy...... lactating mammary epithelial cells, nor to systemic endocrine changes. This suggests that lowered mammary nutrient uptake must have been associated with reduced mammary blood flow, metabolic activity, or both, most likely as a result of disturbed lactogenesis I prepartum or lactogenesis II postpartum...... triggered by as yet unknown local mechanisms. Milk protein content was elevated by 0.4 percentage units in the continuously milked cows. The underlying reason is unknown, but given the current pricing system for milk, it deserves to be further investigated....

  5. Lactational Terror in Virtual Space

    OpenAIRE

    Marcinkiewicz, Aleksandra

    2014-01-01

    The aim of paper is to show problem of putting social pressure on mothers to breastfeeding. The internet forum about terror lactation was analyzed. In research used qualitative analyses of context. The results of study had shown the ratio of mothers to breastfeed, forms of pressure on mothers and social groups which put this pressure. It was shown stereotypes which exist in virtual space about women and breastfeeding. 1 119 134 7 Kultura-Społeczeństwo-Edukacja

  6. Treatment of mastitis during lactation

    OpenAIRE

    Pyörälä S

    2009-01-01

    Abstract Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, bec...

  7. B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity in U937 cells

    Directory of Open Access Journals (Sweden)

    Zhang W

    2015-07-01

    function of B7-H3 and a promising therapeutic approach targeting B7-H3 in acute monocytic leukemia. Keywords: B7-H3, acute monocytic leukemia, cancer gene therapy, chemosensitivity

  8. Comparison of the ability of some radiosensitizers undergoing clinical trials to act as chemosensitizers

    International Nuclear Information System (INIS)

    The abilities of misonidazole, Ro 05-9963, Ro 03-8799 and Sr-2508 to enhance the action of the drugs cyclophosphamide (CY) and melphalan (L-PAM) have been compared in two mouse fibrosarcomas at acute and chronic sensitizer doses. SR-2508 was not effective with either CY or L-PAM in either tumor. Some enhancement of CY was obtained with Ro 05-9963 and Ro 03-8799; however, the degree of enhancement varied according to tumor and acute or chronic sensitizer dose. In all cases, the degree of enhancement was less than that obtained with an equivalent dose of misonidazole in both tumor systems. Of the four compounds tested, MISO would appear to have the most potential as a chemosensitizer

  9. Lactate transport and receptor actions in cerebral malaria

    DEFF Research Database (Denmark)

    Mariga, Shelton T; Kolko, Miriam; Gjedde, Albert;

    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...

  10. Chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the chemosensitivity of irradiated resistant cells of multicellular spheroids in A549 lung adenocarcinoma. Methods: The A549 irradiated resistant cells were the 10th regrowth generations after irradiated with 2.5 Gy of 6 MV X-ray, the control groups were A549 parent cells and MCFY/VCR resistant cells. The 6 kinds of chemotherapeutic drugs were DDP, VDS, 5-FU, HCP, MMC and ADM respectively, with verapamil (VPL) as reverse agent. The treatment effect was compared with MTT assay, and the multidrug resistant gene expressions of mdrl and MRP were measured with RT-PCR method. Results: A549 cells and irradiated resistant cells were resistant to DDP, but sensitivity to VDS,5-FU, HCP, MMC and ADM. The inhibitory rates of VPL to the above two cells were 98% and 25% respectively(P2-MG and MRP/β2-MG of all A549 cells were about 0 and 0.7 respectively, and those of MCFT/VCR cells were 35 and 4.36. Conclusion: The chemosensitivity of A549 irradiated resistant cells had not changed markedly, the decreased sensitivity to VPL could not be explained by the gene expression of mdrl and MRP. It is conferred that some kinds of changes in the cell membrane and decreased regrowth ability to result in resistance. Unlike multidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to irradiated resistant cells. The new kinds of biological preparation should be sought to combine chemotherapy to treat recurring tumor with irradiated resistance. (authors)

  11. The Effect of Primary Cancer Cell Culture Models on the Results of Drug Chemosensitivity Assays: The Application of Perfusion Microbioreactor System as Cell Culture Vessel

    OpenAIRE

    Chia-Hsun Hsieh; Yi-Dao Chen; Shiang-Fu Huang; Hung-Ming Wang; Min-Hsien Wu

    2015-01-01

    To precisely and faithfully perform cell-based drug chemosensitivity assays, a well-defined and biologically relevant culture condition is required. For the former, a perfusion microbioreactor system capable of providing a stable culture condition was adopted. For the latter, however, little is known about the impact of culture models on the physiology and chemosensitivity assay results of primary oral cavity cancer cells. To address the issues, experiments were performed. Results showed that...

  12. Chemosensitivity assay in mice prostate tumor: Preliminary report of flow cytometry, DNA fragmentation, ion ratiometric methods of anti-neoplastic drug monitoring

    OpenAIRE

    Kline Richard; Sharma Rakesh

    2004-01-01

    Abstract Flow cytometry, DNA fragmentation, ion ratiomateric analysis and NMR peaks characterized drug chemosensitivity of antineoplastic drugs. Hypotheses were: 1. The chemosensitive effect of different cancer cell lines is characteristic; 2. DNA fragmentation, ion ratiometric analysis suggest apoptosis status of tumor cells. Methods PC-3 cell lines were compared with DU-145, LNCaP cell lines in culture for the [Na]i and [Ca]i ion sensing dyes, cell death, NMR peaks and apoptosis staining fo...

  13. Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling

    OpenAIRE

    Nilov, D.; Prokhorova, E.; Švedas, V.

    2015-01-01

    The human lactate dehydrogenase isoform A plays an important role in the anaerobic metabolism of tumour cells and therefore constitutes an attractive target in the oncology field. Full-atom models of lactate dehydrogenase A (in complex with NADH and in the apo form) have been generated to enable structure-based design of novel inhibitors competing with pyruvate and NADH. The structural criteria for the selection of potential inhibitors were established, and virtual screening of a library of l...

  14. Aptamer-polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing

    Directory of Open Access Journals (Sweden)

    Shen QL

    2016-05-01

    Full Text Available Qinglin Shen1,2,*, Caixia Peng2,3,*, Yan Zhan1, Liang Fan1, Mengyi Wang1, Qing Zhou4, Jue Liu2,4, Xiaojuan Lv1, Qiu Tang1, Jun Li1,2, Xiaodong Huang2, Jiahong Xia2 1Department of Oncology, 2Key Laboratory for Molecular Diagnosis of Hubei Province, 3Central Laboratory, 4Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs, which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer–poly (N-isopropylacrylamide functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush, which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate–tumor chemosensitivity

  15. Lactate metabolism in the fetal rabbit lung

    International Nuclear Information System (INIS)

    Lactate is frequently overlooked as a potential substrate for the fetal lung, even though it is present in the fetal circulation in concentrations as high as 8 mM. These high concentrations, coupled with the relatively low levels of glucose in the fetal blood, may indicate that lactate can substitute for glucose in pulmonary energy generation and phospholipid synthesis. A series of experiments was therefore undertaken in order to investigate the role of lactate in perinatal pulmonary development. Explants from 30 day gestation fetal rabbit lungs were incubated in Krebs-Ringer bicarbonate buffer supplemented with 3 mM (U-14C)-glucose and varying levels of lactate. In the absence of medium lactate, fetal rabbit lung explants were capable of producing lactate at a rate of approximately 200 etamoles/mg protein/hour. The addition of lactate to the bathing medium immediately reduced net lactate production and above 4 mM, fetal rabbit lung explants became net utilizers of lactate. Media lactate concentrations of 2.5 mM, 5 mM and 10 mM also decreased glucose incorporation into total tissue disaturated phosphatidylcholine by approximately 20%, 35%, and 45%, respectively. Glucose incorporation into surfactant phosphatidylcholine was also reduced by approximately 50%, when lactate was present in the incubation medium at a concentration of 5 mM. Additional experiments also revealed that fetal lung lactate dehydrogenase activity was almost twice that found in the adult rabbit lung. These data indicate that lactate may be an important carbon source for the developing lung and could be a significant component in the manufacture of surfactant phosphatidylcholine during late gestation

  16. Lactate fuels the human brain during exercise

    DEFF Research Database (Denmark)

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

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up...... suggests that lactate may partially replace glucose as a substrate for oxidation. Thus, the notion of the human brain as an obligatory glucose consumer is not without exceptions....... blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation...

  17. Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

    DEFF Research Database (Denmark)

    Wan, P; Li, Q; Eklund, AC;

    2012-01-01

    The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333...... compounds with reliable experimental half maximum growth inhibitions (GI(50)) values for 30 cell lines from the NCI60 data set and evaluated their growth inhibitory effect (chemosensitivity) with respect to tissue of origin. This was done by identifying natural clusters in the chemosensitivity data set and...... in a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively...

  18. Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data

    DEFF Research Database (Denmark)

    Wan, Peng; Li, Qiyuan; Larsen, Jens Erik Pontoppidan;

    2012-01-01

    The NCI60 database is the largest available collection of compounds with measured anti-cancer activity. The strengths and limitations for using the NCI60 database as a source of new anti-cancer agents are explored and discussed in relation to previous studies. We selected a sub-set of 2333...... compounds with reliable experimental half maximum growth inhibitions (GI50) values for 30 cell lines from the NCI60 data set and evaluated their growth inhibitory effect (chemosensitivity) with respect to tissue of origin. This was done by identifying natural clusters in the chemosensitivity data set and in...... a data set of expression profiles of 1901 genes for the corresponding tumor cell lines. Five clusters were identified based on the gene expression data using self-organizing maps (SOM), comprising leukemia, melanoma, ovarian and prostate, basal breast, and luminal breast cancer cells, respectively...

  19. Endurance training increases brain lactate uptake during hypoglycemia by up regulation of brain lactate transporters.

    Science.gov (United States)

    Aveseh, Malihe; Nikooie, Rohollah; Sheibani, Vahid; Esmaeili-Mahani, Saeed

    2014-08-25

    The capacity of the brain to metabolize non-glucose substrates under hypoglycemic state maintains its energy requirements. We hypothesized that exercise-induced increase in capacity for brain utilization of lactate by up regulation of the monocarboxylate transporters (MCTs) may contribute metabolic substrates during hypoglycemia in diabetic rats induced by streptozotocin. The induced diabetes increased MCT1 and MCT2 expression in the cortex and the hippocampus in the sedentary diabetic animals. There were exercise-induced increases in MCT1 in the cortex and the hippocampus and MCT2 expression in the cortex in trained diabetic animals; whereas, no changes were found in the healthy trained animals. Both diabetic and healthy trained animals showed higher values for brain lactate uptake during insulin-induced hypoglycemia when animals were intraperitoneally injected by L(+)-lactic acid. However, the response of counterregulatory hormones during hypoglycemia were blunted in the diabetic trained animals which indicates to carefully monitoring of glycemic targets both during and following prolonged exercise. PMID:25004253

  20. Lactate clearance in cardiorespiratory emergency

    OpenAIRE

    Serena Greco; Giovanna Guiotto; Antonino Maffei; Stefania Martino; Giuseppe Romano; Fernando Schiraldi

    2007-01-01

    Early goal directed therapy has been found to improve prognosis in septic patients, if the therapeutic goal is achieved within the first six hours. The aim of our study is to demonstrate that in patients with acute cardiorespiratory failure, rapid (within 2 hours) lactate clearance can help define patients’ prognosis. 67 consecutive patients, admitted to our 16-bed Emergency Medicine ward for acute cardiorespiratory failure (age 75,9 ± 9,8) (APACHE II score 19,0 ± 4,1), we...

  1. Clinical significance of chemosensitivity in chronic heart failure: influence on neurohormonal derangement, Cheyne-Stokes respiration and arrhythmias

    OpenAIRE

    Giannoni, Alberto; Emdin, Michele; Poletti, Roberta; Bramanti, Francesca; Prontera, Concetta; Piepoli, Massimo; Passino, Claudio

    2007-01-01

    Abstract Increased chemosensitivity has been observed in heart failure (HF). To investigate its pathophysiological and clinical relevance, we evaluated its impact on neurohormonal balance, breathing pattern, response to exercise, and arrhythmic profile. Sixty patients with chronic HF (age 66?1 years, left ventricular ejection fraction, EF, 31?1%, mean?SEM) underwent assessment of hypoxic-normocapnic (HVR) and hypercapnic-normoxic ventilatory response (HCVR), neurohormonal evaluat...

  2. Impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer

    OpenAIRE

    Xu, Ke; Liu, Bin; Liu, Yongyu

    2015-01-01

    The objective of the current study was to investigate the impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer (NSCLC). In 115 archived NSCLC tissue samples, the expression of Brachyury was observed to be significantly higher than that in adjacent normal lung tissues. In addition, the current study demonstrated that the expression of Brachyury is closely associated with TNM staging, lymph node metastasis and the prognosis of NSCLC, altho...

  3. Integration of photothermal therapy and synergistic chemotherapy by a porphyrin self-assembled micelle confers chemosensitivity in triple-negative breast cancer.

    Science.gov (United States)

    Su, Shishuai; Ding, Yanping; Li, Yiye; Wu, Yan; Nie, Guangjun

    2016-02-01

    Triple-negative breast cancer is a malignant cancer type with a high risk of early recurrence and distant metastasis. Unlike other breast cancers, triple-negative breast cancer is lack of targetable receptors and, therefore, patients largely receive systemic chemotherapy. However, inevitable adverse effects and acquired drug resistance severely constrain the therapeutic outcome. Here we tailor-designed a porphyrin-based micelle that was self-assembled from a hybrid amphiphilic polymer comprising polyethylene glycol, poly (d, l-lactide-co-glycolide) and porphyrin. The bilayer micelles can be simultaneously loaded with two chemotherapeutic drugs with synergistic cytotoxicity and distinct physiochemical properties, forming a uniform and spherical nanostructure. The drug-loaded micelles showed a tendency to accumulate in the tumor and can be internalized by tumor cells for drug release in acidic organelles. Under near-infrared laser irradiation, high density of self-quenched porphyrins in the hydrophobic layer absorbed light efficiently and converted into an excited state, leading to the release of sufficient heat for photothermal therapy. The integration of localized photothermal effect and synergistic chemotherapy conferred great chemosensitivity to cancer cells and achieved tumor regression using about 1/10 of traditional drug dosage. As a result, chemotherapy-associated adverse effects were successfully avoided. Our present study established a novel porphyrin-based nanoplatform with photothermal activity and expanded drug loading capacity, providing new opportunities for challenging conventional chemotherapy and fighting against stubborn triple-negative breast cancer. PMID:26708642

  4. STUDY ON RELATIONSHIP BETWEEN CHEMOSENSITIVITY OF BREAST CANCER AND EXPRESSION OF p73α AND p53

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xin; SUN Zhi-jun

    2005-01-01

    Objective: To investigate the relationship between the expression of p73α and p53 versus the chemosensitivity in breast cancer cells. Methods: Twelve surgical samples of breast cancer diagnosed by pathology were used. The cancer sample cells were separately cultured in the incubator at 37℃, 5% CO2 in vitro. The relative inhibition rate of cancer cells by 4 kinds of anticancer drugs, which were EPI, MMC, 5-Fu and DDP, were assayed by MTT method. Immunocytochemistry was used to detect the expression of p73α and p53 in the cancer cells. Results: The positive expression of p73α was found in 5/12 (41.67%), and p53 positive expression rate was 50.0% (6/12). The relative inhibition rate of MMC, EPI, 5-Fu and DDP were significantly higher in the p73α positive cancer cells than in the p73α negative cancer cells. A positive correlation was found between expression of p73α and chemosensitivity for all the four anticancer drugs. Conclusion: The expression of p73α is related with the chemosensitivity of the breast cancer cells, and it may become one of the markers for judging the effect of chemotherapy in clinic.

  5. Physiological and Biochemical Characteristics of Lactation in Half-lactating Yak

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yu-cai; ZHONG Guang-hui; WANG Yong; PENG Xian-wen; MAO Yong-jiang; ZOU Si-xiang; CHEN Wei-hua; CHEN Jie

    2002-01-01

    Yaks of two lactating types, the half-lactating yak and the total lactating yak, were investigated in their milk compositions, milk coagulation properties, and contents of three kinds of hormones, glucose,and protein in plasma. The half-lactating Maiwa yak and Jiulong yak contained significantly higher contents of protein, fat, and activities of alkaline phosphatase and γ-glutamyl transpeptidase in milk than that of the corresponding total-lactating yak breeds, with reduced milk yield and similar lactose level and relative percentages of main milk protein components. The half-lactatin yak resembled yaks in a late stage of lactation in their biochemical composition of milk; however, significant differences were also observed, which indicated that the former was in a special stage of lactation quite different from dairy cows. Milk of the total-lactating or halflactating yaks could be coagulated normally by adding chymosin, with a similar coagulation time. No significant difference was observed between prolactin and progesterone concentrations in plasma of the half-lactating yaks and total-lactating yaks; however, half-lactating yaks had significantly lower level of oestradiol-17 β in plasma than total-lactating yaks.

  6. Modeling cerebral arteriovenous lactate kinetics after intravenous lactate infusion in the rat

    NARCIS (Netherlands)

    Leegsma-Vogt, G; van der Werf, T; Venema, K; Korf, J

    2004-01-01

    Venous-arterial lactate differences across the brain during lactate infusion in rats were studied, and the fate of lactate was described with a mathematical model that includes both cerebral and extracerebral kinetics. Ultrafiltration was used to sample continuously and simultaneously arterial and v

  7. Lactation associated with herpes zoster pectoralis.

    Science.gov (United States)

    Bhattacharya, S K; Girgla, H S

    1976-05-01

    The phenomenon of lactation associated with herpes zoster is unexpected. To our knowledge such an association has been reported only once. A case is reported in whom spontaneous lactation occurred in the ipsilateral breast following herpes zoster. It is believed to have resulted from stimulation of the intercostal nerve endings supplying the overlying skin of the breast. PMID:945354

  8. Interaction of Factors Related to Lactation Duration

    OpenAIRE

    Boettcher, Joan P; Chezem, Jo Carol; Roepke, Judith; Whitaker, Tracy Adams

    1999-01-01

    Perceived social support and interpersonal dependency were studied as potential factors associated with lactation duration based upon previous breastfeeding experience. Inexperienced breastfeeding mothers perceived more social support than experienced breastfeeding mothers did. Perceived social support was not significantly correlated with lactation duration. An ancillary finding was that women providing a combination of breast milk and human milk substitutes had significantly lower social se...

  9. Lactate transport and signaling in the brain

    DEFF Research Database (Denmark)

    Bergersen, Linda Hildegard

    2015-01-01

    Lactate acts as a ‘buffer’ between glycolysis and oxidative metabolism. In addition to being exchanged as a fuel by the monocarboxylate transporters (MCTs) between cells and tissues with different glycolytic and oxidative rates, lactate may be a ‘volume transmitter’ of brain signals. According to...

  10. Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eun Ah Song

    2016-08-01

    Full Text Available The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA, shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells’ molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies.

  11. Role of EGFR mutations in lung cancers: prognosis and tumor chemosensitivity.

    Science.gov (United States)

    Suda, Kenichi; Mitsudomi, Tetsuya

    2015-08-01

    Lung cancers with an epidermal growth factor receptor (EGFR) gene mutation account for ~40 % of adenocarcinomas in East Asians and ~15 % of those in Caucasians and African Americans, which makes them one of the most common molecularly defined lung cancer subsets. The discriminative clinical and pathological features of lung cancers with EGFR mutations have been intensively studied, and the predictive role of an EGFR mutation for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) is well established. However, controversial issues remain regarding the clinical and therapeutic implications of EGFR mutations in lung cancers. These include the prognostic impact of the EGFR mutation, its predictive implication for successful treatment with anticancer agents other than EGFR-TKIs, appropriate cytotoxic agents for lung cancers with this mutation, and the chemosensitivity of EGFR-mutation-positive lung cancers after acquisition of resistance to EGFR-TKIs. In this review, we discuss these unanswered but important questions, referring to in vitro studies, basic research, retrospective analyses, and the results of phase III clinical trials. PMID:25983263

  12. Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.

    Science.gov (United States)

    Gruosso, Tina; Mieulet, Virginie; Cardon, Melissa; Bourachot, Brigitte; Kieffer, Yann; Devun, Flavien; Dubois, Thierry; Dutreix, Marie; Vincent-Salomon, Anne; Miller, Kyle Malcolm; Mechta-Grigoriou, Fatima

    2016-01-01

    Anti-cancer drugs often increase reactive oxygen species (ROS) and cause DNA damage. Here, we highlight a new cross talk between chronic oxidative stress and the histone variant H2AX, a key player in DNA repair. We observe that persistent accumulation of ROS, due to a deficient JunD-/Nrf2-antioxidant response, reduces H2AX protein levels. This effect is mediated by an enhanced interaction of H2AX with the E3 ubiquitin ligase RNF168, which is associated with H2AX poly-ubiquitination and promotes its degradation by the proteasome. ROS-mediated H2AX decrease plays a crucial role in chemosensitivity. Indeed, cycles of chemotherapy that sustainably increase ROS reduce H2AX protein levels in Triple-Negative breast cancer (TNBC) patients. H2AX decrease by such treatment is associated with an impaired NRF2-antioxidant response and is indicative of the therapeutic efficiency and survival of TNBC patients. Thus, our data describe a novel ROS-mediated regulation of H2AX turnover, which provides new insights into genetic instability and treatment efficacy in TNBC patients. PMID:27006338

  13. The chemosensitizing agent lubeluzole binds calmodulin and inhibits Ca(2+)/calmodulin-dependent kinase II.

    Science.gov (United States)

    Bruno, Claudio; Cavalluzzi, Maria Maddalena; Rusciano, Maria Rosaria; Lovece, Angelo; Carrieri, Antonio; Pracella, Riccardo; Giannuzzi, Giulia; Polimeno, Lorenzo; Viale, Maurizio; Illario, Maddalena; Franchini, Carlo; Lentini, Giovanni

    2016-06-30

    An affinity capillary electrophoresis (ACE) method to estimate apparent dissociation constants between bovine brain calmodulin (CaM) and non-peptidic ligands was developed. The method was validated reproducing the dissociation constants of a number of well-known CaM ligands. In particular, the potent antagonist 125-C9 was ad hoc synthesized through an improved synthetic procedure. The ACE method was successfully applied to verify CaM affinity for lubeluzole, a well-known neuroprotective agent recently proved useful to potentiate the activity of anti-cancer drugs. Lubeluzole was slightly less potent than 125-C9 (Kd = 2.9 ± 0.7 and 0.47 ± 0.06 μM, respectively) and displayed Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibition (IC50 = 40 ± 1 μM). Possible binding modes of lubeluzole to CaM were explored by docking studies based on the X-ray crystal structures of several trifluoperazine-CaM complexes. An estimated dissociation constant in good agreement with the experimental one was found and the main aminoacidic residues and interactions contributing to complex formation were highlighted. The possibility that interference with Ca(2+) pathways may contribute to the previously observed chemosensitizing effects of lubeluzole on human ovarian adenocarcinoma and lung carcinoma cells are discussed. PMID:27043269

  14. Yeast cell-based analysis of human lactate dehydrogenase isoforms.

    Science.gov (United States)

    Mohamed, Lulu Ahmed; Tachikawa, Hiroyuki; Gao, Xiao-Dong; Nakanishi, Hideki

    2015-12-01

    Human lactate dehydrogenase (LDH) has attracted attention as a potential target for cancer therapy and contraception. In this study, we reconstituted human lactic acid fermentation in Saccharomyces cerevisiae, with the goal of constructing a yeast cell-based LDH assay system. pdc null mutant yeast (mutated in the endogenous pyruvate decarboxylase genes) are unable to perform alcoholic fermentation; when grown in the presence of an electron transport chain inhibitor, pdc null strains exhibit a growth defect. We found that introduction of the human gene encoding LDHA complemented the pdc growth defect; this complementation depended on LDHA catalytic activity. Similarly, introduction of the human LDHC complemented the pdc growth defect, even though LDHC did not generate lactate at the levels seen with LDHA. In contrast, the human LDHB did not complement the yeast pdc null mutant, although LDHB did generate lactate in yeast cells. Expression of LDHB as a red fluorescent protein (RFP) fusion yielded blebs in yeast, whereas LDHA-RFP and LDHC-RFP fusion proteins exhibited cytosolic distribution. Thus, LDHB exhibits several unique features when expressed in yeast cells. Because yeast cells are amenable to genetic analysis and cell-based high-throughput screening, our pdc/LDH strains are expected to be of use for versatile analyses of human LDH. PMID:26126931

  15. Inhibition of Bcl-2 expression by a novel tumor-specific RNA interference system increases chemosensitivity to 5-fluorouracil in Hela cells

    Institute of Scientific and Technical Information of China (English)

    Sheng-lin HUANG; Yi WU; Hai YU; Ping ZHANG; Xing-qian ZHANG; Lei YING; Han-fang ZHAO

    2006-01-01

    Aim: RNA interference (RNAi) has been proposed as a potential treatment for cancer, but the lack of cellular targets limits its use in cancer gene therapy. No current technology has achieved direct tumor-specific gene silencing using RNAi.In the present study we attempt to develop a tumor-specific RNAi system using the human telomerase reverse transcriptase (hTERT) promoter; furthermore, we analyzed its inhibitive effect on Bcl-2 expression. Methods: The vectors containing a small hairpin RNA (shRNA) to target exogenous reporters [firefly luciferase and enhanced green fluorescent protein (EGFP)] and endogenous gene (Bcl-2)were constructed. Luciferase expression was determined by dual luciferase assay.Reverse transcription-polymerase chain reaction (RT-PCR), fluorescence microscopy and fluorescence-activated cell sorting (FACS) were used to measure EGFP expression. Inhibition of Bcl-2 was evaluated by RT-PCR and Western blotting.Cell proliferation and viability were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. FACS was used to analyze the cell cycle distribution profile. Results: We showed that with the hTERT promoter directly driving shRNA transcription, expression of the exogenous reporters (LUC and EGFP) in tumor cells, but not normal cells, was specifically inhibited in vitro. The hTERT promoter-driven shRNA also depressed the expression of Bcl-2. Inhibition of Bcl-2 did not affect cell proliferation, but increased the chemosensitivity of HeLa cells to 5-fluorouracil. Conclusion: The present study describes an efficient RNAi system for gene silencing that is specific to tumor cells using the hTERT promoter. Suppression of Bcl-2 by using this system sensitized HeLa cells to 5-fluorouracil. This system may be useful for RNAi therapy.

  16. Managing antiepileptic drugs during pregnancy and lactation

    DEFF Research Database (Denmark)

    Sabers, Anne; Tomson, Torbjörn

    2009-01-01

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

  17. Lactational mastitis caused by Streptococcus lactarius.

    Science.gov (United States)

    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. PMID:27220606

  18. L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis

    Directory of Open Access Journals (Sweden)

    Jaroslav Zelenka

    2015-01-01

    Full Text Available A moderate elevation of reactive oxygen species (ROS production and a mild inhibition of mitochondrial respiratory chain have been associated with a health promotion and a lifespan extension in several animal models of aging. Here, we tested whether this phenomenon called mitohormesis could be mediated by L-lactate. The treatment with 5 mM L-lactate significantly increased H2O2 production and slightly inhibited the respiration in cultured skin fibroblasts and in isolated mitochondria. The L-lactate exposure was associated with oxidation of intracellular glutathione, phosphorylation of 5′AMP-activated protein kinase (AMPK, and induction of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α transcription. A replicative aging of fibroblasts (L0 with a constant (LC, or intermittent 5 mM L-lactate (LI in media showed that the high-passage LI fibroblasts have higher respiration, lower H2O2 release, and lower secretion of L-lactate compared to L0 and LC. This protection against mitochondrial dysfunction in LI cells was associated with lower activity of mechanistic target of rapamycin complex 1 (mTORC1, less signs of cellular senescence, and increased autophagy compared to L0 and LC. In conclusion, we demonstrated that intermittent but not constant exposure to L-lactate triggers mitohormesis, prevents aging-associated mitochondrial dysfunction, and improves other markers of aging.

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

    KAUST Repository

    Boury-Jamot, B

    2015-10-27

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

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

    Science.gov (United States)

    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. PMID:26503760

  1. Inhibition of stress mediated cell death by human lactate dehydrogenase B in yeast.

    Science.gov (United States)

    Sheibani, Sara; Jones, Natalie K; Eid, Rawan; Gharib, Nada; Arab, Nagla T T; Titorenko, Vladimir; Vali, Hojatollah; Young, Paul A; Greenwood, Michael T

    2015-08-01

    We report the identification of human L- lactate dehydrogenase B (LDHB) as a novel Bax suppressor. Yeast heterologously expressing LDHB is also resistant to the lethal effects of copper indicating that it is a general suppressor of stress mediated cell death. To identify potential LDHB targets, LDHB was expressed in yeast mutants defective in apoptosis, necrosis and autophagy. The absence of functional PCD regulators including MCA1, YBH3, cyclophilin (CPR3) and VMA3, as well as the absence of the pro-survival autophagic pathway (ATG1,7) did not interfere with the LDHB mediated protection against copper indicating that LDHB functions independently of known PCD regulators or by simply blocking or stimulating a common PCD promoting or inhibitory pathway. Measurements of lactate levels revealed that short-term copper stress (1.6 mM, 4 h), does not increase intracellular levels of lactate, instead a three-fold increase in extracellular lactate was observed. Thus, yeast cells resemble mammalian cells where different stresses are known to lead to increased lactate production leading to lactic acidosis. In agreement with this, we found that the addition of exogenous lactic acid to growth media was sufficient to induce cell death that could be inhibited by the expression of LDHB. Taken together our results suggest that lactate dehydrogenase is a general suppressor of PCD in yeast. PMID:26032856

  2. miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kinya Okamoto

    Full Text Available BACKGROUND AND AIMS: Cholangiocarcinoma (CCA is highly resistant to chemotherapy, including gemcitabine (Gem treatment. MicroRNAs (miRNAs are endogenous, non-coding, short RNAs that can regulate multiple genes expression. Some miRNAs play important roles in the chemosensitivity of tumors. Here, we examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. METHODS: Microarray analysis was used to determine the miRNA expression profiles of two CCA cell lines, HuH28 and HuCCT1. To determine the effect of candidate miRNAs on Gem sensitivity, expression of each candidate miRNA was modified via either transfection of a miRNA mimic or transfection of an anti-oligonucleotide. Ontology-based programs were used to identify potential target genes of candidate miRNAs that were confirmed to affect the Gem sensitivity of CCA cells. RESULTS: HuCCT1 cells were more sensitive to Gem than were HuH28 cells, and 18 miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221 restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment. Selective siRNA-mediated downregulation of either of two software-predicted targets, PIK3R1 (target of miR-29b and miR-221 or MMP-2 (target of miR-29b, also conferred Gem sensitivity to HuH28. CONCLUSIONS: miRNA expression profiling was used to identify key miRNAs that regulate Gem sensitivity in CCA cells, and software that predicts miRNA targets was used to identify promising target genes for anti-tumor therapies.

  3. Augmenting the Activity of Monoterpenoid Phenols against Fungal Pathogens Using 2-Hydroxy-4-methoxybenzaldehyde that Target Cell Wall Integrity.

    Science.gov (United States)

    Kim, Jong H; Chan, Kathleen L; Mahoney, Noreen

    2015-01-01

    Disruption of cell wall integrity system should be an effective strategy for control of fungal pathogens. To augment the cell wall disruption efficacy of monoterpenoid phenols (carvacrol, thymol), antimycotic potency of benzaldehyde derivatives that can serve as chemosensitizing agents were evaluated against strains of Saccharomyces cerevisiae wild type (WT), slt2Δ and bck1Δ (mutants of the mitogen-activated protein kinase (MAPK) and MAPK kinase kinase, respectively, in the cell wall integrity pathway). Among fourteen compounds investigated, slt2Δ and bck1Δ showed higher susceptibility to nine benzaldehydes, compared to WT. Differential antimycotic activity of screened compounds indicated "structure-activity relationship" for targeting the cell wall integrity, where 2-hydroxy-4-methoxybenzaldehyde (2H4M) exhibited the highest antimycotic potency. The efficacy of 2H4M as an effective chemosensitizer to monoterpenoid phenols (viz., 2H4M + carvacrol or thymol) was assessed in yeasts or filamentous fungi (Aspergillus, Penicillium) according to European Committee on Antimicrobial Susceptibility Testing or Clinical Laboratory Standards Institute M38-A protocols, respectively. Synergistic chemosensitization greatly lowers minimum inhibitory or fungicidal concentrations of the co-administered compounds. 2H4M also overcame the tolerance of two MAPK mutants (sakAΔ, mpkCΔ) of Aspergillus fumigatus to fludioxonil (phenylpyrrole fungicide). Collectively, 2H4M possesses chemosensitizing capability to magnify the efficacy of monoterpenoid phenols, which improves target-based (viz., cell wall disruption) antifungal intervention. PMID:26569223

  4. Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of clear cell renal cell carcinoma.

    Science.gov (United States)

    Zhao, Ziyi; Chen, Changjin; Lin, Junzhi; Zeng, Wentong; Zhao, Juan; Liang, Yindan; Tan, Qinrui; Yang, Chao; Li, Hui

    2016-09-01

    The von Hippel-Lindau tumor suppressor (VHL; E3 ubiquitin ligase gene) is frequently mutated or undetectable in clear cell renal cell carcinoma (CCRCC), and therefore these tumors are highly resistant to chemotherapeutic agents, including adriamycin (ADM) and sunitinib. A mutation in the tumor protein p53 (TP53) also leads to chemoresistance in tumors; however, in CCRCC, TP53 is frequently functional, yet the tumors remain highly insensitive to chemotherapy. This indicates the possibility of a synergistic effect of VHL and P53 in CCRCC. The present study aimed to detect the chemosensitivity of CCRCC. The expression of VHL in the MZ1257 cell line sensitized these cells to ADM and sunitinib, and a knockdown of VHL in the ACHN cells increased their chemoresistance. To confirm that VHL and P53 are both required for chemosensitivity, VHL and P53 were co‑expressed in 786‑O cells. The results of the functional antagonist assay (which assessed the IC50 values, i.e. the half maximal inhibitory concentration) confirmed that VHL and P53 act in synergy to promote chemosensitivity. Cell cycle arrest was measured by propidium iodide staining following treatment with ADM or sunitinib. Further analysis indicated that co‑expression of VHL and P53 inhibited cell proliferation by completely inhibiting the cell cycle at the G0/G1 phase, and promoted apoptosis following treatment with ADM or sunitinib. These findings demonstrated that VHL and P53 act synergistically in the regulation of cell proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles in the regulation of cell proliferation and apoptosis in CCRCC. Furthermore, the regulatory role of VHL is dependant on the activation P53. PMID:27485825

  5. Effect of Recepteur d'Origine Nantais expression on chemosensitivity and tumor cell behavior in colorectal cancer.

    Science.gov (United States)

    Kim, Nuri; Cho, Sung-Bum; Park, Young-Lan; Park, Sun-Young; Myung, Eun; Kim, Seung-Hun; Yu, Hyung-Min; Son, Young-Ae; Myung, Dae-Seong; Lee, Wan-Sik; Joo, Young-Eun

    2016-06-01

    Recepteur d'Origine Nantais (RON) expression is known to induce oncogenic properties including tumor cell growth, survival, motility, angiogenesis and chemoresistance. In the present study, we evaluated whether RON affects chemosensitivity and oncogenic behavior of colorectal cancer cells and investigated its prognostic value in colorectal cancer. To evaluate the impact of RON on chemosensitivity and tumor cell behavior, we treated colorectal cancer cells with small interfering RNAs specific to RON. This was followed by flow cytometric analyses and migration, Matrigel invasion and endothelial tube formation assays. The expression of RON was investigated by immunohistochemistry in colorectal cancer tissues. TUNEL assay and immunohistochemical staining for CD34 and D2-40 were deployed to determine apoptosis, angiogenesis and lymphangiogenesis. RON knockdown enhanced 5-fluorouracil (FU)-induced apoptosis by upregulating the activities of caspases and expression of proapoptotic genes. Moreover, it enhanced 5-FU-induced cell cycle arrest by decreasing the expression of cyclins and cyclin‑dependent kinases and inducing that of p21. Furthermore, RON knockdown augmented the 5-FU-induced inhibition of invasion and migration of colorectal cancer cells. The β-catenin signaling cascade was blocked by RON knockdown upon 5-FU treatment. RON knockdown also decreased endothelial tube formation and expression of VEGF-A and HIF-1α and increased angiostatin expression. Furthermore, it inhibited lymphatic endothelial cell tube formation and the expression of VEGF-C and COX-2. RON expression was observed to be associated with age, tumor size, lymphovascular and perineural invasion, tumor stage, lymph node and distant metastasis, and poor survival rate. The mean microvessel density value of RON-positive tumors was significantly higher than that of RON-negative ones. These results indicate that RON is associated with tumor progression by inhibiting chemosensitivity and enhancing

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

    OpenAIRE

    Liam P. Andrus; Rachel Unruh; Wisniewski, Natalie A; McShane, Michael J.

    2015-01-01

    An optical biosensor for lactate detection is described. By encapsulating enzyme-phosphor sensing molecules within permeable hydrogel materials, lactate-sensitive emission lifetimes were achieved. The relative amount of monomer was varied to compare three homo- and co-polymer materials: poly(2-hydroxyethyl methacrylate) (pHEMA) and two copolymers of pHEMA and poly(acrylamide) (pAam). Diffusion analysis demonstrated the ability to control lactate transport by varying the hydrogel composition,...

  7. Lactate metabolism in chronic liver disease

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Barlow John W

    2013-02-01

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

  9. NEURAL PATHWAYS UNDERLYING LACTATE INDUCED PANIC

    OpenAIRE

    Johnson, Philip L.; Truitt, William A.; Fitz, Stephanie D; Lowry, Christopher A.; Shekhar, Anantha

    2007-01-01

    Panic disorder is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as 0.5 M sodium lactate infusions. Although studied for four decades, the mechanism of lactate sensitivity in panic disorder has not been understood. The dorsomedial hypothalamus/perifornical region (DMH/PeF) coordinates rapid mobilization of behavioral, autonomic, respiratory and endocrine responses to stress, and rats with disrupted GABA inhibi...

  10. ROLE OF LACTATION IN FAMILY PLANNING

    OpenAIRE

    Surekha Kishore; B S Garg; P R Deshmukh; Pradeep Aggarwal

    2010-01-01

    Objectives: 1. To evaluate the role of Lactational Amenorrhea Method (LAM) as a spacing method. 2. To assess knowledge attitude and practices regarding breastfeeding. 3. To bring awareness regarding importance of breastfeeding on child health and as a method of family planning so that exclusive breast feeding is promoted. Study Design: Cross sectional study. Setting: In rural village of district Wardha. Study Universe : All the lactating mothers who had2 children (one of which was less than 3...

  11. Intracellular Shuttle: The Lactate Aerobic Metabolism

    Directory of Open Access Journals (Sweden)

    Rogério Santos de Oliveira Cruz

    2012-01-01

    Full Text Available Lactate is a highly dynamic metabolite that can be used as a fuel by several cells of the human body, particularly during physical exercise. Traditionally, it has been believed that the first step of lactate oxidation occurs in cytosol; however, this idea was recently challenged. A new hypothesis has been presented based on the fact that lactate-to-pyruvate conversion cannot occur in cytosol, because the LDH enzyme characteristics and cytosolic environment do not allow the reaction in this way. Instead, the Intracellular Lactate Shuttle hypothesis states that lactate first enters in mitochondria and only then is metabolized. In several tissues of the human body this idea is well accepted but is quite resistant in skeletal muscle. In this paper, we will present not only the studies which are protagonists in this discussion, but the potential mechanism by which this oxidation occurs and also a link between lactate and mitochondrial proliferation. This new perspective brings some implications and comes to change our understanding of the interaction between the energy systems, because the product of one serves as a substrate for the other.

  12. Working memory and blood lactate levels.

    Science.gov (United States)

    Perciavalle, Valentina; Maci, Tiziana; Perciavalle, Vincenzo; Massimino, Simona; Coco, Marinella

    2015-11-01

    The accumulation of lactate in the blood after a high-intensity exercise is associated with an increase of lactate extractions by the brain. Previously, a negative influence of blood lactate on attentional processes has been observed. The present study was carried out to examine the association of high blood lactate levels, induced with a maximal cycling, with another cognitive domain: working memory. For evaluation of working memory two different protocols were used: the first (Self-Ordered Pointing Task) capable of analyzing non-spatial working memory requiring the ability to generate and monitor a sequence of responses and the second for evaluating motor working memory necessary to perform a motor task. The study was carried out in 30 students (15 males and 15 females) who performed exhaustive exercise. In each subject, blood lactate was measured and motor as well as non-motor forms of working memory were evaluated before the exercise, at its end as well as 15 min after the exhaustion. It was observed that an increase of blood lactate levels is associated with a worsening of both types of working memory. PMID:26169760

  13. The Therapeutic Role of Vasopressin on Improving Lactate Clearance During and After Vasogenic Shock: Microcirculation, Is It The Black Box?

    Science.gov (United States)

    Barzegar, Elchin; Ahmadi, Arezoo; Mousavi, Sarah; Nouri, Masoumeh; Mojtahedzadeh, Mojtaba

    2016-01-01

    Arginine vasopressin as a supplementary vasopressor in septic shock restores vascular tone and mean arterial pressure, meanwhile decreases dose and exposure time to catecholamines. The objective of this study was to evaluate the effect of vasopressin on lactate and lactate clearance as markers of tissue perfusion during septic shock. In this prospective, randomized, controlled trial, 30 patients with septic shock were enrolled in two groups. One group received norepinephrine infusion (titrated to reach the target MAP of ≥65 mm Hg) and the other group in addition to norepinephrine, received vasopressin at a constant rate of 0.03 u/min. Serum lactate levels were assessed at baseline, 24 and 48 hours after randomization. Lactate clearance was estimated for each patient at 24 and 48 hours. Venous lactate was measured in both groups. Despite a tendency toward higher venous lactate at 24 and 48 hours in the norepinephrine group (3.1 vs. 2.5, P=0.67 and 1.7 vs. 1.1, P=0.47), the conflict was not statistically significant among them. While lactate clearance after 24 hours was significantly higher in vasopressin treatment group (46% vs. 20%, respectively; P=0.048), the 48-hour lactate clearance did not differ from statistic viewpoints despite their clinical values (66% vs. 40%, P=0.17). Although lactate levels did not significantly differ between treatment groups, lactate clearance at 24 hours was significantly higher in vasopressin group. This may be the effect of vasopressin effect on microcirculation and tissue hypoperfusion or its catecholamine sparing effect. PMID:26853286

  14. The Therapeutic Role of Vasopressin on Improving lactate Clearance During and After Vasogenic Shock: Microcirculation, Is it The Black Box?

    Directory of Open Access Journals (Sweden)

    Elchin Barzegar

    2016-01-01

    Full Text Available Arginine vasopressin as a supplementary vasopressor in septic shock restores vascular tone and mean arterial pressure, meanwhile decreases dose and exposure time to catecholamines. The objective of this study was to evaluate the effect of vasopressin on lactate and lactate clearance as markers of tissue perfusion during septic shock. In this prospective, randomized, controlled trial, 30 patients with septic shock were enrolled in two groups. One group received norepinephrine infusion (titrated to reach the target MAP of ≥65 mm Hg and the other group in addition to norepinephrine, received vasopressin at a constant rate of 0.03 u/min. Serum lactate levels were assessed at baseline, 24 and 48 hours after randomization. Lactate clearance was estimated for each patient at 24 and 48 hours. Venous lactate was measured in both groups. Despite a tendency toward higher venous lactate at 24 and 48 hours in the norepinephrine group (3.1 vs. 2.5, P=0.67 and 1.7 vs. 1.1, P=0.47, the conflict was not statistically significant among them. While lactate clearance after 24 hours was significantly higher in vasopressin treatment group (46% vs. 20%, respectively; P=0.048, the 48-hour lactate clearance did not differ from statistic viewpoints despite their clinical values (66% vs. 40%, P=0.17. Although lactate levels did not significantly differ between treatment groups, lactate clearance at 24 hours was significantly higher in vasopressin group. This may be the effect of vasopressin effect on microcirculation and tissue hypoperfusion or its catecholamine sparing effect.

  15. The effect of adenovirus expressing wild-type p53 on 5-fiuorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Sven Eisold; Michael Linnebacher; Eduard Ryschich; Dalibor Antolovic; Ulf Hinz; Ernst Klar; Jan Schmidt

    2004-01-01

    AIM: There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU).Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status.METHODS: Human pancreatic cancer cell lines Capan-1p53mut,Capan-2p53wt, FAMPACp53mut, PANC1p53mut, and rat pancreatic cancer cell lines ASp53wt and DSL6Ap53null were used for in vitro studies. Following infection with different ratios of Adp53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivo studies.Tumor size, apoptosis (TUNEL) and survival were determined.RESULTS: Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitro and in vivo analyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU.CONCLUSION: Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

  16. Radiation-induced defects in magnesium lactate as ESR dosimeter

    CERN Document Server

    Hassan, G M; Takaki, S

    1999-01-01

    Magnesium lactate (Mg-lactate: (CH sub 3 CH(OH)COO) sub 2 Mg), magnesium lactate doped with lithium lactate (Mg(Li)-lactate) and nominal pure lithium lactate (CH sub 3 CH(OH)COOLi) doped with Mg-lactate (Li(Mg)-lactate) were irradiated by gamma-rays to study radicals for materials of radiation dosimeter with electron spin resonance (ESR). Quartet spectra were ascribed to lactate radicals in Mg-lactate and Li(Mg)-lactate with the spectroscopic splitting factors (g-factor) of 2.0032+-0.004 and 2.0029+-0.004 and the intensity ratio of 1:3:3:1 due to the hyperfine coupling constants of (A/g beta) of 1.92+-0.06 and 1.82+-0.06 mT, respectively. The response to gamma-ray dose and the thermal stability as well as the effect of UV-illumination have been studied to establish this material as an ESR dosimeter. The number of free radicals per 100 eV (G-value) was obtained to be 1.15+-0.32, 1.35+-0.35, 0.46+-0.14 and 0.78+-0.24 for Mg-lactate, Mg(Li)-lactate, Li-lactate and Lie(Mg)-lactate, respectively. Thermoluminescenc...

  17. Antitumor activity of 7-aminocarboxycoumarin derivatives, a new class of potent inhibitors of lactate influx but not efflux.

    Science.gov (United States)

    Draoui, Nihed; Schicke, Olivier; Seront, Emmanuel; Bouzin, Caroline; Sonveaux, Pierre; Riant, Olivier; Feron, Olivier

    2014-06-01

    High lactate concentration in tumors is associated with bad prognosis. Lactate is released by glycolytic cells in tumors and recaptured by oxidative cancer cells to feed the tricarboxylic acid (TCA) cycle after conversion into pyruvate. Monocarboxylate transporters (MCT) mediate these fluxes of proton-linked lactate and represent attractive targets to interrupt lactate shuttle and to inhibit tumor growth. Here, we investigated the properties of 7-aminocarboxycoumarins (7ACC) developed to selectively interfere with lactate fluxes in the lactate-rich tumor microenvironment. The pharmacologic properties of two compounds of this family, including their effects on lactate influx and efflux and antitumor activity, were investigated using human cancer cell lines and mouse xenograft models. Contrary to the reference MCT1 inhibitor AR-C155858, 7ACC unexpectedly inhibited lactate influx but not efflux in tumor cells expressing MCT1 and MCT4 transporters. 7ACC delayed the growth of cervix SiHa tumors, colorectal HCT116 tumors, and orthoptopic MCF-7 breast tumors. MCT target engagement was confirmed by the lack of activity of 7ACC on bladder UM-UC-3 carcinoma that does not express functional MCT. 7ACC also inhibited SiHa tumor relapse after treatment with cisplatin. Finally, we found that contrary to AR-C155858, 7ACC did not prevent the cell entry of the substrate-mimetic drug 3-bromopyruvate (3BP) through MCT1, and contributed to the inhibition of tumor relapse after 3BP treatment. In conclusion, our results indicate that 7ACC selectively affects a single part of the MCT symporter translocation cycle, leading to strict inhibition of lactate influx. This singular activity is associated with antitumor effects less prone to resistance and side effects. PMID:24672058

  18. Wild type p53 increased chemosensitivity of drug-resistant human hepatocellular carcinoma Be17402 / 5-FU cells

    Institute of Scientific and Technical Information of China (English)

    Yu-xiuLI; Zhi-binLIN; Huan-ranTAN

    2004-01-01

    AIM: To study the effect of wild type (wt) p53 gene transfection on drug resistant human hepatocellular carcinoma(HCC) cells induced by 5-Fluorouracil (5-FU). METHODS: The cytotoxicity of anticancer drugs on Be17402 and Be17402/5-FU cells was assessed using SRB assay, p53 expression was detected at its mRNA level by RT-PCR assay and at its protein level Western blot or immunocytochemistry assay in Be17402/5-FU cells transfected with either control vector or wt p53. AnnexinV-FITC/PI double labeled assay was performed to detect apoptosis. The chemosensitivity of Be17402/5-FU cells transfected with wt p53 was assessed using SRB assay. RESULTS: Be17402/5-FU cells exhibited cross-resistance to vincristine, doxorubicin, paclitaxel, and so on. wt p53 gene transfection upregulated the expression of p53 in Be17402/5-FU cells, wt p53 was able to greatly inhibit cell proliferation and significantly induce apoptosis in Be17402/5-FU cells. Moreover, wt p53 gene transfection increased the chemosensitivity of Be17402/5-FU cells to some anticancer drugs. CONCLUSION: These results indicated that the wt p53 gene transfection not only induced suppression of cell growth, but also increased the sensitivity of Be17402/5-FU cells to 5-FU, vincristine, and doxorubicin.

  19. Restoration of IGFBP-rP1 increases radiosensitivity and chemosensitivity in hormone-refractory human prostate cancer

    International Nuclear Information System (INIS)

    We previously reported the tumor-suppressive activity of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) through induction of apoptosis in human prostate cancer cells. The aim of this study was to investigate the effects of IGFBP-rP1 for radiosensitivity and chemosensitivity in hormone-refractory human prostate PC-3 cancer cells. Five assays were performed using PC-3 cells transfected with IGFBP-rP1 (PC-3rP1) and control cells transfected with an empty vector (PC-3N): PC-3rP1 and PC-3N were compared by clonogenic survival assay, cell cycle analysis and apoptotic assay for radiosensitivity. The number of colonies of PC-3rP1 cells significantly decreased after 4 and 8 Gy of irradiation, compared with those of PC-3N in the clonogenic survival assay. After 16 hr irradiation at 8 Gy, the percentage of apoptotic cells significantly increased in PC-3rP1 compared with PC-3N. Growth of PC-3rP1 was significantly lower than that of PC-3N after docetaxel treatment both in vitro and in vivo. These results indicate that restoration of IGFBP-rP1 to PC-3 cells increases both their radiosensitivity and chemosensitivity. (author)

  20. Chemosensitizing effect of podophyllotoxin acetate on topoisomerase inhibitors leads to synergistic enhancement of lung cancer cell apoptosis

    Science.gov (United States)

    HONG, WAN GI; CHO, JEONG HYUN; HWANG, SANG-GU; LEE, EUNAH; LEE, JAESEOK; KIM, JONG-IL; UM, HONG-DUCK; PARK, JONG KUK

    2016-01-01

    Podophyllotoxin acetate (PA) acts as a radiosensitizer against non-small cell lung cancer (NSCLC) in vitro and in vivo. In this study, we examined its potential role as a chemosensitizer in conjunction with the topoisomerase inhibitors etoposide (Eto) and camptothecin (Cpt). The effects of combinations of PA and Eto/Cpt were examined with CompuSyn software in two NSCLC cell lines, A549 and NCI-H1299. Combination index (CI) values indicated synergistic effects of PA and the topoisomerase inhibitors. The intracellular mechanism underlying synergism was further determined using propidium iodide uptake, immunoblotting and electrophoretic mobility shift assay (EMSA). Combination of PA with Eto/Cpt promoted disruption of the dynamics of actin filaments, leading to subsequent enhancement of apoptotic cell death via induction of caspase-3, -8, and -9, accompanied by increased phosphorylation of p38. Conversely, suppression of p38 phosphorylation blocked the apoptotic effect of the drug combinations. Notably, CREB-1, a transcription factor, was constitutively activated in both cell types, and synergistically inhibited upon combination treatment. Our results collectively indicate that PA functions as a chemosensitizer by enhancing apoptosis through activation of the p38/caspase axis and suppression of CREB-1. PMID:27035096

  1. Design and characterization of a lactate biosensor based on immobilized lactate oxidase onto gold surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Parra, A. [Departamento de Quimica Analitica y Analisis Instrumental, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Casero, E. [Departamento de Quimica Analitica y Analisis Instrumental, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Vazquez, L. [Instituto de Ciencia de Materiales de Madrid (CSIC), C/Sor Juana Ines de la Cruz, No 3, 28049 Madrid (Spain); Pariente, F. [Departamento de Quimica Analitica y Analisis Instrumental, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain); Lorenzo, E. [Departamento de Quimica Analitica y Analisis Instrumental, Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid (Spain)]. E-mail: encarnacion.lorenzo@uam.es

    2006-01-12

    The design and characterization of a lactate biosensor and its application to the determination of this analyte in wine and beer are described. The biosensor is developed through the immobilization of lactate oxidase (LOx) using two different strategies including direct adsorption and covalent binding. The characterization of the resulting lactate oxidase monolayers was performed in aqueous phosphate buffer solutions using atomic force microscopy (AFM) and quartz crystal microbalance (QCM) techniques. In presence of lactate and using hydroxymethylferrocene as a redox mediator, biosensors obtained by either direct adsorption or by covalent binding exhibit a clear electrocatalytic activity, and lactate could be determined amperometrically at 300 mV versus SSCE. Results obtained under these conditions give a linear current response versus lactate concentration up to 0.3 mM, with a detection limit of 10 {mu}M of lactate and a sensitivity of 0.77 {+-} 0.08 {mu}A mM{sup -1}. Finally, biosensors were applied to the determination of lactate in wine and beer. The results obtained are in good agreement with those obtained by a well-established enzymatic-spectrophotometric assay kit.

  2. Voluntary exercise during pregnancy and lactation and its effect on lactational performance in mice.

    Science.gov (United States)

    Karasawa, K; Suwa, J; Kimura, S

    1981-01-01

    The amount of voluntary exercise during pregnancy and lactation and its effect on the lactational performance in mice were investigated. Female mice were housed in exercise cages with treadwheels during periods of growth, pregnancy and lactation and the amounts of exercise were measured. It was observed that growing female mice exercised voluntarily at a level of approximately 5,000 rotations (diameter of treadwheel; 13.5 cm) per day during the 4-week growth period. After conception, the amount of exercise gradually decreased and in late pregnancy running activity decreased markedly. Throughout the lactational period dams exercised lightly. As indices of lactational performance, the body weights of pups nursed in litters of 8, milk yield and cellular development of abdominal-inguinal mammary glands were examined. There were no significant differences in the final body weights of pups, milk yield per day or development of mammary glands between exercise and non-exercise groups. PMID:7328442

  3. Chemosensitization of aflatoxigenic fungi to antimycin A and strobilurin using salicylaldehyde, a volatile natural compound targeting cellular antioxidation system

    Science.gov (United States)

    Salicylaldehyde (SA), a volatile natural compound, exhibited potent antifungal and antiaflatoxigenic activities to Aspergillus flavus and A. parasiticus. Exposure to volatilized SA, inhibited growth of A. parasiticus from 10% - 75% at 9.5 - 16.0 mM, with complete inhibition at 19.0 mM. Similar trend...

  4. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    International Nuclear Information System (INIS)

    Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO) in combination with sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells. Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC50: 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC50: 11.8 μM in LX2; 9.9 μM in HepG2). In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr) drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC)

  5. Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review

    Directory of Open Access Journals (Sweden)

    Navid Kashaninejad

    2016-07-01

    Full Text Available With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1 Lung; (2 Bone marrow; (3 Brain; (4 Breast; (5 Urinary system (kidney, bladder and prostate; (6 Intestine; and (7 Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET of

  6. Leg and arm lactate and substrate kinetics during exercise

    DEFF Research Database (Denmark)

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

    2002-01-01

    To study the role of muscle mass and muscle activity on lactate and energy kinetics during exercise, whole body and limb lactate, glucose, and fatty acid fluxes were determined in six elite cross-country skiers during roller-skiing for 40 min with the diagonal stride (Continuous Arm + Leg) followed...... by 10 min of double poling and diagonal stride at 72-76% maximal O(2) uptake. A high lactate appearance rate (R(a), 184 +/- 17 micromol x kg(-1) x min(-1)) but a low arterial lactate concentration ( approximately 2.5 mmol/l) were observed during Continuous Arm + Leg despite a substantial net lactate...... release by the arm of approximately 2.1 mmol/min, which was balanced by a similar net lactate uptake by the leg. Whole body and limb lactate oxidation during Continuous Arm + Leg was approximately 45% at rest and approximately 95% of disappearance rate and limb lactate uptake, respectively. Limb lactate...

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

    Directory of Open Access Journals (Sweden)

    Keri Linda Carpenter

    2015-04-01

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

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

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2010-01-01

    Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during exercise is much debated. In the early days skeletal muscle was mainly seen as the site of lactate production during contraction and lactate production...... lactate metabolism at rest and during exercise and suggestions are put forward to explain the simultaneous lactate uptake and release; and (2) lactate metabolism in the heart, liver, kidneys, brain, adipose tissue and lungs will be discussed and its potential importance in these tissues....

  9. Staphylococcus aureus lactate- and malate-quinone oxidoreductases contribute to nitric oxide resistance and virulence.

    Science.gov (United States)

    Spahich, Nicole A; Vitko, Nicholas P; Thurlow, Lance R; Temple, Brenda; Richardson, Anthony R

    2016-06-01

    Staphylococcus aureus is a Gram-positive pathogen that resists many facets of innate immunity including nitric oxide (NO·). Staphylococcus aureus NO-resistance stems from its ability to evoke a metabolic state that circumvents the negative effects of reactive nitrogen species. The combination of l-lactate and peptides promotes S. aureus growth at moderate NO-levels, however, neither nutrient alone suffices. Here, we investigate the staphylococcal malate-quinone and l-lactate-quinone oxidoreductases (Mqo and Lqo), both of which are critical during NO-stress for the combined utilization of peptides and l-lactate. We address the specific contributions of Lqo-mediated l-lactate utilization and Mqo-dependent amino acid consumption during NO-stress. We show that Lqo conversion of l-lactate to pyruvate is required for the formation of ATP, an essential energy source for peptide utilization. Thus, both Lqo and Mqo are essential for growth under these conditions making them attractive candidates for targeted therapeutics. Accordingly, we exploited a modelled Mqo/Lqo structure to define the catalytic and substrate-binding residues.We also compare the S. aureus Mqo/Lqo enzymes to their close relatives throughout the staphylococci and explore the substrate specificities of each enzyme. This study provides the initial characterization of the mechanism of action and the immunometabolic roles for a newly defined staphylococcal enzyme family. PMID:26851155

  10. Wearable Sensor System Powered by a Biofuel Cell for Detection of Lactate Levels in Sweat

    Science.gov (United States)

    Garcia, S. O.; Ulyanova, Y. V.; Figueroa-Teran, R.; Bhatt, K. H.; Singhal, S.; Atanassov, P.

    2016-01-01

    An NAD+-dependent enzymatic sensor with biofuel cell power source system for non-invasive monitoring of lactate in sweat was designed, developed, and tested. The sensor component, based on lactate dehydrogenase, showed linear current response with increasing lactate concentrations with limits of detection from 5 to 100 mM lactate and sensitivity of 0.2 µA.mM−1 in the presence of target analyte. In addition to the sensor patch a power source was also designed, developed and tested. The power source was a biofuel cell designed to oxidize glucose via glucose oxidase. The biofuel cell showed excellent performance, achieving over 80 mA at 0.4 V (16 mW) in a footprint of 3.5 × 3.5 × 0.7 cm. Furthermore, in order to couple the sensor to the power source, system electronic components were designed and fabricated. These consisted of an energy harvester (EH) and a micropotentiostat (MP). The EH was employed for harvesting power provided by the biofuel cell as well as up-converting the voltage to 3.0 V needed for the operation of the MP. The sensor was attached to MP for chronoamperometric detection of lactate. The Sensor Patch System was demonstrated under laboratory conditions.

  11. The Effectiveness of Lactation Consultants and Lactation Counselors on Breastfeeding Outcomes.

    Science.gov (United States)

    Patel, Sanjay; Patel, Shveta

    2016-08-01

    Breastfeeding for all infants starting at birth and continuing until at least 6 months of age has been recommended by the World Health Organization and the American Academy of Pediatrics. The health benefits to infants and mothers have been demonstrated in many studies. Dedicated lactation specialists may play a role in providing education and support to pregnant women and new mothers wishing to breastfeed to improve breastfeeding outcomes. The objective of this review was to assess if lactation education or support programs using lactation consultants or lactation counselors would improve rates of initiation and duration of any breastfeeding and exclusive breastfeeding compared with usual practice. A systematic literature review of the evidence was conducted using electronic databases. The review was limited to randomized trials and yielded 16 studies with 5084 participants. It was found that breastfeeding interventions using lactation consultants and counselors increase the number of women initiating breastfeeding (odds ratio [OR] for any initiation vs not initiating breastfeeding = 1.35; 95% confidence interval [CI], 1.10-1.67). The interventions improve any breastfeeding rates (OR for any breastfeeding up to 1 month vs not breastfeeding = 1.49; 95% CI, 1.09-2.04). In addition, there were beneficial effects on exclusive breastfeeding rates (OR for exclusive breastfeeding up to 1 month vs not exclusive breastfeeding = 1.71; 95% CI, 1.20-2.44). Most of the evidence would suggest developing and improving postpartum support programs incorporating lactation consultants and lactation counselors. PMID:26644419

  12. Targeted Therapies in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jurjees Hasan

    2010-02-01

    Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  13. Targeted Therapies in Epithelial Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

    2010-02-23

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  14. Targeted Therapies in Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer

  15. Treatment of insufficient lactation is often not evidence-based

    DEFF Research Database (Denmark)

    Axelsson, Paul Bryde; Bjerrum, Flemming; Løkkegaard, Ellen Christine Leth

    2014-01-01

    consultant. CONCLUSION: Despite lack of evidence, half of the Danish obstetric departments and neonatal wards use metoclopramide and syntocinon for insufficient lactation. Domperidone might provide an alternative, but no departments reported its use. Management of insufficient lactation should always be...

  16. Suppression of SPIN1-mediated PI3K-Akt pathway by miR-489 increases chemosensitivity in breast cancer.

    Science.gov (United States)

    Chen, Xu; Wang, Ya-Wen; Xing, Ai-Yan; Xiang, Shuai; Shi, Duan-Bo; Liu, Lei; Li, Yan-Xiang; Gao, Peng

    2016-08-01

    Drug resistance is one of the major obstacles for improving the prognosis of breast cancer patients. Increasing evidence has linked the association of aberrantly expressed microRNAs (miRNAs) with tumour development and progression as well as chemoresistance. Despite recent advances, there is still little known about the potential role and mechanism of miRNAs in breast cancer chemoresistance. Here we describe that 16 miRNAs were found to be significantly down-regulated and 11 up-regulated in drug-resistant breast cancer tissues compared with drug-sensitive tissues, using a miRNA microarray. The results also showed miR-489 to be one of the most down-regulated miRNAs in drug-resistant tissues and cell lines, as confirmed by miRNA microarray screening and real-time quantitative PCR. A decrease in miR-489 expression was associated with chemoresistance as well as lymph node metastasis, increased tumour size, advanced pTNM stage and poor prognosis in breast cancer. Functional analysis revealed that miR-489 increased breast cancer chemosensitivity and inhibited cell proliferation, migration and invasion, both in vitro and in vivo. Furthermore, SPIN1, VAV3, BCL2 and AKT3 were found to be direct targets of miR-489. SPIN1 was significantly elevated in drug-resistant and metastatic breast cancer tissues and inversely correlated with miR-489 expression. High expression of SPIN1 was associated with higher histological grade, lymph node metastasis, advanced pTNM stage and positive progesterone receptor (PR) status. Increased SPIN1 expression enhanced cell migration and invasion, inhibited apoptosis and partially antagonized the effects of miR-489 in breast cancer. PIK3CA, AKT, CREB1 and BCL2 in the PI3K-Akt signalling pathway, demonstrated to be elevated in drug-resistant breast cancer tissues, were identified as downstream effectors of SPIN1. It was further found that either inhibition of SPIN1 or overexpression of miR-489 suppressed the PI3K-Akt signalling pathway. These data

  17. Predictive value of MTT assay as an in vitro chemosensitivity testing for gastric cancer: One institution's experience

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Jin-Shui Zhu; Yi Zhang; Wei-Ming Shen; Qiang Zhang

    2008-01-01

    AIM: To investigate the predictive clinical value of in vitro 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay for directing chemosensitivity in patients with gastric cancer.METHODS: Results of a total of 353 consecutive patients with gastric cancer treated with MTT-directed chemotherapy or physician's empirical chemotherapy from July 1997 to April 2003 were reviewed and analyzed retrospectively.RESULTS: The overall 5-year survival rate of MTTsensitive group (MSG) and control group (CG) was 47.5% and 45.1%, respectively. The results of subgroup analysis with Cox proportional-hazards model were favorable for the MSG-sensitive group. However, no statistically significant difference in survival rate was observed between the two groups.CONCLUSION: Individualized chemotherapy based on in vitro MTT assay is beneficial, but needs to be confirmed by further randomized controlled trials.

  18. Lactate uptake against a concentration gradient

    DEFF Research Database (Denmark)

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

    2014-01-01

    The recently published article by Jalloh et al (Jalloh I, Helmy A, Shannon RJ, Gallagher CN, Menon D, Carpenter K, Hutchinson P. Lactate uptake by the injured human brain - evidence from an arterio-venous gradient and cerebral microdialysis study. J Neurotrauma. 2013 Aug 22. [Epub ahead of print]...... is of fundamental importance the misconception should be corrected....

  19. Lactate: panicking doctor or panicking patient?

    OpenAIRE

    de Ridder, Stijn; Kuijpers, Petra; Crijns, Harry

    2010-01-01

    We report a case of a 51-year-old man with a first panic attack associated with high serum lactate due to hyperventilation induced alkalosis. Hyperlactataemia may trigger somatically oriented tests and divert attention from diagnosing panic disorder (PD). Factors associated with underdiagnosis of PD as well as pathophysiology of hyperlactataemia will be discussed.

  20. Genetics Home Reference: lactate dehydrogenase deficiency

    Science.gov (United States)

    ... throughout the body and is important for creating energy for cells. There are five different forms of this enzyme, each made up of four ... and lactate dehydrogenase-B subunits make up the different forms of the ... large amounts of energy during high-intensity physical activity when the body's ...

  1. 21 CFR 73.165 - Ferrous lactate.

    Science.gov (United States)

    2010-04-01

    ... shall meet the specifications given in the Food Chemicals Codex, 4th ed. (1996), pp. 154 to 155, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Ferrous lactate. 73.165 Section 73.165 Food...

  2. NEUROENDOCRINE ACTIONS AND REGULATION OF HYPOTHALAMIC NEUROPEPTIDE Y DURING LACTATION

    OpenAIRE

    Crowley, W,R.; Ramoz, G.; Torto, R.; Keefe, K.A.; Wang, J.J.; Kalra, S.P.

    2007-01-01

    The expression of neuropeptide Y (NPY) and its co-messenger, agouti-related peptide (AgRP), in arcuate neurons of the hypothalamus is increased during lactation in rats. Our research has been addressing the questions of the physiological actions of these peptides during lactation and the physiological signals associated with lactation that result in increased expression of their genes. Our studies indicate that NPY and AgRP exert pleiotropic actions during lactation that help integrate neuroe...

  3. Chemosensitizing effects of carbon-based nanomaterials in cancer cells: enhanced apoptosis and inhibition of proliferation as underlying mechanisms

    Science.gov (United States)

    Erdmann, Kati; Ringel, Jessica; Hampel, Silke; Rieger, Christiane; Huebner, Doreen; Wirth, Manfred P.; Fuessel, Susanne

    2014-10-01

    Recent studies have shown that carbon nanomaterials such as carbon nanofibres (CNFs) and multi-walled carbon nanotubes (CNTs) can exert antitumor activities themselves and sensitize cancer cells to conventional chemotherapeutics such as carboplatin and cisplatin. In the present study, the chemosensitizing effect of CNFs and CNTs on cancer cells of urological origin was investigated regarding the underlying mechanisms. Prostate cancer (DU-145, PC-3) and bladder cancer (EJ28) cells were treated with carbon nanomaterials (CNFs, CNTs) and chemotherapeutics (carboplatin, cisplatin) alone as well as in combination for 24 h. Forty-eight (EJ28) or 72 h (DU-145, PC-3) after the end of treatment the effects on cellular proliferation, clonogenic survival, cell death rate and cell cycle distribution were evaluated. Depending on the cell line, simultaneous administration of chemotherapeutics and carbon nanomaterials produced an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98%, respectively, compared to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced antiproliferative effects were accompanied by an elevated cell death rate, which was predominantly mediated via apoptosis and not by necrosis. The antitumor effects of combinations with CNTs were less pronounced than those with CNFs. The enhanced effects of the combinatory treatments on cellular function were mostly of additive to partly synergistic nature. Furthermore, cell cycle analysis demonstrated an arrest at the G2/M phase mediated by a monotreatment with chemotherapeutics. Following combinatory treatments, mostly less than or nearly additive increases of cell fractions in the G2/M phase could be observed. In conclusion, the pronounced chemosensitizing effects of CNFs and CNTs were mediated by an enhanced apoptosis and inhibition of proliferation. The combination of carbon-based nanomaterials and conventional chemotherapeutics represents a novel

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pösö AR

    2002-06-01

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

  6. Mustard bran in lactating dairy cow diets.

    Science.gov (United States)

    Maiga, H A; Bauer, M L; Dahlen, C R; Badaruddin, M; Scholljegerdes, E J

    2011-06-01

    Two trials using lactating Holstein cows were conducted to evaluate effects of a diet containing oriental mustard bran on dry matter intake (DMI), milk production, milk components, and organoleptic properties. In experiment 1, 34 lactating cows (24 multiparous and 10 primiparous; days in milk ≥ 50 d) were used in a switchback design to determine the lactational response and organoleptic quality of milk when the diet contained 8% oriental mustard bran (MB) versus a control diet (CON). Mustard bran replaced a portion of soybean meal and all the beet pulp in the CON diet. Milk yields were greater for cows fed the MB diet; however, no differences were found in DMI, 3.5% fat- (FCM) or solids-corrected milk. Milk components and components production were not affected by treatment. Milk organoleptic qualities were not affected by diet. In experiment 2, 22 lactating cows (16 multiparous and 6 primiparous; days in milk ≥ 21 d) were assigned randomly within parity to receive MB or CON from wk 4 to 19 postpartum in a randomized complete block design. Cows were fed CON wk 1 to 3 postpartum. The MB diet contained the same ingredients as the CON, except sunflower seed and a portion of soybean meal were replaced with mustard bran. Milk and components data were collected during wk 3 postpartum and used as covariates to adjust treatment means. Intake was greater for cows fed the MB diet; however, daily milk, 3.5% FCM, and solids-corrected milk yields were not different between diets. Milk components and component yields were not affected by treatment. Milk urea concentration was less for cows fed the MB diet. Although cows fed the MB diet had greater DMI, this was not translated into a higher milk 3.5% FCM/DMI production efficiency ratio. During experiment 2, many cows fed MB experienced minor to severe hemolysis with bloody urine. This hemolysis believed to be caused by the S-methyl-cysteine sulfoxide contained in mustard bran could have affected milk production efficiency

  7. Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

    OpenAIRE

    Kim, J. C.; Ha, Y J; Roh, S A; Choi, E. Y.; Yoon, Y.S.; Kim, K P; Hong, Y S; Kim, T. W.; Cho, D H; Kim, S. Y.; Kim, Y.S.

    2013-01-01

    Background: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. Methods: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of t...

  8. The stress signalling pathway nuclear factor E2-related factor 2 is activated in the liver of sows during lactation

    Directory of Open Access Journals (Sweden)

    Rosenbaum Susann

    2012-10-01

    Full Text Available Abstract Background It has recently been shown that the lactation-induced inflammatory state in the liver of dairy cows is accompanied by activation of the nuclear factor E2-related factor 2 (Nrf2 pathway, which regulates the expression of antioxidant and cytoprotective genes and thereby protects tissues from inflammatory mediators and reactive oxygen species (ROS. The present study aimed to study whether the Nrf2 pathway is activated also in the liver of lactating sows. Findings Transcript levels of known Nrf2 target genes, UGT1A1 (encoding glucuronosyltransferase 1 family, polypeptide A1, HO-1 (encoding heme oxygenase 1, NQO1 (encoding NAD(PH dehydrogenase, quinone 1, GPX1 (encoding glutathione peroxidase, PRDX6 (encoding peroxiredoxin 6, TXNRD1 (encoding thioredoxin reductase 1, and SOD (encoding superoxide dismutase, in the liver are significantly elevated (between 1.7 and 3.1 fold in lactating sows compared to non-lactating sows. The inflammatory state in the liver was evidenced by the finding that transcript levels of genes encoding acute phase proteins, namely haptoglobin (HP, fibrinogen γ (FGG, complement factor B (CFB, C-reactive protein (CRP and lipopolysaccharide-binding protein (LBP, were significantly higher (2 to 8.7 fold in lactating compared to non-lactating sows. Conclusions The results of the present study indicate that the Nrf2 pathway in the liver of sows is activated during lactation. The activation of Nrf2 pathway during lactation in sows might be interpreted as a physiologic means to counteract the inflammatory process and to protect the liver against damage induced by inflammatory signals and ROS.

  9. Effects of hypoxia on expression of a panel of stem cell and chemosensitivity markers in glioblastoma cell line-derived spheroids

    DEFF Research Database (Denmark)

    Kolenda, Jesper; Jensen, Stine Skov; Aaberg-Jessen, Charlotte;

    entire immunohistochemical panel included hypoxia (HIF-1α, HIF-2α), proliferation (Ki-67) and stem cell (CD133, nestin, podoplanin, Bmi-1, Sox-2) markers as well as markers related to chemosensitivity (MGMT, MDR-1, TIMP-1, Lamp-1). Since spheroids derived in hypoxia were smaller than in normoxia, a set...... differences were found for podoplanin, nestin and TIMP-1 as well as for Ki-67. Hif-2α, Sox-2, MGMT and MDR-1 were not detectable in normoxic and hypoxic U87 spheroids. In conclusion, the expression of tumor stem cell and chemosensitivity markers seems to depend on the oxygen tension suggesting that future...... oxygen tensions below 1-5% O2 has been attributed to play a crucial role in tumorigenesis and therapeutic resistance in glioblastoma. This is in contrast to most in vitro experiments in this field being performed in atmospheric air with 21% O2. In this study the influence of hypoxia on the expression of...

  10. Glucose regulated protein 78 (GRP78) inhibits apoptosis and attentinutes chemosensitivity of gemcitabine in breast cancer cell via AKT/mitochondrial apoptotic pathway.

    Science.gov (United States)

    Xie, Jie; Tao, Zhong-Hua; Zhao, Jiang; Li, Ting; Wu, Zheng-Hua; Zhang, Jin-Feng; Zhang, Jian; Hu, Xi-Chun

    2016-06-01

    The underlying mechanism of gemcitabine resistance during breast cancer treatment remains unclear. Glucose regulated protein 78 (GRP78) frequently triggered by anticancer agents, was substantially elevated in gemcitabine resistant sublines. Ectopic expression of GRP78 changes gemcitabine chemosensitivity and apoptosis levels in breast cancer cells. Further experiments showed an involvement of caspase 9, not caspase 8, in gemcitabine resistance and GRP78-mediated chemosensitivity, suggesting that mitochondria apoptotic pathway was activated by GRP78. This finding was further supported by the observations of AKT activation, Bcl-2 increase, Bax and Bim decrease. Conclusively, GRP78 plays a vital role in gemcitabine resistance and clinical strategy to improve gemcitabine efficacy in breast cancer by manipulating GRP78 should be explored. PMID:27012209

  11. Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): Protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study

    International Nuclear Information System (INIS)

    toxicity or to drug targets, 3) to assess genomic rearrangements associated with response or resistance to FOLFOX treatment, 4) to identify an immunologic signature associated with metabolic tumor response to FOLFOX therapy and, finally, 5) to create a bank of frozen tumor samples for future studies. PePiTA is the first study to use the primitive tumor chemosensitivity assessed by metabolic imaging as a guidance for adjuvant therapy in colon cancer. It could pave the way for tailoring the treatment and avoiding useless toxicities for the patients and inadequate expenses for the society. It could also give an interesting insight into tumoral heterogeneity, resistance to chemotherapy, genetic predisposants to oxaliplatin toxicity and immune response to cancer. 2009-011445-13 ClinicalTrials.gov number, http://www.clinicaltrials.gov/NCT00994864

  12. Influence of cell heterogeneity on skeletal muscle lactate kinetics

    International Nuclear Information System (INIS)

    Lactate and [14C]lactate kinetics were studied in three rabbit skeletal muscle preparations with distinct fiber type profiles, glycolytic (99.1 +/- 0.2% type IIb fibers), oxidative (97.5 +/- 0.6% type I fibers), and mixed (type I, IIa, and IIb fibers). Single-pass perfusions were carried out for 2 h in the presence of lactate (1 mM), glucose (5 mM), [6-3H]glucose, and [U-14C]lactate. All preparations displayed net lactate release, [14C]lactate removal, and 14CO2 release. Net lactate release was greatest in the glycolytic preparation, 9.7 +/- 0.5 mumol.100 g-1.min-1, and least in the oxidative preparation, 3.7 +/- 0.2 mumol.100 g-1.min-1. [14C]lactate arteriovenous difference was greatest in the mixed preparation, 1,688 +/- 58 (disintegrations/min)/ml (dpm/ml), and least in the glycolytic preparation, 505 +/- 10.3 dpm/ml. Steady-state incorporation of [14C]lactate was observed in CO2, amino acids, and pyruvate. Tissue lactate specific activity (LSA) in all preparations was significantly lower than arterial LSA, but not significantly different from venous LSA. Estimates of lactate removal based on venous LSA were not significantly different from net glycolytic flux. In conclusion, (1) under basal, resting conditions net lactate release and [14C]lactate removal are properties of all fiber types, and (2) tracer estimates of lactate turnover in skeletal muscle reflect net glycolytic flux through pyruvate

  13. Chemosensitivity Predicted by BluePrint 80-Gene Functional Subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST)

    OpenAIRE

    Whitworth, Pat; Stork-Sloots, Lisette; de Snoo, Femke A.; Richards, Paul; Rotkis, Michael; Beatty, Jennifer; Mislowsky, Angela; Pellicane, James V.; Nguyen, Bichlien; Lee, Laura; Nash, Charles; Gittleman, Mark; Akbari, Stephanie; Beitsch, Peter D.

    2014-01-01

    Purpose The purpose of the NBRST study is to compare a multigene classifier to conventional immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) subtyping to predict chemosensitivity as defined by pathological complete response (pCR) or endocrine sensitivity as defined by partial response. Methods The study includes women with histologically proven breast cancer, who will receive neoadjuvant chemotherapy (NCT) or neoadjuvant endocrine therapy. BluePrint in combination with Mam...

  14. The Reset Hypothesis: Lactation and Maternal Metabolism

    OpenAIRE

    Stuebe, Alison M.; Rich-Edwards, Janet W.

    2008-01-01

    For maternal metabolism, pregnancy ends not with delivery, but with weaning. In several recent epidemiological studies, authors have reported an association between duration of breast-feeding and reduced maternal risk of metabolic disease. These findings parallel data from animal models showing favorable changes in metabolism associated with lactation. During gestation, visceral fat accumulates, and insulin resistance and lipid and triglyceride levels increase. These changes appear to reverse...

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

    Science.gov (United States)

    Andrus, Liam P; Unruh, Rachel; Wisniewski, Natalie A; McShane, Michael J

    2015-01-01

    An optical biosensor for lactate detection is described. By encapsulating enzyme-phosphor sensing molecules within permeable hydrogel materials, lactate-sensitive emission lifetimes were achieved. The relative amount of monomer was varied to compare three homo- and co-polymer materials: poly(2-hydroxyethyl methacrylate) (pHEMA) and two copolymers of pHEMA and poly(acrylamide) (pAam). Diffusion analysis demonstrated the ability to control lactate transport by varying the hydrogel composition, while having a minimal effect on oxygen diffusion. Sensors displayed the desired dose-variable response to lactate challenges, highlighting the tunable, diffusion-controlled nature of the sensing platform. Short-term repeated exposure tests revealed enhanced stability for sensors comprising hydrogels with acrylamide additives; after an initial "break-in" period, signal retention was 100% for 15 repeated cycles. Finally, because this study describes the modification of a previously developed glucose sensor for lactate analysis, it demonstrates the potential for mix-and-match enzyme-phosphor-hydrogel sensing for use in future multi-analyte sensors. PMID:26198251

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

    Directory of Open Access Journals (Sweden)

    Liam P. Andrus

    2015-07-01

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

  17. Extended lactation in dairy cows: effects of milking frequency, calving season and nutrition on lactation persistency and milk quality.

    Science.gov (United States)

    Sorensen, Annette; Muir, D Donald; Knight, Christopher H

    2008-02-01

    Twelve spring-calving and twelve winter-calving cows were managed for extended lactation cycles of 18-months duration, with the former group then completing a second extended lactation. Half of the cows were fed according to standard management practice for the herd; the other half received supplementary concentrate from week 9 of lactation onwards. Commencing at the same time, half of the udder of each cow was subjected to increased milking frequency (thrice daily rather than twice daily). Lactation persistency (and hence total milk yield) was significantly increased by frequent milking. Winter calving cows and supplemented cows also exhibited better persistency, but this was only evident up until the point of re-breeding, at around lactation week 33. Milk composition was measured in the spring-calving cows in both their first and second extended lactations. Composition altered during the course of the lactation, protein and fat percentages increasing and lactose percentage decreasing, irrespective of treatment. The quality of the milk for processing into cheese, fermented products, heat-treated products and cream liqueurs was assessed by calculation of casein number (casein protein as a proportion of total protein). Processing quality declined across the course of lactation in those groups that showed poor persistency but not in those that maintained a persistent lactation. Milk hygienic quality (somatic cell counts) showed parallel changes. Body condition score increased during the course of lactation but was not affected by supplementation; none of the cows became excessively fat. All cows remained healthy throughout the extended lactations and the majority (33/36) re-bred successfully. By demonstrating that lactation persistency is plastic and can be improved by simple management interventions, the results lend support to the economic arguments in favour of extended lactation cycles. The likely welfare benefits of extended lactation are also discussed. PMID

  18. Co-expression of ING4 and P53 enhances hypopharyngeal cancer chemosensitivity to cisplatin in vivo.

    Science.gov (United States)

    Ren, Xin; Liu, Hao; Zhang, Mingjie; Wang, Mengjun; Ma, Shiyin

    2016-09-01

    Hypopharyngeal cancer is a distinct type of malignant head and neck tumor, which exhibits low sensitivity to anti-cancer drugs. The importance of developing methods for reducing chemotherapy resistance, and improving and enhancing prognosis has previously been emphasized and is considered a challenge for effective clinical treatment of hypopharyngeal cancer. The current study investigated the effects of co‑expression of inhibitor of growth protein 4 (ING4) and P53, a tumor suppressor gene, on chemosensitivity to cisplatin in human hypopharyngeal cancer xenografts in vivo, and the potential molecular mechanisms involved. A tumor model was established by injecting athymic nude mice with FADU human hypopharyngeal cancer cells. Five days after intratumoral and peritumoral injections of an empty adenoviral vector (Ad), Ad‑ING4‑P53, cisplatin, or a combination of Ad‑ING4‑P53 and cisplatin (Ad‑ING4‑P53 + cisplatin) every other day for 5 days, the mice were euthanized and their tumors, livers, and kidneys were removed. The tumor weights were used to calculate the inhibition rate, and the expression levels of ING4 and P53 were detected by reverse transcription‑polymerase chain reaction. Additionally, apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunohistochemistry determined the levels ING4, P53, B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2 associated X protein (Bax) protein expression. The results demonstrated increased expression of ING4 and P53 in the Ad‑ING4‑P53 groups compared with PBS and Ad groups, indicating successful introduction of the genes into the tumor cells. Notably, the Ad‑ING4‑P53 + cisplatin group exhibited a higher inhibition rate compared with the four other groups. The results of immunohistochemistry analysis demonstrated that Bax expression was increased and Bcl‑2 was decreased in the Ad‑ING4‑P53 + cisplatin group. This suggested that the enhanced

  19. Assessment of central chemosensitivity and cardiac sympathetic nerve activity using I-123 MIBG imaging in central sleep apnea syndrome in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Iodine-123 m-iodobenzylguanidine (MIBG) imaging has been used to study cardiac sympathetic function in various cardiac diseases. Central sleep apnea syndrome (CSAS) occurs frequently in patients with chronic heart failure (CHF) and is reported to be associated with a poor prognosis. One of the mechanisms of its poor prognosis may be related to impaired cardiac sympathetic activity. However, the relationship between chemosensitivity to carbon dioxide, which is reported to correlate with the severity of CSAS, and cardiac sympathetic activity has not been investigated. Therefore, this study was undertaken to assess cardiac sympathetic function and chemosensitivity to carbon dioxide in CHF patients. The oxygen desaturation index (ODI) was evaluated in 21 patients with dilated cardiomyopathy (male/female: 19/2, left ventricular ejection fraction (LVEF)5 times/h underwent polysomnography. Patients with an apnea hypopnea index >15/h but without evidence of obstructive apnea were defined as having CSAS. Early (15 min) and delayed (4 hr) planar MIBG images were obtained from these patients. The mean counts in the whole heart and the mediastinum were obtained. The heart-to-mediastinum count ratio of the delayed image (H/M) and the corrected myocardial washout rate (WR) were also calculated. The central chemoreflex was assessed with the rebreathing method using a hypercapnic gas mixture (7% CO2 and 93% O2). Ten of the 21 patients had CSAS. The H/M ratio was similar in patients both with and without CSAS (1.57±0.18 vs. 1.59±0.14, p=0.82). However, the WR was higher in patients with CSAS than in patients without CSAS (40±8% vs. 30±12%, p<0.05). ODI significantly correlated with central chemosensitivity to carbon dioxide. Moreover, there was a highly significant correlation between WR and central chemosensitivity (r=0.65, p<0.05). However, there was no correlation between ODI and the WR (r=0.36, p=0.11). Cardiac sympathetic nerve activity in patients with CHF and CSAS is

  20. Lactate-a suicide mode or survival kit

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Cellular energy status is often believed to be crucial in the patho physiology of severe acute diseases involving sepsis or trauma such as multiorgan failure, mu ltiorgan dysfunction syndrome, systemic inflammatory response system, etc. Wit h this in mind increased blood lactate, mainly considered only as a marker or t issue hypoxia is a classical tool used to assess the severity of the illness an d to predict the pejorative outcome. However, during the past years the actual r ole of hypoxia in the pathophysiology of such acute diseases with an increased b lood lactate has been questioned. The association between increased blood lactate concentration and poor prognosi s in ICU patients is well documented but it is clearly not a cause-effect relat ionship. It is similar to what occurs in the case of increased blood ketone I n severe insulin deficient state and it would be a major understanding to be lieve that lactate is a toxic compound in acute states. In acute illness, incre ased lactate concentration or lactate metabolism can be due to the combination of various origin in which the role of splanchnic bed is prominent. In the case of strong reduction in oxygen delivery, such as severe shock, it is quite clear that there is a relationship between cellular energy defect and increased lact ate production. But even in these cases a decrease in lactate metabolism (eithe r oxidative or recycling routes) may also be involved. In septic states, the ro le of blood lactate is a matter of controversy and several reports have e mphasiz ed the fact that hyperlactatemia in sepsis was not due to the oxygen d eficit. It has been shown that mild hyperlactatemia in stable septic patients was due to an impaired lactate clearance rather than overproduction. Besides the main conc lusion that any therapeutic attempts to increase oxygen delivery in such situa tion may not be adapted, another point can be raised concerning the meaning of s uch lactate increase. In fact, increased blood

  1. Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of miRNA related to lactation

    Directory of Open Access Journals (Sweden)

    Li Zhen

    2012-12-01

    Full Text Available Abstract Background MicroRNAs (miRNAs have been implicated in the regulation of milk protein synthesis and development of the mammary gland (MG. However, the specific functions of miRNAs in these regulations are not clear. Therefore, the elucidation of miRNA expression profiles in the MG is an important step towards understanding the mechanisms of lactogenesis. Results Two miRNA libraries were constructed from MG tissues taken from a lactating and a non-lactating Holstein dairy cow, respectively, and the short RNA sequences (18–30 nt in these libraries were sequenced by Solexa sequencing method. The libraries included 885 pre-miRNAs encoding for 921 miRNAs, of which 884 miRNAs were unique sequences and 544 (61.5% were expressed in both periods. A custom-designed microarray assay was then performed to compare miRNA expression patterns in the MG of lactating and non-lactating dairy cows. A total of 56 miRNAs in the lactating MG showed significant differences in expression compared to non-lactating MG (P Conclusion Our study provides a broad view of the bovine MG miRNA expression profile characteristics. Eight hundred and eighty-four miRNAs were identified in bovine MG. Differences in types and expression levels of miRNAs were observed between lactating and non-lactating bovine MG. Systematic predictions aided in the identification of lactation-related miRNAs, providing insight into the types of miRNAs and their possible mechanisms in regulating lactation.

  2. Arterial Lactate Level Changes in First Day after Cardiac Operation

    OpenAIRE

    Shamsi Ghaffari; Majid Malaki

    2013-01-01

    Introduction: Lactate level is an important index for predicting cardiac events. There are some debates about time and type of sampling for defining of its prognostic values.Methods: To assess the prognostic importance of arterial lactate level in patients after cardiac surgery with regarding to operation factors serial arterial lactate levels during and after surgery was measured up to 24 hours, these data were processed by T-independent test and chi-square, P less than 0.01 was significant....

  3. Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation.

    Directory of Open Access Journals (Sweden)

    Nicholas J Jury

    Full Text Available 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

  4. Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel

    Directory of Open Access Journals (Sweden)

    Joana Fonseca

    2016-07-01

    Full Text Available We previously reported that prenylated chalcone 2 (PC2, the O-prenyl derivative (2 of 2′-hydroxy-3,4,4′,5,6′-pentamethoxychalcone (1, induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination.

  5. Factors associated with the preincubation effect of hypoxic cell sensitizers in vitro and their possible implications in chemosensitization

    International Nuclear Information System (INIS)

    The enhancement of melphalan toxicity was observed by preincubation of V-79-379A cells in spinner culture with multiple doses of misonidazole (miso) or SR-2508 under hypoxic conditions. Chemosensitization was shown to be a function of sensitizer concentration and duration of exposure to the alkylating agent. Cells preincubated with miso not only had lower levels of nonprotein thiols, but also were shown to have altered levels of intracellular calcium and a lower threshold to oxidative stress as measured by toxicity to cysteamine or H2O2. Preincubated cells, hypoxic cells, and cells receiving moderate hyperthermia (42.50C for 3 hr) all showed increased sensitivity to either cysteamine or H2O2. The increased killing of preincubated cells by cysteamine was shown to be similar to that of H2O2, and the dramatic reduction of cysteamine toxicity by catalase indicated H2O2 was the major reaction associated with this effect. These results indicate that preincubated cells exhibit a variety of biological effects that may significantly influence their response to further treatment with drugs or radiation, especially where peroxidative and free radical mechanisms are involved

  6. Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

    International Nuclear Information System (INIS)

    Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

  7. Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Lamont Alan

    2003-07-01

    Full Text Available Abstract Background We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. Methods From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse Results The overall response rate was 59% (33/56 per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS was 6.6 months per course of chemotherapy; median overall survival (OAS for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9–12.8 months. Conclusion The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centres.

  8. Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel.

    Science.gov (United States)

    Fonseca, Joana; Marques, Sandra; Silva, Patrícia M A; Brandão, Pedro; Cidade, Honorina; Pinto, Madalena M; Bousbaa, Hassan

    2016-01-01

    We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i) characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii) explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h) in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination. PMID:27483224

  9. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

    International Nuclear Information System (INIS)

    Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy

  10. VEGFR3 Inhibition Chemosensitizes Ovarian Cancer Stemlike Cells through Down-Regulation of BRCA1 and BRCA2

    Directory of Open Access Journals (Sweden)

    Jaeyoung Lim

    2014-04-01

    Full Text Available In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3 inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133+ ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition–mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors.

  11. VEGFR3 Inhibition Chemosensitizes Ovarian Cancer Stemlike Cells through Down-Regulation of BRCA1 and BRCA212

    Science.gov (United States)

    Lim, Jaeyoung; Yang, Kun; Taylor-Harding, Barbie; Wiedemeyer, W. Ruprecht; Buckanovich, Ronald J.

    2014-01-01

    In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133+ ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition–mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors. PMID:24862760

  12. Water extract from Pleurotus pulmonarius with antioxidant activity exerts in vivo chemoprophylaxis and chemosensitization for liver cancer.

    Science.gov (United States)

    Xu, Wen Wen; Li, Bin; Lai, Emily Tsz Ching; Chen, Lei; Huang, Jim Jun Hui; Cheung, Annie Lai Man; Cheung, Peter Chi Keung

    2014-01-01

    Chemoprophylaxis and chemosensitization are promising strategies to combat human cancers. Natural antioxidant agents show great promise in cancer therapy, and the use of edible mushrooms against cancer is receiving more interest globally. In this study, the radical scavenging activities including diphenyl-1-picrylhydrazyl, superoxide anion radical, hydroxyl radical, and hydrogen peroxide were compared among hot water extracts from 3 edible mushrooms, among which Pleurotus pulmonarius (Pp) possessed the highest antioxidant potential. Oral administration of Pp 2 wk in advance could markedly inhibit the incidence and size of tumor (Huh7 liver cancer cells) with an inhibition rate of 93.1% in nude mice. No obvious side effect was observed in the Pp-treated mice as indicated by their body weight and histological analysis of major organs. The cancer prevention by Pp treatment might be explained by the inhibition of cancer cell proliferation indicated by reduction of ki-67 staining and the inactivation of phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in the Pp-treated mice. Furthermore, a significant synergistic effect was observed when the mice were treated with a combination of low dose of cisplatin and Pp. Taken together, these results suggest the potential application of Pp as an adjuvant in the chemotherapy of liver cancer. PMID:25072857

  13. Maternal lactation for preterm newborn infants.

    Science.gov (United States)

    Aguayo, J

    2001-11-01

    In recent decades, neonatologists have made considerable progress in life support techniques, especially in the treatment and prevention of respiratory disorders, which has led to a higher neonatal survival rate. Research into neonatal nutrition has also produced great benefits. It has been found that one of the key points regarding the improved survival rate of infants is the necessity for nutrition that is both adequate and as natural as possible. In this respect, it is necessary to achieve a better understanding of the process, protection, support and maintenance of maternal lactation in neonatal units. Humanization of perinatal attention during delivery, respect for the rights of parents and their children, protection of the mother and child bonding process, early skin contact with the mother and greater attention to individualized care are all key factors in the reinforcement of maternal lactation and are issues that must be addressed within the field of neonatology. Research activities need to concern themselves with: (1) acquiring greater knowledge concerning the common problems and difficulties that arise with mothers and their preterm babies; (2) training healthcare professionals in these aspects, for example in the extraction and storage of milk and in improving techniques of emotional and communicational skills; (3) by means of specific programmes such as the setting up of support groups, so that the effort made to encourage the initiation of breastfeeding is justified by its continuation for as long as possible. Thus, we hope to establish standards of care based on starting, encouraging and prolonging maternal lactation, in sufficient quantity and quality, always remembering that the fundamental goal of our research is the well-being of the child and its family. PMID:11755032

  14. Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions.

    Directory of Open Access Journals (Sweden)

    Robert Haas

    2015-07-01

    Full Text Available Lactate has long been considered a "waste" by-product of cell metabolism, and it accumulates at sites of inflammation. Recent findings have identified lactate as an active metabolite in cell signalling, although its effects on immune cells during inflammation are largely unexplored. Here we ask whether lactate is responsible for T cells remaining entrapped in inflammatory sites, where they perpetuate the chronic inflammatory process. We show that lactate accumulates in the synovia of rheumatoid arthritis patients. Extracellular sodium lactate and lactic acid inhibit the motility of CD4+ and CD8+ T cells, respectively. This selective control of T cell motility is mediated via subtype-specific transporters (Slc5a12 and Slc16a1 that we find selectively expressed by CD4+ and CD8+ subsets, respectively. We further show both in vitro and in vivo that the sodium lactate-mediated inhibition of CD4+ T cell motility is due to an interference with glycolysis activated upon engagement of the chemokine receptor CXCR3 with the chemokine CXCL10. In contrast, we find the lactic acid effect on CD8+ T cell motility to be independent of glycolysis control. In CD4+ T helper cells, sodium lactate also induces a switch towards the Th17 subset that produces large amounts of the proinflammatory cytokine IL-17, whereas in CD8+ T cells, lactic acid causes the loss of their cytolytic function. We further show that the expression of lactate transporters correlates with the clinical T cell score in the synovia of rheumatoid arthritis patients. Finally, pharmacological or antibody-mediated blockade of subtype-specific lactate transporters on T cells results in their release from the inflammatory site in an in vivo model of peritonitis. By establishing a novel role of lactate in control of proinflammatory T cell motility and effector functions, our findings provide a potential molecular mechanism for T cell entrapment and functional changes in inflammatory sites that drive

  15. Nuclear medicine: dosimetric considerations: pregnancy and lactation

    International Nuclear Information System (INIS)

    Radiation exposure of pregnant woman in nuclear medicine is important from the point of view of radiological protection. In this report are presented the most relevant considerations for the internal dosimetry during pregnancy and lactation. The dose estimation to the mother and fetus during pregnancy can be made based in MIRD methodology with specific phantoms of the pregnant woman allowing the dose calculation in the first, second and third month of pregnancy, through the MIRDOSE software. The effective doses in infants and recommendations are also explained in this report

  16. Lactate dehydrogenase in sickle cell disease.

    Science.gov (United States)

    Stankovic Stojanovic, Katia; Lionnet, François

    2016-07-01

    Lactate dehydrogenase (LDH) activity is elevated in many pathological states. Interest in LDH activity in sickle cell disease (SCD) has developed out of an increased comprehension of the pathophysiological process and the clinical course of the disease. Elevated LDH activity in SCD comes from various mechanisms, especially intravascular hemolysis, as well as ischemia-reperfusion damage and tissular necrosis. Intravascular hemolysis is associated with vasoconstriction, platelet activation, endothelial damage, and vascular complications. LDH has been used as a diagnostic and prognostic factor of acute and chronic complications. In this review we have evaluated the literature where LDH activity was examined during steady-state or acute conditions in SCD. PMID:27138446

  17. Etiology and Therapeutic Approach to Elevated Lactate Levels

    DEFF Research Database (Denmark)

    Wiuff Andersen, Lars; Mackenhauer, Julie; Roberts, Jonathan C;

    2013-01-01

    Lactate levels are commonly evaluated in acutely ill patients. Although most often used in the context of evaluating shock, lactate levels can be elevated for many reasons. While tissue hypoperfusion may be the most common cause of elevation, many other etiologies or contributing factors exist...... medication. We provide an overview of the pathogenesis of lactate level elevation followed by an in-depth look at the varied etiologies, including medication-related causes. The strengths and weaknesses of lactate as a diagnostic/prognostic tool and its potential use as a clinical end point of resuscitation...

  18. Emerging evidence of the physiological role of hypoxia in mammary development and lactation

    Institute of Scientific and Technical Information of China (English)

    Yong Shao; Feng-Qi Zhao

    2014-01-01

    Hypoxia is a physiological or pathological condition of a deficiency of oxygen supply in the body as a whole or within a tissue. During hypoxia, tissues undergo a series of physiological responses to defend themselves against a low oxygen supply, including increased angiogenesis, erythropoiesis, and glucose uptake. The effects of hypoxia are mainly mediated by hypoxia-inducible factor 1 (HIF-1), which is a heterodimeric transcription factor consisting ofαandβsubunits. HIF-1βis constantly expressed, whereas HIF-1αis degraded under normal oxygen conditions. Hypoxia stabilizes HIF-1αand the HIF complex, and HIF then translocates into the nucleus to initiate the expression of target genes. Hypoxia has been extensively studied for its role in promoting tumor progression, and emerging evidence also indicates that hypoxia may play important roles in physiological processes, including mammary development and lactation. The mammary gland exhibits an increasing metabolic rate from pregnancy to lactation to support mammary growth, lactogenesis, and lactation. This process requires increasing amounts of oxygen consumption and results in localized chronic hypoxia as confirmed by the binding of the hypoxia marker pimonidazole HCl in mouse mammary gland. We hypothesized that this hypoxic condition promotes mammary development and lactation, a hypothesis that is supported by the following several lines of evidence:i) Mice with an HIF-1αdeletion selective for the mammary gland have impaired mammary differentiation and lipid secretion, resulting in lactation failure and striking changes in milk compositions;ii) We recently observed that hypoxia significantly induces HIF-1α-dependent glucose uptake and GLUT1 expression in mammary epithelial cells, which may be responsible for the dramatic increases in glucose uptake and GLUT1 expression in the mammary gland during the transition period from late pregnancy to early lactation;and ii ) Hypoxia and HIF-1αincrease the

  19. Extended lactation in dairy cows:effects of milking frequency, calving season and nutrition on lactation persistency and milk quality

    OpenAIRE

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

    2008-01-01

    Twelve spring-calving and twelve winter-calving cows were managed for extended lactation cycles of 18-months duration, with the former group then completing a second extended lactation. Half of the cows were fed according to standard management practice for the herd; the other half received supplementary concentrate from week 9 of lactation onwards. Commencing at the same time, half of the udder of each cow was subjected to increased milking frequency (thrice daily rather than twice daily). L...

  20. Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

    Directory of Open Access Journals (Sweden)

    Mahoney Noreen

    2011-05-01

    Full Text Available Abstract Background Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy. Methods Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI. Results Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ and two mitogen-activated protein kinase (MAPK mutants of A. fumigatus (sakAΔ, mpkCΔ, indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC or fungicidal (MFC

  1. ROLE OF LACTATION IN FAMILY PLANNING

    Directory of Open Access Journals (Sweden)

    Surekha Kishore

    2010-06-01

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

  2. Pharmacokinetics of metoprolol during pregnancy and lactation.

    Science.gov (United States)

    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 metoprolol apparent oral clearance was significantly higher during both mid- and late pregnancy (P metoprolol through breast milk was 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

  3. Invited review: Inflammation during the transition to lactation: New adventures with an old flame.

    Science.gov (United States)

    Bradford, B J; Yuan, K; Farney, J K; Mamedova, L K; Carpenter, A J

    2015-10-01

    For dairy cattle, the first several weeks of lactation represent the highest-risk period in their lives after their own neonatal period. Although more than 50% of cows during this period are estimated to suffer from at least one subclinical disorder, the complicated admixture of normal adaptations to lactation, infectious challenges, and metabolic disorders has made it difficult to determine which physiological processes are adaptive and which are pathological during this time. Subacute inflammation, a condition that has been well documented in obesity, has been a subject of great interest among dairy cattle physiologists in the past decade. Many studies have now clearly shown that essentially all cows experience some degree of systemic inflammation in the several days after parturition. The magnitude and likely persistence of the inflammatory state varies widely among cows, and several studies have linked the degree of postpartum inflammation to increased disease risk and decreased whole-lactation milk production. In addition to these associations, enhancing postpartum inflammation with repeated subacute administration of cytokines has impaired productivity and markers of health, whereas targeted use of nonsteroidal anti-inflammatory drugs during this window of time has enhanced whole-lactation productivity in several studies. Despite these findings, many questions remain about postpartum inflammation, including which organs are key initiators of this state and what signaling molecules are responsible for systemic and tissue-specific inflammatory states. Continued in vivo work should help clarify the degree to which mild postpartum inflammation is adaptive and whether the targeted use of anti-inflammatory drugs or nutrients can improve the health and productivity of dairy cows. PMID:26210279

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Reduced hepatic lactate elimination initiates blood lactate accumulation during incremental exercise. In this study, we wished to determine whether renal lactate elimination contributes to the initiation of blood lactate accumulation. The renal arterial-to-venous (a-v) lactate difference...... was determined in nine men during sodium lactate infusion to enhance the evaluation (0.5 mol x L(-1) at 16 ± 1 mL x min(-1); mean ± s) both at rest and during cycling exercise (heart rate 139 ± 5 beats x min(-1)). The renal release of erythropoietin was used to detect kidney tissue ischaemia. At rest, the a-v O......(2) (CaO(2)-CvO(2)) and lactate concentration differences were 0.8 ± 0.2 and 0.02 ± 0.02 mmol x L(-1), respectively. During exercise, arterial lactate and CaO(2)-CvO(2) increased to 7.1 ± 1.1 and 2.6 ± 0.8 mmol x L(-1), respectively (P

  5. Lactic acid and Lactates in Health and wellness

    NARCIS (Netherlands)

    Schaafsma, Gertjan; Schreurs, Victor

    2010-01-01

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

  6. Transient congenital hypothyroidism after topical iodine in pregnancy and lactation.

    OpenAIRE

    Danziger, Y; Pertzelan, A; Mimouni, M

    1987-01-01

    A 6 week old girl with transient congenital hypothyroidism is described. The hypothyroidism was associated with multiple applications of povidone iodine during pregnancy and lactation. This case illustrates the potential hazard of using topical solutions containing iodine during pregnancy and lactation.

  7. Glycogen synthesis from lactate in a chronically active muscle

    International Nuclear Information System (INIS)

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

  8. Kinetics of lactate and pyruvate transport in cultured rat myotubes

    DEFF Research Database (Denmark)

    von Grumbckow, Lena; Elsner, Peter; Hellsten, Ylva;

    1999-01-01

    Skeletal muscle transport of lactate and pyruvate was studied in primary cultures of rat myotubes, applying the pH-sensitive fluorescent indicator 2', 7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. The initial rate of decrease in intracellular pH (pHi) upon lactate or pyruvate incubation was used to...

  9. Regional differences in adipocyte lactate production from glucose

    International Nuclear Information System (INIS)

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

  10. Induction of lactational estrus in organic piglet production

    DEFF Research Database (Denmark)

    Kongsted, Anne Grete; Hermansen, John Erik

    2009-01-01

    The longer lactation period required in organic piglet producing herds reduces the potential number of produced litters per sow per year compared with that of conventional production. Induction and use of lactational estrus may be a way to increase the productivity in organic production. However...... current study indicate that it is possible to combine lactational estrus and batch farrowing procedures to increase the number of weaned piglets per year per sow in organic piglet production based on 8 wk of lactation or more....... in an organic outdoor system based on ad libitum feeding, individual housing until Day 35 in lactation, followed by grouping and introduction of a boar and weaning of piglets after 8 wk. Five groups with four sows ((Danish Yorkshire × Danish Landrace) × Danish Duroc) in each were observed, and rank...

  11. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

    International Nuclear Information System (INIS)

    Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer

  12. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Weigel Marion T

    2010-08-01

    Full Text Available Abstract Background Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Methods Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. Results The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Conclusions Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer.

  13. Regression of Stage IV Pancreatic Cancer to Curative Surgery and Introduction of a Novel Ex-Vivo Chemosensitivity Assay.

    Science.gov (United States)

    Rios Perez, Mayrim V; Dai, Bingbing; Koay, Eugene J; Wolff, Robert A; Fleming, Jason B

    2015-01-01

    Although data suggests little hope for survival when patients present with metastatic pancreatic cancer, recent advances in systemic therapy offer the possibility for dramatic tumor responses like those observed in other disease sites. Here, we present the case of a 50-year-old woman who presented with adenocarcinoma of the pancreas with two liver metastases and a CA 19-9 level of 1,659 U/mL. The patient received FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) with a dramatic reduction in CA 19-9 level to 23.9 U/mL, and complete regression of both liver metastases. The patient then received capecitabine with the maintenance of a normal CA19-9 over the next 12 months. With no evidence of distant disease, concurrent systemic and local therapy with capecitabine-based chemoradiation (CapeXRT) was performed followed by observation for eight months with normal CA 19-9 readings. A mild increase in CA 19-9 (143 U/mL) prompted a restaging demonstrating an active primary tumor but no distant disease. Therefore, a pancreaticoduodenectomy (PD or Whipple) was performed rendering this patient free of detectable cancer. Our team has developed an ex-vivo chemosensitivity assay in which the tumor tissue from an individual patient can be rapidly examined for sensitivity to available systemic therapy treatment strategies. We tested this patient's tumor for its sensitivity to gemcitabine (Gem) versus a combination of 5-fluorouracil, irinotecan, and oxaliplatin (FIRINOX). Remarkably, our assay confirmed a profound sensitivity of this patient's tumor to the agents she had received. PMID:26848412

  14. Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null) cell lines.

    Science.gov (United States)

    Silden, Elisabeth; Hjelle, Sigrun M; Wergeland, Line; Sulen, André; Andresen, Vibeke; Bourdon, Jean-Christophe; Micklem, David R; McCormack, Emmet; Gjertsen, Bjørn Tore

    2013-01-01

    The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null) background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1)), Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(P)H quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level. PMID:23409163

  15. PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer.

    Science.gov (United States)

    Zhu, Haiyan; Wu, Jun; Zhang, Wenwen; Luo, Hui; Shen, Zhaojun; Cheng, Huihui; Zhu, Xueqiong

    2016-01-01

    Pyruvate kinase M2 (PKM2) is a key driver of aerobic glycolysis in cancer cells and has been shown to be up-regulated by mTOR in vitro. Our previous proteomic profiling studies showed that PKM2 was significantly upregulated in cervical cancer tissues after treatment with neoadjuvant chemotherapy (NACT). Whether PKM2 expression predicts cisplatin-based NACT sensitivity and is mTOR dependent in cervical cancer patients remains unclear. Using paired tumor samples (pre- and post-chemotherapy) from 36 cervical cancer patients, we examined mTOR, HIF-1α, c-Myc, and PKM2 expression in cervical cancer samples and investigated the response to cisplatin-based NACT. In addition, we established PKM2 suppressed cervical cancer cell lines and evaluated their sensitivity to cisplatin in vitro. We found that the mTOR/HIF-1α/c-Myc/PKM2 signaling pathway was significantly downregulated in post-chemotherapy cervical cancer tissues. High levels of mTOR, HIF-1α, c-Myc, and PKM2 were associated with a positive chemotherapy response in cervical cancer patients treated with cisplatin-based NACT. In vitro, PKM2 knockdown desensitized cervical cancer cells to cisplatin. Moreover, PKM2 had complex interactions with mTOR pathways. mTOR, HIF1α, c-Myc, and PKM2 expression in cervical cancer may serve as predictive biomarkers to cisplatin-based chemotherapy. PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR pathway in cervical cancer. PMID:27492148

  16. Expression of TP53 isoforms p53β or p53γ enhances chemosensitivity in TP53(null cell lines.

    Directory of Open Access Journals (Sweden)

    Elisabeth Silden

    Full Text Available The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their individual functionality in the p53(null background of cell lines H1299 and SAOS-2 by stable retroviral transduction or transient transfection. Expression status of p53β and p53γ protein was found to correlate with increased response to camptothecin and doxorubicin chemotherapy. Decreased DNA synthesis and clonogenicity in p53β and p53γ congenic H1299 was accompanied by increased p21((CIP1/WAF1, Bax and Mdm2 proteins. Chemotherapy induced p53 isoform degradation, most prominent for p53γ. The proteasome inhibitor bortezomib substantially increased basal p53γ protein level, while the level of p53β protein was unaffected. Treatment with dicoumarol, a putative blocker of the proteasome-related NAD(PH quinone oxidoreductase NQO1, effectively attenuated basal p53γ protein level in spite of bortezomib treatment. Although in vitro proliferation and clonogenicity assays indicated a weak suppressive effect by p53β and p53γ expression, studies of in vivo subcutaneous H1299 tumor growth demonstrated a significantly increased growth by expression of either p53 isoforms. This study suggests that p53β and p53γ share functionality in chemosensitizing and tumor growth enhancement but comprise distinct regulation at the protein level.

  17. Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Mesenchymal stromal cells (MSCs) represent heterogeneous cell population suitable for cell therapies in regenerative medicine. MSCs can also substantially affect tumor biology due to their ability to be recruited to the tumor stroma and interact with malignant cells via direct contacts and paracrine signaling. The aim of our study was to characterize molecular changes dictated by adipose tissue-derived mesenchymal stromal cells (AT-MSCs) and the effects on drug responses in human breast cancer cells SKBR3. The tumor cells were either directly cocultured with AT-MSCs or exposed to MSCs-conditioned medium (MSC-CM). Changes in cell biology were evaluated by kinetic live cell imaging, fluorescent microscopy, scratch wound assay, expression analysis, cytokine secretion profiling, ATP-based viability and apoptosis assays. The efficiency of cytotoxic treatment in the presence of AT-MSCs or MSCs-CM was analyzed. The AT-MSCs altered tumor cell morphology, induced epithelial-to-mesenchymal transition, increased mammosphere formation, cell confluence and migration of SKBR3. These features were attributed to molecular changes induced by MSCs-secreted cytokines and chemokines in breast cancer cells. AT-MSCs significantly inhibited the proliferation of SKBR3 cells in direct cocultures which was shown to be dependent on the SDF-1α/CXCR4 signaling axis. MSC-CM-exposed SKBR3 or SKBR3 in direct coculture with AT-MSCs exhibited increased chemosensitivity and induction of apoptosis in response to doxorubicin and 5-fluorouracil. Our work further highlights the multi-level nature of tumor-stromal cell interplay and demonstrates the capability of AT-MSCs and MSC-secreted factors to alter the anti-tumor drug responses

  18. L-lactate transport in Ehrlich ascites-tumour cells.

    Science.gov (United States)

    Spencer, T L; Lehninger, A L

    1976-02-15

    Ehrlich ascites-tumour cells were investigated with regard to their stability to transport L-lactate by measuring either the distribution of [14C]lactate or concomitant H+ ion movements. The movement of lactate was dependent on the pH difference across the cell membrane and was electroneutral, as evidenced by an observed 1:1 antiport for OH- ions or 1:1 symport with H+ ions. 2. Kinetic experiments showed that lactate transport was saturable, with an apparent Km of approx. 4.68 mM and a Vmax. as high as 680 nmol/min per mg of protein at pH 6.2 and 37 degrees C. 3. Lactate transport exhibited a high temperature dependence (activation energy = 139 kJ/mol). 4. Lactate transport was inhibited competitively by (a) a variety of other substituted monocarboxylic acids (e.g. pyruvate, Ki = 6.3 mM), which were themselves transported, (b) the non-transportable analogues alpha-cyano-4-hydroxycinnamate (Ki = 0.5 mM), alpha-cyano-3-hydroxycinnamate (Ki = 2mM) and DL-p-hydroxyphenyl-lactate (Ki = 3.6 mM) and (c) the thiol-group reagent mersalyl (Ki = 125 muM). 5. Transport of simple monocarboxylic acids, including acetate and propionate, was insensitive to these inhibitors; they presumably cross the membrane by means of a different mechanism. 6. Experiments using saturating amounts of mersalyl as an "inhibitor stop" allowed measurements of the initial rates of net influx and of net efflux of [14C]lactate. Influx and efflux of lactate were judged to be symmetrical reactions in that they exhibited similar concentration dependence. 7. It is concluded that lactate transport in Ehrlich ascites-tumour cells is mediated by a carrier capable of transporting a number of other substituted monocarboxylic acids, but not unsubstituted short-chain aliphatic acids. PMID:7237

  19. Cyolane residues in milk of lactating goats

    International Nuclear Information System (INIS)

    Consecutive feeding of lactating goats with 14C-alkyl labelled cyolane for 5 days at dietary levels 8 and 16 ppm resulted in the appearance of measurable insecticide residues in milk (0.02-0.04 mg/kg). The residue levels were markedly reduced after a withdrawal period of 7 days. Analysis of urine and milk residues showed the presence of similar metabolites in addition to the parent compound. The major part of the residue consisted of mono-, diethyl phosphate and 2 hydrophilic unknown metabolites. The erythrocyte cholinesterase activity was reduced to about 50% after 24 hours whereas the plasma enzyme was only slightly affected. The animals remained symptom-free during the experimental period. (author)

  20. Occurrence of lactational mastitis and medical management

    DEFF Research Database (Denmark)

    Scott, Jane A.; Robertson, Michele; Fitzpatrick, Julie;

    2008-01-01

    questionnaire before discharge from hospital. Cases of mastitis were reported either directly to the researchers or were detected during regular follow-up telephone interviews at weeks 3, 8, 18 and 26. Women experiencing mastitis provided further information of their symptoms and the management and advice they......BACKGROUND: Lactational mastitis is a painful, debilitating condition that if inappropriately managed, may lead women to discontinue breastfeeding prematurely. The aim of this paper is to report the incidence of mastitis in the first six months postpartum in a Scottish population, its impact on...... breastfeeding duration and to describe the type and appropriateness of the support and management received by affected women from health professionals. METHODS: A longitudinal study of 420 breastfeeding women was undertaken in Glasgow in 2004/05. Participants were recruited and completed a baseline...

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

    DEFF Research Database (Denmark)

    Rørbye, Christina; Perslev, Anette; Nickelsen, Carsten

    2016-01-01

    between scalp lactate measured within 15 min prior to delivery and the umbilical cord SBE was low. CONCLUSION: Monitoring non-reassuring deliveries with scalp lactate instead of pH would have resulted in more (155 instead of 56) instrumental deliveries with no decrease in newborns with severe metabolic...... acidosis....

  2. Associations between the time of conception and the shape of the lactation curve in early lactation in Norwegian dairy cattle

    DEFF Research Database (Denmark)

    Andersen, Fredrik; Østerås, Olav; Reksen, Olav;

    2011-01-01

    This study was carried out to determine if an association exists between the shape of the lactation curve before it is influenced by the event of conception and the time from calving to conception in Norwegian dairy cattle. Lactation curves of Norwegian Red cows during 5 to 42 days in milk (DIM) ...

  3. Inflammatory mediators in mastitis and lactation insufficiency.

    Science.gov (United States)

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

    2014-07-01

    Mastitis is a common inflammatory disease during lactation that causes reduced milk supply. A growing body of evidence challenges the central role of pathogenic bacteria in mastitis, with disease severity associated with markers of inflammation rather than infection. Inflammation in the mammary gland may be triggered by microbe-associated molecular patterns (MAMPs) as well as danger-associated molecular patterns (DAMPs) binding to pattern recognition receptors such as the toll-like receptors (TLRs) on the surface of mammary epithelial cells and local immune cell populations. Activation of the TLR4 signalling pathway and downstream nuclear factor kappa B (NFkB) is critical to mediating local mammary gland inflammation and systemic immune responses in mouse models of mastitis. However, activation of NFkB also induces epithelial cell apoptosis and reduced milk protein synthesis, suggesting that inflammatory mediators activated during mastitis promote partial involution. Perturbed milk flow, maternal stress and genetic predisposition are significant risk factors for mastitis, and could lead to a heightened TLR4-mediated inflammatory response, resulting in increased susceptibility and severity of mastitis disease in the context of low MAMP abundance. Therefore, heightened host inflammatory signalling may act in concert with pathogenic or commensal bacterial species to cause both the inflammation associated with mastitis and lactation insufficiency. Here, we present an alternate paradigm to the widely held notion that breast inflammation is driven principally by infectious bacterial pathogens, and suggest there may be other therapeutic strategies, apart from the currently utilised antimicrobial agents, that could be employed to prevent and treat mastitis in women. PMID:24961655

  4. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.; Horn, A.; Secher, Niels Henry

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  5. Portable lactate analyzer for measuring lactate in cerebrospinal fluid (CSF and plasma ? method-comparison evaluations

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2014-07-01

    Full Text Available Increased plasma lactate levels can indicate the presence of metabolic disorders in HIV infected individuals. Objective: To determine whether a portable analyzer is valid for measuring cerebrospinal fluid (CSF and plasma lactate levels in HIV infected individuals. Method: CSF and plasma were collected from 178 subjects. Samples tested by the Accutrend® portable analyzer were compared to those tested by a reference device (SYNCHRON LX® 20. Results: The portable analyzer had in plasma sensitivity of 0.95 and specificity 0.87. For CSF the specificity was 0.95; the sensitivity 0.33; the negative predictive value was 95% and the positive predictive value 33%. Conclusions: These findings support the validity of the portable analyzer in measuring lactate concentrations in CSF that fall within the normal range. The relatively poor positive predictive value indicates that a result above the reference range may represent a “false positive test”, and should be confirmed by the reference device before concluding abnormality.

  6. Determination of the lactate threshold and maximal blood lactate steady state intensity in aged rats.

    Science.gov (United States)

    Cunha, Rafael Rodrigues; Cunha, Verusca Najara de Carvalho; Segundo, Paulo Russo; Moreira, Sérgio Rodrigues; Kokubun, Eduardo; Campbell, Carmen Sílvia Grubert; de Oliveira, Ricardo Jacó; Simões, Herbert Gustavo

    2009-08-01

    The reliability of the lactate threshold (LT) determined in aged rats and its validity to identify an exercise intensity corresponding to the maximal blood lactate steady state (MLSS) were analyzed. Eighteen male aged Wistar rats (approximately 365 days) were submitted to two incremental swimming tests until exhaustion, consisting of an initial load corresponding to 1% of body mass (BM) and increments of 1% BM at each 3-min with blood lactate ([lac]) measurements. The LT was determined by visual inspection (LT(V)) as well by applying a polynomial function on the [lac]/workload ratio (LT(P)) by considering the vertices of the curve. For the MLSS, twelve animals were submitted, on different days, to 3-4 exercise sessions of 30-min with workload corresponding to 4, 5 or 6% BM. The MLSS was considered the highest exercise intensity at which the [lac] variation was not higher than 0.07 mM.min(-1) during the last 20-min. No differences were observed for the test-retest results (4.9 +/- 0.7 and 5.0 +/- 0.8 %BM for LTv; and 6.0 +/- 0.6 and 5.8 +/- 0.6 %BM for LTp) that did not differ from the MLSS (5.4 +/- 0.5 %BM). The LT identified for aged rats in swimming, both by visual inspection and polynomial function, was reliable and did not differ from the MLSS. PMID:19585487

  7. Increased chemosensitivity of paclitaxel by telomeric fusion-induced genomic instability

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Seon Rang; Juhn, Kyoung Mi; Park, Jeong Eun; Ju, Yeun Jin; Yun, Mi Yong; Lee, Kee Ho [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Gil Hong; Kim, Joon [College of Medicine, Korea University, Seoul (Korea, Republic of)

    2009-05-15

    A telomere is a region of repetitive DNA at the end of chromosomes. They protect a cell's chromosomes from fusing with each other or rearranging and so cells are normally destroyed when their telomeres are consumed. Most normal somatic cells lose telomeric repeats after each cell division. Telomeric shortening in humans can induce replicative senescence which blocks cell division. This mechanism appears to prevent genomic instability by limiting the number of cell divisions. Telomerase is an attractive molecular target, since its activity has been found in more than 85% of human cancers. Combination therapy with chemotherapeutic agent is superior to single in overall response rate and progression free survival. In this study, we showed that telomerase null cells are more hypersensitive by paclitaxel treatment than at wild type cells.

  8. Effect of polyphenols on glucose and lactate transport by breast cancer cells.

    Science.gov (United States)

    Martel, F; Guedes, M; Keating, E

    2016-05-01

    One of the cancer molecular hallmarks is a deviant energetic metabolism, known as the Warburg effect, whereby the rate of glucose uptake is significantly increased and a high rate of glycolysis and lactic acid production occurs even when oxygen is present-"aerobic lactatogenesis". Accordingly, GLUT1 and MCT1, which are the main glucose and lactate transporters in cancer cells, respectively, have been proposed as oncogenes and are currently seen as potential therapeutic targets in cancer treatment. Polyphenols, commonly contained in fruits and vegetables, have long been associated with a protective role against cancer. Generally considered as nontoxic, dietary polyphenols are considered ideal chemopreventive and possibly chemotherapeutic agents. Several mechanisms of action of polyphenols in breast cancer cells have been proposed including modulation of intracellular signaling, induction of apoptosis through redox regulation or modulation of epigenetic alterations. Additionally, in vitro studies have shown that several polyphenols act as specific inhibitors of glucose transport in breast cancer cell lines and an association between their anticarcinogenic effect and inhibition of glucose cellular uptake has been described. Also, some polyphenols were found to inhibit lactate transport. Importantly, some polyphenols behave as inhibitors of both glucose and lactate cellular uptake by breast cancer cells and these compounds are thus very interesting in the context of a chemopreventive effect, because they deplete breast cancer cells of their two most important energy suppliers. So, the antimetabolic effect of polyphenols should be regarded as a mechanism of action contributing to their chemopreventive/chemotherapeutic potential in relation to breast cancer. PMID:27097608

  9. Effect of artmether, hemin and Fe3+ on recombinant lactate dehydrogenase from Schistosoma japonicum

    Institute of Scientific and Technical Information of China (English)

    Gang Lu; Xuchu Hu; Can Huang; Yajun Lu; Lixian Wu; Lihua Li; Jing Xu; Xinbing Yu

    2010-01-01

    Objective: To explore antischitosome effects of artemether, hemin and Fe3+ on SjLDH. Methods:Enzyme activity of rSjLDH was assayed in the standard reaction system by adding different concentration of reagents (0.00-0.10 mM artemether, 0.00-0.02 mM hemin, 0.00-0.50 mM Fe3+). Same solvents of the each reagent were used as control. Results: There was no enzyme activity inhibition observed at 0.10 mM artemther; obivious inhibition for lactate oxidation reaction and pyruvate reduction reaction were detected at 0.002 mM and 0.004 mM of hemin, respectively;comparing with that of the control (P<0.05). The relative enzymatic activity inhibitions for pyruvate reduction reaction and lactate oxidation reaction at 0.02 mM hemin were 93.48% and 100.00%, respectively, comparing with that of the control (P<0.01); both pyruvate reduction and lactate oxidation reaction were inhibited completely at 0.50 mM Fe3+, comparing with that of the control (P<0.01). Conclusions: The results implied that SjLDH was not the direct molecular target of artemether. Hemin and Fe3+ are inhibitors of SjLDH.

  10. Gastrointestinal transport of calcium and glucose in lactating ewes.

    Science.gov (United States)

    Klinger, Stefanie; Schröder, Bernd; Gemmer, Anja; Reimers, Julia; Breves, Gerhard; Herrmann, Jens; Wilkens, Mirja R

    2016-06-01

    During lactation, mineral and nutrient requirements increase dramatically, particularly those for Ca and glucose. In contrast to monogastric species, in ruminants, it is rather unclear to which extend this physiological change due to increased demand for milk production is accompanied by functional adaptations of the gastrointestinal tract (GIT). Therefore, we investigated potential modulations of Ca and glucose transport mechanisms in the GIT of lactating and dried-off sheep. Ussing-chamber technique was applied to determine the ruminal and jejunal Ca flux rates. In the jejunum, electrophysiological properties in response to glucose were recorded. Jejunal brush-border membrane vesicles (BBMV) served to characterize glucose uptake via sodium-linked glucose transporter 1 (SGLT1), and RNA and protein expression levels of Ca and glucose transporting systems were determined. Ruminal Ca flux rate data showed a trend for higher absorption in lactating sheep. In the jejunum, small Ca absorption could only be observed in lactating ewes. From the results, it may be assumed that lactating ewes compensate for the Ca loss by increasing bone mobilization rather than by increasing supply through absorption from the GIT Presence of SGLT1 in the jejunum of both groups was shown by RNA and protein identification, but glucose uptake into BBMV could only be detected in lactating sheep. This, however, could not be attributed to electrogenic glucose absorption in lactating sheep under Ussing-chamber conditions, providing evidence that changes in jejunal glucose uptake may include additional factors, that is, posttranslational modifications such as phosphorylation. PMID:27273883

  11. Kinetics of lactate turnover and oxidation in man

    International Nuclear Information System (INIS)

    The turnover and oxidation of lactic acid have been studied in man by means of 14C-lactic acid, 14C-glucose, and 14C-alanine. The use of these labels in separate studies has enabled us to describe a complete scheme for the kinetics of lactic acid in man. We have determined that lactate arises from a minimum of two sources in overnight fasted man. 66% of lactate at this time arises from the metabolism of glucose while approximately 15% is derived from alanine. These sources and others unidentified supply lactate to the body pool at a rate of approximately 95 mg per kg per h. The disposal of this quantity of lactate is achieved through a minimum of three routes. Approximately 57% of the lactate turnover is oxidized to carbon dioxide, 15% is reduced to glucose, and approximately 25% is converted to alanine. The quantitative changes in the kinetics of this system that are brought on by fasting add an interesting dimension to the system. In agreement with the concepts of fuel economy in fasting the contribution of glucose carbon to lactic acid falls and, in turn, the contribution of lactate carbon to body glucose rises. The study of additional permutations of this system suggest that lactate, with pyruvate, is in the main stream of the intermediary metabolism of the body. The authors suggest that the study of this system offers promise of a fuller understanding of the derangements of metabolic disease. (author)

  12. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.M.; Gao, S.J.; Guo, X.F.; Sun, W.J. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Yan, Z.Q. [Department of Breast Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Wang, W.X.; Xu, Y.Q.; Lu, D. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China)

    2014-03-21

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

  13. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    International Nuclear Information System (INIS)

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression

  14. Using 99mTc-MIBI to Evaluate the Effects of Chemosensitizer on P-glycoprotein in Multidrug-resistant Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANGZhenwei; ZHANGXuemei; WUHua; ZHAOMing; XIANYUZhiqun; ZHOUJian; LAIShiying

    2005-01-01

    Objective: To establish a method to evaluate the effects of chemosensitizer on P-glycoprotein using 99mTc-MIBI, and observe the changes of 99mTc-MIBI uptake kinetics and P-glycoprotein levels after using verapamil in MDR human breast cells MCF-7/Adr. Methods: MDR breast carcinoma cells, MCF-7/Adr, were incubated and different protocols were performed. Protocol I: a chemosensitizer, verapamil (10μmol/L), was added into cell culture medium, while in control group, the same volume of DMEM was given. Cells were harvested after 2 h incubation with 99mTc-MIBI. Protocol Ⅱ: Verapamil (10μmol/L) was added into cell culture medium and incubated for 20 min, 40 min, 60 rain, 80 min, 8 h, 24 h, 48 h and 72 h respectively. Cells were harvested after 2 h incubation with 99mTc-MIBI. The radioactivity of the cells was measured and P-glycoprotein expression levels were determined with immunohistochemical stain. Results: Protocol I: After 2h incubation with verapamil the cellular uptake of 99mTc-MIBI was remarkably higher than control group (t=2.33, P0.05). Protocol

  15. Blood lactate changes during exercise at high altitude.

    OpenAIRE

    Binns, N.; Wright, A. D.; Singh, B. M.; Coote, J.H.; Bradwell, A R

    1987-01-01

    Blood lactate concentrations were measured in 18 normal subjects at the end of an exercise test designed to maintain heart rate at 85% of maximum for 15 minutes. Blood lactate concentrations were reduced at high altitude (4846 m) and correlated positively with basal pH and negatively with basal Pa,O2 levels. Blood lactate concentrations tended to be lower in those subjects on acetazolamide but were not correlated with the severity of acute mountain sickness or with the workload of the exercis...

  16. Blood lactate levels in 31 female dogs with pyometra

    Directory of Open Access Journals (Sweden)

    Karlstam Erika

    2009-01-01

    Full Text Available Abstract Background Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1 the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2 if these levels are related with the clinical status or other biochemical or hematological disorders. Methods In total 31 female dogs with pyometra admitted for surgical ovariohysterectomy and 16 healthy female control dogs were included in the present study. A complete physical examination including SIRS-status determination was performed. Blood samples for lactate concentrations, hematological and biochemical parameters, acid-base and blood gas analysis and other laboratory parameters were collected and subsequently analysed. The diagnosis pyometra was verified with histopathological examination of the uterus and ovaries. Increased hospitalisation length and presence of SIRS were used as indicators of outcome. Results In the pyometra group the median blood lactate level was 1,6 mmol l-1 (range -1. In the control group the median lactate level was 1,2 mmol l-1 (range -1. Of the 31 bitches 19 (61% fulfilled 2 or more criteria for SIRS at inclusion, 10 bitches (32% fulfilled 3 of the SIRS criteria whereas none accomplished more than 3 criteria. Lactate levels did not differ significantly between the pyometra and control group, or between the SIRS positive and SIRS negative dogs with pyometra. Increased lactate concentration (>2.5 mmol l-1 was demonstrated in one female dog with pyometra (3%, and was not associated with longer hospitalisation or presence of SIRS. Lactate

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

    International Nuclear Information System (INIS)

    Full text: Lactate, as metabolite of the glycolysis is a source of energy of the nerves. In vitro and in vivo experiments showed the neuroprotective effect of lactate and improvement of brain function after ischaemic injury. Intravenous infusion of lactate increases the global cerebral blood flow (CBF). In Alzheimer disease (AD) characteristic regional blood flow abnormalities and in the cerebrospinal fluid abnormal lactate levels were detected. Since disturbed CBF and vasoregulation was found in AD the effect of intravenous Na-lactate on CBF and related metabolic parameters was examined in order to assess the CBF response in the AD brain. In twenty (14 woman, 6 man, age ± SD.: 74 ± 7 years) patients with Alzheimer's disease (DSM IV, MMT.:13 ± 6) self-control study was performed. rCBF SPECT (99mTc-HMPAO) investigations were fulfilled during 5 mg/kg body weight 0.5 M Na-lactate infusion and in control state (0.9 % saline infusion) one week apart. The rCBF changes visually and by statistical parametric mapping were analyzed. ECG, blood pressure, heart rate, venous blood pH, pCO2, bicarbonate, serum lactate and cortisol level were measured before and after the SPECT investigation. Acute panic inventory and anxiety rating scales were used to access the psychiatric effect of lactate. The serum lactate levels increased in average from 0.8 mmol/L to 4.6 mmol/L, and 6.1 mmol/L 10 and 20 minutes after lactate infusion respectively. Compensatory changes were found in the venous blood pH, pCO2 and bicarbonate levels. Significant psychiatric symptoms and blood pressure and heart rate increase were not observed. The serum cortisol level remained unchanged. At the baseline investigation all of the patients have bilateral temporal or parietal hypoperfused areas in 8 patients with other additional localization of abnormalities. In 12 patients the global cerebral blood flow increased, in 8 decreased rCBF was detected by visual evaluation. According to the SPM analysis the

  18. Breast cancer during pregnancy and lactation

    International Nuclear Information System (INIS)

    We report 3 cases of gestational breast cancer that were encountered by the authors over a year period (1998) and discuss the diagnostic dilemma and modern management options. The first case was a 38-year-old Saudi female who was 8 month pregnant presented with 3 month history of left breast lump and intermittent bloody nipple discharge. She started menarche at the age of 13 years and denied any past history of benign breast diseases or oral contraceptive pill. There was no family history of malignant breast disease. Clinical examination revealed an irregular hard lump (3x3 cm) in the subareolar area of the left breast with no palpable axillary or supraclavicular lymph nodes. Fine needle aspiration cytology (FNAC) showed infiltrating ductal carcinoma. She underwent left simple mastectomy and axillary clearance together with cesarian section (CS) and tubal ligation at the same time. Histology revealed grade II infiltrating ductal carcinoma with 2 of the 11 level I nodes were positive for malignancy. She later underwent adjuvant chemoradiation and remained well with no evidence of locoregional recurrence 34 months later. The second case was a 40-year-old Saudi female who has been lactating for 10 months presented with a left breast lump of one week duration. There was no history of breast pain or nipple discharge and denied any past history of benign breast disease. There was no family history of breast cancer. Clinically, there was a 2x3 cm irregular left breast mass, in the upper outer quadrant with no palpable axillary lymphadenopathy. Mammography revealed suspicious opacity in the left breast but bone scan and ultrasonography showed no bone or liver metastases. Fine needle aspiration cytology showed suspicious of malignancy. She underwent a wide excision and left axillary clearance. Histopathology showed grade II medullary carcinoma and 2 out of 20 axillary lymph nodes were malignant. She later underwent systemic chemotherapy and radiation to left breast and

  19. NAD-Independent l-Lactate Dehydrogenase Required for l-Lactate Utilization in Pseudomonas stutzeri A1501

    OpenAIRE

    Gao, Chao; WANG, YUJIAO; Zhang, Yingxin; Lv, Min; Dou, Peipei; Xu, Ping; Ma, Cuiqing

    2015-01-01

    NAD-independent l-lactate dehydrogenases (l-iLDHs) play important roles in l-lactate utilization of different organisms. All of the previously reported l-iLDHs were flavoproteins that catalyze the oxidation of l-lactate by the flavin mononucleotide (FMN)-dependent mechanism. Based on comparative genomic analysis, a gene cluster with three genes (lldA, lldB, and lldC) encoding a novel type of l-iLDH was identified in Pseudomonas stutzeri A1501. When the gene cluster was expressed in Escherichi...

  20. Mammary remodeling in primiparous and multiparous dairy goats during lactation

    DEFF Research Database (Denmark)

    Safayi, Sina; Theil, Peter Kappel; Elbrønd, Vibeke Sødring;

    2010-01-01

    obtained from both mammary glands of 3 PP and 6 MP (=2 parity) dairy goats at parturition (d 1), d 10, 60, and 180 of lactation. Gene transcription relating to MEC turnover and vascular function was quantified by real-time reverse transcription-PCR, mammary morphology was characterized (quantitative...... histology), and cell turnover was determined (terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Ki-67). Primiparous glands showed higher expression for the genes involved in angiogenesis; namely, vascular endothelial growth factor receptor 2, and angiopoietin 1 and 2 and their receptor......, a few days after parturition (d 10). Primiparous glands also had higher rates of MEC proliferation in early lactation. It therefore appears that initiation of lactation is associated with development and growth of the mammary gland into early lactation, which continues for a longer period in PP...

  1. multivariate measure of lactation persistency for dairy sheep

    Directory of Open Access Journals (Sweden)

    A. Cappio-Borlino

    2011-03-01

    Full Text Available The persistency of lactation, i.e. the ability of animals to maintain a rconstant level of production after the lactation peak, represents an interesting trait for animal breeding strategies, allowing for the increase of profitability of animal husbandry via the reduction of production costs. Dairy cattle with flatter curves show a higher reproductive efficiency, a better metabolic status and have their nutritional requirements more constantly spread throughout lactation, allowing for the use of cheaper feeds (Dekkers et al., 1998; Solkner and Fucks, 1987. Also in dairy sheep the persistency could represent an interesting trait for breeding purposes. A main problem for the introduction of this trait in an aggregate genotype is represented by the difficulty in finding an objective measure: several measurements of lactation persistency have been proposed but none of them is widely accepted (Gengler, 1996..........

  2. Ultrasonographic findings of breast diseases during pregnancy and lactating period

    International Nuclear Information System (INIS)

    To evaluate ultrasonographic findings and usefulness in the diagnosis of breast diseases during pregnancy and lactating period. The authors evaluated the ultrasonographic findings of 18 breast diseases during pregnancy and lactation retrospectively. The ultrasonographic examinations were performed with linear-array 5 MHz transducer (ATL). Final diagnoses were obtained by the excisional biopsy, fine needle aspiration and clinical follow-up. Total 18 cases of breast diseases were consisted of 8 cases of galactocele, 4 cases of fibroadenoma, 3 cases of axillary accessory breast, 2 cases of lactating adenoma, and 1 case of phylloides tumor. The ultrasonographic findings of the above breast diseases were valuable in the diagnosis and therapeutic planning. Ultrasonography is the initial and useful method of diagnosing breast diseases during pregnancy and lactating period

  3. Death Losses for Lactating Cows in Herds Enrolled in Dairy Herd Improvement Test Plans

    Science.gov (United States)

    Factors that affect frequency of death were investigated for lactating cows in 45,032 herds for lactations from 1995 through 2005. Analyses included effects of herd, year, month, and stage of lactation in which lactation ended, parity, breed, and milk yield. A sample of 1,645 herds was employed to ...

  4. Energy Flux, Lactate Shuttling, Mitochondrial Dynamics, and Hypoxia.

    Science.gov (United States)

    Brooks, George A

    2016-01-01

    Our understanding of what happens in working muscle and at the whole-body level at sea level and at high altitude is different from that a few years ago. If dietary CHO and nutrition are adequate, at sea level metabolism shifts from a mix of lipid and CHO-derived fuels toward carbohydrate (glycogen, glucose, and lactate) oxidation at moderate and greater exercise intensities. As given by the Crossover Concept, a percentage to total energy expenditure, lipid oxidation is greatest at exercise power outputs eliciting 45-50 % of VO2max with greater intensities requiring relatively more CHO and lesser lipid oxidation. At altitude, a given exercise power output is achieved at a greater relative intensity expressed as % VO2max. Hence, exercise under conditions of hypoxia requires greater glycolytic flux, and lactate production than does the same effort at sea level, normoxic conditions. Glycolytic flux is further augmented at altitude by the effect of hypoxemia on sympathetic nervous system activity. Hence, augmented lactate production during exercise is adaptive. Over the short term, accelerated lactate flux provides ATP supporting muscle contraction and balances cytosolic redox. As well, lactate provides and energy substrate and gluconeogenic precursor. Over a longer term, via redox and ROS-generating mechanisms, lactate may affect adaptations in mitochondrial biogenesis and solute (glucose and lactate) transport. While important, the energy substrate, gluconeogenic, and signaling qualities of lactate production and disposal at altitude need to be considered within the context of overall dietary energy intake and expenditure during exercise at sea level and high altitude. PMID:27343113

  5. Lactate Kinetics during Exercise in Chronic Obstructive Pulmonary Disease

    OpenAIRE

    François Maltais; Sarah Bernard; Jean Jobin; Roger Belleau; Pierre LeBlanc

    1997-01-01

    OBJECTIVES: To examine whether the lactate kinetics during exercise are abnormal in patients with chronic obstructive pulmonary disease (COPD) and to evaluate the relationship of lactate kinetics with functional status.POPULATION: Fifty-four patients with COPD (forced expiratory volume in 1 s [FEV1] [mean ± SD] 36±12% predicted, range 19 to 70) and 10 healthy, age-matched normal men were included in this study.INTERVENTION: Each subject performed a stepwise exercise test up to maximal capacit...

  6. Gastrointestinal transport of calcium and glucose in lactating ewes

    OpenAIRE

    Klinger, Stefanie; Schröder, Bernd; Gemmer, Anja; Reimers, Julia; Breves, Gerhard; Herrmann, Jens; Wilkens, Mirja R.

    2016-01-01

    Abstract During lactation, mineral and nutrient requirements increase dramatically, particularly those for Ca and glucose. In contrast to monogastric species, in ruminants, it is rather unclear to which extend this physiological change due to increased demand for milk production is accompanied by functional adaptations of the gastrointestinal tract (GIT). Therefore, we investigated potential modulations of Ca and glucose transport mechanisms in the GIT of lactating and dried‐off sheep. Ussing...

  7. Process intensification for the ethyl lactate synthesis : integrated pervaporation reactor

    OpenAIRE

    Pereira, C.S.M.; Silva, V.M.T.M.; Pinho, Simão; A. E. Rodrigues

    2011-01-01

    Ethyl lactate is an important organic ester, which is biodegradable, produced by renewable resources and can be used as food additive, perfumery, flavor chemicals, solvent and pharmaceutical preparations[1]. It is a green solvent and could replace a range of environment-damaging halogenated and toxic solvents (for example: Nmethylpyrrolidone, toluene)[2]. The conventional way to produce ethyl lactate is the esterification of lactic acid with ethanol in the presence of an acid cata...

  8. Initiation of lactation and establishing relactation in outpatients.

    Science.gov (United States)

    Banapurmath, Shobha; Banapurmath, C R; Kesaree, Nirmala

    2003-04-01

    The present study was conducted to evaluate whether mothers with babies less than 6 weeks of age can be helped to initiate or establish lactation in outpatient department. One thousand mothers with babies less than 6 weeks of age who completed 10 days of follow-up in outpatient have been analyzed. Mothers who had either stopped breastfeeding or were not able to initiate breastfeeding were helped with establishing lactation at outpatient clinic. Sick babies and mothers having breast problem and systemic illness were excluded. 91.6% of mothers succeeded in establishing lactation within 10 days. 83.4% mothers achieved complete lactation and 8.2% of mothers achieved partial lactation in 10 days. However, 8.4% of mothers could not be helped in this study. They had to be hospitalized because of various reasons. It is possible to help majority of mothers with lactation difficulties at the outpatient when the baby is less than 6 weeks of age. Helping mothers with proper attachment at the breast appears to be crucial for success. PMID:12736408

  9. D-lactate metabolism in the alga, Chlamydomonas Reinhardtii

    International Nuclear Information System (INIS)

    [14C]D-lactate rapidly accumulates in Chlamydomonas cells under anaerobic conditions from the sugar-phosphate pools which are labeled during photosynthesis with 14CO2. A soluble D-lactate dehydrogenase (30 μmol NADH oxidized/h/mg Chl), which functions only in the direction of pyruvate reduction, has been partially purified and characterized. The D-lactate is reoxidized in Chlamydomonas by a mitochondrial membrane-bound dehydrogenase. This enzyme is known in the plant literature as glycolate dehydrogenase, an enzyme of the oxidative photosynthetic carbon (C2) cycle. This dehydrogenase may be linked to the mitochondrial electron transport chain, although the direct electron acceptor is unknown. Therefore, D-lactate accumulation may be, in part, due to the shut down of electron transport during anaerobiosis. In vivo chase experiments have shown that the D-lactate turns over rapidly when algal cells, which have been grown with air levels of CO2 (0.04%), are returned to aerobic conditions in the light. Such turnover is not observed in cells which had been grown with 1 to 5% CO2. Cells grown with high CO2 have lower levels of glycolate dehydrogenase activity. They are currently using mutants of Chlamydomonas deficient in mitochondrial respiration to study the role of D-lactate oxidation in these algae

  10. Bioconversion of methane to lactate by an obligate methanotrophic bacterium

    Science.gov (United States)

    Henard, Calvin A.; Smith, Holly; Dowe, Nancy; Kalyuzhnaya, Marina G.; Pienkos, Philip T.; Guarnieri, Michael T.

    2016-01-01

    Methane is the second most abundant greenhouse gas (GHG), with nearly 60% of emissions derived from anthropogenic sources. Microbial conversion of methane to fuels and value-added chemicals offers a means to reduce GHG emissions, while also valorizing this otherwise squandered high-volume, high-energy gas. However, to date, advances in methane biocatalysis have been constrained by the low-productivity and limited genetic tractability of natural methane-consuming microbes. Here, leveraging recent identification of a novel, tractable methanotrophic bacterium, Methylomicrobium buryatense, we demonstrate microbial biocatalysis of methane to lactate, an industrial platform chemical. Heterologous overexpression of a Lactobacillus helveticus L-lactate dehydrogenase in M. buryatense resulted in an initial titer of 0.06 g lactate/L from methane. Cultivation in a 5 L continuously stirred tank bioreactor enabled production of 0.8 g lactate/L, representing a 13-fold improvement compared to the initial titer. The yields (0.05 g lactate/g methane) and productivity (0.008 g lactate/L/h) indicate the need and opportunity for future strain improvement. Additionally, real-time analysis of methane utilization implicated gas-to-liquid transfer and/or microbial methane consumption as process limitations. This work opens the door to develop an array of methanotrophic bacterial strain-engineering strategies currently employed for biocatalytic sugar upgrading to “green” chemicals and fuels. PMID:26902345

  11. Effects of Pregnancy and Lactation on Iron Metabolism in Rats

    Directory of Open Access Journals (Sweden)

    Guofen Gao

    2015-01-01

    Full Text Available In female, inadequate iron supply is a highly prevalent problem that often leads to iron-deficiency anemia. This study aimed to understand the effects of pregnancy and lactation on iron metabolism. Rats with different days of gestation and lactation were used to determine the variations in iron stores and serum iron level and the changes in expression of iron metabolism-related proteins, including ferritin, ferroportin 1 (FPN1, ceruloplasmin (Cp, divalent metal transporter 1 (DMT1, transferrin receptor 1 (TfR1, and the major iron-regulatory molecule—hepcidin. We found that iron stores decline dramatically at late-pregnancy period, and the low iron store status persists throughout the lactation period. The significantly increased FPN1 level in small intestine facilitates digestive iron absorption, which maintains the serum iron concentration at a near-normal level to meet the increase of iron requirements. Moreover, a significant decrease of hepcidin expression is observed during late-pregnancy and early-lactation stages, suggesting the important regulatory role that hepcidin plays in iron metabolism during pregnancy and lactation. These results are fundamental to the understanding of iron homeostasis during pregnancy and lactation and may provide experimental bases for future studies to identify key molecules expressed during these special periods that regulate the expression of hepcidin, to eventually improve the iron-deficiency status.

  12. Bioconversion of methane to lactate by an obligate methanotrophic bacterium.

    Science.gov (United States)

    Henard, Calvin A; Smith, Holly; Dowe, Nancy; Kalyuzhnaya, Marina G; Pienkos, Philip T; Guarnieri, Michael T

    2016-01-01

    Methane is the second most abundant greenhouse gas (GHG), with nearly 60% of emissions derived from anthropogenic sources. Microbial conversion of methane to fuels and value-added chemicals offers a means to reduce GHG emissions, while also valorizing this otherwise squandered high-volume, high-energy gas. However, to date, advances in methane biocatalysis have been constrained by the low-productivity and limited genetic tractability of natural methane-consuming microbes. Here, leveraging recent identification of a novel, tractable methanotrophic bacterium, Methylomicrobium buryatense, we demonstrate microbial biocatalysis of methane to lactate, an industrial platform chemical. Heterologous overexpression of a Lactobacillus helveticus L-lactate dehydrogenase in M. buryatense resulted in an initial titer of 0.06 g lactate/L from methane. Cultivation in a 5 L continuously stirred tank bioreactor enabled production of 0.8 g lactate/L, representing a 13-fold improvement compared to the initial titer. The yields (0.05 g lactate/g methane) and productivity (0.008 g lactate/L/h) indicate the need and opportunity for future strain improvement. Additionally, real-time analysis of methane utilization implicated gas-to-liquid transfer and/or microbial methane consumption as process limitations. This work opens the door to develop an array of methanotrophic bacterial strain-engineering strategies currently employed for biocatalytic sugar upgrading to "green" chemicals and fuels. PMID:26902345

  13. The magnitude of blood lactate increases from high speed workouts.

    Science.gov (United States)

    Caruso, J F; Kucera, S; Jackson, T; Hari, P; Olson, N; McLagan, J; Taylor, S T; Shepherd, C

    2011-05-01

    To examine blood lactate concentrations from high-speed exercise resistive exercise, subjects performed workouts on an inertial kinetic exercise (Oconomowoc, WI) device. Workouts entailed two 60-s sets of elbow flexor (curling) repetitions. Pre- and post-exercise blood lactate concentrations were measured, via a fingertip blood drop, with an analyzer. From workouts the average acceleration, maximum force and total torque were derived. Blood lactate concentrations were analyzed with a 2 (gender)×2 (time) ANOVA, with repeated measures for time. Average acceleration, maximum force and total torque were analyzed with one-way (gender) ANOVAs. With an α=0.05, blood lactate concentrations had a time (prewomen) effects. Current blood lactate concentrations were commensurate with other studies that used a modest level of resistance and engaged a small muscle mass. Given the current workout protocol and muscle mass engaged, as well as parallels to other results, our study appears to offer a valid portrayal of subsequent changes in blood lactate concentrations from high-speed resistive exercise. PMID:21380973

  14. Application of L-lactate-cytochrome c-oxidoreductase for development of amperometric biosensor for L-lactate determination

    Directory of Open Access Journals (Sweden)

    Dzyadevych S. V.

    2009-06-01

    Full Text Available Aim. Development of amperometric biosensor based on L-lactate-cytochrome c-oxidoreductase (flavocytochrome b2, FC b2 for lactate determination. Methods. All experiments were performed using the amperometric method of detection. The methods of electrochemical polymerization and immobilization in glutaraldehyde vapors were used for FC b2 immobilization on the surface of electrodes. Results. The FC b2 preparation, which demonstrated the best operational characteristics after immobilization in poly (3,4-ethylen dioxythiophene, was selected. The selectivity, operational and storage stability, and pH-optimum for operation of the created biosensor were determined. The analysis of L-lactate in the model solutions and wine samples was carried outusing the developed biosensor. Conclusion. The FC b2-based biosensor due to its high stability can be effectively used for lactate determination in blood and other liquids containing no ethanol. After the selectivity optimization, the devise can be also applied for wine analysis.

  15. Expression of the apoptosis-related genes BCL-2 and BAD in human breast carcinoma and their associated relationship with chemosensitivity

    Directory of Open Access Journals (Sweden)

    Fan Yuan-ming

    2010-08-01

    Full Text Available Abstract Objective To evaluate the expression of BCL-2 and BAD genes in tissues of breast carcinoma and investigate the relationship between the expression of BCL-2 and BAD in breast cancer cells with chemosensitivity. Methods Immunohistochemical technique was used to detect the expression of BCL-2, BAD in 10 normal breast tissues, 10 breast fibroadenoma tissues, 40 youth human breast carcinoma tissues, 40 menopause human breast carcinoma tissues. And to detect the expression of ER, PR in 80 human breast carcinoma tissues. 20 Surgical samples of breast cancer, diagnosed by pathology, were obtained from The First Affiliated Hospital of Chongqing Medical University. The cancer sample cells were cultured separately in the incubator at 37°C, 5% CO2 in vitro. The rate of inhibition of cancer cells in 4 kinds of anticancer drugs-- Epirubicin Adriamycin (EADM,5-Fluorouracil (5-Fu, Navelbine(NVB and Diaminedichloroplatinum (DDP, were assayed by MTT method. Results The expression of BCL-2, BAD genes in young human breast carcinoma tissues were lower than that in menopause human breast carcinoma tissues (P . There was a negative correlation between the positive expression rate of BCL-2 and histologic grade or the lymph node metastasis (P . There was a positive correlation between the expression rates of BCL-2 and of ER, PR (P . The expression of BAD had no relationship with the expression of ER, PR, histologic grade and the lymph node metastasis(P = NS. Sensitivity rates of 20 breast cancer cells in 0.1 × PPC within 48 h in vitro were 30% EADM,20% 5-Fu,45% NVB and 25% DDP. Respectively, the rate of inhibition of EADM,5- Fu, NVB and DDP were significantly higher in the BCL-2 negative cancer cells than in the BCL-2 positive cancer cells. A negative correlation was found between expression of BCL-2 and chemosensitivity for all the 4 anticancer drugs. The inhibition rates of EADM and NVB were significantly lower in the BAD negative cancer cells than in the

  16. Hematological and biochemical findings in pregnant, postfoaling, and lactating jennies.

    Science.gov (United States)

    Bonelli, F; Rota, A; Corazza, M; Serio, D; Sgorbini, M

    2016-04-15

    The aims of this study were to (1) verify if significant changes occur in hematological and biochemical parameters in jennies during the last 2 months of pregnancy and the first 2 months of lactation, and (2) determine any differences with mares. Hematological and biochemical parameters were evaluated in jennies every 15 days during late pregnancy, parturition, and early lactation. The Kolmogorov-Smirnov test, analysis of variance for repeated measurements and Tukey's multiple comparison test as post hoc were applied. The significance level was set at P Cells (RBC) count and Hematocrit (HCT), White Blood Cells (WBC) count, platelet count (PLT), total proteins, blood urea, triglycerides and total cholesterol concentrations, aspartate aminotransferase, gamma-glutamyltransferase, creatine-phosphokinase activities, sodium (Na) and potassium (K). RBC and HCT were higher in late pregnancy than at foaling and during lactation. The relative anemia might be due to increased water ingestion because of fluid losses. The WBC count was higher at foaling than during late pregnancy and lactation. This could be related to the release of cortisol and catecholamine during delivery. The PLT trend showed lower values from delivery to the first 2 months of lactation compared to late gestation. Blood urea increased near parturition, and then remained constant during delivery and lactation, which might be due to the high energy demand at the beginning of lactation. Triglycerides and total cholesterol showed a decrease from delivery through the lactation period. Thus, jennies seem to have a similar metabolism of fats to ponies and draft horse mares, characterized by a greater fat content and mobilization than light breed horses. Aspartate aminotransferase activity decreased at parturition and early lactation, probably because of a predominance of anabolic over catabolic processes during pregnancy. Gamma-glutamyltransferase activity was lower at delivery and during lactation than at

  17. Vitamin D Levels Among Pregnant and Lactating Women

    International Nuclear Information System (INIS)

    Objective: To assess the serum level of vitamin D in pregnant and lactating women. Study Design: Case-control study. Place and Duration of Study: Gynaecological Unit 1 of Jinnah Hospital, Lahore, from December 2010 to May 2011. Methodology: A total of 100 women comprised of three groups: pregnant (n = 40), lactating (n = 40) and control (n = 20) groups. The information regarding age, educational level, socioeconomic status, exposure to sunlight and dietary vitamin D intake were collected through self-structured questionnaire. Serum concentration of vitamin D was measured by ELISA and serum calcium and phosphate levels were measured by chemistry analyzer. Statistical analysis was done using SPSS (version 13). The values were considered significant at 0.05 level of significance. Results: The mean serum vitamin D level in the pregnant and lactating mothers was 26.5 +- 17.1 nmol/L and 21.4 +- 16.3 nmol/L respectively and in control group was 33.8 +- 21.1 nmol/L. The mean calcium level in the pregnant, lactating and control group was 10.3 +- 1.2 mg/dL, 9.7 +- 1.3 mg/dL and 9.7 +- 1.3 mg/dL respectively. The mean phosphate in pregnant was 3.2 +- 0.76 mg/dl, in lactating was 3.3 +- 0.76 mg/dl and in control was 3.5 +- 0.92 mg/dl. Significant difference (p = 0.041 and p = 0.037 respectively) in the serum levels of vitamin D and calcium was observed among the pregnant and lactating women as compared to control group. Conclusion: Low serum vitamin D concentration was observed in lactating women and pregnant women as compared to control group. (author)

  18. Iodine Status in Pregnant Women, Lactating Mothers, and Newborns in an Area with More Than Two Decades of Successful Iodine Nutrition.

    Science.gov (United States)

    Nazeri, Pantea; Zarghani, Najmeh Hamzavi; Mirmiran, Parvin; Hedayati, Mehdi; Mehrabi, Yadollah; Azizi, Fereidoun

    2016-07-01

    Pregnant women, lactating mothers, and their newborns constitute the target population for prevention and control of iodine deficiency. Hence, the aim of this study was to evaluate the iodine nutrition status among these vulnerable groups in an area with more than two decades of successful elimination of iodine deficiency. In this cross-sectional study conducted in health care centers of Tehran, 100 pregnant women and 84 lactating mothers and their newborn were randomly selected. Urinary iodine concentration and iodine content of salts were measured using the Sandell-Kolthoff and titration methods, respectively. Urinary iodine concentration mammary glands. PMID:26631051

  19. Growth-inhibitory and chemosensitizing effects of the glutathione-S-transferase-π-activated nitric oxide donor PABA/NO in malignant gliomas.

    Science.gov (United States)

    Kogias, Evangelos; Osterberg, Nadja; Baumer, Brunhilde; Psarras, Nikolaos; Koentges, Christoph; Papazoglou, Anna; Saavedra, Joseph E; Keefer, Larry K; Weyerbrock, Astrid

    2012-03-01

    Glutathione-S-transferases (GSTs) are upregulated in malignant gliomas and contribute to their chemoresistance. The nitric oxide (NO) donor PABA/NO (O(2) -{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) generates NO upon selective enzymatic activation by GST-π-inducing selective biological effects in tumors. Tumor cell killing and chemosensitization were observed in a variety of tumors after exposure to GST-activated NO donor drugs. In our project, cytotoxic and chemosensitizing effects of PABA/NO in combination with carboplatin (CPT) and temozolomide (TMZ) were studied in human U87 glioma cells in vitro and in vivo. U87 glioma cells were exposed to PABA/NO alone or in combination with CPT or TMZ for 24 hr. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after 24-hr incubation and 48 hr after drug removal. The antiproliferative effect of PABA/NO was assessed in an intracranial U87 glioma nude rat model comparing subcutaneous administration and intratumoral delivery by convection-enhanced delivery. PABA/NO monotherapy showed a strong dose-dependent growth-inhibitory effect in U87 glioma cells in vitro, and a strong synergistic effect was observed after concomitant treatment with TMZ, but not with CPT. Systemic and intratumoral PABA/NO administration significantly reduced cell proliferation, but this did not result in prolonged survival in nude rats with intracranial U87 gliomas. PABA/NO has potent antiproliferative effects, sensitizes U87 glioma cells to TMZ in vitro and shows some in vivo efficacy. Further studies are still required to consolidate the role of NO donor therapy in glioma treatment. PMID:21455987

  20. Tumor-derived hepatocyte growth factor is associated with poor prognosis of patients with glioma and influences the chemosensitivity of glioma cell line to cisplatin in vitro

    Directory of Open Access Journals (Sweden)

    Guo You-feng

    2012-06-01

    Full Text Available Abstract Background We examined the association of tumor-derived hepatocyte growth factor (HGF with the clinicopathological features of gliomas and investigated the effect of HGF inhibition on the biological behavior of tumor cells in vitro in order to determine whether HGF is a valuable prognostic predictor for glioma patients. Methods Seventy-six cases of glioma were collected. The tumor-derived HGF expression, cell proliferation index (PI and intratumoral microvessels were evaluated by immunohistochemistry. Correlation between immunostaining and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. U87MG glioma cells were transfected with short interference (si-RNA for HGF, and the cell viability, migratory ability and chemosensitivity to cisplatin were evaluated in vitro. Results Both high HGF expression in tumor cells (59.2%, 45/76 and high PI were significantly associated with high-grade glioma and increased microvessels in tumors (P P = 0.004 and high-expression of HGF (P = 0.008 emerged as independent prognostic factors for the overall survival of glioma patients. The tumor-derived HGF mRNA and protein expressions were significantly decreased in vitro after transfection of HGF siRNA. HGF siRNA inhibited the cell growth and reduced cell migratory ability. Moreover, HGF siRNA transfection enhanced the chemosensitivity of U87MG glioma cells to cisplatin. Conclusion This study indicated that there was significant correlation among tumor cell-derived HGF, cell proliferation and microvessel proliferation in gliomas. HGF might influence tumor progression by modulating the cell growth, migration and chemoresistance to drugs. Increased expression of HGF may be a valuable predictor for prognostic evaluation of glioma patients.

  1. ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel

    Directory of Open Access Journals (Sweden)

    Wang Tingting

    2008-04-01

    Full Text Available Abstract Background One of the major challenges in currently chemotherapeutic theme is lacking effective biomarkers for drug response and sensitivity. Our current study focus on two promising biomarkers, ERCC1 (excision repair cross-complementing group 1 and BRCA1 (breast cancer susceptibility gene 1. To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases, we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with cisplatin and/or docetaxel chemosensitivity. Methods Real-time quantitative PCR is used to analysis related genes expression in forty-six malignant effusions prospectively collected from non-small cell lung cancer (NSCLC, gastric and gynecology cancer patients. Viable tumor cells obtained from malignant effusions are tested for their sensitivity to cisplatin and docetaxel using ATP-TCA assay. Results ERCC1 expression level is negatively correlated with the sensitivity to cisplatin in NSCLC patients (P = 0.001. In NSCLC and gastric group, BRCA1 expression level is negatively correlated with the sensitivity to cisplatin (NSCLC: P = 0.014; gastric: P = 0.002 while positively correlated with sensitivity to docetaxel (NSCLC: P = 0.008; gastric: P = 0.032. A significant interaction is found between ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P = 0.010, n = 45. Conclusion Our results demonstrate that ERCC1 and BRCA1 mRNA expression levels are correlated with in vitro chemosensitivity to cisplatin and/or docetaxel in malignant effusions of NSCLC and gastric cancer patients. And combination of ERCC1 and BRCA1 may have a better role on predicting the sensitivity to cisplatin than the single one is considered.

  2. ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel

    International Nuclear Information System (INIS)

    One of the major challenges in currently chemotherapeutic theme is lacking effective biomarkers for drug response and sensitivity. Our current study focus on two promising biomarkers, ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer susceptibility gene 1). To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases, we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with cisplatin and/or docetaxel chemosensitivity. Real-time quantitative PCR is used to analysis related genes expression in forty-six malignant effusions prospectively collected from non-small cell lung cancer (NSCLC), gastric and gynecology cancer patients. Viable tumor cells obtained from malignant effusions are tested for their sensitivity to cisplatin and docetaxel using ATP-TCA assay. ERCC1 expression level is negatively correlated with the sensitivity to cisplatin in NSCLC patients (P = 0.001). In NSCLC and gastric group, BRCA1 expression level is negatively correlated with the sensitivity to cisplatin (NSCLC: P = 0.014; gastric: P = 0.002) while positively correlated with sensitivity to docetaxel (NSCLC: P = 0.008; gastric: P = 0.032). A significant interaction is found between ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P = 0.010, n = 45). Our results demonstrate that ERCC1 and BRCA1 mRNA expression levels are correlated with in vitro chemosensitivity to cisplatin and/or docetaxel in malignant effusions of NSCLC and gastric cancer patients. And combination of ERCC1 and BRCA1 may have a better role on predicting the sensitivity to cisplatin than the single one is considered

  3. Lactation in Al-Quran Perspective

    Directory of Open Access Journals (Sweden)

    Nanang Rokhman Saleh

    2015-11-01

    Full Text Available 800x600 One of the provisions of law which has been described in the Qur'an is the problem radha'ah (feeding or lactation. The word of Radha'ah in the Qur’an is used for two meaning: first, as one reason for marriage forbidden due to foster sister (QS. al-Nisa’: 23, and second, as the activity of breastfeeding for the mother to her baby, in which the milk becomes the main food for babies, especially the first six months of birth, and highly recommended it be given to infants until two years old (Surah al-Baqarah: 233. Feeding activity is a series of pregnancy, childbirth and infant care. The fourth activity has been established by Allah to each of women as the nature  and the trust as well. All of these gifts, recognized by the Qur'an as a condition that is very exhausting and burdensome to mother, but noble in the sight of Allah. Therefore, children must be grateful, respectful and dutiful to his parents, so that they can remember the good, service, and the struggle of his parents (Luqman: 14, al-Ahqaf: 15 Radha'ah as the main activity of the mother after the birth of her baby, bring benefits to both mother and baby. Breastfeeding can build psychological situation of calm and full of affection between mother and child. However, in practice, interest of mother in giving breastfeed declined, whereas the Qur’an has set the terms of breastfeeding, obligations and rights of mothers to breastfeed, breastfeeding and weaning time limit. The father should provide to mother during breastfeeding or find a woman to give breastfeeding and these conditions causes mahram. In addition, breast-feeding should be intended for the worship of Allah so the mother had the pleasure and reward from Him. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso

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

    Directory of Open Access Journals (Sweden)

    Antonello Cannas

    2010-01-01

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

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

    Science.gov (United States)

    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 11kg/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 5kg/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 1kg/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. PMID:26805998

  6. PELOD score, serum procalcitonin, and lactate levels in pediatric sepsis

    Directory of Open Access Journals (Sweden)

    Jufitriani Ismy

    2016-11-01

    Full Text Available Background Sepsis remains a major cause of morbidity andmortality among critically ill children in the pediatric intensivecare unit (PICU. Procalcitonin and lactate have been used asbiomarkers of sepsis, as they have been correlated with diseaseseverity, organ failure and death. The Pediatric Logistic OrganDysfunction (PELOD score is a tool to assess the severity oforgan dysfunction in critically ill children.Objective To investigate the correlation between PELOD scoreand procalcitonin and lactate levels in pediatric sepsis.Methods A cross-sectional study was conducted in childrenwith sepsis who were admitted to the PICU from April to July2012. Sepsis was defined as systemic inflammatory responsesyndrome (SIRS, as a result of suspected or proven infection.Proven infection was defined as positive culture findings (blood, mL. Spearman’s test was used to assess for correlations betweenPELOD scores and procalcitonin as well as lactate levels.Results Thirty-two patients were analyzed, consisting of 18 malesand 14 females with an age range of 1-432 months (median 21months. There was no statistically significant correlation betweenprocalcitonin level and PELOD score (r=- 0.186, 95%CI -0.502to 0.174, P=0.308 nor between lactate level(r=-0.069, 95%CI-0.408 to 0.287, P=0.709 and PELOD score.Conclusion Serum procalcitonin and lactate levels are notcorrelated with PELOD scores in children with sepsis.

  7. Theoretical predictions of lactate and hydrogen ion distributions in tumours.

    Directory of Open Access Journals (Sweden)

    Maymona Al-Husari

    Full Text Available High levels of lactate and H(+-ions play an important role in the invasive and metastatic cascade of some tumours. We develop a mathematical model of cellular pH regulation focusing on the activity of the Na(+/H(+ exchanger (NHE and the lactate/H(+ symporter (MCT to investigate the spatial correlations of extracellular lactate and H(+-ions. We highlight a crucial role for blood vessel perfusion rates in determining the spatial correlation between these two cations. We also predict critical roles for blood lactate, the activity of the MCTs and NHEs on the direction of the cellular pH gradient in the tumour. We also incorporate experimentally determined heterogeneous distributions of the NHE and MCT transporters. We show that this can give rise to a higher intracellular pH and a lower intracellular lactate but does not affect the direction of the reversed cellular pH gradient or redistribution of protons away from the glycolytic source. On the other hand, including intercellular gap junction communication in our model can give rise to a reversed cellular pH gradient and can influence the levels of pH.

  8. Blood lactate concentration at selected of olympic modes weightlifting.

    Science.gov (United States)

    Gupta, S; Goswami, A

    2001-04-01

    This study highlights the blood lactate response of weightlifters (N = 5) in two modes of olympic lifts: Snatch (SN) and Clean & Jerk (CJ), during three types of training namely (1) one repetition lift (ORL), (2) Multiple set session (MSS) and (3) one set session (OSS). In ORL, 30, 40, 50, and 60 kg, each of one repetition only, were lifted with an interval of 5 min between two consecutive loads. Both MSS and OSS consisted of 6 sets of lift: 50% x 6 (i.e. 50% of 1 Repetition Maximum x 6 repetitions), 60% x 5, 70% x 4, 80% x 3, 90% x 2, and 100% x 1. In MSS, 3 to 3.5 min interval was given between two successive sets whereas in OSS the interval was approximately 24 hours. Lactate levels were very low (< 3.5 mM) in ORL. In MSS, lactate reached peak at an intermediate set, but, it was maximum at the first set and then declined gradually in OSS. In most of the cases, however, lactate were significantly higher in CJ than SN. The study concludes that: (a) anaerobic glycolysis is not stimulated considerably when the lifting time is only 4-5 sec, (b) repetition of lift plays more important role, than intensity, in lactate production, (c) CJ is more strenuous than SN for a given %RM. PMID:11480232

  9. Polyhydroxybutyrate production from lactate using a mixed microbial culture.

    Science.gov (United States)

    Jiang, Yang; Marang, Leonie; Kleerebezem, Robbert; Muyzer, Gerard; van Loosdrecht, Mark C M

    2011-09-01

    In this study we investigated the use of lactate and a lactate/acetate mixture for enrichment of poly-3-hydroxybutyrate (PHB) producing mixed cultures. The mixed cultures were enriched in sequencing batch reactors (SBR) that established a feast-famine regime. The SBRs were operated under conditions that were previously shown to enable enrichment of a superior PHB producing strain on acetate (i.e., 12 h cycle length, 1 day SRT and 30°C). Two new mixed cultures were eventually enriched from activated sludge. The mixed culture enriched on lactate was dominated by a novel gammaproteobacterium. This enrichment can accumulate over 90 wt% PHB within 6 h, which is currently the best result reported for a bacterial culture in terms of the final PHB content and the biomass specific PHB production rate. The second mixed culture enriched on a mixture of acetate and lactate can produce up to 84 wt% PHB in just over 8 h. The predominant bacterial species in this culture were Plasticicumulans acidivorans and Thauera selenatis, which have both been reported to accumulate large amounts of PHB. The data suggest that P. acidivorans is a specialist on acetate conversion, whereas Thauera sp. is a specialist on lactate conversion. The main conclusion of this work is that the use of different substrates has a direct impact on microbial composition, but has no significant effect on the functionality of PHB production process. PMID:21455932

  10. Quinone-dependent D-lactate dehydrogenase Dld (Cg1027) is essential for growth of Corynebacterium glutamicum on D-lactate

    OpenAIRE

    Oikawa Tadao; Matsui Daisuke; Stansen K Corinna; Youn Jung-Won; Kato Osamu; Wendisch Volker F

    2010-01-01

    Abstract Background Corynebacterium glutamicum is able to grow with lactate as sole or combined carbon and energy source. Quinone-dependent L-lactate dehydrogenase LldD is known to be essential for utilization of L-lactate by C. glutamicum. D-lactate also serves as sole carbon source for C. glutamicum ATCC 13032. Results Here, the gene cg1027 was shown to encode the quinone-dependent D-lactate dehydrogenase (Dld) by enzymatic analysis of the protein purified from recombinant E. coli. The abso...

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

    Science.gov (United States)

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

    2015-09-01

    We have developed a 3D cell/tissue culture bioreactor compatible with hyperpolarized (HP) (13)C MR and interrogated HP [1-(13)C]lactate production and efflux in human renal cell carcinoma (RCC) cells. This platform is capable of resolving intracellular and extracellular HP lactate pools, allowing the kinetic measurement of lactate production and efflux in the context of cancer aggressiveness and response to therapy. HP (13)C MR studies were performed on three immortalized human renal cell lines: HK2, a normal renal proximal tubule cell line from which a majority of RCCs arise, UMRC6, a cell line derived from a localized RCC, and UOK262, an aggressive and metastatic RCC. The intra- (Lacin ) and extracellular (Lacex ) HP lactate signals were robustly resolved in dynamic (13)C spectra of the cell lines due to a very small but reproducible chemical shift difference (0.031 ± 0.0005 ppm). Following HP [1-(13)C]pyruvate delivery, the ratio of HP Lacin /Lacex was significantly lower for UOK262 cells compared with both UMRC6 and HK2 cells due to a significant (p culture bioreactor to study not only cellular metabolism but also transport. Additionally, this platform offers a sophisticated way to follow therapeutic interventions and screen novel therapies that target lactate export. PMID:26202449

  12. Successful induced non-puerperal lactation in surrogate mothers.

    Science.gov (United States)

    Banapurmath, C R; Banapurmath, S; Kesaree, N

    1993-01-01

    Ten surrogate mothers seen between 1986-91 were encouraged to breast-feed their babies varying in age between 8 days to 5 months. All the 10 surrogate mothers had experienced pregnancy and child birth in the past. The lactational gap varied from 1 year to 16 years. Presence of milk was noted on 3rd to 8th day after attempting induced lactation in 5 mothers. No milk was seen on manual expression of the nipple even after 2 weeks in the other 5 surrogate mothers. Two mothers achieved complete breast-feeding and they fed their babies for 2 years. Three mothers could achieve partial lactation and these mothers fed for 1 year or more. All these 5 babies registered satisfactory growth. PMID:8157333

  13. 14C-coumaphos residues in Egyptian lactating goats

    International Nuclear Information System (INIS)

    14C-coumaphos was applied dermally to two lactating goats, with 2 weeks interval. One goat was sacrificed 24 hours after the second application, and the second animal after a withdrawal period of two weeks. The results showed that coumaphos has a slow penetration rate when dermally applied to lactating goats. Milk residues were 0.20-0.25 ppm following appication, declining gradually to 0.03-0.06 ppm after 2 weeks. The liver and kidney were found to contain considerable amounts of coumaphos residues in comparison with other organs and milk after the withdrawal period. (author)

  14. Squalamine lactate for exudative age-related macular degeneration.

    Science.gov (United States)

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies. PMID:16935213

  15. Postpartum Sexuality and the Lactational Amenorrhea Method for Contraception.

    Science.gov (United States)

    Labbok, Miriam H

    2015-12-01

    This chapter reviews the literature on postpartum coital behavior, anovulatory and ovulatory bleeding episodes, and the methodology and efficacy of Lactational Amenorrhea Method and progesterone-only oral contraceptives. Of interest is the finding that breastfeeding women may resume coital behavior earlier postpartum, but report increased discomfort over time. The high efficacy of the Lactational Amenorrhea Method is confirmed and data illustrating possible relaxation of some criteria are presented. The conflicting guidance of CDC and WHO concerning immediate postpartum use of progestin-only methods is presented. The dearth of recent studies calls for new research on these topics. PMID:26457855

  16. Early Life Triclocarban Exposure During Lactation Affects Neonate Rat Survival

    OpenAIRE

    Rebekah C. M. Kennedy; Menn, Fu-Min; Healy, Laura; Kellie A. Fecteau; Hu, Pan; Bae, Jiyoung; Gee, Nancy A.; Lasley, Bill L; Zhao, Ling; Chen, Jiangang

    2015-01-01

    Triclocarban (3,4,4′-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation onl...

  17. Properties of Lactate Dehydrogenase in a Psychrophilic Marine Bacterium

    OpenAIRE

    Mitchell, P; Yen, H. C.; Mathemeier, P. F.

    1985-01-01

    Lactate dehydrogenase (EC 1.1.1.27) from Vibrio marinus MP-1 was purified 15-fold and ammonium activated. The optimum pH for pyruvate reduction was 7.4. Maximum lactate dehydrogenase activity occurred at 10 to 15 degrees C, and none occurred at 40 degrees C. The crude-extract enzyme was stable between 15 and 20 degrees C and lost 50% of its activity after 60 min at 45 degrees C. The partially purified enzyme was stable between 8 and 15 degrees C and lost 50% of its activity after 60 min at 30...

  18. Interpreting lactate measurement in critically ill horses: diagnosis, treatment, and prognosis.

    Science.gov (United States)

    Tennent-Brown, Brent S

    2012-01-01

    In hospitalized horses, hypovolemia and the resulting decrease in tissue perfusion is the most common cause of hyperlactatemia. Therefore, measurement of blood lactate concentration can be a useful tool for guiding fluid therapy. Similarly, measuring blood lactate concentration can be used to assess the need for and adequacy of transfusions in horses receiving whole blood. Inflammatory leukocytes within closed body cavities consume glucose and produce lactate. Simultaneous measurement of blood lactate concentration and lactate concentration of peritoneal, pleural, or synovial fluid has been used to help differentiate septic from nonseptic effusions. A fluid lactate concentration higher than the blood lactate concentration provides evidence for a bacterial cause of the effusion. In horses evaluated for colic, a peritoneal lactate concentration higher than the simultaneously measured blood lactate concentration is indicative of intestinal strangulation and ischemia. Veterinary studies have suggested that serial blood lactate measurements might be a more useful prognostic indicator than a single lactate measurement. In hospitalized adult horses and foals, blood lactate concentration is higher at all time points in nonsurvivors compared with survivors, although the differences tend to be subtle. Measuring the rate at which lactate concentrations return to normal might also prove useful in equine medicine, but this requires further investigation. PMID:22271469

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

    Science.gov (United States)

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

    2011-11-22

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

  20. Pharmacokinetics of ceftazidime administered to lactating and non-lactating goats

    Directory of Open Access Journals (Sweden)

    R. Rule

    2011-05-01

    Full Text Available The aim of this work was to determine the pharmacokinetics of intravenous (iv and intramuscular (im ceftazidime administered to lactating (LTG; n = 6 and non-lactating (NLTG; n=6 healthy Creole goats in 2 trials (T1 and T2. During T1 and T2, goats randomly received a single dose of im or iv ceftazidime (10 mg/kg. Serum concentration of iv ceftazidime in NLTG and LTG goats is best described by 2 and 3 compartment models, respectively. The pharmacokinetic parameters of iv and im ceftazidime administered to LTG and NLTG showed statistically significant differences (P<0.05 in the constants (λz, T1 vs T2 [iv] 0.5±0.1 vs 0.3±0.1 /h; T1 vs T2 [im] 0.5±0.2 vs 0.3±0.1 /h and in the mean times (t1/2, T 1 vs T 2 [iv] 1.6±0.3 vs 2.3±0.6 h; T 1 vs T 2 [im] 1.6±0.7 vs 2.6±0.9 h of elimination. The bioavailability of ceftazidime in LTG and NLTG was 113.0 ± 17.8 and 96.0 ± 18.0 %, respectively. Ceftazidime concentration in milk at 2 h was: iv = 1.9 ± 0.2 and im = 2.4 ± 0.5 μg/m ; the penetration in milk was iv = 18.3 ± 13.5 and im = 14.3 ± 10.6 %. Ninety-six hours after iv and im administration, residues of the drug were not found in milk. In conclusion, ceftazidime, when administered to goats, showed high concentration times in serum, good penetration into milk and a bioavailability that makes it suitable to be used by the im route.

  1. Hydrogen Peroxide Production in Streptococcus pyogenes: Involvement of Lactate Oxidase and Coupling with Aerobic Utilization of Lactate

    OpenAIRE

    Seki, Masanori; Iida, Ken-Ichiro; Saito, Mitsumasa; Nakayama, Hiroaki; Yoshida, Shin-Ichi

    2004-01-01

    Streptococcus pyogenes strains can be divided into two classes, one capable and the other incapable of producing H2O2 (M. Saito, S. Ohga, M. Endoh, H. Nakayama, Y. Mizunoe, T. Hara, and S. Yoshida, Microbiology 147:2469-2477, 2001). In the present study, this dichotomy was shown to parallel the presence or absence of H2O2-producing lactate oxidase activity in permeabilized cells. Both lactate oxidase activity and H2O2 production under aerobic conditions were detectable only after glucose in t...

  2. Heat stress abatement for dry cows: Does cooling improve transition into lactation?

    Science.gov (United States)

    Environmental factors, especially temperature and photoperiod, influence health and productivity of dairy cows during lactation, possibly via similar physiological effects. For example, heat stress is a critical component of lowered milk yield during summer. Long days improve yield during lactation...

  3. Blood lactate is an important energy source for the human brain

    DEFF Research Database (Denmark)

    G., van Hall; Stromstad, M.; Rasmussen, P.; Jans, O.; Zaar, M.; Gam, Christiane Marie Bourgin; Quistorff, B.; Secher, Niels H.; Nielsen, H.B.

    2009-01-01

    Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion...... is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.Journal of Cerebral Blood Flow & Metabolism advance online publication, 1 April 2009; doi:10.1038/jcbfm.2009.35.......Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion...

  4. The Effect of Maternal Stress Activation on the Offspring during Lactation in Light of Vasopressin

    Directory of Open Access Journals (Sweden)

    Anna Fodor

    2014-01-01

    Full Text Available Although it is obvious that preconceptional effects as well as stressors during pregnancy profoundly influence the progeny, the lactation period seems to be at least as important. Here we summarize how maternal stressors during the lactation period affect the offspring. As vasopressin is one of the crucial components both for stress adaptation and social behavior, special emphasis was given to this neuropeptide. We can conclude that stressing the mother does not have the same acute effect on the hypothalamo-pituitary-adrenocortical axis (as the main target of stress adaptation of the pups as stressing the pups, but later endocrine and behavioral consequences can be similar. Vasopressin plays a role in acute and later consequences of perinatal stressor applied either to the mother or to the offspring, thereby contributing to transmitting the mothers’ stress to the progeny. This mother-infant interaction does not necessarily mean a direct transmission of molecules, but rather is the result of programming the brain development through changes in maternal behavior. Thus, there is a time lag between maternal stress and stress-related changes in the offspring. The interactions are bidirectional as not only stress in the dam but also stress in the progeny has an effect on nursing.

  5. Electrochemical lactate biosensor based upon chitosan/carbon nanotubes modified screen-printed graphite electrodes for the determination of lactate in embryonic cell cultures.

    Science.gov (United States)

    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. PMID:26579934

  6. Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression

    International Nuclear Information System (INIS)

    Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression. Transformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24 h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive

  7. Somatic cell count distributions during lactation predict clinical mastitis

    NARCIS (Netherlands)

    Green, M.J.; Green, L.E.; Schukken, Y.H.; Bradley, A.J.; Peeler, E.J.; Barkema, H.W.; Haas, de Y.; Collis, V.J.; Medley, G.F.

    2004-01-01

    This research investigated somatic cell count (SCC) records during lactation, with the purpose of identifying distribution characteristics (mean and measures of variation) that were most closely associated with clinical mastitis. Three separate data sets were used, one containing quarter SCC (n = 14

  8. KNaY-zeolite catalyzed dehydration of methyl lactate

    Institute of Scientific and Technical Information of China (English)

    Hai Feng Shi; Yao Chi Hu; Yang Wang; He Huang

    2007-01-01

    A promising catalyst, KNaY was prepared by an ion exchange method with aqueous potassium chloride solution. Compared with NaY, KNaY was an effective catalyst for the dehydration of methyl lactate to methyl acrylate. Under the optimized conditions,an improved yield of 37.9 mol% was achieved.

  9. 21 CFR 862.1440 - Lactate dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactate dehydrogenase test system. 862.1440 Section 862.1440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  10. Blood lactate diagnostics in exercise testing and training.

    Science.gov (United States)

    Beneke, Ralph; Leithäuser, Renate M; Ochentel, Oliver

    2011-03-01

    A link between lactate and muscular exercise was seen already more than 200 years ago. The blood lactate concentration (BLC) is sensitive to changes in exercise intensity and duration. Multiple BLC threshold concepts define different points on the BLC power curve during various tests with increasing power (INCP). The INCP test results are affected by the increase in power over time. The maximal lactate steady state (MLSS) is measured during a series of prolonged constant power (CP) tests. It detects the highest aerobic power without metabolic energy from continuing net lactate production, which is usually sustainable for 30 to 60 min. BLC threshold and MLSS power are highly correlated with the maximum aerobic power and athletic endurance performance. The idea that training at threshold intensity is particularly effective has no evidence. Three BLC-orientated intensity domains have been established: (1) training up to an intensity at which the BLC clearly exceeds resting BLC, light- and moderate-intensity training focusing on active regeneration or high-volume endurance training (Intensity MLSS). High-performance endurance athletes combining very high training volume with high aerobic power dedicate 70 to 90% of their training to intensity domain 1 (Intensity < Threshold) in order to keep glycogen homeostasis within sustainable limits. PMID:21487146

  11. Attention and blood lactate levels in equestrians performing show jumping.

    Science.gov (United States)

    Perciavalle, Valentina; Di Corrado, Donatella; Scuto, Claudia; Perciavalle, Vincenzo; Coco, Marinella

    2014-06-01

    In equestrian show jumping, attention is particularly important to ensure maximum accuracy. Due to the anaerobic nature of the jumping and its requirement for precision coordination between human and horse, there may be a relation between the onset of lactic threshold and decrease in attention. In 12 healthy and injury-free equestrians (6 men, 6 women), the effects (blood lactate and glucose) of a show jumping course (250 m long with eight vertical obstacles with a height of 1.15 m height) on capacity and selectivity of attention was assessed. A typical reaction time paradigm and test of divided attention were administered. At the end of the course a significant increase of blood lactate was observed, whereas blood glucose did not significantly change. A deterioration of attention (intensity and selectivity) and a worsening of performance with increasing of blood lactate were observed. The present results led to the conclusion that the increase in blood lactate that occurs in riders executing a show jumping course is associated with worsening of both attentive capabilities and performance. PMID:25068743

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

    Directory of Open Access Journals (Sweden)

    Piero Bonelli

    2013-05-01

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

  13. Impact of bovine subclinical mastitis and effect of lactational treatment

    NARCIS (Netherlands)

    van den Borne, B.H.P.

    2010-01-01

    This thesis aimed to quantify the impact of subclinical mastitis in dairy cattle in the Netherlands and to explore the epidemiologic and economic effects of antimicrobial treatment of recently acquired subclinical mastitis during lactation. First, the occurrence of (sub)clinical mastitis was estimat

  14. Puerperium and lactation: Physiology of the reproductive system

    Science.gov (United States)

    This chapter describes changes in the physiology of the female reproductive system during the period of recovery from childbirth and throughout lactation. Normal and abnormal clinical findings are described, together with evidence-based treatment options for normal care and problem management. Ute...

  15. Effect of stage of lactation on the immune competence of goat mammary gland.

    Science.gov (United States)

    Albenzio, M; Santillo, A; Caroprese, M; Ciliberti, M G; Marino, R; Sevi, A

    2016-05-01

    The present research was undertaken to evaluate the effect of stage of lactation on immune competence of the goat mammary gland. The prevalence and etiology of intramammary infections and cytokine pattern were studied in individual caprine milk during lactation. A total of 1,200 caprine milk samples were collected during early, mid, and late lactation (less than 40 d, from 110 to 130 d, and more than 200 d in lactation, respectively) and analyzed for milk quality, bacterial cell load, and cytokine pattern. Contagious and environmental pathogens associated with intramammary infection were isolated from caprine milk. Nutritional components of caprine milk were affected by stage of lactation; fat, protein, casein, and whey protein increased along with lactation due to the lowest milk yield. Lactose content showed an opposite trend, with a reduced percentage passing from early to late lactation. The impaired rheological properties detected in early and late lactation milk were associated with a modification of milk quality. An impairment of microbial quality was detected at the end of lactation as a consequence of a major susceptibility of mammary gland to infections. The percentage of bacteriologically positive caprine milk samples was 44% throughout lactation. The incidence of bacteria associated with intramammary infection was different according to the stage of lactation with a major prevalence of Staphylococcus aureus, Enterobacteriaceae, Staphylococcus hyicus, and Streptococcus uberis in early lactation milk, Staphylococcus chromogenes, Streptococcus bovis, and Staphylococcus epidermidis in mid lactation, and Pseudomonas aeruginosa and Staphylococcus caprae in late lactation milk. The higher values of IL-1β, tumor necrosis factor-α, and IL-6 were ascribed to the major prevalence of Staphylococcus aureus at the beginning of lactation, whereas a higher level of IL-10 was detected in mid-lactation caprine milk and correlated with Staphylococcus chromogenes

  16. Blood lactate level in Wistar rats after four and twelve week intermittent aerobic training

    OpenAIRE

    Dewi N. Sari; Sutjahjo Endardjo; Dewi I.S. Santoso

    2013-01-01

    Background: Aerobic training can be done not only continuously, but also intermittently. Intermittent aerobic training aimed to get blood lactate level lower than continuous aerobic training. Blood lactate concentration in one of the various factors that determine training performance. However, until recently, little studies about intermittent aerobic training and blood lactate levels have been done. Therefore, this study aimed to measure blood lactate levels in Wistar rats after 4 and 12 wee...

  17. Continuous lactate measurement that combines a portable ultrafiltration storage device with an enzyme sensor

    NARCIS (Netherlands)

    Cheng, S; Kaptein, WA; Gruendig, B; Yuen, Y; Korf, J; Renneberg, R

    2000-01-01

    A simple portable continuous L-lactate monitoring system combining elegant ultrafiltration sample collection and storage with a lactate biosensor has been developed. The sensor has a detection range from 0.05mM to 30mM lactate dependent on different assignments of the PCS hydrogel complex layer. The

  18. Nursing frequency alters circadian patterns of mammary gene expression in lactating mice

    Science.gov (United States)

    Milking frequency impacts lactation in dairy cattle and in rodent models of lactation. The role of circadian gene expression in this process is unknown. The hypothesis tested was that changing nursing frequency alters the circadian patterns of mammary gene expression. Mid-lactation CD1 mice were stu...

  19. Pregnancy rate as an indicator of nutritional status in Rangifer. implications of lactational infertility

    OpenAIRE

    K. L. Gerhart; White, R G; R. D. Cameron; D. E. Russell; D. van de Wetering

    1997-01-01

    Monitofing pregnancy rates to detect changes in nutrition is best accomplished by sampling lactating females because they will be more responsive to changes in nutrienr availability: nutrition influences pregnancy fate of lactating caribou both through autumn body condition and lactational infertility.

  20. Pregnancy rate as an indicator of nutritional status in Rangifer. implications of lactational infertility

    Directory of Open Access Journals (Sweden)

    K. L. Gerhart

    1997-04-01

    Full Text Available Monitofing pregnancy rates to detect changes in nutrition is best accomplished by sampling lactating females because they will be more responsive to changes in nutrienr availability: nutrition influences pregnancy fate of lactating caribou both through autumn body condition and lactational infertility.

  1. Study of chemosensitivity testing in vitro on astrocytoma%星形细胞瘤体外化疗药物敏感程度的研究

    Institute of Scientific and Technical Information of China (English)

    滕晓华; 刘波; 周蓉; 曾年菊; 卢明

    2011-01-01

    目的 了解星形细胞瘤对常用化疗药物的敏感程度,探讨化疗药物体外敏感试验对于胶质瘤化疗的指导意义,比较不同WHO分级星形细胞瘤对化疗药物敏感度的差异,为临床治疗提供依据.方法 收集手术切除的新鲜星形细胞瘤标本共142例,其中低级别星形细胞瘤(Ⅰ、Ⅱ级)55例,高级别星形细胞瘤(Ⅲ、Ⅳ级)87例,分别进行星形细胞瘤细胞分离培养,采用MTT法检测临床常用11种化疗药物对肿瘤细胞的生长抑制情况,判定药物敏感程度.结果 142例患者中有78例(54.93%)获临床推荐使用药物,其中低级别星形细胞瘤为41.82%(23/55),而高级别星形细胞瘤为63.22%(55/87).不同WHO分级星形细胞瘤敏感化疗药物基本相似,以替尼泊苷、卡铂、长春新碱更为敏感.结论 化疗药物体外敏感试验对于胶质瘤的化疗药物筛选具有一定的指导意义,恶性程度越高,作用越突出.不同WHO分级的星形细胞瘤在化疗药物的选择上差异不明显.%Objective To observe the sensitivity ofastrocytoma to chemotherapeutic drugs, in order to explore the drug selection using chemosensitivity testing in vitro on astrocytoma. Comparing different WHO grade astrocytoma to chemotherapeutic drugs sensitivity differences,providing the basis data for clinical treatment. Methods The astrocytoma cells were seperated and cultured in vitro from 142 tumor tissues by glioma resection, including 55 cases of low-grade astrocytoma (WHO grade Ⅰ , Ⅱ) and 87 cases of high-grade astrocytoma (WHO grade Ⅲ, Ⅳ). The proliferation inhibition and chemosensitivity of tumor cells to 11 drugs were investigated by using MTT method. Results There were 54.93% (78/142) patients recommended chemotherapeutic drug in 142 cases. The percentage was 41.82%(23/55) in the low-grade astrocytoma, and 63.22% (55/87) in the high-grade astrocytoma respectively. Teniposide,carboplatin,vincristine as the sensitive drugs were similar in

  2. Lactate-An Integrative Mirror of Cancer Metabolism.

    Science.gov (United States)

    Walenta, Stefan; Voelxen, Nadine F; Mueller-Klieser, Wolfgang

    2016-01-01

    The technique of induced metabolic bioluminescence imaging (imBI) has been developed to obtain a "snapshot" of the momentary metabolic status of biological tissues. Using cryosections of snap-frozen tissue specimens, imBI combines highly specific and sensitive in situ detection of metabolites with a spatial resolution on a microscopic level and with metabolic imaging in relation to tissue histology. Here, we present the application of imBI in human colorectal cancer. Comparing the metabolic information of one biopsy with that of 2 or 3 biopsies per individual cancer, the classification into high versus low lactate tumors, reflecting different glycolytic activities, based on a single biopsy was in agreement with the result from multiple biopsies in 83 % of all cases. We further demonstrate that the metabolic status of tumor tissue can be preserved at least over 10 years by storage in liquid nitrogen, but not by storage at -80 °C. This means that tissue banking with long-term preservation of the metabolic status is possible at -180 °C, which may be relevant for studies on long-term survival of cancer patients. As with other tumor entities, tissue lactate concentration was shown to be correlated with tumor development and progression in colorectal cancer. At first-time diagnosis, lactate values were low in rectal normal tissue and adenomas, were significantly elevated to intermediate levels in non-metastatic adenocarcinomas, and were very high in carcinomas with distant metastasis. There was an inverse behavior of tissue glucose concentration under corresponding conditions. The expression level of monocarboxylate transporter-4 (MCT4) was positively correlated with the tumor lactate concentration and may thus contribute to high lactate tumors being associated with a high degree of malignancy. PMID:27557533

  3. PELOD score, serum procalcitonin, and lactate levels in pediatric sepsis

    Directory of Open Access Journals (Sweden)

    Jufitriani Ismy

    2015-11-01

    Full Text Available Background Sepsis remains a major cause of morbidity and mortality among critically ill children in the pediatric intensive care unit (PICU. Procalcitonin and lactate have been used as biomarkers of sepsis, as they have been correlated with disease severity, organ failure and death. The Pediatric Logistic Organ Dysfunction (PELOD score is a tool to assess the severity of organ dysfunction in critically ill children. Objective To investigate the correlation between PELOD score and procalcitonin and lactate levels in pediatric sepsis. Methods A cross-sectional study was conducted in children with sepsis who were admitted to the PICU from April to July 2012. Sepsis was defined as systemic inflammatory response syndrome (SIRS, as a result of suspected or proven infection. Proven infection was defined as positive culture findings (blood, urine ot other specimens and/or serum procalcitonin >2 ng/mL. Spearman’s test was used to assess for correlations between PELOD scores and procalcitonin as well as lactate levels. Results Thirty-two patients were analyzed, consisting of 18 males and 14 females with an age range of 1-432 months (median 21 months. There was no statistically significant correlation between procalcitonin level and PELOD score (r=- 0.186, 95%CI -0.502 to 0.174, P=0.308 nor between lactate level(r=-0.069, 95%CI-0.408 to 0.287, P=0.709 and PELOD score. Conclusion Serum procalcitonin and lactate levels are not correlated with PELOD scores in children with sepsis.

  4. 胰岛素增加肿瘤细胞化疗敏感性的研究%The effect of insulin on the chemosensitivity of cancer cells

    Institute of Scientific and Technical Information of China (English)

    孙龙昊; 何向辉; 朱理玮

    2010-01-01

    Objective To investigate the effect and mechanism of insulin and hypoglycemia on the chemosensitivity of cancer cells. Methods Human colon cancer cells SW480, mouse colon cancer cells CT-26 and mouse breast cancer cells 4T1 were cultured and treated with insulin and chemotheraputic drugs, 5-fluorouracil or methotrexate. MTT assay was used to measure the cytotoxity. Fluorescence microscopy and flow cytometry were used to determine the effects of insulin on the uptake of fluorescent methotrexate by cancer cells. Mouse breast cancer cells 4T1 were inoculated into syngeneic BALB/C mice. Insulin was administrated to the mice before giving methotrexate and the therapeutic effect was monitored. Results (1) Insulin enhanced the chemocytotoxity of chemotheraputic drugs on cancer cells by 4. 1% to 11.5%;(2) Insulin increased the uptake of fluorescent methotrexate by cancer cells in vitro by 141. 9% ;(3) Insulin and hypoglycemia enhanced the chemotherapeutic effect of methotrexate on mouse breast cancer models by 20. 1%. Conclusion Insulin and hypoglycemia increase absorption of chemotherapeutic agents by cancer cells and enhance the chemosensitivity of cancer cells.%目的 探讨胰岛素对肿瘤细胞化疗敏感性的影响及机制.方法 以胰岛素和甲氨蝶呤(MTX)或5-氟尿嘧啶(5-Fu)处理人结肠癌细胞SW480,小鼠结肠癌细胞CT-26及小鼠乳腺癌细胞4T1,噻唑蓝(MTT)法分析细胞活力,荧光显微镜和流式细胞术观察肿瘤细胞对荧光标记MTX的摄取,并利用小鼠荷瘤模型,观察胰岛素及低MTX糖对MTX化疗疗效的影响.结果 (1)胰岛素增加MTX和5-Fu的细胞毒作用4.1%-11.5%.(2)胰岛素增加肿瘤细胞对MTX摄取141.9%.(3)胰岛素及低血糖状态增强MTX抑瘤作用20.1%.结论 胰岛素及低血糖状态增加肿瘤细胞对化疗药物的吸收,提高肿瘤细胞对化疗药物的敏感性.

  5. Unsolved Mysteries of the Human Mammary Gland: Defining and Redefining the Critical Questions from the Lactation Consultant's Perspective.

    Science.gov (United States)

    Marasco, Lisa Ann

    2014-12-01

    Despite advances in knowledge about human lactation, clinicians face many problems when advising mothers who are experiencing breastfeeding difficulties that do not respond to normal management strategies. Primary insufficient milk production is now being acknowledged, but incidence rates have not been well studied. Many women have known histories of infertility, polycystic ovary syndrome, obesity, hypertension, insulin resistance, thyroid dysfunction, hyperandrogenism or other hormonal imbalances, while others have no obvious risk factors. Some present with obviously abnormal breasts that are pubescent, tuberous/tubular or asymmetric in shape, raising the question of insufficient mammary gland tissue. Other women have breasts that appear within normal limits yet do not lactate normally. Endocrine disruptors may underlie some of these cases but their impact on human milk production has not been well explored. Similarly, any problem with prolactin such as a deficiency in serum prolactin or receptor number, receptor resistance, or poor bioavailability or bioactivity could underlie some cases of insufficient lactation, yet these possibilities are rarely investigated. A weak or suppressed milk ejection reflex, often assumed to be psychosomatic, could be related to thyroid dysfunction or caused by downstream post-receptor pathway problems. In the absence of sufficient data regarding these situations, desperate mothers may turn to non-evidence-based remedies, sometimes at considerable cost and unknown risk. Research targeted to these clinical dilemmas is critical in order to develop evidence-based strategies and increase breastfeeding duration and success rates. PMID:26084427

  6. Contribution to the study of rare earth separation by ion exchange, using ammonium lactate

    International Nuclear Information System (INIS)

    Using the technique of chromatography on a column of Dowex 50 resin, heated to 87 deg. C, we have studied the separation of rare earths (from holmium to praseodymium) which may be produced with the cyclotron by heavy ions, α or protons. From an ammonium lactate solution M at pH 5, separations are carried out by varying the dilution as a function of the quantity of the target rare earth and of its position during elution. When weighable quantities of the rare earth (more than 5 mg) appear towards the end of the elution, the separation is little affected this case approaches that of a tracer mixture of rare earths; if on the other hand weighable quantities of the rare earth are washed through at the beginning of the chromatogram, the dilution must be adjusted in order to obtain a good separation. (author)

  7. Application value of ATP based bioluminescence tumor chemosensitivity assay in the chemotherapy for hydrothorax caused by non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Kaijian Le; Yuming Jia; Jing Wang; Maoqiong Jiang

    2013-01-01

    Objective: The aim of the study was to investigate the clinical value and application of ATP based bioluminescencetumor chemosensitivity assay (ATP-TCA) in the chemotherapy for hydrothorax caused by non-small cell lung cancer(NSCLC). Methods: Hydrothorax specimens from 120 NSCLC patients were analyzed by ATP-TCA and the most sensitivechemotherapeutic drugs were used in NSCLC patients (treatment group). At the same time, 56 NSCLC patients with hydrothoraxwere admitted in our Hospital (Department of Oncology, The No. 2 People's Hospital of Yibin, China) and given chemotherapywithout guidance of the ATP-TCA (control group). Before the third chemotherapeutic cycle, clinical outcomes wereanalyzed in the two groups. Results: Effective rate of hydrothorax in treatment group was 67%, while 46% in control group(P < 0.05). In refractory hydrothorax patients, they were 69% and 40% (P < 0.05), respectively. In vitro results correlated wellwith clinical outcomes (P < 0.01). Conclusion: Effective rate of chemotherapy for hydrothorax in NSCLC is higher in treatmentgroup than that in control group. ATP-TCA is especially helpful for refractory hydrothorax.

  8. MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

    Science.gov (United States)

    Pascual-Serra, Raquel; García-Cano, Jesus; Garcia-Gil, Elena; De la Cruz-Morcillo, Miguel; Ortega-Muelas, Marta; Serrano-Oviedo, Leticia; Gutkind, J. Silvio; Sánchez-Prieto, Ricardo

    2015-01-01

    The adenoviral gene E1a is known to enhance the antitumor effect of cisplatin, one of the cornerstones of the current cancer chemotherapy. Here we study the molecular basis of E1a mediated sensitivity to cisplatin in an experimental model of Non-small cell lung cancer. Our data show how E1a blocks the induction of autophagy triggered by cisplatin and promotes the apoptotic response in resistant cells. Interestingly, at the molecular level, we present evidences showing how the phosphatase MKP1 is a major determinant of cisplatin sensitivity and its upregulation is strictly required for the induction of chemosensitivity mediated by E1a. Indeed, E1a is almost unable to promote sensitivity in H460, in which the high expression of MKP1 remains unaffected by E1a. However, in resistant cell as H1299, H23 or H661, which display low levels of MKP1, E1a expression promotes a dramatic increase in the amount of MKP1 correlating with cisplatin sensitivity. Furthermore, effective knock down of MKP1 in H1299 E1a expressing cells restores resistance to a similar extent than parental cells. In summary, the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. PMID:26689986

  9. [The Teratology Information Service: medicines during pregnancy and lactation].

    Science.gov (United States)

    de Vries, Loes C; de Swart, Irene W; van Puijenbroek, Eugène P

    2016-01-01

    Many women use medication during pregnancy. Both the healthcare professional and the pregnant woman often have many questions about the possible adverse effects of the medication that are not always answered in the product information. The Teratology Information Service (TIS), a part of the Netherlands Pharmacovigilance Centre Lareb, is a centre of expertise in the field of the safety of medication use and other external influences during spermatogenesis, pregnancy and lactation. The TIS collects, interprets, and disseminates information that can contribute to patient care. Healthcare professionals can contact the TIS for information and individual risk assessments. In this article we discuss the background and positioning of the TIS, the characteristics of telephone consultations, the collection of data and the considerations that are important for the use of medication during pregnancy and lactation. PMID:27165457

  10. Reduced gluconeogenesis and lactate clearance in Huntington's disease

    DEFF Research Database (Denmark)

    Josefsen, Knud; Nielsen, Signe M B; Campos, André;

    2010-01-01

    We studied systemic and brain glucose and lactate metabolism in Huntington's disease (HD) patients in response to ergometer cycling. Following termination of exercise, blood glucose increased abruptly in control subjects, but no peak was seen in any of the HD patients (2.0 ± 0.5 vs. 0.0 ± 0.2mM, P...... hepatic glucose output in the HD mouse model R6/2 following a lactate challenge, combined with reduced phosphoenolpyruvate carboxykinase and increased pyruvate kinase activity in the mouse liver suggest a reduced capacity...... for gluconeogenesis in HD, possibly contributing to the clinical symptoms of HD. We propose that blood glucose concentration in the recovery from exercise can be applied as a liver function test in HD patients....

  11. Lactation following conservation surgery and radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    A 38-year-old woman with early stage invasive breast cancer was treated with wide excision of the tumor, axillary lymph node dissection, and breast irradiation. Three years later, she gave birth to a normal baby. She attempted breast feeding and had full lactation from the untreated breast. The irradiated breast underwent only minor changes during pregnancy and postpartum but produced small amounts of colostrum and milk for 2 weeks postpartum. There are only a few reports of lactation after breast irradiation. These cases are reviewed, and possible factors affecting breast function after radiotherapy are discussed. Because of scant information available regarding its safety for the infant, nursing from the irradiated breast is not recommended

  12. Life-Threatening Lactation or "Bovine" Ketoacidosis: A Case Report.

    Science.gov (United States)

    Greaney, David J; Benson, Pat

    2016-08-15

    Lactation or "bovine" ketoacidosis is a rare cause of raised anion gap metabolic acidosis whereby a perfect storm of negative calorie balance (starvation/glucose preferentially used for milk production) and insulin resistance (counter regulatory stress hormone release/infection) leads to a dysregulated ketogenic state. We present a case of life-threatening lactation-related ketoacidosis in a patient 9 weeks postpartum, who presented to the emergency department with an arterial pH of 6.88, HCO3 of 5.8 mmol/L and blood ketone level of 5.8 mmol/L. Treatment consists of aggressive glucose loading, triggering supraphysiologic endogenous insulin release, and subsequent inhibition of ketone body formation. PMID:27310899

  13. Intracellular behaviour of samarium and europium in lactating mammary gland

    Institute of Scientific and Technical Information of China (English)

    Ayadi Ahlem; Maghraoui Samira; El Hili Ali; Galle Pierre; Tekaya Leila

    2012-01-01

    The subcellular localization of samarium and europium,two rare-earths,increasingly used in both medical and industrial fields,has been studied in several organs such as liver and kidney but never in the mammary gland despite of its importance in the biology of lactation and nutrition domains.The intracellular behaviour of samarium and europium after their intra-peritoneal administration in the lactating mammary gland cells was investigated.The results showed the presence of very electron dense deposits in the glandular epithelial cell lysosomes.These particular lysosomes were never observed in the marnrnary cell lysosomes of control rats.These intralysosomal deposits were probably composed of insoluble samarium or europium phosphates by analogy with previous studies,the transmission electron microscopy,the ion mass microscopy and the electron probe microanalysis,and other techniques allowing the identification of the chemical structure of the intralysosomal deposits.

  14. The Role of Monocarboxylate Transporters and Their Chaperone CD147 in Lactate Efflux Inhibition and the Anticancer Effects of Terminalia chebula in Neuroblastoma Cell Line N2-A

    Science.gov (United States)

    Messeha, S. S.; Zarmouh, N. O.; Taka, E.; Gendy, S. G.; Shokry, G. R.; Kolta, M. G.; Soliman, K. F. A.

    2016-01-01

    Aims In the presence of oxygen, most of the synthesized pyruvate during glycolysis in the cancer cell of solid tumors is released away from the mitochondria to form lactate (Warburg Effect). To maintain cell homeostasis, lactate is transported across the cell membrane by monocarboxylate transporters (MCTs). The major aim of the current investigation is to identify novel compounds that inhibit lactate efflux that may lead to identifying effective targets for cancer treatment. Study Design In this study, 900 ethanol plant extracts were screened for their lactate efflux inhibition using neuroblastoma (N2-A) cell line. Additionally, we investigated the mechanism of inhibition for the most potent plant extract regarding monocarboxylate transporters expression, and consequences effects on viability, growth, and apoptosis. Methodology The potency of lactate efflux inhibition of ethanol plant extracts was evaluated in N2-A cells by measuring extracellular lactate levels. Caspase 3- activity and acridine orange/ethidium bromide staining were performed to assess the apoptotic effect. The antiproliferative effect was measured using WST assay. Western blotting was performed to quantify protein expression of MCTs and their chaperone CD147 in treated cells lysates. Results Terminalia chebula plant extract was the most potent lactate efflux inhibitor in N2-A cells among the 900 - tested plant extracts. The results obtained show that extract of Terminalia chebula fruits (TCE) significantly (P = 0.05) reduced the expression of the MCT1, MCT3, MCT4 and the chaperone CD147. The plant extract was more potent (IC50 of 3.59 ± 0.26 μg/ml) than the MCT standard inhibitor phloretin (IC50 76.54 ± 3.19 μg/ml). The extract also showed more potency and selective cytotoxicity in cancer cells than DI-TNC1 primary cell line (IC50 7.37 ± 0.28 vs. 17.35 ± 0.19 μg/ml). Moreover, TCE Inhibited N2-A cell growth (IG50 = 5.20 ± 0.30 μg/ml) and induced apoptosis at the 7.5 μg/ml concentration

  15. Obesity impairs lactation performance in mice by inducing prolactin resistance

    OpenAIRE

    Buonfiglio, Daniella C.; Angela M. Ramos-Lobo; Freitas, Vanessa M.; Thais T. Zampieri; Vanessa S. Nagaishi; Magna Magalhães; Jose Cipolla-Neto; Nathalie Cella; Jose Donato Jr.

    2016-01-01

    Obesity reduces breastfeeding success and lactation performance in women. However, the mechanisms involved are not entirely understood. In the present study, female C57BL/6 mice were chronically exposed to a high-fat diet to induce obesity and subsequently exhibited impaired offspring viability (only 15% survival rate), milk production (33% reduction), mammopoiesis (one-third of the glandular area compared to control animals) and postpartum maternal behaviors (higher latency to retrieving and...

  16. Lactation and suckling behavior in the Iberian lynx.

    Science.gov (United States)

    Yerga, Javier; Calzada, Javier; Manteca, Xavier; Herrera, Irene; Vargas, Astrid; Rivas, Antonio

    2016-05-01

    Understanding the behavior of endangered species is crucial to improve the management tools to breed animals in captivity and, thus, to increase the success of ex situ conservation programs. In this study, we monitored suckling behavior of 26 cubs born between 2008 and 2012 at "El Acebuche" Iberian Lynx Breeding Centre. The cubs devoted 251 ± 19.7 min (mean ± SE) to lactation on the day of birth, while mothers spent 426 ± 27 min (mean ± SE) nursing their offspring. The time cubs spent suckling decreased exponentially as they grown, until they were fully weaned at 65 ± 2.6 days. The onset of weaning (first intake of solid food) occurred at 54 ± 1.35 days (mean ± SE). Thus, the strict lactation period occupied most of the overall lactation period. Both suckling and maternal behavior were affected by litter size. In twins and triplets, the competition between siblings caused a decrease in the time spent suckling, in spite of the mothers spending more time nursing their young. Finally, no significant differences were found in time spent suckling between littermates or depending on the sex of the cub. Lactation appeared to play a key role in the nutrition of the Iberian lynx and should therefore be conveniently managed in captive breeding programs of this threatened species. Zoo Biol. 35:216-221, 2016. © 2016 Wiley Periodicals, Inc. PMID:27038075

  17. Use of ionophores in lactating dairy cattle: a review.

    OpenAIRE

    Duffield, T F; Bagg, R N

    2000-01-01

    Ionophores are feed additives that alter rumen microbial populations through ion transfer across cell membranes. Although ionophores have been used widely in the beef industry for improved feed efficiency and control of coccidiosis, there has been limited use by the dairy industry. In Canada, the label warning prohibiting the use of monensin premix in lactating dairy cattle was removed in June 1996. Following this, in December 1997, a controlled release capsule containing monensin was approve...

  18. Lactation curves in captive Iberian red deer (Cervus elaphus hispanicus)

    OpenAIRE

    García Díaz, Andrés; Landete Castillejos, Tomás; Molina Casanova, Ana María; Albiñana, Bernardo; Fernández, Carlos; Garde López-Brea, José Julián; Gallego Martínez, Laureano

    1999-01-01

    This study examines milk production and the effect of milk production and sex of calf on body weights and gains of red deer calves and hinds of the Iberian subspecies (Cervus elaphus hispanicus). Milk production was assessed in 14 hinds by weighing calves before and after suckling and by adjusting these values to the Gamma function. Gamma estimates of total milk production up to d 105 were similar to the amounts computed directly from double weighing. Hinds showed two types of lactation cu...

  19. Histological and Morphometric Study of Lactating Mammary Glands in Sows

    OpenAIRE

    Svätoslav Hluchý; Norbert Bolcsó

    2011-01-01

    This work deals with the quantitative histological morphometric description of the mammary glands of sows during the stage of lactation. As experimental animals were used White meat breed pigs (5 animals) kept in standard conditions VÚŽV in Nitra. After killing the animals we sampled mammary glands and have them processed by conventional histological and histochemical methods. Morphometric methods, we found that glandular parenchyma of mammary glands of sows consists of a lobules width 615.28...

  20. Clinical Features and Ultrasonographic Findings of Lactating Adenoma

    International Nuclear Information System (INIS)

    Purpose: This study was designed to evaluate the clinical manifestations and characteristic ultrasonographic findings of lactating adenoma in pregnant or lactating women. Ultrasonographic findings of nine lactating adenomas in nine patients (age range, 19-38 years; mean age, 30.4 years) were retrospectively reviewed. All of the lesions were histologically diagnosed with the use of an ultrasound (US) guided core needle biopsy. Ultrasonographic findings were categorized according to the ACR/BI-RADS classification. The size of the lesions varied from 13 to 43 mm (mean, 27.8 mm). The most common findings of the breast lesions were an oval-shape (n = 9, 100%), presence of circumscribed margins (n = 5, 55.6%), a location parallel to the chest wall (n = 9, 100%), the presence of complex or hypoechoic lesions (n = 7, 77.8%), posterior acoustic enhancement (n = 5, 55.6%) and no microcalcifications (n = 8, 88.9%). Six lesions (66.7%) were classified as category 3 (probably benign lesions) and three lesions (33.3%) were classified as category 4A (low-suspicion for malignancy). Followup ultrasonography was performed in six patients; four (66.7%) patients showed complete resolution and two (33.3%) patients showed a decreased size of the lesions. One patient developed a milk fistula as a complication of the core needle biopsy as seen on a follow-up evaluation. Conclusion: Ultrasonographic findings of lactating adenomas are generally benign, with some lesions displaying suspicious malignant findings. On follow-up US images after the use of an US-guided core needle biopsy, all lesions showed complete regression or a decreased size

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

    OpenAIRE

    Janet C. King; Carmen Marino Donangelo

    2012-01-01

    Zinc plays critical roles during embryogenesis, fetal growth, and milk secretion, which increase the zinc need for pregnancy and lactation. Increased needs can be met by increasing the dietary zinc intake, along with making homeostatic adjustments in zinc utilization. Potential homeostatic adjustments include changes in circulating zinc, increased zinc absorption, decreased zinc losses, and changes in whole body zinc kinetics. Although severe zinc deficiency during pregnancy has devastating e...

  2. Evaluation of the Lactate Threshold during Downhill Running in Rats

    OpenAIRE

    Tsumiyama, Wakako; Oki, Sadaaki; Umei, Namiko; Shimizu, Michele Eisemann; Ono, Takeya; Otsuka, Akira

    2014-01-01

    [Purpose] The purpose of the present study was to investigate if lactate thresholds in rats could be accurately determined during downhill running in rats. [Subjects] Twenty-four female Wistar rats were used in this study. Rats were randomly divided into two groups: the level running group and downhill running group. [Methods] Catheters were inserted into the right external jugular veins of the rats. Two days after the operation, the rats performed incremental exercise tests. The level runnin...

  3. Early life triclocarban exposure during lactation affects neonate rat survival.

    Science.gov (United States)

    Kennedy, Rebekah C M; Menn, Fu-Min; Healy, Laura; Fecteau, Kellie A; Hu, Pan; Bae, Jiyoung; Gee, Nancy A; Lasley, Bill L; Zhao, Ling; Chen, Jiangang

    2015-01-01

    Triclocarban (3,4,4'-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups nursed by control dams survived regardless of their in utero exposure status. Microscopic evaluation of dam mammary tissue revealed involution to be a secondary outcome of TCC exposure rather than a primary effect of compound administration. The average concentration of TCC in the milk was almost 4 times that of the corresponding maternal serum levels. The results demonstrate that gestational TCC exposure does not affect the ability of dams to carry offspring to term but TCC exposure during lactation has adverse consequences on the survival of offspring although the mechanism of reduced survival is currently unknown. This information highlights the importance of evaluating the safety of TCC application in personal care products and the impacts during early life exposure. PMID:24803507

  4. Blood lactate levels in 31 female dogs with pyometra

    OpenAIRE

    Karlstam Erika; Bergström Ledin Hanna; Reezigt Bert Jan; Hagman Ragnvi

    2009-01-01

    Abstract Background Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS) and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1)...

  5. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia

    OpenAIRE

    Herzog, Raimund I.; Jiang, Lihong; Herman, Peter; Zhao, Chen; Sanganahalli, Basavaraju G.; Mason, Graeme F.; Hyder, Fahmeed; Rothman, Douglas L.; Sherwin, Robert S.; BEHAR, Kevin L

    2013-01-01

    Hypoglycemia occurs frequently during intensive insulin therapy in patients with both type 1 and type 2 diabetes and remains the single most important obstacle in achieving tight glycemic control. Using a rodent model of hypoglycemia, we demonstrated that exposure to antecedent recurrent hypoglycemia leads to adaptations of brain metabolism so that modest increments in circulating lactate allow the brain to function normally under acute hypoglycemic conditions. We characteri...

  6. Lactate Produced by Glycogenolysis in Astrocytes Regulates Memory Processing

    OpenAIRE

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

    2011-01-01

    When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocy...

  7. Impact of bovine subclinical mastitis and effect of lactational treatment

    OpenAIRE

    van den Borne, B.H.P.

    2010-01-01

    This thesis aimed to quantify the impact of subclinical mastitis in dairy cattle in the Netherlands and to explore the epidemiologic and economic effects of antimicrobial treatment of recently acquired subclinical mastitis during lactation. First, the occurrence of (sub)clinical mastitis was estimated in a one-year observational study. It was concluded that herds in the Netherlands varied substantially in their mastitis occurrence, indicating room for improvement of udder health. The relation...

  8. Obesity impairs lactation performance in mice by inducing prolactin resistance.

    Science.gov (United States)

    Buonfiglio, Daniella C; Ramos-Lobo, Angela M; Freitas, Vanessa M; Zampieri, Thais T; Nagaishi, Vanessa S; Magalhães, Magna; Cipolla-Neto, Jose; Cella, Nathalie; Donato, Jose

    2016-01-01

    Obesity reduces breastfeeding success and lactation performance in women. However, the mechanisms involved are not entirely understood. In the present study, female C57BL/6 mice were chronically exposed to a high-fat diet to induce obesity and subsequently exhibited impaired offspring viability (only 15% survival rate), milk production (33% reduction), mammopoiesis (one-third of the glandular area compared to control animals) and postpartum maternal behaviors (higher latency to retrieving and grouping the pups). Reproductive experience attenuated these defects. Diet-induced obese mice exhibited high basal pSTAT5 levels in the mammary tissue and hypothalamus, and an acute prolactin stimulus was unable to further increase pSTAT5 levels above basal levels. In contrast, genetically obese leptin-deficient females showed normal prolactin responsiveness. Additionally, we identified the expression of leptin receptors specifically in basal/myoepithelial cells of the mouse mammary gland. Finally, high-fat diet females exhibited altered mRNA levels of ERBB4 and NRG1, suggesting that obesity may involve disturbances to mammary gland paracrine circuits that are critical in the control of luminal progenitor function and lactation. In summary, our findings indicate that high leptin levels are a possible cause of the peripheral and central prolactin resistance observed in obese mice which leads to impaired lactation performance. PMID:26926925

  9. The Role of the Proper Breastfeeding Training in Promoting Lactation

    Directory of Open Access Journals (Sweden)

    Kazem Sakha

    2009-12-01

    Full Text Available Objective:Insufficient lactation is the most common complaint of nursing mothers in a first few months after delivery; this is known to be partly due to the mothers deficient knowledge of proper breastfeeding. The goal of this study was to find out whether training of nursing mothers for proper lactation can enhance their lactation. Methods:During one year from May 20, 2007 to June 20, 2008 we consecutively enrolled 63 nursing mothers who had been referred to the clinic of Tabriz childrens hospital for counselling and prescription of infant formula because of insufficient lactation during 30 to 60 days after parturition. At first all infants were weighed under similar controlled condition. Their weight was then compared with recorded data in their nursery discharge sheet and growth surveillance card. Term infants with weight gain of less than 500 g/month were consecutively enrolled in the study. All mothers passed a short training course on nutritional and immunological benefits of mother milk for growth of their baby as well as latch and positioning techniques of breast feeding. After 15 days we weighed the infants again and compared the two recorded weights to assess the sufficiency of breastfeeding and effect of training. Statistical analysis was done with independent sample test and paired t- test using SPSS software. Findings: In 63 breastfed infants with an age of 30 to 60 days, before training course of mothers, minimum, maximum and mean weight gain was 8.3, 16 and 12.5 (±3.8 g/day respectively; 15 days after training of mothers these figures were 7.6, 34.6 and 21.1 (±13.5 g/day respectively. Results showed that weight gain in 54 (85.7% infants was satisfactory which was statistically meaningful (P<0.001. Conclusion:This study showed that counseling nursing mothers for proper lactation is the main clinical pathway toward a successful and sustained breastfeeding and must be considered in obstetrics and medical centers.

  10. D- and L-lactate dehydrogenases during invertebrate evolution

    Directory of Open Access Journals (Sweden)

    Stillman Jonathon H

    2008-10-01

    Full Text Available Abstract Background The L-lactate and D-lactate dehydrogenases, which are involved in the reduction of pyruvate to L(--lactate and D(+-lactate, belong to evolutionarily unrelated enzyme families. The genes encoding L-LDH have been used as a model for gene duplication due to the multiple paralogs found in eubacteria, archaebacteria, and eukaryotes. Phylogenetic studies have suggested that several gene duplication events led to the main isozymes of this gene family in chordates, but little is known about the evolution of L-Ldh in invertebrates. While most invertebrates preferentially oxidize L-lactic acid, several species of mollusks, a few arthropods and polychaetes were found to have exclusively D-LDH enzymatic activity. Therefore, it has been suggested that L-LDH and D-LDH are mutually exclusive. However, recent characterization of putative mammalian D-LDH with significant similarity to yeast proteins showing D-LDH activity suggests that at least mammals have the two naturally occurring forms of LDH specific to L- and D-lactate. This study describes the phylogenetic relationships of invertebrate L-LDH and D-LDH with special emphasis on crustaceans, and discusses gene duplication events during the evolution of L-Ldh. Results Our phylogenetic analyses of L-LDH in vertebrates are consistent with the general view that the main isozymes (LDH-A, LDH-B and LDH-C evolved through a series of gene duplications after the vertebrates diverged from tunicates. We report several gene duplication events in the crustacean, Daphnia pulex, and the leech, Helobdella robusta. Several amino acid sequences with strong similarity to putative mammalian D-LDH and to yeast DLD1 with D-LDH activity were found in both vertebrates and invertebrates. Conclusion The presence of both L-Ldh and D-Ldh genes in several chordates and invertebrates suggests that the two enzymatic forms are not necessarily mutually exclusive. Although, the evolution of L-Ldh has been punctuated by

  11. Immunological study of lactate dehydrogenase from Streptococcus mutans and evidence of common antigenic domains with lactate dehydrogenases from lactic bacteria.

    OpenAIRE

    Sommer, P.; Klein, J P; Ogier, J. A.; Frank, R M

    1986-01-01

    Rabbit polyclonal antibodies directed against purified Streptococcus mutans L-(+)-lactate dehydrogenase reacted with the purified enzyme, giving a marked deviation of its kinetic parameters. The enzyme affinity for pyruvate or NADH decreased in the presence of antibody, the affinity for fructose 1,6-diphosphate (FDP) appeared to be slightly affected, and the cooperativity of the ligand binding was lowered. A partial protective effect was observed when the enzyme was preincubated with FDP prio...

  12. Metabolism of D-lactate and structurally related organic acids in Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    During the initial minutes of anaerobiosis, 14C-labeled D-lactate, derived from the photosynthetic sugar phosphate pool, accumulated in the unicellular green alga, Chlamydomonas reinhardtii. The production of the D-isomer of lactate by algae is in contrast to plant and mammalian cells in which L-lactate is formed. After initial lactate formation, Chlamydomonas exhibits a mixed-acid type fermentation, thereby avoiding lactate accumulation and enabling the cells to tolerate extended periods of anaerobiosis. A pyruvate reductase which catalyzes the formation of D-lactate in Chlamydomonas was partially purified and characterized. Lactate produced anaerobically was metabolized only when Chlamydomonas cells were returned to aerobic conditions, and reoxidation of the D-lactate was apparently catalyzed by a mitochondrial membrane-bound dehydrogenase, rather than by the soluble pyruvate reductase. Mutants of Chlamydomonas, deficient in mitochondrial respiration, were used to demonstrate that lactate metabolism was linked to the mitochondrial electron transport chain. In addition, the oxidation of glycolate, a structural analog of lactate, was also linked to mitochondrial electron transport in vivo

  13. Lactation transcriptomics in the Australian marsupial, Macropus eugenii: transcript sequencing and quantification

    Directory of Open Access Journals (Sweden)

    Whitley Jane C

    2007-11-01

    Full Text Available Abstract Background Lactation is an important aspect of mammalian biology and, amongst mammals, marsupials show one of the most complex lactation cycles. Marsupials, such as the tammar wallaby (Macropus eugenii give birth to a relatively immature newborn and progressive changes in milk composition and milk production regulate early stage development of the young. Results In order to investigate gene expression in the marsupial mammary gland during lactation, a comprehensive set of cDNA libraries was derived from lactating tissues throughout the lactation cycle of the tammar wallaby. A total of 14,837 express sequence tags were produced by cDNA sequencing. Sequence analysis and sequence assembly were used to construct a comprehensive catalogue of mammary transcripts. Sequence data from pregnant and early or late lactating specific cDNA libraries and, data from early or late lactation massively parallel sequencing strategies were combined to analyse the variation of milk protein gene expression during the lactation cycle. Conclusion Results show a steady increase in expression of genes coding for secreted protein during the lactation cycle that is associated with high proportion of transcripts coding for milk proteins. In addition, genes involved in immune function, translation and energy or anabolic metabolism are expressed across the lactation cycle. A number of potential new milk proteins or mammary gland remodelling markers, including noncoding RNAs have been identified.

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

    Science.gov (United States)

    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. PMID:27158130

  15. Lactic acid-producing yeast cells having nonfunctional L- or D-lactate:ferricytochrome C oxidoreductase cells

    Science.gov (United States)

    Miller, Matthew; Suominen, Pirkko; Aristidou, Aristos; Hause, Benjamin Matthew; Van Hoek, Pim; Dundon, Catherine Asleson

    2012-03-20

    Yeast cells having an exogenous lactate dehydrogenase gene ae modified by reducing L- or D-lactate:ferricytochrome c oxidoreductase activity in the cell. This leads to reduced consumption of lactate by the cell and can increase overall lactate yields in a fermentation process. Cells having the reduced L- or D-lactate:ferricytochrome c oxidoreductase activity can be screened for by resistance to organic acids such as lactic or glycolic acid.

  16. Effects of an individual weight-adjusted feeding strategy in early lactation on milk production of Holstein cows during extended lactation

    DEFF Research Database (Denmark)

    Gaillard, Charlotte; Friggens, N.C.; Taghipoor, M.; Weisbjerg, Martin Riis; Lehmann, Jesper Overgård; Sehested, Jakob

    2016-01-01

    feed intake, daily LW, and body condition score every second week were recorded. The fda package of R was used to model the curves of these different variables for the 53 cows that had a lactation over 400 d. The fitted values of these curves and the associated slopes were then compared for parity and...... treatment effects using a linear mixed-effects model. The HD-LD and LD-LD cows had a similar length of lactation (461 ± 7 d). The HD diet reduced the intensity of the mobilization period and increased the milk production of the multiparous cows in early lactation compared with the cows fed the LD diet. The......Extending lactation by voluntarily delaying rebreeding aims to improve fertility and milk production in the modern dairy cow. Previous studies have shown that increased energy concentrations in the ration induced greater total milk yield and lactation persistency defined by the duration and the...

  17. Role of cell type in net lactate removal by skeletal muscle

    International Nuclear Information System (INIS)

    Net lactate uptake and subsequent pathways for removal were studied in three rabbit skeletal muscle preparations of distinct fiber type composition, i.e., glycolytic (99.1 +/- 0.2% type IIb fibers), oxidative (97.5 +/- 0.6% type I fibers), and mixed (type I, IIa, and IIb fibers). Single-pass perfusions were carried out for 3 h in the presence of glucose, lactate, and [U-14C]lactate. Lactate levels, initially set at either 1 mM (n = 4/prep) or 2 mM (n = 4/prep), were elevated twice during the perfusion at 60 and 120 min. Net lactate uptake (mumol.100 g-1.min-1) was first observed in the oxidative preparation, 1.4 +/- 0.2, at an arterial lactate concentration of approximately 2.5 mM, whereas net lactate uptake in the glycolytic, 0.7 +/- 0.2, and mixed preparations, 7.0 +/- 0.5, was first observed at 4 mM. Net lactate balance, [14C]lactate removal, and 14CO2 release demonstrated strong linear correlations (r = 0.94-0.98) with arterial lactate concentration. To quantify the fate of [14C]lactate, preparations were perfused at a single elevated lactate concentration (approximately 8 mM) for 2 h. Oxidation was the primary means of disposal in the oxidative and mixed preparations, whereas glyconeogenesis dominated removal in the glycolytic preparation. The arterial lactate concentration at which a given muscle switches from net production to net removal, the rate of removal, and subsequent pathway(s) for disposal are a function of that muscle's fiber type composition

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

    Directory of Open Access Journals (Sweden)

    Gaieski, David G

    2013-02-01

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

  19. Luminal lactate in acute pancreatitis - validation and relation to disease severity

    Directory of Open Access Journals (Sweden)

    Pynnönen Lauri

    2012-04-01

    Full Text Available Abstract Background Increased rectal luminal lactate concentration may be associated with the severity of the septic shock and high dose of vasopressors. It suggests hypoperfusion of the gut mucosa. This is potentially associated with bacterial translocation from the gut leading to local and systemic inflammation. In acute pancreatitis (AP bacterial translocation is considered as the key event leading to infection of necrotic pancreatic tissue and high severity of illness. Methods We used rectal luminal equilibration dialysis for the measurement of gut luminal lactate in 30 consecutive patients admitted to hospital due to acute pancreatitis to test the hypothesis that a single measurement of rectal luminal lactate predicts the severity of acute pancreatitis, the length of hospital stay, the need of intensive care and ultimately, mortality. We also tested the physiological validity of luminal lactate concentration by comparing it to luminal partial tension of oxygen. Additionally, a comparison between two different L-lactate analyzers was performed. Results High rectal luminal lactate was associated with low mucosal partial tension of oxygen (R = 0.57, p = 0.005 thereby indicating the physiological validity of the method. Rectal luminal lactate at the hospital admission was not associated with the first day or the highest SOFA score, CRP level, hospital length of stay, length of stay in intensive care or mortality. In this cohort of unselected consecutive patients with acute pancreatitis we observed a tendency of increased rectal lactate in the severe cases. Low precision and high bias was observed between two lactate analyzers. Conclusions The association between rectal luminal lactate and oxygen tension indicates that luminal lactate is a marker mucosal anaerobiosis. Comparison between two different analyzers showed poor, non-constant precision over the range of lactate concentrations. Rectal luminal lactate concentration at the time of

  20. Metabolic, endocrine, and reproductive responses of beef heifers submitted to different growth strategies during the lactation and rearing periods.

    Science.gov (United States)

    Rodríguez-Sánchez, J A; Sanz, A; Tamanini, C; Casasús, I

    2015-08-01

    The effects of different feeding strategies (0.7 kg/d target ADG [LO] and 1.0 kg/d target ADG [HI] during the lactation period (LACT; 0-6 mo) and the rearing period (REAR; 6-15 mo; HI-HI, HI-LO, LO-HI, and LO-LO treatments) on the growth and reproductive parameters of beef heifers bred by fixed-time AI at 15 mo were analyzed. Animal weights were recorded weekly (from birth to 18 mo), and size measures were recorded at 6 and 15 mo. Heifers were bled to determine the onset of puberty and the metabolic and endocrine (IGF-I and leptin) status. During lactation, calves in the high lactation treatment (LactHI) had greater weight ( heifers at weaning was reflected in greater concentrations of plasma glucose ( heifers had a greater growth rate than did LactHI heifers ( heifers. The IGF-I profile was highly correlated with animal performance traits and metabolic profiles, providing a useful indicator of growth, nutritional, and metabolic status at key points in development. By contrast, the function of leptin as an indicator of growth and reproductive development of heifers was less clear. All treatments had similar weights at puberty onset (55.9% mature BW), although LactLO ( heifers were older than the others. The animals with greater glucose and IGF-I levels at weaning and greater cholesterol concentrations during REAR reached puberty earlier. The fertility rate (86%) was similar among treatments. The heifers in the high rearing treatment (RearHI) required more AI services to become pregnant and were older at conception ( breeding at 15 mo, 6 mo earlier than usual for these conditions, without any negative effect on heifer reproductive performance. PMID:26440167

  1. Reversing multidrug resistance in breast cancer cells by silencing ABC transporter genes with nanoparticle-facilitated delivery of target siRNAs

    Directory of Open Access Journals (Sweden)

    Li YT

    2012-06-01

    Full Text Available Yong Tsuey Li,1 Ming Jang Chua,1 Anil Philip Kunnath,1 Ezharul Hoque Chowdhury,1,21Faculty of Medicine and Health Science, International Medical University (IMU, No 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia; 2Jeffrey Cheah School of Medicine and Health Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University Kuala Lumpur, MalaysiaBackground: Multidrug resistance, a major impediment to successful cancer chemotherapy, is the result of overexpression of ATP-binding cassette (ABC transporters extruding internalized drugs. Silencing of ABC transporter gene expression with small interfering RNA (siRNA could be an attractive approach to overcome multidrug resistance of cancer, although delivery of siRNA remains a major hurdle to fully exploit the potential of siRNA-based therapeutics. Recently, we have developed pH-sensitive carbonate apatite nanoparticles to efficiently carry and transport siRNA across the cell membrane, enabling knockdown of the cyclin B1 gene and consequential induction of apoptosis in synergy with anti-cancer drugs.Methods and results: We report that carbonate apatite-mediated delivery of the siRNAs targeting ABCG2 and ABCB1 gene transcripts in human breast cancer cells which constitutively express both of the transporter genes dose-dependently enhanced chemosensitivity to doxorubicin, paclitaxel and cisplatin, the traditionally used chemotherapeutic agents. Moreover, codelivery of two specific siRNAs targeting ABCB1 and ABCG2 transcripts resulted in a more robust increase of chemosensitivity in the cancer cells, indicating the reversal of ABC transporter-mediated multidrug resistance.Conclusion: The delivery concept of multiple siRNAs against ABC transporter genes is highly promising for preclinical and clinical investigation in reversing the multidrug resistance phenotype of breast cancer.Keywords: carbonate apatite, siRNA, gene expression, transfection, breast cancer, ABC transporter

  2. 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.

    Science.gov (United States)

    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

  3. BIOKID: Randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991

    Directory of Open Access Journals (Sweden)

    Misselwitz Joachim

    2004-10-01

    Full Text Available Abstract Background Peritoneal dialysis (PD is the preferred dialysis modality in children. Its major drawback is the limited technique survival due to infections and progressive ultrafiltration failure. Conventional PD solutions exert marked acute and chronic toxicity to local tissues. Prolonged exposure is associated with severe histopathological alterations including vasculopathy, neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial cell layer. Recently, more biocompatible PD solutions containing reduced amounts of toxic glucose degradation products (GDPs and buffered at neutral pH have been introduced into clinical practice. These solutions contain lactate, bicarbonate or a combination of both as buffer substance. Increasing evidence from clinical trials in adults and children suggests that the new PD fluids may allow for better long-term preservation of peritoneal morphology and function. However, the relative importance of the buffer in neutral-pH, low-GDP fluids is still unclear. In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD fluids. The BIOKID trial is designed to clarify the clinical significance of the buffer choice in biocompatible PD fluids. Methods/design The objective of the study is to test the hypothesis that bicarbonate based PD solutions may allow for a better preservation of peritoneal transport characteristics in children than solutions containing lactate buffer. Secondary objectives are to assess any impact of the buffer system on acid-base status, peritoneal tissue integrity and the incidence and severity of peritonitis. After a run-in period of 2 months during which a targeted cohort of 60 patients is treated with a conventional, lactate buffered, acidic, GDP containing PD fluid, patients will be stratified according to residual renal function and type of phosphate binding medication and randomized to receive either the lactate-containing Balance solution or the

  4. Effect of oral calcium bolus supplementation on early-lactation health and milk yield in commercial dairy herds.

    Science.gov (United States)

    Oetzel, G R; Miller, B E

    2012-12-01

    -equivalent milk production (greater than 105% of herd rank) and supplemented with oral Ca boluses produced 2.9 kg more milk at their first test after calving compared with cows with higher previous lactation milk yields that were not supplemented. Results of this study indicate that lame cows and higher producing cows responded favorably to supplementation with oral Ca boluses. Supplementing targeted subpopulations of cows with oral Ca boluses was beneficial even for dairies with a very low incidence of hypocalcemia. PMID:23040027

  5. Relationship between Milk Microbiota, Bacterial Load, Macronutrients, and Human Cells during Lactation.

    Science.gov (United States)

    Boix-Amorós, Alba; Collado, Maria C; Mira, Alex

    2016-01-01

    Human breast milk is considered the optimal nutrition for infants, providing essential nutrients and a broad range of bioactive compounds, as well as its own microbiota. However, the interaction among those components and the biological role of milk microorganisms is still uncovered. Thus, our aim was to identify the relationships between milk microbiota composition, bacterial load, macronutrients, and human cells during lactation. Bacterial load was estimated in milk samples from a total of 21 healthy mothers through lactation time by bacteria-specific qPCR targeted to the single-copy gene fusA. Milk microbiome composition and diversity was estimated by 16S-pyrosequencing and the structure of these bacteria in the fluid was studied by flow cytometry, qPCR, and microscopy. Fat, protein, lactose, and dry extract of milk as well as the number of somatic cells were also analyzed. We observed that milk bacterial communities were generally complex, and showed individual-specific profiles. Milk microbiota was dominated by Staphylococcus, Pseudomonas, Streptococcus, and Acinetobacter. Staphylococcus aureus was not detected in any of these samples from healthy mothers. There was high variability in composition and number of bacteria per milliliter among mothers and in some cases even within mothers at different time points. The median bacterial load was 10(6) bacterial cells/ml through time, higher than those numbers reported by 16S gene PCR and culture methods. Furthermore, milk bacteria were present in a free-living, "planktonic" state, but also in equal proportion associated to human immune cells. There was no correlation between bacterial load and the amount of immune cells in milk, strengthening the idea that milk bacteria are not sensed as an infection by the immune system. PMID:27148183

  6. Relationship between Milk Microbiota, Bacterial Load, Macronutrients, and Human Cells during Lactation

    Science.gov (United States)

    Boix-Amorós, Alba; Collado, Maria C.; Mira, Alex

    2016-01-01

    Human breast milk is considered the optimal nutrition for infants, providing essential nutrients and a broad range of bioactive compounds, as well as its own microbiota. However, the interaction among those components and the biological role of milk microorganisms is still uncovered. Thus, our aim was to identify the relationships between milk microbiota composition, bacterial load, macronutrients, and human cells during lactation. Bacterial load was estimated in milk samples from a total of 21 healthy mothers through lactation time by bacteria-specific qPCR targeted to the single-copy gene fusA. Milk microbiome composition and diversity was estimated by 16S-pyrosequencing and the structure of these bacteria in the fluid was studied by flow cytometry, qPCR, and microscopy. Fat, protein, lactose, and dry extract of milk as well as the number of somatic cells were also analyzed. We observed that milk bacterial communities were generally complex, and showed individual-specific profiles. Milk microbiota was dominated by Staphylococcus, Pseudomonas, Streptococcus, and Acinetobacter. Staphylococcus aureus was not detected in any of these samples from healthy mothers. There was high variability in composition and number of bacteria per milliliter among mothers and in some cases even within mothers at different time points. The median bacterial load was 106 bacterial cells/ml through time, higher than those numbers reported by 16S gene PCR and culture methods. Furthermore, milk bacteria were present in a free-living, “planktonic” state, but also in equal proportion associated to human immune cells. There was no correlation between bacterial load and the amount of immune cells in milk, strengthening the idea that milk bacteria are not sensed as an infection by the immune system.

  7. Lactate dehydrogenase from autotrophic and heterotrophic cells of the marine diatom Cylindrotheca fusiformis Reimann & Lewin.

    Science.gov (United States)

    Darley, W M; Smiley, R H

    1976-10-01

    Cultures of Cylindrotheca furisormis grown either autotrohpically or heterotrophically on lactate contained significant amounts of NAD-dependent L(+)-lactate dehydrogenase (EC 1.1.1.27). Polyacylamide gel electrophoresis of crude enzyme extracts revealed a single band which was indistinguishable between autotrohpic and heterotrohpic cells. The Km for lactate of partially purified preparations was lower under heterotrophic conditions. The specific activity in crude extracts was higher under autotrophic than heterotrophic conditions; it dropped precipitously when autotrophic cells were transferred to the dark, increasing again only in the presence of lactate. These and related observations suggest that this enzyme has at most only a minor role in the assimilation of lactate during heterotrophic growth on lactate. PMID:184899

  8. Lactate production and clearance in exercise. Effects of training. A mini-review

    DEFF Research Database (Denmark)

    Stallknecht, B; Vissing, J; Galbo, H

    1998-01-01

    Lactate accumulates if pyruvate formation exceeds pyruvate oxidation. Accelerated glycogenolysis is essential for lactate production. Glycogen and epinephrine enhance glycogen phosphorylase activity and this is higher in type II b than in type I fibers. Pyruvate oxidation is enhanced by exercise......-induced increase in pyruvate dehydrogenase activity and is relatively impaired by low oxygen availability and low mitochondrial oxidative capacity. During exercise lactate is eliminated in liver, heart, and resting and working muscle. In muscle, elimination depends on plasma concentration, fiber type, and fiber...... conditions. Due to influence on hormonal response, mitochondrial oxidative capacity and fiber recruitment, training diminishes glycogenolysis and lactate production. Training also increases lactate clearance. This reflects increased hepatic capacity for gluconeogenesis as well as increased lactate transport...

  9. Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P.N.; Hauerberg, J.; Frederiksen, Hans-Jørgen;

    2008-01-01

    pressure (CPP). RESULTS: The cerebral glutamine concentration was 4,396 (1,011-9,712) microM, lactate 2.15 (1.1-4.45) mM, and pyruvate 101 (43-255) microM. The lactate-pyruvate ratio was 21 (16-40), ICP 20 (2-28) mmHg, and CPP 72 (56-115) mmHg. Cerebral glutamine concentration correlated with the lactate......-pyruvate ratio (r = 0.89, P < 0.05). Also the ICP, but not CPP, correlated to the lactate-pyruvate ratio (r = 0.64, P < 0.05). CONCLUSION: ICP and the cerebral glutamine concentration in patients with ALF correlate to the lactate-pyruvate ratio. Since CPP was sufficient in all patients the rise in lactate...

  10. Measurement of lactate extraction ratio by centrifugal analyzer to assess myocardial ischemia.

    Science.gov (United States)

    Townsend, R M; Gotelli, G; Weingartner, D; Marton, L J

    1977-01-01

    The measurement of blood lactate to determine myocardial lactate extraction ratio requires a high degree of within-run precision, since small changes between arterial and coronary sinus lactate may occur. These changes in man may take place at lactate levels in the normal range, 5-18 mg/dl (0.56-2.00 mmol/l). The authors have developed a method for blood lactate determination utilizing commercially available reagents in a centrifugal analyzer (Centrifichem). Within-run precision in the low normal range, 5.4 mg/dl (0.60 mmol/l), showed a coefficient of variation of 7%. Precision extends to 50 mg/dl (5.55 mmol/l), and agreement with blood lactate values obtained with the Dupont ACA is good. PMID:831458

  11. Biostimulative effects of Nd:YAG Q-switch dye on normal human fibroblast cultures: study of a new chemosensitizing agent for the Nd:YAG laser

    Energy Technology Data Exchange (ETDEWEB)

    Castro, D.J.; Saxton, R.E.; Fetterman, H.R.; Castro, D.J.; Ward, P.H.

    1987-12-01

    Kodak Q-switch II is a new chemical with an absorption maxima at 1051 nm, designed to be used as an Nd:YAG dye laser. The potential for this dye as a new chemosensitizing agent in the treatment of connective tissue diseases and wound healing with low energy Nd:YAG laser was examined. Two normal fibroblast cell lines were tested for sensitivity to various levels of this dye in vitro. These cells were exposed to Q-switch II dye at concentrations of 0.01, 0.1, 1, 10, 50, and 100 micrograms/ml for 1 and 24 hours. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of (/sup 3/H)-thymidine at 6 and 24 hours postexposure to Q-switch II dye. At concentrations up to 10 micrograms/ml, both cell lines tested showed no changes in cell viability. However, at concentrations equal or higher than 50 micrograms/ml, more than 40% of the fibroblasts incorporated trypan blue after 24 hours of exposure to this dye, indicating significant cell destruction. The results indicate that Q-switch II dye is nontoxic to normal human fibroblast cultures and showed significant biostimulative effects on cell duplication at concentrations equal to or lower than 10 micrograms/ml. Further studies will be required to determine the usefulness of Q-switch II dye as a new photochemosensitizing agent for potential biostimulation of wound healing and/or treatment of connective tissue diseases with the Nd:YAG laser (near infrared, 1060 nm) at nonthermal levels of energies.

  12. Biostimulative effects of Nd:YAG Q-switch dye on normal human fibroblast cultures: study of a new chemosensitizing agent for the Nd:YAG laser

    International Nuclear Information System (INIS)

    Kodak Q-switch II is a new chemical with an absorption maxima at 1051 nm, designed to be used as an Nd:YAG dye laser. The potential for this dye as a new chemosensitizing agent in the treatment of connective tissue diseases and wound healing with low energy Nd:YAG laser was examined. Two normal fibroblast cell lines were tested for sensitivity to various levels of this dye in vitro. These cells were exposed to Q-switch II dye at concentrations of 0.01, 0.1, 1, 10, 50, and 100 micrograms/ml for 1 and 24 hours. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of [3H]-thymidine at 6 and 24 hours postexposure to Q-switch II dye. At concentrations up to 10 micrograms/ml, both cell lines tested showed no changes in cell viability. However, at concentrations equal or higher than 50 micrograms/ml, more than 40% of the fibroblasts incorporated trypan blue after 24 hours of exposure to this dye, indicating significant cell destruction. The results indicate that Q-switch II dye is nontoxic to normal human fibroblast cultures and showed significant biostimulative effects on cell duplication at concentrations equal to or lower than 10 micrograms/ml. Further studies will be required to determine the usefulness of Q-switch II dye as a new photochemosensitizing agent for potential biostimulation of wound healing and/or treatment of connective tissue diseases with the Nd:YAG laser (near infrared, 1060 nm) at nonthermal levels of energies

  13. Lactate dehydrogenase is not a mitochondrial enzyme in human and mouse vastus lateralis muscle

    DEFF Research Database (Denmark)

    Rasmussen, Hans N; van Hall, Gerrit; Rasmussen, Ulla F

    The presence of lactate dehydrogenase in skeletal muscle mitochondria was investigated to clarify whether lactate is a possible substrate for mitochondrial respiration. Mitochondria were prepared from 100 mg samples of human and mouse vastus lateralis muscle. All fractions from the preparation......, furthermore, showed high specific rates of state 3 respiration. This excluded artificial loss from the mitochondria of all activity of a possible LDH. It was concluded that skeletal muscle mitochondria are devoid of LDH and unable to metabolize lactate....

  14. Lactate Oxidation Coupled to Iron or Electrode Reduction by Geobacter sulfurreducens PCA

    KAUST Repository

    Call, D. F.

    2011-10-14

    Geobacter sulfurreducens PCA completely oxidized lactate and reduced iron or an electrode, producing pyruvate and acetate intermediates. Compared to the current produced by Shewanella oneidensis MR-1, G. sulfurreducens PCA produced 10-times-higher current levels in lactate-fed microbial electrolysis cells. The kinetic and comparative analyses reported here suggest a prominent role of G. sulfurreducens strains in metaland electrode-reducing communities supplied with lactate. © 2011, American Society for Microbiology.

  15. Cotransport of H+, lactate, and H2O in porcine retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Kiilgaard, Jens Folke; la Cour, Morten;

    2003-01-01

    The retinal pigment epithelium (RPE) of the eye transports water and lactate ions in the direction from retina to choroid. The water transport is important in maintenance of retinal adhesion and the transport of lactate ions serves to regulate the lactate levels and pH of the subretinal space. Th...... mammalian tissue and supports our previous study performed by an invasive technique in an amphibian tissue....

  16. Milk residues and performance of lactating dairy cows administered high doses of monensin

    OpenAIRE

    Bagg, Randal; Vessie, Gordon H.; Dick, C. Paul; Duffield, Todd; Wilson, Jeff B.; Aramini, Jeff J

    2005-01-01

    Milk residues and performance were evaluated in lactating cows that were fed up to 10 times the recommended dose of monensin. Following an acclimatization period of 14 d, during which cows were fed a standard lactating cow total mixed ration containing 24 ppm monensin, 18 lactating Holstein dairy cows were grouped according to the level of feed intake and then randomly assigned within each group to 1 of 3 challenge rations delivering 72, 144, and 240 ppm monensin. Outcome measurements include...

  17. Reduction of 3-mercaptopyruvate in rat liver is catalyzed by lactate dehydrogenase.

    OpenAIRE

    Ohta,Jun; Ubuka,Toshihiko

    1989-01-01

    It has been assumed that the in vivo reduction of 3-mercaptopyruvate, an intermediate of cysteine metabolism, to 3-mercaptolactate is catalyzed by lactate dehydrogenase (EC 1.1.1.27) though no definitive evidence has been presented. In order to examine this assumption, reduction of 3-mercaptopyruvate and its inhibition were studied using rat liver homogenate, lactate dehydrogenase purified from rat liver and anti-lactate dehydrogenase antiserum. Reduction of 3-mercaptopyruvate was actively ca...

  18. Vulva Fibroadenoma Associated with Lactating Adenoma in a 26-Year-Old Nigerian Female

    OpenAIRE

    Anunobi, C. C.; F. J. N. Obiajulu; Banjo, A. A. F.; Okonkwo, A. O. E.

    2013-01-01

    Background. Vulva lactating adenoma is rare and may be misdiagnosed as adenocarcinoma in frozen section and aspiration cytology if breast tissue is not anticipated. Objective. To raise the awareness of lactating vulva ectopic breast lesion among clinicians and pathologists. Case Report. We present a case of vulva fibroadenoma associated with lactating adenoma in a 26-year-old Nigerian female. Conclusion. The rarity of vulva ectopic breast tissue can present a diagnostic challenge for both the...

  19. ENVIRONMENTAL FACTORS AFFECTING MILK YIELD AND LACTATION LENGTH IN SAHIWAL CATTLE

    OpenAIRE

    I. R. Bajwa, M. S. Khan, M. A. Khan1 and K. Z. Gondal2

    2004-01-01

    Weekly milk yield records on 661 Sahiwal cows calving during 1990-2000 at the Livestock Experiment Station Bahadurnagar, Okara were used to study how milk yield and lactation length were affected by different environmental factors. Lactation milk yield averaged 1475  651 kg for an average lactation length of 248  67 days (n=2039). Year of calving and season of calving both significantly (P

  20. Strategic test-day recording regimes to estimate lactation yield in tropical dairy animals

    OpenAIRE

    McGill, D. M.; Thomson, P.C.; Mulder, H.A.; Lievaart, J.J.

    2014-01-01

    Background In developing dairy sectors, genetic improvement programs have limited resources and recording of herds is minimal. This study evaluated different methods to estimate lactation yield and sampling schedules with fewer test-day records per lactation to determine recording regimes that (1) estimate lactation yield with a minimal impact on the accuracy of selection and (2) optimise the available resources. Methods Using Sahiwal cattle as a tropical dairy breed example, weekly milk reco...

  1. Effects of lactation upon circulating plasma metabolites in cafeteria-fed rats

    OpenAIRE

    Salvadó, J.; Segués Piqué, Teresa; Alemany, Marià; Arola i Ferrer, Lluís

    1986-01-01

    1. The effects of "cafeteria feeding" on primiparous Wistar rats during lactation have been studied by measuring circulating levels of glucose, amino acids, lactate, urea and ammonia as well as glycogen levels in liver and muscle. 2. No significant changes in glucose levels were observed despite alterations in blood glucose compartmentation. 3. Compared with controls, the dams given the cafeteria diet had higher liver glycogen stores which were more easily mobilized at the peak of lactation. ...

  2. Determination of anaerobic threshold in rats using the lactate minimum test

    OpenAIRE

    Voltarelli F.A.; Gobatto C.A.; Mello M.A.R. de

    2002-01-01

    The break point of the curve of blood lactate vs exercise load has been called anaerobic threshold (AT) and is considered to be an important indicator of endurance exercise capacity in human subjects. There are few studies of AT determination in animals. We describe a protocol for AT determination by the "lactate minimum test" in rats during swimming exercise. The test is based on the premise that during an incremental exercise test, and after a bout of maximal exercise, blood lactate decreas...

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

    OpenAIRE

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

    2011-01-01

    We report that in the rat hippocampus learning leads to a significant increase in extracellular lactate levels, which derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in-vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter...

  4. Therapeutic Effect of Nisin Z on Subclinical Mastitis in Lactating Cows▿

    OpenAIRE

    Wu, Junqiang; Hu, Songhua; Cao, Liting

    2007-01-01

    Bovine subclinical mastitis is an inflammation of the mammary gland caused by bacterial intramammary infection, accounting for large economic losses. Treatment of subclinical mastitis is not suggested for lactating cows due to the risk of milk contamination. The objectives of this study were to evaluate an antimicrobial peptide, nisin, in the treatment of subclinical mastitis in lactating cows. A total of 90 lactating Holstein cows with subclinical mastitis were randomly divided into nisin-tr...

  5. Glucose and Lactate Biosensors for Scanning Electrochemical Microscopy Imaging of Single Live Cells

    OpenAIRE

    Ciobanu, Madalina; Taylor, Dale E.; Wilburn, Jeremy P.; Cliffel, David E

    2008-01-01

    We have developed glucose and lactate ultramicroelectrode (UME) biosensors based on glucose oxidase and lactate oxidase (with enzymes immobilized onto Pt UMEs by either electropolymerization or casting) for scanning electrochemical microscopy (SECM), and have determined their sensitivity to glucose and lactate, respectively. The results of our evaluations reveal different advantages for sensors constructed by each method: improved sensitivity and shorter manufacturing time for hand-casting, a...

  6. Energy turnover in European hares is centrally limited during early, but not during peak lactation

    OpenAIRE

    Valencak, Teresa G.; Ruf, Thomas

    2009-01-01

    We investigated metabolizable energy intake (MEI) and milk energy output in European hares throughout gestation and lactation in females raising three young, i.e., close to maximum litter size in this precocial species. We hypothesized that herbivorous hares may face a central limitation of energy turnover during lactation, imposed by maximum capacity of the gastrointestinal tract. Females were provided with low-energy or high-energy diets, either continually, or during lactation only. Unexpe...

  7. CERN: Fixed target targets

    International Nuclear Information System (INIS)

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become

  8. [Treatment of Chronic Functional Constipation during Pregnancy and Lactation].

    Science.gov (United States)

    Gharehbaghi, K; Gharehbaghi, D R; Wierrani, F; Sliutz, G

    2016-02-01

    Natural fibres (bulk-forming agents), docusate sodium (stool-softener), mineral oils (lubricant laxatives), macrogol (polyethylene glycol, PEG), sugars and sugar alcohols (osmotic laxatives) and anthraquinones and diphenolic laxatives (stimulant laxatives) seem to be safe medicaments regarding teratogenicity and lactation. The US Food and Drug Administration (FDA) risk categories for these substances taken during pregnancy and lactation are often the result of the lack of studies than of evidence-based information. So risk categories do not help in the decision-making for the right laxative. Alternative solutions such as proposals of the American College of Gastroenterology's Committee on FDA related matters, (ACG-FDA) and the Motherisk Programme try to improve decision-making. For newer compounds such as chloride-channel-activators and procinetics no data regarding safe use in pregnancy and during breast-feeding are available as yet. We suggest the use of macrogol and lactulose as the first-line therapy in treating chronic constipation during pregnancy. Macrogol shows some advantages, such as faster onset of bowel action and fewer flatulences. If this treatment does not work or starts but then stops working, we recommend in the second and third trimenon a second-line treatment with diphenolic laxatives such as bisacodyl and and sodium picosulfate. During pregnancy the decision on the application of these laxatives is largely determined by the side-effects of tenesmus associated with preterm births. During lactation we recommend macrogol (preferable to lactulose due to the lack of data), lactulose, bisacodyl and sodium picosulfate, according to the nature of the conditions. PMID:26866689

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

    Directory of Open Access Journals (Sweden)

    V.M.T. Trindade

    2013-05-01

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

  10. Daily intake of lactating crossbred cows grazing elephant grass rotationally

    OpenAIRE

    Aroeira Luiz Januário Magalhães; Lopes Fernando César Ferraz; Soares João Paulo Guimarães; Deresz Fermino; Verneque Rui da Silva; Arcuri Pedro Braga; Matos Leovegildo Lopes de

    2001-01-01

    The goal of this trial was to estimate the total dry matter (TDMI) and daily pasture dry matter intakes (PDMI) by lactating crossbred Holstein - Zebu cows grazing elephant grass (Pennisetum purpureum Schum.) paddocks submitted to different rest periods. Three groups of 24 cows were used during two years. The paddocks were grazed during three days at the stocking rate of 4.5 cows/ha. Treatments consisted of resting periods of 30 days without concentrate and resting periods of 30, 37.5 and 45 d...

  11. Milk yield prediction at late lactation in reproductive rabbit does

    Directory of Open Access Journals (Sweden)

    Alberto Arnau-Bonachera

    2015-06-01

    Full Text Available Separating kits and mother to determine milk yield at 4th wk of lactation (MY4 could have negative consequences on the training and development of young rabbits. In this work, a total of 313 lactation curves (28 d long, taken from 2 different trials, were used to fit regression models to estimate MY4. In both trials, females were subjected to a semi-intensive reproductive rhythm [insemination at 11 d post-partum (dpp and weaning at 28 dpp], but diets, genetic types, parity order and day of controls were slightly different. The models included variables which, according to the bibliography, are related to milk yield and are often recorded in joint management (without separation of litters  rom mothers, such as litter size at weaning (LSW; both linear and quadratic, joint energy intake of doe plus litter at 4th wk of lactation (JEI; both linear and quadratic, perirenal fat thickness change (ΔPFTd and milk yield at 3rd wk (MY3. The overlapping degree (OL between current lactation and next pregnancy was included as a dummy variable, as well as their interactions with quantitative traits. To fit these models, 3  procedures were proposed to obtain accurate equations with biological meaning: Eq1, multiple linear regression (MLR of data; Eq2, MLR with previous smoothing of sample distribution; and Eq3, MLR with previous smoothing and avoiding redundant samples and collinearities among variables. MY3 had a positive and relevant linear effect on MY4 for the 3 equations obtained (responsible for 39 to 50% of MY4 prediction. JEI had also a relevant role in MY4 prediction (28 to 61%, its positive effect being linear on Eq1, quadratic on Eq2 and both linear and quadratic on Eq3. ΔPFTd and LSW related traits were only included in Eq3, with a low relative weight, and OL inclusion did not improve prediction in any equation. Predicting MY4 was possible with the variables used, although certain precautions must be taken. Traditional MLR seems to predict

  12. Metabolism of antimony-124 in lactating dairy cows

    International Nuclear Information System (INIS)

    Lactating cows received oral and intravenous administrations of radioactive antimony (III) chloride to study its intestinal and urinary excretion, secretion into milk and organ distribution. Milk samples were taken twice a day and the milk, feces and urine assayed using gamma spectroscopy. Cows administered orally were sacrificed at 102 days and those injected intravenously at 70 days. Distribution of 124 Sb in the organs was determined at the time of sacrifice. Excretion of 124Sb occurs mainly via urine, little is secreted into milk. Highest organ concentrations are in the spleen, liver and bone. (U.K.)

  13. Analysis of early lactation reproductive characteristics in Holstein cows.

    OpenAIRE

    Walters, Anneke H.

    2000-01-01

    Ultrasound-guided transvaginal follicular aspiration was used to obtain oocytes from cows to study follicular development and oocyte morphology. Follicular aspiration was conducted once during wk 1 to 12 postpartum on 120 lactating cows with 6 groups, separated by biweekly intervals. Approximately one half of the aspirated cows at each session were from the early groups (wk 1-2, 3-4, or 5-6) and the other half from the later groups (wk 7-8, 9-10, or 11-12). On the day of aspiration the numbe...

  14. Estimating the Lactation Curve on a.m./p.m. Milkings in Dairy Cows

    Directory of Open Access Journals (Sweden)

    Ludovic Toma Cziszter

    2013-10-01

    Full Text Available A pilot study was conducted in order to assess the effect of a.m./p.m. milkings on the shape of the lactation curve during a normal lactation. Data from a.m. and p.m. milkings from 86 Romanian Spotted cows were used. Cows calved during January, February and March 2011 and concluded their lactations by the end of February 2012. Results showed that there was a difference between morning and evening milkings regarding the shape of the lactation curve. The shape of the lactation curve for morning milking was more resembling to the shape of the lactation curve for total daily milk. Modelling the lactation curve with gamma incomplete function led to a milk production estimate very close to the real production, although the model overestimated the yield in early lactation and underestimated it in middle lactation. If alternative milkings are going to use for milk yield estimation it is preferable to measure the evening milking at the beginning.

  15. Sputter target

    Science.gov (United States)

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

    The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

  16. Quinone-dependent D-lactate dehydrogenase Dld (Cg1027 is essential for growth of Corynebacterium glutamicum on D-lactate

    Directory of Open Access Journals (Sweden)

    Oikawa Tadao

    2010-12-01

    Full Text Available Abstract Background Corynebacterium glutamicum is able to grow with lactate as sole or combined carbon and energy source. Quinone-dependent L-lactate dehydrogenase LldD is known to be essential for utilization of L-lactate by C. glutamicum. D-lactate also serves as sole carbon source for C. glutamicum ATCC 13032. Results Here, the gene cg1027 was shown to encode the quinone-dependent D-lactate dehydrogenase (Dld by enzymatic analysis of the protein purified from recombinant E. coli. The absorption spectrum of purified Dld indicated the presence of FAD as bound cofactor. Inactivation of dld resulted in the loss of the ability to grow with D-lactate, which could be restored by plasmid-borne expression of dld. Heterologous expression of dld from C. glutamicum ATCC 13032 in C. efficiens enabled this species to grow with D-lactate as sole carbon source. Homologs of dld of C. glutamicum ATCC 13032 are not encoded in the sequenced genomes of other corynebacteria and mycobacteria. However, the dld locus of C. glutamicum ATCC 13032 shares 2367 bp of 2372 bp identical nucleotides with the dld locus of Propionibacterium freudenreichii subsp. shermanii, a bacterium used in Swiss-type cheese making. Both loci are flanked by insertion sequences of the same family suggesting a possible event of horizontal gene transfer. Conclusions Cg1067 encodes quinone-dependent D-lactate dehydrogenase Dld of Corynebacterium glutamicum. Dld is essential for growth with D-lactate as sole carbon source. The genomic region of dld likely has been acquired by horizontal gene transfer.

  17. Oxidation of Exogenous Lactate by Lactate Dehydrogenase C in the Midpiece of Rat Epididymal Sperm is Essential for Motility and Oxidative Activity

    Directory of Open Access Journals (Sweden)

    Hideaki Yamashiro

    2009-01-01

    Full Text Available Problem statement: To identify the metabolic reaction-glycolysis or oxidative phosphorylation that is mainly involved in the production of energy required for rat sperm mobilization. Approach: Epididymal sperm were collected from Wistar rats and extended in lactate-containing or lactate-free raffinose-modified Krebs-Ringer Bicarbonate solution (mKRB-egg yolk medium supplemented with 0, 1, 2, or 3 mM 2-Deoxy-D-Glucose (2 DG and 1, 2, or 3 mM sodium Oxamate (OX. Sperm motility, straight-line velocity (VSL and oxygen consumption were evaluated. Further, immunofluorescent localization of Lactate Dehydrogenase C (LDH-C in sperm was also performed. Results: Low concentrations of 2DG (1 and 2 mM did not significantly affect motility, VSL and oxygen consumption of sperm extended in the lactate-containing medium. While sperm motility and oxygen consumption were significantly inhibited by even 1mM 2DG in sperm extended in lactate-free medium. Sperm motility significantly inhibited in the case of sperm extended in lactate-containing and free-medium with 1 mM OX. We also found that sperm motility was not maintained in the absence of lactate throughout the 3 h incubation period. Immunofluorescence study revealed that mainly LDH-C was may be localized in the intramitochondrial region of the sperm. Conclusion: These results suggest that exogenous lactate enhances lactate oxidation by LDH-C, thereby promoting mitochondrial oxidative reactions in the midpiece and maintaining the mobilization of rat epididymal sperm.

  18. Orthodontic Force Application in Correlation with Salivary Lactate Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Erik Husin

    2013-07-01

    Full Text Available Orthodontic tooth movement generate mechanical forces to periodontal ligament and alveolar bone. The forces correlate with initial responses of periodontal tissues and involving many metabolic changes. One of the metabolic changes detected in saliva is lactate dehydrogenase (LDH activity. Objectives: To evaluate the correlation between orthodontic interrupted force application, lactate dehydrogenase activity and the distance of tooth movement. Methods: upper premolar, pre-retraction of upper canine and 1, 7, 14, 21 and 28 days post-retraction of upper canine with 100g interrupted orthodontic force. Results: duration of force (F=11.926 p 14 and 28 days post-retraction of canine. The region of retraction correlated with the distance of tooth movement (F=7.377 p=0.007. The duration of force correlated with the distance of tooth movement (F=66.554 p=0.000. retraction of canine. Conclusion: This study concluded that orthodontic interrupted force application on canine could increase the distance of tooth movement and LDH activity in saliva.

  19. Testicular lactate content is compromised in men with Klinefelter Syndrome.

    Science.gov (United States)

    Alves, Marco G; Martins, Ana D; Jarak, Ivana; Barros, Alberto; Silva, Joaquina; Sousa, Mário; Oliveira, Pedro F

    2016-03-01

    Klinefelter syndrome (KS) is the most common genetic cause of human infertility, but the mechanism(s) responsible for its phenotype remain largely unknown. KS is associated with alterations in body composition and with a higher risk of developing metabolic diseases. We therefore hypothesized that KS men seeking fertility treatment possess an altered testicular metabolism profile that may hamper the nutritional support of spermatogenesis. Testicular biopsies from control (46, XY) (n = 6) and KS (47, XXY) (n = 6) individuals were collected and analyzed by proton high-resolution magic-angle spinning nuclear magnetic resonance spectroscopy. The mRNA and protein expression of crucial glycolysis-associated enzymes and transporters were evaluated in parallel by quantitative PCR and Western blot, respectively. Our data revealed altered regulation of glucose transporters (GLUT1 and GLUT3); phosphofructokinase 1, liver isoform (PFKL); and lactate dehydrogenase A (LDHA) expression in the testis of KS patients. Moreover, we detected a severe reduction in lactate and creatine accumulation within testicular tissue from KS men. The aberrant levels of the biomarkers detected in testicular biopsies of KS men may therefore be associated with the infertility phenotypes presented by these men. Mol. Reprod. Dev. 83: 208-216, 2016. © 2015 Wiley Periodicals, Inc. PMID:26676340

  20. Tb-160 metabolism in the rat during lactation and suckling

    International Nuclear Information System (INIS)

    Terbium metabolism in the rat during lactation and suckling was studied. The study comprised 160 female Wistar rats with 160TbCl3 administered i.v. during various periods of lactation and their offspring. The largest amounts of Tb-160 were found in the liver (2,5% of the administered dose per gram of the organ) and bones (1,1% per gram) of female rats. The peak terbium uptake was found in the milk gland (2,1% of the dose) 2 hours after the i.v. administration. The uptakes in infants increased with age. No significant differences were observed in the specific activity of terbium in the stomach, large and small intestines of infants 1-21 days old. Biological half-lives for the stomach, small and large intestines were 0,60 ± 0,11, 1,89 ± 0,95 and 3,65 ± 0,12 days. 27 refs., 3 tabs. (author)

  1. Adverse effects of lactational exposure to chlorpyrifos in suckling rats.

    Science.gov (United States)

    Mansour, S A; Mossa, A H

    2010-02-01

    The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg(-1) body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg(-1) b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg(-1) b.wt. (1/100 lethal dose [LD(50)]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother's milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF. PMID:20028704

  2. A Natural Method for Family Planning: Lactational Amenorrhea Method

    Directory of Open Access Journals (Sweden)

    Ayten Senturk Erenel

    2010-08-01

    Full Text Available Use of an family planning method during the postpartum period is important both to space births, and to prevent unwanted pregnancies. Under-utilization of family planning services during this period not only leads to adverse conditions caused by excessive fertility, but also has negative effects on both maternal and infant health. Women are in close contact with health care providers before, during, and after childbirth, when they are most likely to be impressed by the services they receive. Effective provision of health care services in these periods is therefore of great importance. Literature indicates high rates of success and compliance with family planning services provided during these periods. Many women neglect to use a modern contraceptive method in the postpartum period believing that breastfeeding alone ensures sufficient protection against pregnancy. Indeed, breastfeeding can be 98% effective as a contraceptive method; however, this is only true if certain criteria are observed. There are three basic criteria for the lactational amenorrhea method to be effective: the baby must be less than six months old, must be exclusively or almost exclusively breast-fed, and the mother must not be menstruating. In a conference held in Bellago in August 1988 by the World Health Organization and other international agencies, a consensus was developed for effective use of lactational amenorrhea method, and it was agreed to adopt breastfeeding as a potential family planning method in maternal and child health programs. [TAF Prev Med Bull 2010; 9(4.000: 383-390

  3. Estimation of the Maximal Lactate Steady State in Endurance Runners.

    Science.gov (United States)

    Llodio, I; Gorostiaga, E M; Garcia-Tabar, I; Granados, C; Sánchez-Medina, L

    2016-06-01

    This study aimed to predict the velocity corresponding to the maximal lactate steady state (MLSSV) from non-invasive variables obtained during a maximal multistage running field test (modified University of Montreal Track Test, UMTT), and to determine whether a single constant velocity test (CVT), performed several days after the UMTT, could estimate the MLSSV. Within 4-5 weeks, 20 male runners performed: 1) a modified UMTT, and 2) several 30 min CVTs to determine MLSSV to a precision of 0.25 km·h(-1). Maximal aerobic velocity (MAV) was the best predictor of MLSSV. A regression equation was obtained: MLSSV=1.425+(0.756·MAV); R(2)=0.63. Running velocity during the CVT (VCVT) and blood lactate at 6 (La6) and 30 (La30) min further improved the MLSSV prediction: MLSSV=VCVT+0.503 - (0.266·ΔLa30-6); R(2)=0.66. MLSSV can be estimated from MAV during a single maximal multistage running field test among a homogeneous group of trained runners. This estimation can be further improved by performing an additional CVT. In terms of accuracy, simplicity and cost-effectiveness, the reported regression equations can be used for the assessment and training prescription of endurance runners. PMID:27116348

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

    Science.gov (United States)

    2015-07-01

    Cannabis sativa (marijuana) is the illicit drug most commonly used during pregnancy. The self-reported prevalence of marijuana use during pregnancy ranges from 2% to 5% in most studies. A growing number of states are legalizing marijuana for medicinal or recreational purposes, and its use by pregnant women could increase even further as a result. Because of concerns regarding impaired neurodevelopment, as well as maternal and fetal exposure to the adverse effects of smoking, women who are pregnant or contemplating pregnancy should be encouraged to discontinue marijuana use. Obstetrician-gynecologists should be discouraged from prescribing or suggesting the use of marijuana for medicinal purposes during preconception, pregnancy, and lactation. Pregnant women or women contemplating pregnancy should be encouraged to discontinue use of marijuana for medicinal purposes in favor of an alternative therapy for which there are better pregnancy-specific safety data. There are insufficient data to evaluate the effects of marijuana use on infants during lactation and breastfeeding, and in the absence of such data, marijuana use is discouraged. PMID:26241291

  5. Kinematical Analysis along Maximal Lactate Steady State Swimming Intensity

    Directory of Open Access Journals (Sweden)

    Pedro Figueiredo, Rafael Nazario, Marisa Sousa, Jailton Gregório Pelarigo, João Paulo Vilas-Boas, Ricardo Fernandes

    2014-09-01

    Full Text Available The purpose of this study was to conduct a kinematical analysis during swimming at the intensity corresponding to maximal lactate steady state (MLSS. Thirteen long distance swimmers performed, in different days, an intermittent incremental protocol of n x 200 m until exhaustion and two to four 30-min submaximal constant speed bouts to determine the MLSS. The video analysis, using APAS System (Ariel Dynamics Inc., USA, allowed determining the following relevant swimming determinants (in five moments of the 30-min test: 0, 25, 50, 75, and 100%: stroke rate, stroke length, trunk incline, intracyclic velocity variation, propelling efficiency, index of coordination and the time allotted to propulsion per distance unit. An ANOVA for repeated measures was used to compare the parameters mean values along each moment of analysis. Stoke rate tended to increase and stroke length to decrease along the test; a tendency to decrease was also found for intracyclic velocity variation and propelling efficiency whereas the index of coordination and the propulsive impulse remained stable during the MLSS test. It can be concluded that the MLSS is not only an intensity to maintain without a significant increase of blood lactate concentration, but a concomitant stability for some biomechanical parameters exists (after an initial adaptation. However, efficiency indicators seem to be more sensitive to changes occurring during swimming at this threshold intensity.

  6. Heart rate and blood lactate responses during competitive Olympic boardsailing.

    Science.gov (United States)

    Guével, A; Maïsetti, O; Prou, E; Dubois, J J; Marini, J F

    1999-02-01

    The rules of competitive boardsailing events were changed before the Atlanta Olympic Games. Pumping the sail (pulling repeatedly on the rig) is now allowed and the duration of races has been shortened. Eight members of the French national team (mean age 23+/-2.7 years) participated in this study. Their cardiac and metabolic responses were assessed by measuring heart rate and blood lactate concentration during various competitive events in two strengths of wind (light vs. moderate). Heart rate was higher in light (87.4+/-4.3% HRmax; mean racing time 37 min) than in moderate wind conditions (82.9+/-5.3% HRmax; mean racing time 33 min). The mean post-race blood lactate concentration (5.2+/-1.0 mmol x l(-1)) was not affected by the wind conditions. Mean heart rate was highest during downwind legs (88.0+/-3.1% HRmax; duration 7-10 min). The races consisted of two laps, the first of which induced significantly higher cardiac demands than the second. We conclude that the changes to the rules of competitive boardsailing have increased the cardiac and metabolic efforts involved. PMID:10069270

  7. Offspring's hydromineral adaptive responses to maternal undernutrition during lactation.

    Science.gov (United States)

    Nuñez, P; Arguelles, J; Perillan, C

    2015-12-01

    Early development, throughout gestation and lactation, represents a period of extreme vulnerability during which susceptibility to later metabolic and cardiovascular injuries increases. Maternal diet is a major determinant of the foetal and newborn developmental environment; maternal undernutrition may result in adaptive responses leading to structural and molecular alterations in various organs and tissues, such as the brain and kidney. New nephron anlages appear in the renal cortex up to postnatal day 4 and the last anlages to be formed develop into functional nephrons by postnatal day 10 in rodents. We used a model of undernutrition in rat dams that were food-restricted during the first half of the lactation period in order to study the long-term effects of maternal diet on renal development, behaviour and neural hydromineral control mechanisms. The study showed that after 40% food restriction in maternal dietary intake, the dipsogenic responses for both water and salt intake were not altered; Fos expression in brain areas investigated involved in hydromineral homeostasis control was always higher in the offspring in response to isoproterenol. This was accompanied by normal plasma osmolality changes and typical renal histology. These results suggest that the mechanisms for the control of hydromineral balance were unaffected in the offspring of these 40% food-restricted mothers. Undernutrition of the pups may not be as drastic as suggested by dams' restriction. PMID:26234469

  8. BIOLOGICAL AND PRODUCTIVE RESOURCES OF LACTATING COWS AT DENITRIFICATION

    Directory of Open Access Journals (Sweden)

    Kokaeva M. G.

    2015-09-01

    Full Text Available The article presents the results obtained in the process of two scientific-practical experiments carried jut on two milk cows (Shvitskay breed aimed at the antioxidants detoxication properties and mould inhibitor revealing. This factor is actual in the Republic of North Ossetia-Alania as the intensive technologies of the fodder crops cultivation using the nitrate fertilizers are widely applied in the region leading to the excess nitrates and nitrite penetration into the animals’ organism. During the first experiment, the antioxidants of epophen and vitamin C were added into the ration of the lactating cows with the subtoxic dosage of nitrates both separately and in complex. The complex feeding proved to increase the milk productivity, the fat mass and protein mass in milk while reducing the fodder expenditure per product unit. Beside, the lactating cows revealed the digestive and intermediate exchange betterment and the reduction of nitrates and nitrites level in blood. The second experiment helped to study Khadoks antioxidant and mould inhibitor called Mold-Zap efficiency use for the nitrates and aflotoxicin B1 detoxication. The researches showed that the complex admixtures of the said preparations introduction into the rations of the animals increased the milk productivity, fat and protein content and reduced aflatoxineM1 content. The cows activated the digestive and intermediate exchange, accompanied with the nitrates and nitrites level reduction in the organism

  9. Intrinsic and chemo-sensitizing activity of SMAC-mimetics on high-risk childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Schirmer, M; Trentin, L; Queudeville, M; Seyfried, F; Demir, S; Tausch, E; Stilgenbauer, S; Eckhoff, S M; Meyer, L H; Debatin, K-M

    2016-01-01

    SMAC-mimetics represent a targeted therapy approach to overcome apoptosis resistance in many tumors. Here, we investigated the efficacy of the SMAC-mimetic BV6 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In ALL cell lines, intrinsic apoptosis sensitivity was associated with rapid cIAP degradation, NF-κB activation, TNF-α secretion and induction of an autocrine TNF-α-dependent cell death loop. This pattern of responsiveness was also observed upon ex vivo analysis of 40 primograft BCP-ALL samples. Treatment with BV6 induced cell death in the majority of ALL primografts including leukemias with high-risk and poor-prognosis features. Inhibition of cell death by the TNF receptor fusion protein etanercept demonstrated that BV6 activity is dependent on TNF-α. In a preclinical NOD/SCID/huALL model of high-risk ALL, marked anti-leukemia effectivity and significantly prolonged survival were observed upon BV6 treatment. Interestingly, also in vivo, intrinsic SMAC-mimetic activity was mediated by TNF-α. Importantly, BV6 increased the effectivity of conventional induction therapy including vincristine, dexamethasone and asparaginase leading to prolonged remission induction. These data suggest SMAC-mimetics as an important addendum to efficient therapy of pediatric BCP-ALL. PMID:26775704

  10. Conversion of L-lactate into n-caproate by a continuously fed reactor microbiome.

    Science.gov (United States)

    Kucek, Leo A; Nguyen, Mytien; Angenent, Largus T

    2016-04-15

    Conversion of lactate to n-caproate had been described for the type strain Megasphaera elsdenii in batch systems. Recently, investigators have also described production of n-caproate from endogenous or exogenous lactate with batch-fed reactor microbiome systems. However, no reports exist of lactate to n-caproate conversion within a continuously fed bioreactor. Since continuously fed systems are advantageous for biotechnology production platforms, our objective was to develop such a system. Here, we demonstrated continuous lactate to n-caproate conversion for more than 165 days. The volumetric n-caproate production rate (productivity) was improved when we decreased the operating pH from 5.5 to 5.0, and was again improved when we utilized in-line product recovery via pertraction (membrane-based liquid-liquid extraction). We observed a maximum n-caproate productivity of 6.9 g COD/L-d for a period of 17 days at an L-lactate loading rate of 9.1 g COD/L-d, representing the highest sustained lactate to n-caproate conversion rate ever reported. We had to manage two competing lactate conversion pathways: 1) the reverse β-oxidation pathway to n-caproate; and 2) the acrylate pathway to propionate. We found that maintaining a low residual lactate concentration in the bioreactor broth was necessary to direct lactate conversion towards n-caproate instead of propionate. These findings provide a foundation for the development of new resource recovery processes to produce higher-value liquid products (e.g., n-caproate) from carbon-rich wastewaters containing lactate or lactate precursors (e.g., carbohydrates). PMID:26905795

  11. L-Lactate-selective microbial sensor based on flavocytochrome b2-enriched yeast cells using recombinant and nanotechnology approaches.

    Science.gov (United States)

    Karkovska, Maria; Smutok, Oleh; Stasyuk, Nataliya; Gonchar, Mykhailo

    2015-11-01

    In the recent years, nanotechnology is the most developing branch due to a wide variety of potential applications in biomedical, biotechnological and agriculture fields. The binding nanoparticles with various biological molecules makes them attractive candidates for using in sensor technologies. The particularly actual is obtaining the bionanomembranes based on biocatalytic elements with improved sensing characteristics. The aim of this investigation is to study the properties of microbial L-lactate-selective sensor based on using the recombinant Hansenula polymorpha yeast cells overproducing flavocytochrome b2 (FC b2), as well as additionally enriched by the enzyme bound with gold nanoparticles (FC b2-nAu). Although, the high permeability of the living cells to nanoparticles is being intensively studied (mostly for delivery of drugs), the idea of using both recombinant technology and nanotechnology to increase the amount of the target enzyme in the biosensing layer is really novel. The FC b2-nAu-enriched living and permeabilized yeast cells were used for construction of a bioselective membrane of microbial L-lactate-selective amperometric biosensor. Phenazine methosulphate was served as a free defusing electron transfer mediator which provides effective electron transfer from the reduced enzyme to the electrode surface. It was shown that the output to L-lactate of FC b2-nAu-enriched permeabilized yeast cells is 2.5-fold higher when compared to the control cells. The obtained results confirm that additional enrichment of the recombinant yeast cell by the enzyme bound with nanoparticles improves the analytical parameters of microbial sensor. PMID:26452947

  12. 流式细胞术应用于抗肿瘤药物敏感性实验的可行性研究%The feasibility of antitumor drugs chemosensitivity testing by flow Cytometry

    Institute of Scientific and Technical Information of China (English)

    Jing Yao; Jianhong Wu; Daxing Xie; Xiaolan Li; Deding Tao; Junbo Hu; Jianping Gong

    2007-01-01

    Objective:To investigate the feasibility of chemosensitivity testing of antitumor drugs by flow cytometry in clinical applications so as to provide experimental and theoretical basis for the establishment of a novel antitumor drugs sensitivity testing and the screening of particular antitumor drugs.Methods:Detect the apoptosis rate of 12 cases of Molt-4 cell line.57 cases of fresh clinical gastrointestinal tumor cells by Sub-G1 and Annexin V assay of flow cytometry under the effects of antitumor drugs at different times and the outcomes were compared with the ones of the MTT(3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide)assay.Results:The lethality of drugs on Molt-4 cell clinica gastrointestinal tumor cells had a positive correlation with the acting time of antidrugs by employing Annexin V.Sub-G1 and MTT assay.Drug-incurring maximum lethality of Annexin V assay was higher than MTT colorimetric assay.that of Sub-G1 was lower than MTT assay.the virtual times of Annexin V and Sub-G1 assay were obviously earlier than that of MTT colorimetric assay.Conclusion:Annexin V and Sub-G1 assay of flow cytometry can be taken as potent protocols testing anti-tumor drug chemosensitivity.Annexin V assay is featured by more sensitive,concise,reliable compared with the classical chemosensilivity testing assay Of MTT colorimetric assay and it possesses clinical applied value.

  13. Target capture and target ghosts

    Science.gov (United States)

    Auerbach, Steven P.

    1996-05-01

    Optimal detection methods for small targets rely on whitened matched filters, which convolve the measured data with the signal model, and whiten the result with the noise covariance. In real-world implementations of such filters, the noise covariance must be estimated from the data, and the resulting covariance estimate may be corrupted by presence of the target. The resulting loss in SNR is called 'target capture'. Target capture is often thought to be a problem only for bright targets. This presentation shows that target capture also arises for dim targets, leading to an SNR loss which is independent of target strength and depends on the averaging method used to estimate the noise covariance. This loss is due to a 'coherent beat' between the true noise and that portion of the estimated noise covariance due to the target. This beat leads to 'ghost targets', which diminish the target SNR by producing a negative target ghost at the target's position. A quantitative estimate of this effect will be given, and shown to agree with numerical results. The effect of averaging on SNR is also discussed for data scenes with synthetic injected targets, in cases where the noise covariance is estimated using 'no target' data. For these cases, it is shown that the so-called 'optimal' filter, which uses the true noise covariance, is actually worse than a 'sub-optimal' filter which estimates the noise from scene. This apparent contradiction is resolved by showing that the optimal filter is best if the same filter is used for many scenes, but is outperformed by a filter adapted to a specific scene.

  14. Fermentation characteristics ofMegasphaera elsdeniiJ6 derived from pig feces on different lactate isomers

    Institute of Scientific and Technical Information of China (English)

    JIANG Xiao-lin; SU Yong; ZHU Wei-yun

    2016-01-01

    D-Lactate-utilizing bacteria play important roles in maintaining the balance of gut lactate; however, studies on gut D-lactate-uti-lizing bacteria have been limited. This study aimed to isolate and identify D-lactate-utilizing bacteria from pig gut using the Hungate rol-tube method, and to investigate their metabolic characteristicsin vitro. Six different anaerobes were isolated from pig feces, which were identiifed as related toBacteroides fragilis, Bacteroides acidifaciens,Veilonela denticariosi, Veilonela caviae,Bacteroides uniformis, andMegasphaera elsdenibased on the 16S rRNA gene sequences. Al strains had a signiifcant ability to utilize D-lactate, which was concluded afterin vitro fermentation with 25 mmol L–1 D-lactate as the primary carbon source. Of al 6 strains,M. elsdeniJ6 showed the highest efifciency of D-lactate utilization and produced a higher ratio of butyrate in total short chain fatty acids (SCFAs). Thus, thein vitro fermentation characteristics of this strain in D-, L-, and DL-lactate mixtures (D-lactate:L-lactate=1:1 or 1:2) were further studied. The results showed that M. elsdeni J6 preferred utilizing D-lactate, and produced more SCFA when using D-lactate as the primary carbon source. The ifndings suggest that the administration of D-lactate-utilizing bacteria such asM. elsdeni J6 may have a potential advantage in the aleviation of D-lactic acidosis in the animal gut.

  15. L- and D-lactate as biomarkers of arterial-induced intestinal ischemia

    DEFF Research Database (Denmark)

    Nielsen, Casper Hornskov; Mortensen, Frank V; Erlandsen, Erland J; Lindholt, Jes Sanddal

    2012-01-01

    Intestinal ischemia is difficult to diagnose, and search for new biomarkers has led to interest in D-lactate, which arises from bacterial fermentation in the gastrointestinal tract.......Intestinal ischemia is difficult to diagnose, and search for new biomarkers has led to interest in D-lactate, which arises from bacterial fermentation in the gastrointestinal tract....

  16. Umbilical cord blood lactate: a valuable tool in the assessment of fetal metabolic acidosis

    DEFF Research Database (Denmark)

    Gjerris, Anne Cathrine Roslev; Staer-Jensen, Jette; Jørgensen, Jan Stener;

    2008-01-01

    The aim of the present study was (1) to evaluate the relationship between umbilical cord arterial blood lactate and pH, standard base excess (SBE), and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of umbilical cord arterial blood lactate in predicting fetal asphyxia usi...

  17. Umbilical cord blood lactate: a valuable tool in the assessment of fetal metabolic acidosis

    DEFF Research Database (Denmark)

    Gjerris, A.C.; Staer-Jensen, J.; Jorgensen, J.S.;

    2008-01-01

    OBJECTIVE: The aim of the present study was (1) to evaluate the relationship between umbilical cord arterial blood lactate and pH, standard base excess (SBE), and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of umbilical cord arterial blood lactate in predicting fetal a...

  18. Scalp blood lactate for intra-partum assessment of fetal metabolic acidosis

    NARCIS (Netherlands)

    Heinis, A.M.; Spaanderman, M.E.A.; Gunnewiek, J.M.; Lotgering, F.K.

    2011-01-01

    Objective. To study to what extent the fetal scalp blood lactate concentration during labor correlates with fetal scalp pH and base deficit, and metabolic acidosis at birth, and to suggest lactate cut-off values to serve as indicators for either reassurance or immediate intervention. Design. A retro

  19. Excess post-hypoxic oxygen consumption is independent from lactate accumulation in two cyprinid fishes

    DEFF Research Database (Denmark)

    Genz, J.; Jyde, M.B.; Svendsen, Jon Christian;

    2013-01-01

    Carassius carassius responds to hypoxic conditions by conversion of lactate into ethanol, which is excreted over the gills. However, a closely related species, Cyprinus carpio, does not possess the ability to produce ethanol and would be expected to accumulate lactate during hypoxic exposure. Whi...

  20. Lactate concentrations in the rectal lumen in patients in early septic shock

    DEFF Research Database (Denmark)

    Ibsen, Michael; Tenhunen, J.; Wiis, J.; Waldau, T; Lauritsen, A.O.; Thornberg, K.; Joensen, H; Perner, A.

    2010-01-01

    Previously, we observed that rectal luminal lactate was higher in non-survivors compared with survivors of severe sepsis or septic shock persisting >24 h. The present study was initiated to further investigate this tentative association between rectal luminal lactate and mortality in a larger...... population of patients in early septic shock....

  1. Short communication: Best prediction of 305-day lactation yields with regional and seasonal effects

    Science.gov (United States)

    In the United States, lactation yields are calculated using best prediction (BP), a method in which test day (TD) data are compared to breed- and parity-specific herd lactation curves that do not account for differences among regions of the country or seasons of calving. This may result in biased es...

  2. Tin-containing silicates: Alkali salts improve methyl lactate yield from sugars

    DEFF Research Database (Denmark)

    Tolborg, Søren; Sádaba, Irantzu; Osmundsen, Christian Mårup;

    2015-01-01

    This study focuses on increasing the selectivity to methyl lactate from sugars using stannosilicates as heterogeneous catalyst. All group I ions are found to have a promoting effect on the resulting methyl lactate yield. Besides, the alkali ions can be added both during the preparation of the...

  3. Short communication: Projecting milk yield using best prediction and the MilkBot lactation model

    Science.gov (United States)

    The accuracy and precision of three lactation models was estimated by summarizing means and variability in projection error for next-test milk and actual 305-d milk yield (M305) for 50-day intervals in a large DHIA data set. Lactations were grouped by breed (Holstein, Jersey and crossbred) and parit...

  4. LLC-PK1 cells express Na+-lactate cotransport in apical membranes after confluency

    International Nuclear Information System (INIS)

    L-[3H]lactate uptake was characterized in LLC-PK1 cell apical membrane vesicles obtained by intensive culture on microcarrier beads. The apical membrane preparation technique involved MgCl2 precipitation. Na+-dependent L-[3H]lactate uptake was present only after confluency; its appearance paralleled the subcellular localization of aminopeptidase in apical membranes. L-[3H]lactate uptake was Na+-dependent and electrogenic. Only the Na+-dependent component of L[3H]lactate uptake was saturable with one family of independent carriers. The apparent affinity constant was 1.1 ± 0.25 mM and the apparent maximal velocity was 29 ± 3 nmol·mg-1·min-1. The Na+-lactate cotransport stoichiometry was 2 Na+ for 1 lactate. The specificity of the L-lactate transport system was compatible with that of the monocarboxylic acid pathway described previously brush-border membranes of kidney cortex and discrete from the tricarboxylic acid carrier, the D-glucose transporter, and the general pathway for anions. The LLC-PK1 cell line appears to be a useful tool for study of the regulation of L-lactate uptake and biosynthesis of the renal monocarboxylic acid transporter

  5. Energy metabolism and lactation performance of primiparous sows as affected by dietary fat and vitamin E.

    NARCIS (Netherlands)

    Babinszky, L.

    1992-01-01

    In this thesis different levels of dietary fat (37, 43, 75 and 125 g/kg DM, respectively) and vitamin E (from 14 to 151 mg α-tocopherol/kg diet) in the lactation diet, were studied for their effect on the energy metabolism, and lactation performance of primiparous sows. The effects of different leve

  6. Lactate and Energy Metabolism During Exercise in Patients With Blocked Glycogenolysis (McArdle Disease)

    DEFF Research Database (Denmark)

    Ørngreen, Mette Cathrine; Jeppesen, Tina Dysgaard; Taivassalo, Tanja; Hauerslev, Simon; Preisler, Nicolai; Heinicke, Katja; Haller, Ronald G; Vissing, John; van Hall, Gerrit

    2015-01-01

    CONTEXT: Patients with blocked muscle glycogen breakdown (McArdle disease) have severely reduced exercise capacity compared to healthy individuals and are not assumed to produce lactate during exercise. OBJECTIVES: The objectives were: 1) to quantify systemic and muscle lactate kinetics and oxida...

  7. Liver protein expression in dairy cows with high liver triglycerides in early lactation

    DEFF Research Database (Denmark)

    Sejersen, Henrik; Sørensen, Martin Tang; Larsen, Torben;

    2012-01-01

    the liver proteome between early lactation dairy cows with a low or high liver TG content. The liver proteome analysis indicated that a high liver TG content in early lactation dairy cows is associated with increased oxidation of saturated fatty acids, oxidative stress, and urea synthesis and...

  8. Consecutive daily measurements of luminal concentrations of lactate in the rectum in septic shock patients

    DEFF Research Database (Denmark)

    Ibsen, Michael; Wiis, Jørgen; Waldau, Tina; Perner, Anders

    2012-01-01

    In a recent study we found no difference in the concentrations of luminal lactate in the rectum between nonsurvivors and survivors in early septic shock (......In a recent study we found no difference in the concentrations of luminal lactate in the rectum between nonsurvivors and survivors in early septic shock (...

  9. Production of Ammonium Lactate by Fed-batch Fermentation of Rhizopus oryzae from Corncob Hydrolysate

    Institute of Scientific and Technical Information of China (English)

    BAI Dong-mei; LI Shi-zhong; LIN Fang-qian

    2004-01-01

    L- (+)-Lactic acid production from corncob hydrolysate as a cheap carbohydrate source by fed-batch fermentation of Rhizopus oryzae HZS6 was studied. After 96 h of fermentation in a 5 L fermentor, the final concentration of ammonium L-(+)-lactate, average productivity(based on initial xylose concentration) and max(+)-lactate was 98.8%.

  10. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

    DEFF Research Database (Denmark)

    Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja;

    2015-01-01

    We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes the ...

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

    KAUST Repository

    Yang, Jiangyan

    2014-07-28

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

  12. Pregnane × Receptor (PXR expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation

    Directory of Open Access Journals (Sweden)

    Lumbroso Serge

    2010-03-01

    Full Text Available Abstract Background Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11 is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane × Receptor (PXR, we hypothesized that PXR could play a key role in colon cancer cell response to irinotecan. Results PXR mRNA expression was quantified by RT-quantitative PCR in a panel of 14 colon tumor samples and their matched normal tissues. PXR expression was modulated in human colorectal cancer cells LS174T, SW480 and SW620 by transfection and siRNA strategies. Cellular response to irinotecan and its active metabolic SN38 was assessed by cell viability assays, HPLC metabolic profiles and mRNA quantification of PXR target genes. We showed that PXR was strongly expressed in colon tumor samples and displayed a great variability of expression. Expression of hPXR in human colorectal cancer cells led to a marked chemoresistance to the active metabolite SN38 correlated with PXR expression level. Metabolic profiles of SN38 showed a strong enhancement of SN38 glucuronidation to the inactive SN38G metabolite in PXR-expressing cells, correlated with an increase of UDPglucuronosyl transferases UGT1A1, UGT1A9 and UGT1A10 mRNAs. Inhibition of PXR expression by lentivirus-mediated shRNA, led to SN38 chemoresistance reversion concomitantly to a decrease of UGT1A1 expression and SN38 glucuronidation. Similarly, PXR mRNA expression levels correlated to UGT1A subfamily expression in human colon tumor biopsies

  13. Effects of dietary star anise (Illicium verum Hook f) supplementation during gestation and lactation on the performance of lactating multiparous sows and nursing piglets.

    Science.gov (United States)

    Wang, Gong Ying; Yang, ChongWu; Yang, Zaibin; Yang, Weiren; Jiang, Shuzhen; Zhang, Guiguo; Guo, Yixuan; Wei, Maolian

    2015-04-01

    Thirty-two sows were allocated to four treatments to evaluate the effect of dietary star anise (SA) supplementation during gestation and lactation on the lactational performance of sows. At 85 days of gestation, sows were randomly allotted to one of two diets supplemented with 0.5% SA or basal diet. After farrowing, sows were further allotted to one of two lactation diets supplemented with 0.5% SA or basal diet. On a weekly basis, body weight (BW) of sows and piglets was measured. Blood and milk samples were obtained from the sows and piglets. Number of days from weaning to estrus, milk yield and feed intake were also recorded. Weight gain of piglets from sows fed the SA-supplemented diet during lactation was greater between days 7 and 14, days 14 and 21 and the overall experimental period compared with control groups. Supplementation of SA during lactation improved weaning weight of piglets, milk yield and average daily feed intake (ADFI) of sows. The SA diet increased concentrations of insulin-like growth factor-1 (IGF-1) in ordinary milk and prolactin (PRL) in serum of sows. In conclusion, this study has indicated the beneficial effects of dietary SA addition in improving the lactation performance of sows. PMID:25438815

  14. A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    WEI Hai-bo; HU Jing; SHANG Li-hua; ZHANG Yun-yan; LU Fei-fei; WEI Min; YU Yan

    2012-01-01

    Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer (NSCLC) patients.To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC,we performed a meta-analysis to compare chemosensitivity to platinum with different ERCC1 C118T/MDR1 C3435T single-nucleotide polymorphism (SNP).Methods Relevant studies were identified by searching the PubMed,Embase,Cochrane,OVID,Springer,EBSCO and CNKI databases.Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy,an evaluated polymorphism of ERCC/MDR1 and overall response rate.We excluded duplicate publications,letters and review articles.The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment.Results A total of 11 studies were included in this meta-analysis.For studies evaluating ERCC1 C118T,test for heterogeneity was done (x2=13.41,P=0.1),and the odds ratio (OR) for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 (95% CI 1.09-2.06,P=-0.01).In four studies evaluating MDR1 polymorphism,test for heterogeneity was also done (x2=3.22,P=0.36),and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 (95% CI 1.44-3.68,P=0.0005).Conclusions The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 C118T and MDR1 C3435T SNP.In further perspective studies,the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.

  15. The effect of lactation length on greenhouse gas emissions from the national dairy herd.

    Science.gov (United States)

    Wall, E; Coffey, M P; Pollott, G E

    2012-11-01

    Many governments have signed up to greenhouse gas emission (GHGE) reduction programmes under their national climate change obligations. Recently, it has been suggested that the use of extended lactations in dairy herds could result in reduced GHGE. Dairy GHGE were modelled on a national basis and the model was used to compare emissions from lactations of three different lengths (305, 370 and 440 days), and a current 'base' scenario on the basis of maintaining current milk production levels. In addition to comparing GHGE from the average 'National Herd' under these scenarios, results were used to investigate how accounting for lactations of different lengths might alter the estimation of emissions calculated from the National Inventory methodology currently recommended by Intergovernmental Panel on Climate Change. Data for the three lactation length scenarios were derived from nationally recorded dairy performance information and used in the GHGE model. Long lactations required fewer milking cows and replacements to maintain current milk yield levels than short ones, but GHGEs were found to rise from 1214 t of CO2 equivalent (CE)/farm per year for lactations of 305 days to 1371 t CE/farm per year for 440-day lactations. This apparent anomaly can be explained by the less efficient milk production (kg milk produced per kg cow weight) found in later lactation, a more pronounced effect in longer lactations. The sensitivity of the model to changes in replacement rate, persistency and level of milk yield was investigated. Changes in the replacement rate from 25% to 20% and in persistency by −10% to +20% resulted in very small changes in GHGE. Differences in GHGE due to the level of milk yield were much more dramatic with animals in the top 10% for yield, producing about 25% less GHGE/year than the average animal. National Inventory results were investigated using a more realistic spread of lactation lengths than recommended for such calculations using emissions

  16. [Mercury in the hair of pregnant and lactating Chilean mothers].

    Science.gov (United States)

    Bruhn, C G; Rodríguez, A A; Barrios, C A; Jaramillo, V H; Gras, N T; Becerra, J; Núñez, E; Reyes, O C

    1995-11-01

    Mercury-containing industrial waste has been released into the coastal waters of the Eighth Region of Chile for around two decades. This study, carried out from 1991 to 1993, sought to measure mercury concentrations in the hair of pregnant and lactating women from villages near the coast and in the interior of the region in order to examine the relationship between the concentration of mercury and seafood consumption. The survey questionnaire used in 1991 to determine seafood consumption did not ask about the frequency of consumption of fish, shellfish, and algae but only whether the women who were pregnant or breast-feeding consumed a minimum of one fish-based meal per week. The questionnaire used in 1992 and 1993 asked about the daily and weekly consumption of seafood in general (fish, shellfish, and algae). Spectrophotometry was used to determine the total mercury concentration in samples of 100 mg of hair from 153 pregnant and lactating women in 11 fishing villages of the Eighth Region where seafood is regularly consumed. None of the women had occupational exposure to mercury. Total mercury concentration was also determined in hair samples from a control group composed of 26 pregnant and lactating women from Pinto and El Carmen, villages in the interior of the same region where seafood was rarely eaten. The arithmetic mean of the total mercury concentration in hair was 1.81 mg/kg of body weight for the study group (standard deviation [SD] 1.52) and 0.42 mg/kg for the control group (SD 0.15)--a statistically significant difference (P < 0.01). Pairwise comparisons also revealed statistically significant differences (P < 0.05) between the mean for the interior group and the means for the women in the nine villages closest to the sources of the pollution, but not between the mean for the interior group and those for women in the two villages at the extreme north and south of the study zone, who lived farthest from the contaminated waters. The total mercury

  17. Buffalo behavioural response to machine milking in early lactation

    Directory of Open Access Journals (Sweden)

    Elisabetta Canali

    2010-01-01

    Full Text Available Buffalo farming in Italy is traditionally oriented towards mozzarella cheese production and over the last decade it has been rapidly increased. As a result, intensive techniques and mechanisation of farm activities have been introduced. Those sudden changes in rearing techniques have aroused a general concern about buffaloes welfare and its possible consequences on products quality.Human-animal interactions are recognized to have an impact on productivity, behaviour and welfare, particularly in dairy farms, where the milking process involves a close interaction with a human handler. Focusing on the first month of lactation, this preliminary study aimed at evidencing buffalo behavioural responses to machine milking. Relationship between behaviour and oxytocin administrations, often performed to allow milk let down, has been also investigated. The experiment included 8 multiparous and 6 primiparous buffaloes, calving in the same period. Starting from the first entrance in the milking parlour, the animals were followed two days/ week during the morning milking for the first 5 weeks of lactation. Behaviour observation was performed following a “focal animal sampling” (continuous recording technique. Proportional frequencies of the following behaviours were calculated: kicking, stepping, defecating, urinating, vocalizing, pulling the teat cup off the teats. The exogenous oxytocin administration at milking was recorded. Pearson Chi-Square test was used to verify the presence of differences between primiparous and multiparous cows’ behaviour at milking. Cochran’s Q test was used to assess the variability of behaviour over time and a binomial regression was performed in order to verify the correlations between animal behaviours and the need to administer oxytocin. Considering lactation number, every behavioural pattern in primiparous cows, except for stepping, resulted to be more frequently performed (36.67% vs 24.36% for kicking; 5% vs 2

  18. Effects of Downregulation of Bcl - 2 Expression by Small Interfering RNA on Cell Growth and Chemosensitivity to Methotrexate in Human Hepatoma Cell Line Hep3B%siRNA介导的Bcl-2表达下调对肝癌细胞Hep3B的影响及对氨甲蝶呤化疗敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    黄维亮; 徐丹; 谢元林

    2012-01-01

    目的 构建靶向Bcl -2基因的siRNA表达质粒,观察其对肝癌细胞Hep3B的影响及对氨甲蝶呤(MTX)化疗敏感性的影响.方法 根据siRNA设计原则,设计并合成Bcl -2的siRNA序列,克隆到pRNAT- U6.1/Neo质粒U6启动子下游构建重组质粒;经序列分析确认质粒构建成功后,将重组质粒转染入人肝癌细胞Hep3B,通过RT- PCR、Western blot分析Bcl -2的表达,细胞生长实验分析其对肝癌细胞生长的影响及对MTX化疗敏感性的影响.结果 重组质粒pRNAT- U6.1/Neo- Bcl-2经过基因序列分析,siRNA片段成功插入,转染此质粒可使Bcl -2的翻译和蛋白表达水平一定程度的降低,并且可抑制Hep3B细胞的生长,增加其对MTX化疗的敏感性.结论 成功构建并筛选出靶向Bcl-2基因的siRNA表达载体,它能抑制肝癌细胞Hep3B的生长及增加其对MTX化疗的敏感性,为基因治疗肝癌提供了新策略和实验基础.%Objective To construct small interfering RNA (siRNA) expression plasmid to Bel -2 gene and observe its effects on cell growth and chemosensitivity to methotrexate (MTX) in human hepatoma cell line Hep3B. Methods Bel - 2 siRNA sequence was designed, synthesized and cloned into the downstream of U6 promoter of the pRNAT - U6.1/Neo plasmid to construct recombinant plasmid. After the successful construction was confirmed by sequence analysis, the recombinant plasmid was transfected into human hepatoma cell line Hep3B. The expression of Bel - 2 was analyzed by RT - PCR and Western blot. Its effects on the cell growth and chemosensitivity to MTX in Hep3B cell was detected by cell growth assay. Results Sequence analysis of the recombinant plasmid pRNAT - U6.1/Neo - Bel -2 confirmed that the siRNA fragments were successfully inserted into the plasmid. Transfection of the recombinant plasmid into Hep3B cell could reduce the translation and expression of Bel - 2 by a certain extent. It can also inhibit the growth of Hep3B and increase its sensitivity to

  19. Interstitial lactate levels in human skin at rest and during an oral glucose load

    DEFF Research Database (Denmark)

    Petersen, Lars Jelstrup

    1999-01-01

    In vitro data have suggested that the skin is a significant lactate source. The purpose of the present study was to measure lactate and glucose concentrations in intact human skin in vivo using the microdialysis technique. Microdialysis fibres of 216 microns were inserted intradermally and perfused...... at a rate of 3 microliters min-1. In the first experimental protocol, dialysis fibres were calibrated by the method of no net flux in eight subjects. Skin lactate concentrations of 2.48 +/- 0.17 mmol l-1 were significantly greater than lactate concentrations of 0.84 +/- 0.15 mmol l-1 in venous plasma...... (P < 0.01). Glucose concentrations in skin and venous plasma were similar (5.49 +/- 0.18 vs. 5.26 +/- 0.24 mmol l-1). In the second experimental protocol, changes in lactate and glucose levels were studied in 10 subjects after an oral glucose tolerance test (OGTT). After the OGTT, plasma glucose and...

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

    DEFF Research Database (Denmark)

    Zong, Geng; Grandjean, Philippe; Wang, Xiaobin;

    2016-01-01

    hemoglobin A1c >6.5%. Twenty-four POPs were measured in serum among subsamples of 668 to 1073 participants. RESULTS: Compared with women without lactation history, odds ratios (95% confidence intervals) of having diabetes among those with 1-2 and ≥3 lactation periods were 0.83(0.61, 1.13) and 0.63(0.44, 0......OBJECTIVE: Lactation may help curb diabetes risk and is also known as an excretion route for some environmental pollutants. We evaluated associations of lifetime lactation history with serum concentrations of persistent organic pollutants (POPs) in the National Health and Nutrition Examination...... Survey 1999-2006, and examined whether potentially diabetogenic POPs account for associations between lactation and diabetes. RESEARCH DESIGN AND METHODS: Among 4479 parous women, breastfeeding history was defined as the number of children breastfed ≥1 month. Diabetes was identified by self-report or...

  1. Cotransport of H+, lactate, and H2O in porcine retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Kiilgaard, Jens Folke; la Cour, Morten;

    2003-01-01

    The retinal pigment epithelium (RPE) of the eye transports water and lactate ions in the direction from retina to choroid. The water transport is important in maintenance of retinal adhesion and the transport of lactate ions serves to regulate the lactate levels and pH of the subretinal space. This...... placed in a perfusion chamber in which the solution facing the retinal membrane could be changed rapidly. Two types of experiments were performed: Changes in cell water volume were measured by self-quenching of the fluorescent dye Calcein, and changes in intracellular pH were measured ratiometrically...... using the fluorescent dye BCECF. In lactate-free solutions, mannitol addition to the retinal bath caused intracellular acidification and cell shrinkage, given by a single osmotic water permeability of 1.2+/-0.1 x 10(-4)cmsec(-1) (osmoll(-1))(-1). In solutions containing 50 mmoll(-1) lactate, however...

  2. Higher blood lactate concentration in Göttingen minipigs compared with domestic pigs

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen

    2016-01-01

    Measurements of blood lactate concentration is useful as a monitoring tool during anaesthesia of animals and people. Recently, blood lactate has been used to monitor anaesthetized pigs, but very little is known about variations in blood lactate concentrations in pigs. We therefore evaluate...... the effects of breed (domestic pigs vs. Göttingen minipigs), body weight (40 kg vs. 70 kg), type of anaesthesia (inhalation vs. infusion) and surgery (minor vs. major surgery) on blood lactate concentrations in pigs. Anaesthesia reports from 81 pigs are included. We find significantly higher blood lactate...... levels in minipigs anaesthetised with isofluorane (2.53 ± 1.10 mmol/l) compared to domestic pigs (0.68 ± 0.48 mmol/l) (P

  3. Thin-film amperometric multibiosensor for simultaneous determination of lactate and glucose in wine.

    Science.gov (United States)

    Shkotova, Lyudmyla V; Piechniakova, Nataliia Y; Kukla, Oleksandr L; Dzyadevych, Sergei V

    2016-04-15

    An amperometric multi-biosensor based on lactate and glucose oxidases has been developed for determination of lactate and glucose in wine. Gold thin-film amperometric electrodes were used as multi-transducers. Analytical characteristics of the multi-biosensor developed were studied. The minimum detectable concentration was 5×10(-6) mol/l for both glucose and lactate. High reproducibility and storage stability of the multi-biosensor are demonstrated in this paper. Lactate and glucose were determined in wine, and a good correlation was obtained with concentrations determined using high-performance liquid chromatography (correlation coefficient for glucose R(2)=0.998, for lactate R(2)=0.718). PMID:26617042

  4. Preliminary X-ray crystallographic analysis of a nitric oxide-inducible lactate dehydrogenase from Staphylococcus aureus

    International Nuclear Information System (INIS)

    A nitric oxide-inducible lactate dehydrogenase from S. aureus, Sa-LDH-1, has been cloned, expressed, purified and crystallized in space group C2, with unit-cell parameters a = 131.4, b = 74.4, c = 103.2 Å, β = 133.4°. Recent studies have indicated that Staphylococcus aureus can survive the nitrosative stress (caused by the radical nitric oxide; NO·) mounted by the immune system of the infected host. It does this by expressing a nitric oxide-inducible l-lactate dehydrogenase (Sa-LDH-1). Therefore, if efficient inhibitors of Sa-LDH-1 can be designed then Sa-LDH-1 could be a potential drug target against the pathogen S. aureus. For this purpose, the nitric acid-inducible LDH-1 from S. aureus COL strain has been cloned into the expression vector pET-28a(+) and the protein has been expressed, purified and crystallized. The Sa-LDH-1 crystal diffracted to 2.4 Å resolution at a home X-ray source and belonged to space group C2, with unit-cell parameters a = 131.4, b = 74.4, c = 103.2 Å, β = 133.4°

  5. Haematological and blood biochemical profile in lactating buffaloes in and around Parbhani city

    Directory of Open Access Journals (Sweden)

    S. D. Hagawane

    Full Text Available Forty buffaloes in early, mid and late lactation with a drop in a milk production were screened for haematological and blood biochemical profile. In early stage of lactation haemoglobin concentration showed lowered trend as compared to recorded means in other groups of lactating buffaloes.  The mean value of TLC in dry pregnant group of buffaloes was 10.05± 0.89 X 103 /cmm showed slightly higher trend than the normal healthy control group. The blood glucose was significantly higher in dry buffaloes (52.72±4.22 mg/dl than the early and late lactating buffaloes (48.23±3.44 mg/dl. During early stage of lactation the serum total protein values (8.36±0.47 g/dl was slightly elevated than the normal healthy control (8.00±0.57 g/dl. The urea nitrogen values differ significantly (P<0.05 amongst different groups of lactating buffaloes. The descending trend in the serum cholesterol concentration in dry pregnant buffaloes compared to lactating buffaloes was observed. There was drop in calcium level during early stage of lactation (8.19±0.83 mg/dl than the normal healthy buffaloes (11.21±0.19 mg/dl. As the stage of lactation progresses the serum calcium level increased. Serum magnesium concentration in various groups of buffaloes did not differ significantly. Early lactation showed highest susceptibility for ketosis and hypocalcaemia. The metabolic disorder associated with hypophosphatemia was significantly high in dry (advance pregnant buffaloes. [Vet World 2009; 2(12.000: 467-469

  6. Radioimmunological determination of chloramphenicol in the saliva of lactating cows

    International Nuclear Information System (INIS)

    In an effort to search for noninvasive methods suitable to monitor compliance with the ban of chloramphenicol (CAP) in milkproducing animals, the pharmacokinetic behavior of this drug in bovine saliva was investigated. As revealed by studies using a radioimmunological assay, CAP appears following its intracisternal (i.c.) or subcutaneous (s.c.) administration in the saliva of lactating cows. The level of sensitivity of the method (1.5 ng CAP per g saliva) was reached 14 and 18 days after i.c. and s.c. administration, respectively. At present, the question must remain open as to whether the concentration of CAP in the saliva can serve as a reliable indicator for the enforcement of the highest permissible level set at 1 ng CAP per g of milk by German regulations. (orig.)

  7. Feeding concentrate in early lactation based on rumination time

    DEFF Research Database (Denmark)

    Byskov, M.V.; Weisbjerg, Martin Riis; Markussen, B.;

    2015-01-01

    Precision feeding of dairy cows facilitates optimization of milk production. Accordingly, the objective was to study the effect on milk production when stepping up concentrate at 3 rates in early lactation according to individual daily rumination time (RT). Data was collected in 3 commercial dairy...... herds with Holstein cows, where daily RT was recorded by rumination sensors (Qwes HRTM). Cows were fed a partially mixed ration and concentrate at the milking robot. Concentrate was stepped up over the first 28 and 17 days in milk for primiparous and multiparous cows. Cows were assigned to either...... an experimental group (EXP) or a control group (CON) immediately after calving. In addition, all cows in the EXP and CON were assigned to either a high, medial or low rumination group according to their individual RT. Cows in the EXP assigned to the high (EH), medial (EM) or low (EL) rumination group were stepped...

  8. Lactate dehydrogenase assay for assessment of polycation cytotoxicity

    DEFF Research Database (Denmark)

    Parhamifar, Ladan; Andersen, Helene; Moghimi, Seyed Moien

    2013-01-01

    Cellular toxicity and/or cell death entail complex mechanisms that require detailed evaluation for proper characterization. A detailed mechanistic assessment of cytotoxicity is essential for design and construction of more effective polycations for nucleic acid delivery. A single toxicity assay...... cannot stand alone in determining the type and extent of damage or cell death mechanism. In this chapter we describe a lactate dehydrogenase (LDH) assay for high-throughput screening that can be used as a starting point for further detailed cytotoxicity determination. LDH release is considered an early...... event in necrosis but a late event in apoptosis. An accurate temporal assessment of the toxic responses is crucial as late apoptosis may convert into necrosis as well as in situations where cell death is initiated without any visible cell morphological changes or responses in assays measuring late...

  9. Circadian rhythm of lactate dehydrogenase in rat testis.

    Science.gov (United States)

    Vermouth, N T; Ponce, R H; Carriazo, C S; Blanco, A

    1984-01-01

    Activity of total lactate dehydrogenase (LDH) and of the isozyme X (LDH X or C4) have been determined at 2 hr intervals during 24 hr cycles in testis of adult rats maintained since birth in a photoperiod of 14 hr light: 10 hr dark. LDH X activity of epididymal sections (caput, corpus and cauda) from the same animals was also determined. Total LDH and LDH X activities in testis exhibited circadian rhythms with different timing. LDH X in the three portions of epididymis showed diurnal variations similar to those in testis. Rats subjected to constant light or constant dark presented marked modifications of LDH X profiles, indicating that the photoperiod plays a synchronizer role. While total soluble proteins did not show variations in testis of rats exposed to the photoperiod, a circadian rhythm was demonstrated in animals maintained in constant light or dark. PMID:6467917

  10. Fate of 14C-monocrotophos in lactating goats

    International Nuclear Information System (INIS)

    14C-monocrotophos was fed daily to two groups of lactating goats for five days at 5 and 10 mg per goat per day. The radioactivity in urine and faeces accounted for 50% and 7%, respectively, 24 hours after the first dose. About 25% of the radiocarbon was found in various organs. About 1-2% of the administered radiocarbon was secreted in milk. It was concluded that monocrotophos was rapidly eliminated through urine and faeces of teddy goats. 14C-residues in milk and urine were tentatively identified as monocrotophos, dimethylphosphate and N-desmethyl monocrotophos. The erythrocyte cholinesterase activity was reduced to 50% 24 hours after treatment, but no toxic symptoms were observed. (author)

  11. Fate and metabolism of radiolabelled monocrotophos in Egyptian lactating goats

    International Nuclear Information System (INIS)

    Lactating goats receiving two dermal applications of 14C-monocrotophos sprayings did not show any adverse effects related to pesticide applications. Under conditions simulating those of agricultural practice, residues were secreted in milk at a concentration of 0.13 ppm after the first day; declining to 0.02 ppm on the fifth day and to non-detectable levels on the 7th day. The hair and skin contained the highest concentration. In most edible organs, residue levels were generally low following the second application and declined rapidly after a 14-day withdrawal period to levels ranging from trace to 0.04 ppm. The insecticide inhibited both plasma erythrocyte cholinesterase activity significantly one day after application. Slow recovery could be observed during the 14-day withdrawal period. (author)

  12. Niclosamide residues in milk and organs of lactating goats

    International Nuclear Information System (INIS)

    14C-Niclosamide was administered to two groups of lactating goats at levels of 2ppm for five consecutive days and 10ppm as a single dose. Residues of the molluscicide in milk, if at all present, did not exceed 0.001 ppm at any time. About 50% of the administered activity was excreted in faeces, while 30% excreted through urine in animals surviving 6 days after withdrawal. The unchanged molluscicide is present only in relatively trace amounts. The highest residues in organs were found in the liver of both groups (0.01-0.04 ppm). From the results it could be concluded that absorbed niclosamide is completely metabolised and rapidly eliminated through urine, leaving little or no residues of the unchanged molluscicide. Little or no residues were detected in lean muscles and milk which are consumed by humans. There is no preferential deposition of the molluscicide or its metabolites in fat

  13. Lactate dehydrogenase (LDH isoenzymes patterns in ocular tumours

    Directory of Open Access Journals (Sweden)

    Singh Rajendra

    1991-01-01

    Full Text Available Estimation of lactate dehydrogenase (LDH isoenzymes in the serum and aqueous humor was carried out in 15 cases of benign ocular tumour, 15 cases of malignant tumor and 15 normal cases. Cases of both sexes aged between 1 year and 75 years were included. LDH, isoenzymes specially LDH4 and LDH5 are higher and LDH1 and LDH2 lower in sera of patients with malignant tumor specially retinoblastoma as compared to benign tumor cases and control cases. LDH isoenzymes in aqueous humor are significantly higher and show a characteristic pattern in retinoblastoma cases, the concentration was presumably too low in the control, malignant tumor other than retinoblastoma and benign tumor cases as its fractionation was not possible.

  14. An Herbal Galactagogue Mixture Increases Milk Production and Aquaporin Protein Expression in the Mammary Glands of Lactating Rats

    OpenAIRE

    Haibin Liu; Ying Hua; Hui Luo; Zhaojun Shen; Xuejiao Tao; Xueqiong Zhu

    2015-01-01

    Background. Herbal galactagogues have been increasingly used to treat postpartum hypogalactia. The mechanism of action of herbal galactagogues remains unclear. The purpose of this study was to investigate the effect of an herbal galactagogue mixture on milk production and aquaporin (AQP) expression in lactating rats. Methods. Thirty female Sprague Dawley rats were randomized into virgin, lactating + H2O, and lactating + galactagogue groups (n = 10 per group). Lactating rats were administered ...

  15. STUDY REGARDING THE INFLUENCE OF SEASON AND LACTATION ORDER ON MILK YIELD, MAJOR COMPONENTS AND SOMATIC CELL COUNT OF MILK

    OpenAIRE

    S. ACATINCĂI; ADELA MARCU; L.T. CZISZTER; SIMONA BAUL; ANDREEA FERENCZ; D. GĂVOJDEAN

    2013-01-01

    The effects of lactation order and season on the milk production, chemical compositionand somatic cell number during a normal lactation (305 days) were studied. Researcheswere carried out on Romanian Black and White cows from the Didactical StationTimişoara. Cows calved in autumn and finished their lactation by the end of the nextyear. Milk production increased progressively in the second and third lactation, thusfat, protein and lactose yields increased, too. During the warm season (April-Se...

  16. Short communication: Circulating and milk adiponectin change differently during energy deficiency at different stages of lactation in dairy cows

    OpenAIRE

    Singh, S.P.; Häussler, S.; Gross, Josef Johann; Schwarz, F.J.; Bruckmaier, Rupert; Sauerwein, H.

    2014-01-01

    Adiponectin, one of the most abundant adipokines in circulation, is known for its role in regulation of body metabolism. The aim of this study was to evaluate the effects of a negative energy balance (NEB) at 2 stages of lactation (lactational NEB at the onset of lactation and an induced NEB by feed restriction near 100 d of lactation) on circulating adiponectin concentrations. We also investigated the effect of feed restriction on adiponectin concentrations in milk and the relationships of b...

  17. Kinematical Analysis along Maximal Lactate Steady State Swimming Intensity

    Science.gov (United States)

    Figueiredo, Pedro; Nazario, Rafael; Sousa, Marisa; Pelarigo, Jailton Gregório; Vilas-Boas, João Paulo; Fernandes, Ricardo

    2014-01-01

    The purpose of this study was to conduct a kinematical analysis during swimming at the intensity corresponding to maximal lactate steady state (MLSS). Thirteen long distance swimmers performed, in different days, an intermittent incremental protocol of n x 200 m until exhaustion and two to four 30-min submaximal constant speed bouts to determine the MLSS. The video analysis, using APAS System (Ariel Dynamics Inc., USA), allowed determining the following relevant swimming determinants (in five moments of the 30-min test: 0, 25, 50, 75, and 100%): stroke rate, stroke length, trunk incline, intracyclic velocity variation, propelling efficiency, index of coordination and the time allotted to propulsion per distance unit. An ANOVA for repeated measures was used to compare the parameters mean values along each moment of analysis. Stoke rate tended to increase and stroke length to decrease along the test; a tendency to decrease was also found for intracyclic velocity variation and propelling efficiency whereas the index of coordination and the propulsive impulse remained stable during the MLSS test. It can be concluded that the MLSS is not only an intensity to maintain without a significant increase of blood lactate concentration, but a concomitant stability for some biomechanical parameters exists (after an initial adaptation). However, efficiency indicators seem to be more sensitive to changes occurring during swimming at this threshold intensity. Key Points In MLSS swimming intensity, stability of the stroke length and stroke frequency occurs after an initial adaptation. Efficiency indicators seem to be more sensitive to possible changes occurring through time at MLSS intensity. MLSS is a useful and practical swimming intensity to be maintained for a long period of time, but some constraints in technique can occur. PMID:25177189

  18. IBFAN Africa training initiatives: code implementation and lactation management.

    Science.gov (United States)

    Mbuli, A

    1994-01-01

    As part of an ongoing effort to halt the decline of breast feeding rates in Africa, 35 representatives of 12 different African countries met in Mangochi, Malawi, in February 1994. The Code of Marketing of Breastmilk Substitutes was scrutinized. National codes were drafted based on the "Model Law" of the IBFAN Code Documentation Centre (ICDC), Penang. Mechanisms of implementation, specific to each country, were developed. Strategies for the promotion, protection, and support of breast feeding, which is very important to child survival in Africa, were discussed. The training course was organized by ICDC, in conjunction with IBFAN Africa, and with the support of the United Nations Children's Fund (UNICEF) and the World Health Organization (WHO). Countries in eastern, central, and southern Africa were invited to send participants, who included professors, pediatricians, nutritionists, MCH personnel, nurses, and lawyers. IBFAN Africa has also been conducting lactation management workshops for a number of years in African countries. 26 health personnel (pediatricians, nutritionists, senior nursing personnel, and MCH workers), representing 7 countries in the southern African region, attended a training of trainers lactation management workshop in Swaziland in August, 1993 with the support of their UNICEF country offices. The workshop included lectures, working sessions, discussions, and slide and video presentations. Topics covered included national nutrition statuses, the importance of breast feeding, the anatomy and physiology of breast feeding, breast feeding problems, the International Code of Marketing, counseling skills, and training methods. The field trip to a training course covering primary health care that was run by the Traditional Healers Organization (THO) in Swaziland was of particular interest because of the strong traditional medicine sector in many African countries. IBFAN Africa encourages use of community workers (traditional healers, Rural Health

  19. Comparison of maximal lactate steady state with V2, V4, individual anaerobic threshold and lactate minimum speed in horses

    Directory of Open Access Journals (Sweden)

    O.A.B. Soares

    2014-02-01

    Full Text Available The anaerobic threshold is a physiologic event studied in various species. There are various methods for its assessment, recognized in the human and equine exercise physiology literature, several of these involving the relationship between blood lactate concentration (LAC and exercise load, measured in a standardized exercise test. The aim of this study was to compare four of these methods: V2, V4, individual anaerobic threshold (IAT and lactate minimum speed (LMS with the method recognized as the gold standard for the assessment of anaerobic threshold, maximal lactate steady-state (MLSS. The five tests were carried out in thirteen trained Arabian horses, in which velocities and associated LAC could be measured. The mean velocities and the LAC associated with the anaerobic threshold for the five methods were respectively: V2 = 9.67±0.54; V4 = 10.98±0.47; V IAT = 9.81±0.72; V LMS = 7.50±0.57 and V MLSS = 6.14±0.45m.s-1 and LAC IAT = 2.17±0.93; LAC LMS = 1.17±0.62 and LAC MLSS = 0.84±0.21mmol.L-1. None of the velocities were statistically equivalent to V MLSS (P<0.05. V2, V4 and V LMS showed a good correlation with V MLSS , respectively: r = 0.74; r = 0.78 and r = 0.83, and V IAT did not significantly correlate with V MLSS. Concordance between the protocols was relatively poor, i.e., 3.28±1.00, 4.84±0.30 and 1.43±0.32m.s-1 in terms of bias and 95% agreement limits for V2, V4 and LMS methods when compared to MLSS. Only LAC LMS did not differ statistically from LAC MLSS. Various authors have reported the possibility of the assessment of anaerobic threshold using rapid protocols such as V4 and LMS for humans and horses. This study corroborates the use of these tests, but reveals that adjustments in the protocols are necessary to obtain a better concordance between the tests and the MLSS.

  20. Changes to food intake and nutrition of female red-tailed phascogales (Phascogale calura) during late lactation.

    Science.gov (United States)

    Stannard, Hayley J; Old, Julie M

    2015-11-01

    Reproduction and especially lactation are nutritionally costly for mammals. Maternal access to adequate and optimal nutrients is essential for fecundity, survival of offspring, and offspring growth rates. In eutherian species energy requirements during lactation can be heavily dependent on litter size and the body mass of the female. In marsupials litter size does not appear to affect nutritional requirements during lactation; however, studies of marsupial nutritional requirements during lactation are rare. Marsupials are distinct from eutherians as they give birth to young at a much more underdeveloped state and the majority of their investment into the growth of their offspring occurs postnatally. Nutritional requirements of adult female red-tailed phascogales (Phascogale calura) were measured to determine the differences between those lactating and not lactating. On average females that were lactating had maintenance energy requirements of 1728 ± 195 kJ kg(-0.75) d(-1), double that of non-lactating animals. There was no significant correlation between energy requirements and litter size among lactating female phascogales. Apparent absorption of macronutrients did not differ between lactating and non-lactating individuals. The study has shown that food needs to be increased by at least double during late lactation. Litter size appears to have no influence on maternal nutrient requirements when food is available ad libitum and offspring in smaller litters grow faster than those in larger litters. PMID:26260432

  1. Intracerebral trafficking of lactate in vivo during stress, exercise, electroconvulsive shock and ischemia as studied with microdialysis

    NARCIS (Netherlands)

    Korf, J

    1996-01-01

    We developed techniques to continuously monitor lactate in the living rat ('lactography') based on microdialysis and on-line enzymatic conversion of lactate in the dialysate using either continuous flow technologies or enzyme reactors. Ln vivo lactate was monitored during a single electroconvulsive

  2. Posterior Cingulate Lactate as a Metabolic Biomarker in Amnestic Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Kurt E. Weaver

    2015-01-01

    Full Text Available Mitochondrial dysfunction represents a central factor within the pathogenesis of the Alzheimer’s disease (AD spectrum. We hypothesized that in vivo measurements of lactate (lac, a by-product of glycolysis, would correlate with functional impairment and measures of brain health in a cohort of 15 amnestic mild cognitive impairment (aMCI individuals. Lac was quantified from the precuneus/posterior cingulate (PPC using 2-dimensional J-resolved magnetic resonance spectroscopy (MRS. Additionally, standard behavioral and imaging markers of aMCI disease progression were acquired. PPC lac was negatively correlated with performance on the Wechsler logical memory tests and on the minimental state examination even after accounting for gray matter, cerebral spinal fluid volume, and age. No such relationships were observed between lac and performance on nonmemory tests. Significant negative relationships were also noted between PPC lac and hippocampal volume and PPC functional connectivity. Together, these results reveal that aMCI individuals with a greater disease progression have increased concentrations of PPC lac. Because lac is upregulated as a compensatory response to mitochondrial impairment, we propose that J-resolved MRS of lac is a noninvasive, surrogate biomarker of impaired metabolic function and would provide a useful means of tracking mitochondrial function during therapeutic trials targeting brain metabolism.

  3. Characterization of films based on chitosan lactate and its blends with oxidized starch and gelatin.

    Science.gov (United States)

    Kowalczyk, Dariusz; Kordowska-Wiater, Monika; Nowak, Jakub; Baraniak, Barbara

    2015-01-01

    Minimal inhibitory concentration (MIC) of chitosan lactate (CHL) was tested against bacteria and phytopathogenic fungi. Then, the structural, physicochemical and antimicrobial properties of films based on CHL, oxidized potato starch (OPS), and gelatin (GEL) were investigated. With the exception of Rhizopus nigricans, CHL was effective against the target organisms. Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) were more sensitive to CHL than Gram-negative bacteria (Pectobacterium carotovorum and Escherichia coli). Cryo-SEM images showed total miscibility between the polymers in the blends and the ATR-FTIR spectra revealed that there was an interaction among the polymeric components. Pure CHL films displayed the highest moisture content (25.51%), water vapor permeability (48.78gmmm(-2)d(-1)kPa(-1)), and the lowest tensile and puncture strength (2.00 and 1.45MPa, respectively) among the studied films. CHL50/GEL50 films had lower permeability, higher mechanical strength, and lower elongation compared to CHL50/OPS50 films. Films obtained from CHL and CHL50/GEL50 were completely water-soluble and did not show sorbitol recrystallization. The incorporation of CHL into OPS and GEL films did not affect their transparency and improved UV-blocking capacity. CHL films were the only ones that exhibited antibacterial efficiency. Antifungal activities against Alternaria alternata and Monilinia fructigena were detected for CHL and CHL50/GEL50 films. PMID:25841370

  4. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  5. Effect of sex-sorted sperm dosage on conception rates in Holstein heifers and lactating cows.

    Science.gov (United States)

    DeJarnette, J M; Nebel, R L; Marshall, C E; Moreno, J F; McCleary, C R; Lenz, R W

    2008-05-01

    Ejaculates were collected by artificial vagina from 3 Holstein sires and sorted to 90% purity for X-chromosome-bearing spermatozoa (range 88 to 93%) using flow cytometry. Sorted sperm were diluted to 2.1, 3.5, or 5.0 x 10(6) sperm per dose in an egg yolk (20%), Tris, glycerol (7%) extender. Collections were repeated until >600 straws per sperm dose per sire were obtained. Each sperm dose was loaded into color-coded 0.25-mL French straws, with alternate colors used to define treatments across sires. Within sires, straws were packaged at 9 per cane (3 of each color) and strategically allocated to 75 Holstein herds with targets for 50% use in heifers and 50% in lactating cows. Straw color was recorded in the on-farm record-keeping system at the time of insemination. Data were analyzed separately for cows and heifers. Among heifers, a total of 2,125 usable records were retrieved from 51 herds (238 +/- 5.5 services/ sperm dose per sire, range: 218 to 263). Conception rates in heifers were influenced by the sire x sperm dosage interaction. Within sire A, conception rates of heifers were greater for the 5 x 10(6) (59.5%) than for the 2.1 x 10(6) (46.4%) sperm dose and intermediate for the 3.5 x 10(6) sperm dose (52.2%). However, across sires, sperm dosage had no effect on heifer conception rates (46.7, 51.2, and 52.5% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). Among cows, a total of 2,369 services were retrieved from 56 herds (263 +/- 8.8 services/sperm dose per sire, range: 233 to 303). Conception rates of cows (29.4%) were not affected by sire or sperm dosage (27.0, 29.1, and 30.3% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). In conclusion, these data indicate that an increased sperm dosage may enhance virgin heifer conception rates for some (but not all) sires, whereas neither sire nor sexed-sperm dosage affected conception rates of lactating cows. Additional studies of sexed-sperm dosage across a larger sampling of bulls are

  6. Skeletal muscle lactate overproduction during metformin intoxication: An animal study with reverse microdialysis.

    Science.gov (United States)

    Protti, Alessandro; Properzi, Paolo; Magnoni, Sandra; Santini, Alessandro; Langer, Thomas; Guenzani, Silvia; Ferrero, Stefano; Bassani, Giulia; Stocchetti, Nino; Gattinoni, Luciano

    2016-07-25

    Lactic acidosis during metformin intoxication is classically mainly attributed to diminished lactate clearance through liver gluconeogenesis. Here we studied 6 healthy, sedated and mechanically ventilated pigs to clarify whether high dose of metformin also increases skeletal muscle lactate production. Each animal had two microdialysis catheters inserted in gluteus muscles, one per side. One catheter was infused with saline (control) while the other one was infused with metformin diluted in saline (1M), both at a rate of 0.3μl/min. Dialysate lactate concentration and lactate-to-pyruvate ratio, a marker of the balance between anaerobic glycolysis and aerobic (mitochondrial) metabolism, were measured every 3h, for 12h. Continuous infusion of metformin caused a progressive rise in dialysate lactate level (p=0.007) and lactate-to-pyruvate ratio (p<0.001) compared to that of saline, as for mitochondrial "poisoning". These findings suggest that skeletal muscle lactate overproduction contributes to the development of metformin-induced lactic acidosis. PMID:27178268

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

    Science.gov (United States)

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

    2012-06-01

    Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ∼80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels. PMID:22453629

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

    Science.gov (United States)

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

    2015-08-28

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

  9. Genetic and phenotypic parameters of productivity traits on the first three lactations in Gyr cattle herds

    Directory of Open Access Journals (Sweden)

    Albuquerque Maria do Socorro Maués

    1999-01-01

    Full Text Available Records of Gyr cows selected for milk production were obtained from the National Gyr Dairy Cattle Breeding Program (Embrapa/CNPGL and analyzed, in order to estimate genetic parameters for the first three lactations and to verify the effects of some environmental factors on milk production from 1979 to 1994. Genetic parameters were estimated by REML with an animal model and a group of fixed effects that included classes of herd, year, season and age at calving. Milk production means and standard deviations were 2,183 kg, 707 kg; 2,682 kg, 762 kg and 2,638 kg, 851 kg, for first, second, and third lactations, respectively. Heritability estimates were 0.20, 0.12, and 0.19 for first, second, and third lactations, respectively, and repeatability was 0.44. Genetic correlation estimates were: 0.68 between first and second lactations, 0.84 between first and third lactations and 1.0 between second and third lactations. Results confirm other research for specialized dairy breeds and firmly suggest that even in breeds of Indian origin the best time to make selection decisions is during the first lactation.

  10. Blood dynamics of mercury and selenium in northern elephant seals during the lactation period

    Energy Technology Data Exchange (ETDEWEB)

    Habran, Sarah, E-mail: S.Habran@ulg.ac.be [Laboratory for Oceanology - MARE Center B6c, University of Liege, 4000 Liege (Belgium); Debier, Cathy, E-mail: cathy.debier@uclouvain.be [Unite de Biochimie de la Nutrition, Institut des Sciences de la vie, Universite catholique de Louvain, Place Croix du Sud 2/8, 1348 Louvain-la-Neuve (Belgium); Crocker, Daniel E., E-mail: crocker@sonoma.edu [Department of Biology, Sonoma State University, Rohnert Park, CA 94928 (United States); Houser, Dorian S., E-mail: biomimetica@cox.net [BIOMIMETICA, Santee, CA 92071 (United States); Das, Krishna, E-mail: Krishna.Das@ulg.ac.be [Laboratory for Oceanology - MARE Center B6c, University of Liege, 4000 Liege (Belgium)

    2011-10-15

    The effects of reproduction and maternal investment (i.e., milk transfer) on trace element levels remain poorly understood in marine mammals. We examined the blood dynamics of mercury (Hg) and selenium (Se) during lactation in the northern elephant seal (Mirounga angustirostris), a top predator from the North Pacific Ocean. Total Hg and Se levels were measured in whole blood and milk of 10 mother-pup pairs on days 5 and 22 of lactation. Both Hg and Se were transferred to offspring through the milk. Results suggested that the maternal transfer of Se was prominent during lactation, whereas the Hg transfer was larger during gestation. The lactation period affected Hg and Se levels in the blood of elephant seal mothers and pups. Physiological processes and their relationship to body condition should be considered carefully when interpreting trace element levels in the framework of biomonitoring. - Graphical abstract: Display Omitted Highlights: > The lactation period affects Hg and Se blood levels in elephant seal mothers and pups. > The Hg maternal transfer to offspring is larger during gestation. > The Se maternal transfer to offspring is prominent during lactation via the milk. - Blood levels of total Hg and Se are modified during the 4-week lactating period in northern elephant seals.

  11. Reliability and Accuracy of Six Hand-Held Blood Lactate Analysers

    Directory of Open Access Journals (Sweden)

    Jacinta M. Bonaventura, Ken Sharpe, Emma Knight, Kate L. Fuller, Rebecca K. Tanner, Christopher J. Gore

    2015-03-01

    Full Text Available The reliability and accuracy of five portable blood lactate (BLa analysers (Lactate Pro, Lactate Pro2, Lactate Scout+, Xpress™, and Edge and one handheld point-of-care analyser (i-STAT were compared to a criterion (Radiometer ABL90. Two devices of each brand of analyser were assessed using 22 x 6 mL blood samples taken from five subjects at rest and during exercise who generated lactate ranging ~1-23 mM. Each sample was measured simultaneously ~6 times on each device. Reliability was assessed as the within-sample standard deviation (wsSD of the six replicates; accuracy as the bias compared with the ABL90; and overall error (the root mean squared error (√MSE was calculated as the square root of (wsSD2 and bias2. The √MSE indicated that both the Edge and Xpress had low total error (~0-2 mM for lactate concentrations 15 mM. In all cases, bias (negative was the major contribution to the √MSE. In conclusion, in a clinical setting where BLa is generally <15 mM the Edge and Xpress devices are relevant, but for athlete testing where peak BLa is important for training prescription the Edge and Lactate Pro2 are preferred.

  12. Blood dynamics of mercury and selenium in northern elephant seals during the lactation period

    International Nuclear Information System (INIS)

    The effects of reproduction and maternal investment (i.e., milk transfer) on trace element levels remain poorly understood in marine mammals. We examined the blood dynamics of mercury (Hg) and selenium (Se) during lactation in the northern elephant seal (Mirounga angustirostris), a top predator from the North Pacific Ocean. Total Hg and Se levels were measured in whole blood and milk of 10 mother-pup pairs on days 5 and 22 of lactation. Both Hg and Se were transferred to offspring through the milk. Results suggested that the maternal transfer of Se was prominent during lactation, whereas the Hg transfer was larger during gestation. The lactation period affected Hg and Se levels in the blood of elephant seal mothers and pups. Physiological processes and their relationship to body condition should be considered carefully when interpreting trace element levels in the framework of biomonitoring. - Graphical abstract: Display Omitted Highlights: → The lactation period affects Hg and Se blood levels in elephant seal mothers and pups. → The Hg maternal transfer to offspring is larger during gestation. → The Se maternal transfer to offspring is prominent during lactation via the milk. - Blood levels of total Hg and Se are modified during the 4-week lactating period in northern elephant seals.

  13. Characterization of lactate dehydrogenase enzyme in seminal plasma of Japanese quail (Coturnix coturnix japonica).

    Science.gov (United States)

    Singh, R P; Sastry, K V H; Pandey, N K; Shit, N; Agrawal, R; Singh, K B; Mohan, Jag; Saxena, V K; Moudgal, R P

    2011-02-01

    Lactate dehydrogenase enzyme present in quail seminal plasma has been characterized. Polyacrylamide gel electrophoresis and subsequently with LDH specific staining of seminal plasma revealed a single isozyme in quail semen. Studies on substrate inhibition, pH for optimum activity and inhibitor (urea) indicated the isozyme present in the quail semen has catalytic properties like LDH-1 viz. H-type. Furthermore, unlike other mammalian species, electrophoretic and kinetic investigations did not support the existence of semen specific LDH-X isozyme in quail semen. The effect of exogenous lactate and pyruvate on sperm metabolic activity was also studied. The addition of 1 mM lactate or pyruvate to quail semen increased sperm metabolic activity. Our results suggested that both pyruvate and lactate could be used by quail spermatozoa to maintain their basic functions. Since the H-type isozyme is important for conversion of lactate to pyruvate under anaerobic conditions it was postulated that exogenous lactate being converted into pyruvate via LDH present in semen may be used by sperm mitochondria to generate ATP. During conversion of lactate to pyruvate NADH is being generated that may be useful for maintaining sperm mitochondrial membrane potential. PMID:21074838

  14. Inhalation of Shin-I essential oil enhances lactate clearance in treadmill exercise

    Institute of Scientific and Technical Information of China (English)

    Hsuan-Ying Chen; Ming-Fu Wang; Jun-Ying Lin; Ying-Chieh Tsai; Fu-Chou Cheng

    2014-01-01

    Objective: To evaluate the effect of Shin-I essential oil inhalation on blood lactate changes in rats subjected to treadmill exercise.Methods: Adult male Sprague Dawley rats (n=12) were randomly divided into the control or the Shin-I group. Rats were subjected to a treadmill exercise program (15 m/min for 30 min). After exercise, rats were exposed to 200 µL of water or Shin-I essential oil, respectively, using a nebulizer for 180 min during the recovery period. Blood samples were collected every 15 min. Blood glucose and lactate concentrations were determined in a CMA 600 analyzer.Results: The basal glucose and lactate levels were no significantly different between two groups. After exercise, glucose levels were slightly increased to about 110%-120% of the basal level in both groups. Lactate levels of both groups reached to 110%-140% of basal levels during exercise. In the recovery period, lactate levels further increased to 180% of the basal level and were maintained at a plateau in the control group. However, lactate levels gradually decreased to 60%-65% of the basal level in the Shin-I group. Lactate clearance was significantly enhanced after Shin-I essential oil inhalation.Conclusions: Our results provide evidence that Shin-I essential oil inhalation may accelerate recovery after exercise in rats.

  15. Test-retest reliability of second lactate turnpoint using two different criteria in competitive cyclists.

    Science.gov (United States)

    Hoefelmann, Camila Peter; Diefenthaeler, Fernando; Costa, Vitor Pereira; de Lucas, Ricardo Dantas; Shambrook, Philip; Guglielmo, Luiz Guilherme Antonacci

    2015-01-01

    The aim of this study was to determine the relative and absolute reliability of second lactate turnpoint using fixed and individual blood lactate method in competitive cyclists. Twenty-eight male, well-trained cyclists (30.2 ± 10.1 years, 72.0 ± 7.4 kg, 177.3 ± 4.7 cm) were recruited to participate in this study. Cyclists completed two incremental cycling tests to exhaustion over a period of 7 days to determine their peak power output, maximal oxygen uptake, maximal heart rate, maximal blood lactate concentration and two lactate turnpoint criteria. The fixed blood concentration criterion (3.5 mM) and an individual criterion were assessed by a lactate-power curve, considering power output, heart rate and oxygen uptake. The main finding of this study was that both lactate turnpoint criteria showed identical low within-subject variation for power output (2.8% coefficient of variation). High values for test-retest correlations ranging from r = 0.70 to r = 0.94 were found for all variables in both threshold criteria. In conclusion, the individual and fixed method to determine the second lactate turnpoint showed similar high absolute and relative reliability in competitive cyclists. PMID:25135192

  16. Analysis of raw goat milk microbiota: impact of stage of lactation and lysozyme on microbial diversity.

    Science.gov (United States)

    McInnis, Elizabeth A; Kalanetra, Karen M; Mills, David A; Maga, Elizabeth A

    2015-04-01

    To protect infants from infection, human milk contains high levels of the enzyme lysozyme, unlike the milk of dairy animals. We have genetically engineered goats to express human lysozyme (hLZ milk) in their milk at 68% the amount found in human milk to help extend this protection. This study looked at the effect of hLZ on bacteria in raw milk over time. As the microbial diversity of goats' milk has yet to be investigated in depth using next-generation sequencing (NGS) technologies, we applied NGS and clone library sequencing (CLS) to determine the microbiota of raw goat milk (WT milk) and hLZ milk at early, mid and late lactation. Overall, in WT milk, the bacterial populations in milk at early and mid lactation were similar to each other with a shift occurring at late lactation. Both methods found Proteobacteria as the dominant bacteria at early and mid lactation, while Actinobacteria surged at late lactation. These changes were related to decreases in Pseudomonas and increases in Micrococcus. The bacterial populations in hLZ milk were similar to WT milk at early and mid lactation with the only significant differences occurring at late lactation with the elevation of Bacillaceae, Alicyclobacillaceae, Clostridiaceae and Halomonadaceae. PMID:25475275

  17. Effects of lactation on the border zone formation in the female mastomys (Praomys coucha) adrenal cortex.

    Science.gov (United States)

    Tanaka, S; Nozaki, M; Fujioka, T; Matsuzawa, A

    1991-01-01

    Adrenocortical zonation and especially border zone formation were investigated in relation to reproduction in female mastomys of the wild-colored inbred strain (MWC). The adrenal weight and the whole thickness of the cortex remained relatively constant throughout pregnancy, delivery and lactation. During pregnancy the zona fasciculata increased, but the z. reticularis decreased in thickness. The border zone between the z. fasciculata and the z. reticularis thickened 2-fold during pregnancy and further 2-fold during lactation. This zone was composed of vacuolated cell layers and nodules in females with a normal reproductive career. In young virgins this zone was barely identified by the presence of a few highly vacuolated cells. These cells became prominent during pregnancy and lactation. During lactation two types of cell aggregations, distinguishable by their stainability, vacuolation, localization and cellularity, appeared in the thickened border zone. The nodules first appeared within the z. reticularis after lactation. Neither thickening of both border zone and z. fasciculata nor formation of nodules occurred when lactation was interrupted after delivery. Thus, the changes in the female MWC adrenal, above all the appearance of nodules, seemed to be more dependent upon lactation than pregnancy. The vacuolated cells and the nodules might originate from the thickened z. fasciculata and the thinned z. reticularis, respectively, by the specific metamorphosis of the cells adjacent to the border zone. Their fusion and induction of fibrous tissue migration may result in the wider border zone. PMID:1755290

  18. ENVIRONMENTAL FACTORS AFFECTING MILK YIELD AND LACTATION LENGTH IN SAHIWAL CATTLE

    Directory of Open Access Journals (Sweden)

    I.R. Bajwa, M. S. Khan, M. A. Khan1 and K. Z. Gondal2

    2004-01-01

    Full Text Available Weekly milk yield records on 661 Sahiwal cows calving during 1990-2000 at the Livestock Experiment Station Bahadurnagar, Okara were used to study how milk yield and lactation length were affected by different environmental factors. Lactation milk yield averaged 1475  651 kg for an average lactation length of 248  67 days (n=2039. Year of calving and season of calving both significantly (P<0.01 affected milk yield and lactation length. Age within parity also significantly affected the two traits. Winter calvers produced more milk (1546 kg as compared to summer calvers (1362 kg. Milk yield gradually increased towards 4th and 5th parity and declined thereafter, while highest lactation length (263 days was observed for first parity cows. The repeatability estimates for lactation length and milk yield were 0.326  0.025 and 0.46 ± 0.041, respectively. When milk yield was adjusted for lactation length by different procedures, all the variation in milk yield due to lactation length could not be removed (weeks in milk effect remained significant. The environmental factors such as year, season of calving (and their interaction and age at calving still affected milk yield significantly (P<0.01. The extent of season of calving effect however, reduced. Phenotypic trend for milk yield over the last 10 years was negative while lactation length had a positive trend which needs further exploration. The environmental factors under study were suggested to be incorporated in the models when variation in milk yield needed partitioning into genetic and non-genetic components.

  19. Social stress during lactation, depressed maternal care, and neuropeptidergic gene expression.

    Science.gov (United States)

    Murgatroyd, Christopher A; Taliefar, Mohammad; Bradburn, Steven; Carini, Lindsay M; Babb, Jessica A; Nephew, Benjamin C

    2015-10-01

    Depression and anxiety can be severely detrimental to the health of both the affected woman and her offspring. In a rodent model of postpartum depression and anxiety, chronic social stress exposure during lactation induces deficits in maternal care and increases anxiety. Here, we extend previous findings by expanding the behavioral analyses, assessing lactation, and examining several neural systems within amygdalar and hypothalamic regions involved in the control of the stress response and expression of maternal care that may be mediating the behavioral changes in stressed dams. Compared with control dams, those exposed to chronic social stress beginning on day 2 of lactation show impaired maternal care and lactation and increased maternal anxiety on day 9 of lactation. Saccharin-based anhedonia and maternal aggression were increased and lactation was also impaired on day 16 of lactation. These behavioral changes were correlated with a decrease in oxytocin mRNA expression in the medial amygdala, and increases in the expressions of corticotrophin-releasing hormone mRNA in the central nucleus of the amygdala, glucocorticoid receptor mRNA in the paraventricular nucleus, and orexin 2 receptor mRNA in the supraoptic nucleus of stressed compared with control dams. The increase in glucocorticoid receptor mRNA in the paraventricular nucleus was negatively correlated with methylation of a CpG site in the promoter region. In conclusion, the data support the hypothesis that social stress during lactation can have profound effects on maternal care, lactation, and anxiety, and that these behavioral effects are mediated by central changes in stress and maternally relevant neuropeptide systems. PMID:26061353

  20. Effect of Wheelchair Running on Recovery of Blood Lactate and Physical Performance after High-Intensity Intermittent Exercise – An Experimental Trial

    Directory of Open Access Journals (Sweden)

    Karthikeyan G

    2012-04-01

    Full Text Available Background and Purpose: Repetitive sprint sport players perform high intensity exercise only for a small percentage of a total game and such periods are often instrumental in determining the eventual outcome. Recovery is a key factor for performance, and constant lack of recovery or insufficient recovery turns into overtraining which is detrimental in achieving peak performance. The purpose was to find out the effect of wheelchair running on the physical performance recovery after high-intensity intermittent exercise. Method: Ten sportsmen having the age range from 20 to 29, VO2max Ranges from 60.51 to 64.29 were randomly divided into experimental and control groups. After filling pre-participation questionnaire and 30-min of supine rest, Blood lactate and the field tests for the measurement of static balance, power, speed and agility were applied. The subjects were made to run in the treadmill and to increase the intensity to reach the Target Heart Rate (THR. After 1-min the subjects were given rest for 15-s and after that they started exercise again and thus the subjects completed several bouts of such exercises until exhaustion followed by either Passive rest or wheelchair running for the duration of 10 minutes. Parameters were measures after completed the exercise bout and after the recovery. Results: After the recovery in experimental group significant improvement found only in blood lactate (p<0.01 and no significant changes found in other parameters while in control group no significant changes found in all parameters. There was no significant difference found in all the parameters including blood lactate between the groups. Conclusion: Both wheelchair running and passive recovery are same in the efficiency of blood lactate removal and restoration of physical performance following intense intermittent exercise.

  1. Genetic Parameters for Dry Matter Intake at Different Lactation Stages among Primiparous Holstein, Jersey and Red Cows

    DEFF Research Database (Denmark)

    Li, Bingjie; Løvendahl, Peter; Fikse, W F; Lassen, Jan; Patel, M; Berglund, B

    This study evaluated the genetic variation in Dry Matter Intake (DMI) at 6 lactation stages over the first 24 lactation weeks in a population including Holstein, Jersey and Red cows. In total, 830 primiparous cows from Sweden and Denmark were included. Genetic parameters were estimated based on a...... between DMI across lactation stages ranged from 0.46 to 0.99. The weakest genetic correlation occurred between early and mid lactation, indicating a different genetic basis for DMI along lactation. A potential difference in genetic variation was found between Jersey and the other two breeds, requiring a...

  2. Variation of the transfer coefficient for radiocaesium transport to sheep's milk during a complete lactation period

    International Nuclear Information System (INIS)

    The variation with time in the transfer coefficient for radiocaesium transport to sheep's milk was measured during an entire lactation period. One hundred and forty ewes were used. The animals were segregated into groups of six ewes and throughout their lactation period, every week one of the groups was given a diet of ground wheat, contaminated with radiocaesium from the Chernobyl accident. The results showed an increase of radiocaesium activity concentration in the milk by a factor of three, over the 21-week lactation period. A significant correlation was found between transfer coefficients for radiocaesium and average daily milk yield. (Author)

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

    International Nuclear Information System (INIS)

    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 hemispheric blood flow

  4. Lactate threshold predicting time-trial performance: impact of heat and acclimation

    OpenAIRE

    Lorenzo, Santiago; Minson, Christopher T.; Babb, Tony G.; Halliwill, John R.

    2011-01-01

    The relationship between exercise performance and lactate and ventilatory thresholds under two distinct environmental conditions is unknown. We examined the relationships between six lactate threshold methods (blood- and ventilation-based) and exercise performance in cyclists in hot and cool environments. Twelve cyclists performed a lactate threshold test, a maximal O2 uptake (V̇o2max) test, and a 1-h time trial in hot (38°C) and cool (13°C) conditions, before and after heat acclimation. Eigh...

  5. Flavocytochrome b 2 -Based Enzymatic Method of L-Lactate Assay in Food Products

    OpenAIRE

    Oleh Smutok; Maria Karkovska; Halyna Smutok; Mykhailo Gonchar

    2013-01-01

    L-lactate, a key metabolite of the anaerobic glycolytic pathway, plays an important role as a biomarker in medicine, in the nutritional sector and food quality control. For these reasons, there is a need for very specific, sensitive, and simple analytical methods for the accurate L-lactate measuring. A new highly selective enzymatic method for L-lactate determination based on the use of flavocytochrome b 2 (EC 1.1.2.3; FC b 2) isolated from the recombinant strain of the yeast Hansenula polymo...

  6. DUSP1 is a novel target for enhancing pancreatic cancer cell sensitivity to gemcitabine.

    Directory of Open Access Journals (Sweden)

    Fang Liu

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is a deadly cancer with a poor prognosis that is characterized by excessive mitogenic pathway activation and marked chemoresistance to a broad spectrum of chemotherapeutic drugs. Dual specificity protein phosphatase 1 (DUSP1 is a key negative regulator of mitogen activated protein kinases (MAPKs. Yet, DUSP1 is overexpressed in pancreatic cancer cells (PCCs in PDAC where it paradoxically enhances colony formation in soft agar and promotes in vivo tumorigenicity. However, it is not known whether DUSP1 overexpression contributes to PDAC chemoresistance. Using BxPC3 and COLO-357 human PCCs, we show that gemcitabine activates c-JUN N-terminal kinase (JNK and p38 mitogen activated protein kinase (p38 MAPK, key kinases in two major stress-activated signaling pathways. Gemcitabine-induced JNK and p38 MAPK activation mediates increased apoptosis, but also transcriptionally upregulates DUSP1, as evidenced by increased DUSP1 mRNA levels and RNA polymerase II loading at DUSP1 gene body. Conversely, shRNA-mediated inhibition of DUSP1 enhances JNK and p38 MAPK activation and gemcitabine chemosensitivity. Using doxycycline-inducible knockdown of DUSP1 in established orthotopic pancreatic tumors, we found that combining gemcitabine with DUSP1 inhibition improves animal survival, attenuates angiogenesis, and enhances apoptotic cell death, as compared with gemcitabine alone. Taken together, these results suggest that gemcitabine-mediated upregulation of DUSP1 contributes to a negative feedback loop that attenuates its beneficial actions on stress pathways and apoptosis, raising the possibility that targeting DUSP1 in PDAC may have the advantage of enhancing gemcitabine chemosensitivity while suppressing angiogenesis.

  7. Lactational transfer of mercury and polychlorinated biphenyls in polar bears.

    Science.gov (United States)

    Knott, Katrina K; Boyd, Daryle; Ylitalo, Gina M; O'Hara, Todd M

    2012-07-01

    We examined concentrations of total mercury (tHg, inorganic and methylated forms) and polychlorinated biphenyls (PCBs) in blood and milk from free-ranging Southern Beaufort-Chukchi Sea polar bears (Ursus maritimus) to assess maternal transfer of contaminants during lactation and the potential health risk to nursing young. Concentrations of contaminants in the blood of dependent and juvenile animals (ages 1-5 years) ranged from 35.9 to 52.2 μg kg(-1) ww for tHg and 13.9 to 52.2 μg kg(-1) ww (3255.81-11067.79 μg kg(-1) lw) for ΣPCB(7)s, similar to those of adult females, but greater than adult males. Contaminant concentrations in milk ranged from 5.7 to 71.8 μg tHg kg(-1)ww and 160 to 690 μg ΣPCB(11)s kg(-1) ww (547-5190 μg kg(-1) lw). The daily intake levels for tHg by milk consumption estimated for dependent young were below the tolerable daily intake level (TDIL) of tHg established for adult humans. Although the daily intake levels of PCBs through milk consumption for cubs of the year exceeded the TDIL thresholds, calculated dioxin equivalents for PCBs in milk were below adverse physiological thresholds for aquatic mammals. Relatively high concentrations of non-dioxin like PCBs in polar bear milk and blood could impact endocrine function of Southern Beaufort-Chukchi Sea polar bears, but this is uncertain. Transfer of contaminants during mid to late lactation likely limits bioaccumulation of dietary contaminants in female polar bears during spring. As polar bears respond to changes in their arctic sea ice habitat, the adverse health impacts associated with nutritional stress may be exacerbated by tHg and PCBs exposure, especially in ecologically and toxicologically sensitive polar bear cohorts such as reproductive females and young. PMID:22464860

  8. Drugs reverting multidrug resistance (chemosensitizers)

    Energy Technology Data Exchange (ETDEWEB)

    Gualtieri, F. [Florence Univ. (Italy). Dip. di Scienze Farmaceutiche

    1996-12-01

    Drug resistance is a phenomenon that frequently impairs proper treatment of cancer. Multidrug resistance (MDR) is a particular case of acquired drug resistance, resulting from overexpression of a protein (P-170) that functions as a pump, clearing cells from the chemotherapic. The P-170 protein functions can be inhibited by a variety of lipophilic drugs containing a hydrophilic nitrogen, protonated at physiological pH. A considerable effort is underway to identify new drugs able to reverse MDR. Few of these molecules are already undergoing clinical trials.

  9. The 'lactate paradox', evidence for a transient change in the course of acclimatization to severe hypoxia in lowlanders

    DEFF Research Database (Denmark)

    Lundby, C; Saltin, B; Van Hall, Gerrit

    2000-01-01

    The metabolic response to exercise at high altitude is different from that at sea level, depending on the altitude, the rate of ascent and duration of acclimatization. One apparent metabolic difference that was described in the 1930s is the phenomenon referred to as the 'lactate paradox'. Acute...... exposure to hypoxia results in higher blood lactate accumulation at submaximal workloads compared with sea level, but peak blood lactate remain the same. Following continued exposure to hypoxia or altitude, blood lactate accumulation at submaximal work and peak blood lactate levels are paradoxically...... reduced compared with those at sea level. It has recently been shown, however, that, if the exposure to altitude is sufficiently long, blood lactate responses return to those seen at sea level or during acute hypoxia. Thus, to evaluate the 'lactate paradox' phenomenon in relation to time spent at altitude...

  10. Daily intake of lactating crossbred cows grazing elephant grass rotationally

    Directory of Open Access Journals (Sweden)

    Aroeira Luiz Januário Magalhães

    2001-01-01

    Full Text Available The goal of this trial was to estimate the total dry matter (TDMI and daily pasture dry matter intakes (PDMI by lactating crossbred Holstein - Zebu cows grazing elephant grass (Pennisetum purpureum Schum. paddocks submitted to different rest periods. Three groups of 24 cows were used during two years. The paddocks were grazed during three days at the stocking rate of 4.5 cows/ha. Treatments consisted of resting periods of 30 days without concentrate and resting periods of 30, 37.5 and 45 days with 2 kg/cow/day of 20.6% crude protein concentrate. From July to October, pasture was supplemented with chopped sugarcane plus 1% urea. Total daily dry matter intake was estimated using the extrusa in vitro dry matter digestibility and the fecal output with chromium oxide. Regardless of the treatment the estimated average TDMI was 2.7, 2.9 and 2.9±0.03% and the mean PDMI was 1.9, 2.1 and 2.1±0.03% of body weight in the first, second and third grazing day, respectively (P<0.05. Only during the summer pasture quality was the same whichever the grazing day. Sugarcane effectively replaced grazing pasture, mainly in the first day when pasture dry matter intake was lowest.

  11. Fate of 14C-deltamethrin in lactating dairy cows

    International Nuclear Information System (INIS)

    Fate and residues of radiocarbon (14C) labelled (gem-dimethyl or benzyl) deltamethrin were determined in lactating cows after oral administration for three consecutive days and slaughtering the animals 24 hr after the last dose. Orally administered deltamethrin (10 mg/kg of body weight) appeared to be poorly absorbed, but the insecticide which was absorbed was extensively metabolized and excreted in the bile and urine with very little accumulation in major edible tissues. Approximately 36-43% of the total administered radiocarbon was eliminated in feces mostly as deltamethrin within 24 hr after the last dose. Only 4-6% of the administered 14C was eliminated in urine; and 0.42-1.62% was secreted in the milk. Radiocarbon secreted into milk was higher for the gem-dimethyl portion (0.69 μg/g) than from the benzyl moiety (0.36 μg/g); deltamethrin was the major product in milk (0.1-0.14 μg/g). Radiocarbon residues in tissues were low (<0.1 μg/g), except liver and kidney (1.28-3.19 μg/g), abdominal and subcutaneous fats (0.28-0.62 μg/g). (author)

  12. Effect of housing system on behavioural activity of lactating buffaloes

    Directory of Open Access Journals (Sweden)

    F. Grasso

    2010-04-01

    Full Text Available In order to verify the effect of a pool on behaviour and milk yield, eighty-eight lactating buffalo cows equally allocated to two treatments were used. Group WP was provided with a concrete pool of 208 m2, 36 m2/ head + 10 m2 of outdoor and indoor space allowance, respectively, whereas group NP only received 10 m2. Less animals from group WP were observed idling (P<0.05 compared to buffaloes from group NP, whereas subjects provided with a pool were more often involved in investigative activities (locomotion and exploration than cows without access to it (P< 0.01. A higher number of social interactions (sniffing and nuzzling and allogrooming were observed in group WP than in group NP (P< 0.01 and P< 0.05, respectively. The WP buffalo cows exhibited a higher yield of milk than NP subject (P< 0.05, whereas no differences between the two groups were observed for protein and fat contents. The provision of a pool can have beneficial effects on behaviour and milk production of buffaloes.

  13. Cloning and Polymorphisms of Yak Lactate Dehydrogenase b Gene

    Directory of Open Access Journals (Sweden)

    Yaou Xu

    2013-06-01

    Full Text Available The main objective of this work was to study the unique polymorphisms of the lactate dehydrogenase-1 (LDH1 gene in yak (Bos grunniens. Native polyacrylamide gel electrophoresis revealed three phenotypes of LDH1 (a tetramer of H subunit in yak heart and longissimus muscle extracts. The corresponding gene, ldhb, encoding H subunits of three LDH1 phenotypes was obtained by RT-PCR. A total of six nucleotide differences were detected in yak ldhb compared with that of cattle, of which five mutations cause amino acid substitutions. Sequence analysis shows that the G896A and C689A, mutations of ldhb gene, result in alterations of differently charged amino acids, and create the three phenotypes (F, M, and S of yak LDH1. Molecular modeling of the H subunit of LDH indicates that the substituted amino acids are not located within NAD+ or substrate binding sites. PCR-RFLP examination of G896A mutation demonstrated that most LDH1-F samples are actually heterozygote at this site. These results help to elucidate the molecular basis and genetic characteristic of the three unique LDH1 phenotypes in yak.

  14. Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New

    Science.gov (United States)

    Faloppi, Luca; Bianconi, Maristella; Memeo, Riccardo; Casadei Gardini, Andrea; Giampieri, Riccardo; Bittoni, Alessandro; Andrikou, Kalliopi; Del Prete, Michela; Cascinu, Stefano; Scartozzi, Mario

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80–90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease. PMID:27314036

  15. Expression of Plasmodium falciparum lactate dehydrogenase in Escherichia coli.

    Science.gov (United States)

    Bzik, D J; Fox, B A; Gonyer, K

    1993-05-01

    A Plasmodium falciparum gene is described which encodes lactate dehydrogenase activity (P. falciparum LDH). The P. falciparum LDH gene contains no introns and is present in a single copy on chromosome 13. P. falciparum LDH was expressed in all asexual blood stages as a 1.6-kb mRNA. The predicted 316 amino acid protein coding region of P. falciparum LDH was inserted into the prokaryotic expression vector pKK223-3 and a 33-kDa protein having LDH activity was synthesized in Escherichia coli. P. falciparum LDH primary structure displays high amino acid similarity (50-57%) to vertebrate and bacterial LDH, but lacks the amino terminal extension observed in all vertebrate LDH. The majority of amino acid residues implicated in substrate and coenzyme binding and catalysis of other LDH are well conserved in P. falciparum LDH. However, several notable differences in amino acid composition were observed. P. falciparum LDH contained several distinctive single amino acid insertions and deletions compared to other LDH enzymes, and most remarkably, it contained a novel insertion of 5 amino acids within the conserved mobile loop region near arginine residue 109, a residue which is known to make contact with pyruvate in the ternary complex of other LDH. These results suggest that novel features of P. falciparum LDH primary structure may be correlated with previously characterized and distinctive kinetic, biochemical, immunochemical, and electrophoretic properties of P. falciparum LDH. PMID:8515777

  16. Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Castonguay, Zachary; Auger, Christopher; Thomas, Sean C.; Chahma, M’hamed; Appanna, Vasu D., E-mail: vappanna@laurentian.ca

    2014-11-07

    Highlights: • Nuclear LDH is up-regulated under oxidative stress. • SIRT1 is co-immunoprecipitated bound to nuclear LDH. • Nuclear LDH is involved in histone deacetylation and epigenetics. - Abstract: It is becoming increasingly apparent that the nucleus harbors metabolic enzymes that affect genetic transforming events. Here, we describe a nuclear isoform of lactate dehydrogenase (nLDH) and its ability to orchestrate histone deacetylation by controlling the availability of nicotinamide adenine dinucleotide (NAD{sup +}), a key ingredient of the sirtuin-1 (SIRT1) deacetylase system. There was an increase in the expression of nLDH concomitant with the presence of hydrogen peroxide (H{sub 2}O{sub 2}) in the culture medium. Under oxidative stress, the NAD{sup +} generated by nLDH resulted in the enhanced deacetylation of histones compared to the control hepatocytes despite no discernable change in the levels of SIRT1. There appeared to be an intimate association between nLDH and SIRT1 as these two enzymes co-immunoprecipitated. The ability of nLDH to regulate epigenetic modifications by manipulating NAD{sup +} reveals an intricate link between metabolism and the processing of genetic information.

  17. Patterns of radioiodine uptake by the lactating breast

    Energy Technology Data Exchange (ETDEWEB)

    Bakheet, S.M. (Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)); Hammami, M.M. (Dept. of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia))

    1994-07-01

    Breast uptake of radioiodine, if not suspected, may be misinterpreted as thyroid cancer metastasis to the lung. To characterize the patterns of radioiodine breast uptake, we retrospectively studied 20 radioiodine scans that were performed within 1 week of cessation of breast feeding. Four patterns of uptake were identified: ''full'', ''focal'', ''crescent'' and ''irregular''. The uptake was asymmetric in 60% (left>right in 45%, right>left in 15%), symmetric in 25% and unilateral in 15% of cases. A characteristic full bilateral uptake was present in 40% of cases. In three cases with the irregular pattern, caused in part by external contamination with radioactive milk, the uptake closely mimicked lung metastases. Delayed images, obtained in one case, showed an apparent radioiodine shift from the breast to the thyroid, suggesting that the presence of breast uptake can modulate radioiodine uptake by thyroid tissue. In a case of unilateral breast uptake, a history of mastitis was obtained, which to our knowledge has not been previously reported. Breast uptake of radioiodine may take several scintigraphic patterns that are not always characteristic of the lactating breast and may affect the apparent extent of thyroid remnant/metastasis. (orig.)

  18. Patterns of radioiodine uptake by the lactating breast.

    Science.gov (United States)

    Bakheet, S M; Hammami, M M

    1994-07-01

    Breast uptake of radioiodine, if not suspected, may be misinterpreted as thyroid cancer metastasis to the lung. To characterize the patterns of radioiodine breast uptake, we retrospectively studied 20 radioiodine scans that were performed within 1 week of cessation of breast feeding. Four patterns of uptake were identified: "full", "focal", "crescent" and "irregular". The uptake was asymmetric in 60% (left > right in 45%, right > left in 15%), symmetric in 25% and unilateral in 15% of cases. A characteristic full bilateral uptake was present in 40% of cases. In three cases with the irregular pattern, caused in part by external contamination with radioactive milk, the uptake closely mimicked lung metastases. Delayed images, obtained in one case, showed an apparent radioiodine shift from the breast to the thyroid, suggesting that the presence of breast uptake can modulate radioiodine uptake by thyroid tissue. In a case of unilateral breast uptake, a history of mastitis was obtained, which to our knowledge has not been previously reported. Breast uptake of radioiodine may take several scintigraphic patterns that are not always characteristic of the lactating breast and may affect the apparent extent of thyroid remnant/metastasis. PMID:7957345

  19. Fate of 14C-carbofuran in lactating goats

    International Nuclear Information System (INIS)

    Radiocarbon labeled carbofuran was administered orally to lactating goats at 0.03 mg/kg (single dose), 0.5 and 1.0 mg/kg/day for 7 days, and at 5.0 ppm in the diet (2 kg feed intake/day basis) for 15 days. Radioactive residues were rapidly excreted in the urine after treatment. The major residue identified in urine of the treated goats was carbofuran phenol, a non-toxic metabolite. Only about 1% of the doses was eliminated in the feces of the treated goats. Residues of (14C)carbofuran were secreted into milk, but these residues were in all cases very low. Radioactive residue occurred in tissues at low levels, with patterns as follows: omental fat>liver>subcutaneous fat>kidney>brain>heart>biceps femoris>longissimus dorsi. The residue stored in fat was identified as carbofuran. The liver contained hydroxy carbofuran and one unidentified metabolite but no carbofuran. The other tissues contained only phenolic metabolites. These studies strongly indicate that proper carbofuran use in rice in the Philippines will present no risks to goats that consume treated crop residues, or to humans who consume meat or milk from exposed animals. (author)

  20. Leptophos residues in milk and meat of lactating goats

    International Nuclear Information System (INIS)

    14C-phenyl leptophos was administered to lactating goats at dietary levels of 5 and 10 ppm for seven consecutive days. Leptophos residues in milk were found to be 0.10 - 0.42 ppm during the intoxication period. However, these residues declined to 0.06 - 0.08 ppm after a withdrawal period of seven days. The milk residues consisted of lipophilic (57%) and hydrophilic (39%) compounds and 14C-protein-bound activity (4%). The lipophilic component was mainly leptophos. The hydrophilic products were identified as O-methyl phenyl phosphonic and O-methyl phenyl phosphonothioic acids. Leptophos concentration in the meat was found to be 0.30 - 0.40 ppm. Omental and subcutaneous fat contained much higher residues (up to 5.9 ppm), predominantly as leptophos. The liver, being the site of major metabolic activity, contained as high as 15.0 ppm of 14C-residues. Urinary 14C-metabolites included phenylphosphonic, O-methyl phenyl phosphonic and 0-methyl phenyl phosphonothioic acids and two unknown products. (author)

  1. Serum organochlorine levels and history of lactation in Egypt

    International Nuclear Information System (INIS)

    We conducted a study in Egypt to assess the determinants of organochlorine serum levels among premenopausal women and the risk of premenopausal breast cancer for women with high organochlorine serum levels. We included 69 breast cancer patients and 53 controls consisting of visitors to the hospitals of the cancer patients. We found low levels of dichlorodiphenyldichloroethylene (DDE), total dichlorodiphenyltrichloroethane, and β-hexacholorhexane (β-HCH) in most subjects. Mean DDE levels were 12.7±20.3 ppb for cases and 16.6±30.1 ppb for controls (P=0.60); β-HCH levels were 2.1±3.8 ppb for patients and 2.1±3.9 ppb for controls (P=0.71). Interestingly, subjects with low levels had breast fed their children for an average period of 18 months. Women with no lactation history had much higher organochlorine levels than women who breast fed (P=0.002 for DDE). Younger age, older age at first childbirth, and shorter duration of breast feeding were significant predictors of higher levels of serum DDE levels. Younger age, older age at first childbirth, and higher body mass index were significant predictors of higher β-HCH levels. This study suggests that organochlorine serum levels in Egyptian women are quite low, but indicates an effect of breast feeding in eliminating organochlorines, which would imply exposure to children. Organochlorine serum level was not a risk factor of breast cancer in this population

  2. SERUM VALUES OF ALKALINE PHOSPHATASE AND LACTATE DEHYDROGENASE IN OSTEOSARCOMA

    Science.gov (United States)

    ZUMÁRRAGA, JUAN PABLO; BAPTISTA, ANDRÉ MATHIAS; ROSA, LUIS PABLO DE LA; CAIERO, MARCELO TADEU; CAMARGO, OLAVO PIRES DE

    2016-01-01

    ABSTRACT Objective: To study the relationship between the pre and post chemotherapy (CT) serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) found in specimens after the pre surgical CT in patients with osteosarcoma. Methods: Series of cases with retrospective evaluation of patients diagnosed with osteosarcoma. Participants were divided into two groups according to serum values of both enzymes. The values of AP and LDH were obtained before and after preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens of each patient was also included. Results: One hundred and thirty seven medical records were included from 1990 to 2013. Both the AP as LDH decreased in the patients studied, being the higher in pre CT than post CT. The average LHD decrease was 795.12U/L and AP decrease was 437.40 U/L. The average TN was 34.10 %. There was no statistically significant correlation between the serums values and the percentage of tumoral necrosis. Conclusion: The serum levels values of AP and LDH are not good predictors for the chemotherapy-induced necrosis in patients with osteosarcoma. Level of Evidence IV, Case Series. PMID:27217815

  3. Invited review: Cessation of lactation: Effects on animal welfare.

    Science.gov (United States)

    Zobel, G; Weary, D M; Leslie, K E; von Keyserlingk, M A G

    2015-12-01

    The forced cessation of milk production, or dry-off, is a routine management practice in dairy cattle, sheep, and goats. This practice initiates a dry period, during which the animal is not milked. Milking begins again after parturition. Most of the literature on the dry period has focused on how various drying-off strategies affect milk production and disease; little work to date has addressed how dry-off affects the overall welfare of the dairy animal. The first aim of this review was to present an overview of the importance of dry-off and how it is commonly achieved. Our review shows that much scientific progress has been made in improving health status between lactations. The second aim was to identify important gaps in the literature, of which 2 key research disparities have been identified. We find that much of the work to date has focused on cattle and very little research has examined dry-off in dairy sheep and goats. We also find a lack of research addressing how common dry-off methodologies affect animal welfare on more than just a biological level, regardless of species. PMID:26409963

  4. Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes

    International Nuclear Information System (INIS)

    Highlights: • Nuclear LDH is up-regulated under oxidative stress. • SIRT1 is co-immunoprecipitated bound to nuclear LDH. • Nuclear LDH is involved in histone deacetylation and epigenetics. - Abstract: It is becoming increasingly apparent that the nucleus harbors metabolic enzymes that affect genetic transforming events. Here, we describe a nuclear isoform of lactate dehydrogenase (nLDH) and its ability to orchestrate histone deacetylation by controlling the availability of nicotinamide adenine dinucleotide (NAD+), a key ingredient of the sirtuin-1 (SIRT1) deacetylase system. There was an increase in the expression of nLDH concomitant with the presence of hydrogen peroxide (H2O2) in the culture medium. Under oxidative stress, the NAD+ generated by nLDH resulted in the enhanced deacetylation of histones compared to the control hepatocytes despite no discernable change in the levels of SIRT1. There appeared to be an intimate association between nLDH and SIRT1 as these two enzymes co-immunoprecipitated. The ability of nLDH to regulate epigenetic modifications by manipulating NAD+ reveals an intricate link between metabolism and the processing of genetic information

  5. Patterns of radioiodine uptake by the lactating breast

    International Nuclear Information System (INIS)

    Breast uptake of radioiodine, if not suspected, may be misinterpreted as thyroid cancer metastasis to the lung. To characterize the patterns of radioiodine breast uptake, we retrospectively studied 20 radioiodine scans that were performed within 1 week of cessation of breast feeding. Four patterns of uptake were identified: ''full'', ''focal'', ''crescent'' and ''irregular''. The uptake was asymmetric in 60% (left>right in 45%, right>left in 15%), symmetric in 25% and unilateral in 15% of cases. A characteristic full bilateral uptake was present in 40% of cases. In three cases with the irregular pattern, caused in part by external contamination with radioactive milk, the uptake closely mimicked lung metastases. Delayed images, obtained in one case, showed an apparent radioiodine shift from the breast to the thyroid, suggesting that the presence of breast uptake can modulate radioiodine uptake by thyroid tissue. In a case of unilateral breast uptake, a history of mastitis was obtained, which to our knowledge has not been previously reported. Breast uptake of radioiodine may take several scintigraphic patterns that are not always characteristic of the lactating breast and may affect the apparent extent of thyroid remnant/metastasis. (orig.)

  6. Niclosamide residues in milk and tissues of lactating goats

    International Nuclear Information System (INIS)

    Radiocarbon labeled niclosamide was orally administered to two groups of lactating goats at levels equivalent to about 2 ppm in drinking water for five consecutive days, and at levels equivalent to about 10 ppm in drinking water (1-day basis) as a single dose. Residues of the molluscicide in milk did not exceed 0.001 ppm at any time. About 50% of the administered radioactivity was eliminated in faeces, while about 30% was excreted through urine in treated animals within 6 days after final dosing. TLC analysis revealed the presence of two unidentified niclosamide metabolites. The unchanged molluscicide was present only in trace amounts. Highest radiocarbon residues in tissues of the treated goats occurred in the liver (0.01-0.04 ppm niclosamide equivalent). From these data, it was concluded that absorbed niclosamide is almost completely metabolized and rapidly eliminated through urine of goats. Little or no residues were detected in lean muscles and milk which are consumed by humans. There was no significant deposition of the molluscicide or its metabolites in fat. (author)

  7. Methodological approach to the first and second lactate threshold in incremental cardiopulmonary exercise testing.

    Science.gov (United States)

    Binder, Ronald K; Wonisch, Manfred; Corra, Ugo; Cohen-Solal, Alain; Vanhees, Luc; Saner, Hugo; Schmid, Jean-Paul

    2008-12-01

    Determination of an 'anaerobic threshold' plays an important role in the appreciation of an incremental cardiopulmonary exercise test and describes prominent changes of blood lactate accumulation with increasing workload. Two lactate thresholds are discerned during cardiopulmonary exercise testing and used for physical fitness estimation or training prescription. A multitude of different terms are, however, found in the literature describing the two thresholds. Furthermore, the term 'anaerobic threshold' is synonymously used for both, the 'first' and the 'second' lactate threshold, bearing a great potential of confusion. The aim of this review is therefore to order terms, present threshold concepts, and describe methods for lactate threshold determination using a three-phase model with reference to the historical and physiological background to facilitate the practical application of the term 'anaerobic threshold'. PMID:19050438

  8. Determination of degradation products of squalamine lactate using LC/MS.

    Science.gov (United States)

    Li, Cong-Jun; Kari, U Prasad; Noecker, Lincoln A; Jones, Stephen R; Sabo, Andrew M; McCormick, Timothy J; Johnston, Sean M

    2003-04-24

    Heat, acid and base stress methods were applied to study the stability of squalamine lactate. Liquid chromatography coupled with mass spectrometry was used to analyze the degraded samples and tentative structural identifications were assigned based on their molecular weight measurements, reactivity and MS/MS fragmentation. Solid squalamine lactate generated a new amide, namely lactyl squalamide, when heated to 80 degrees C. Chemical structure for this new compound has been established by NMR and MS data interpretation and confirmed by direct comparison between the degradant and the synthesized compound. Squalamine lactate in pH 4 acetate buffer solution produced more degradants under stressed conditions. These degradants are formed due to the loss of the sulfate functionality. Squalamine lactate is stable in refrigerated conditions as well as in basic solution. PMID:12852451

  9. Performing Drug Safety Research During Pregnancy and Lactation: Biomedical HIV Prevention Research as a Template.

    Science.gov (United States)

    Beigi, Richard H; Noguchi, Lisa; Brown, Gina; Piper, Jeanna; Watts, D Heather

    2016-07-01

    Evidence-based guidance regarding use of nearly all pharmaceuticals by pregnant and lactating women is limited. Models for performing research may assist in filling these knowledge gaps. Internationally, reproductive age women are at high risk of human immunodeficiency virus (HIV) acquisition. Susceptibility to HIV infection may be increased during pregnancy, and risk of maternal-child transmission is increased with incident HIV infection during pregnancy and lactation. A multidisciplinary meeting of experts was convened at the United States National Institutes of Health to consider paradigms for drug research in pregnancy and lactation applicable to HIV prevention. This report summarizes the meeting proceedings and describes a framework for research on candidate HIV prevention agent use during pregnancy and lactation that may also have broader applications to other pharmaceutical products. PMID:23808668

  10. D-lactate is a valid biomarker of intestinal ischemia induced by abdominal compartment syndrome

    DEFF Research Database (Denmark)

    Nielsen, Casper; Kirkegård, Jakob; Erlandsen, Erland J;

    2015-01-01

    BACKGROUND: Intra-abdominal hypertension (IAH) often leads to abdominal compartment syndrome, which is followed by intestinal ischemia and associated with a high mortality. The diagnosis of abdominal compartment syndrome is difficult, and no valid biochemical markers are available. We conducted an...... group) without IAH. Blood samples were taken from the portal and jugular veins at 0, 60, 120, 180, and 240 min after insufflation of carbon dioxide, and concentrations of D-lactate and L-lactate in the two groups were compared using an unpaired t-test. RESULTS: The concentrations of D-lactate were......, respectively). Examination of the intestines revealed both macroscopic and microscopic signs of ischemia in all but one animal in the intervention group and only in one sham-pig. CONCLUSIONS: Our findings suggest that D-lactate could be a useful biochemical marker of intestinal ischemia induced by IAH....

  11. Is lactate a Volume Transmitter of Metabolic States of the Brain?

    Directory of Open Access Journals (Sweden)

    Linda H. Bergersen

    2012-03-01

    Full Text Available We present the perspective that lactate is a volume transmitter of cellular signals in brain that acutely and chronically regulate the energy metabolism of large neuronal ensembles. From this perspective, we interpret recent evidence to mean that lactate transmission serves the maintenance of network metabolism by two different mechanisms, one by regulating the formation of cAMP via the lactate receptor GPR81, the other by adjusting the NADH/NAD+ redox ratios, both linked to the maintenance of brain energy turnover and possibly cerebral blood flow. The roles of lactate as mediator of metabolic information rather than metabolic substrate answer a number of questions raised by the controversial oxidativeness of astrocytic metabolism and its contribution to neuronal function.

  12. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  13. Increased Blood Lactate Level Deteriorates Running Economy in World Class Endurance Athletes.

    Science.gov (United States)

    Hoff, Jan; Støren, Øyvind; Finstad, Arnstein; Wang, Eivind; Helgerud, Jan

    2016-05-01

    Hoff, J, Støren, Ø, Finstad, A, Wang, E, and Helgerud, J. Increased blood lactate level deteriorates running economy in world class endurance athletes. J Strength Cond Res 30(5): 1373-1378, 2016-Blood lactate accumulation is associated with development of muscle fatigue and negatively correlated to endurance performance. No research has quantified the effects of lactate presence at moderate levels of lactate accumulation. The purpose of this study was to test whether 2 moderate blood lactate concentration levels affect running economy (RE) when running at the individual lactate threshold (LT). Seven male world class endurance athletes with an average V[Combining Dot Above]O2max of 80.7 ± 2.7 ml·kg·min or 5.8 ± 0.5 L·min participated in this study. After the V[Combining Dot Above]O2max test, the subjects were resting or walking and in a random order tested for RE at their LT velocity when the blood lactate level reached either 3 mmol·L or 5 mmol·L. After a new 5-minute exercising period at maximal aerobic velocity, the crossover lactate value RE testing was performed. Running economy was significantly (p ≤ 0.05) deteriorated from 0.668 ± 0.044 to 0.705 ± 0.056 ml·kg·m or 5.5% (p ≤ 0.05) for blood lactate level of 3 mmol·L compared with 5 mmol·L, respectively. Increased lactate level from 3 to 5 mmol·L is thus accompanied by deteriorated RE at LT running velocity. The deteriorated RE at moderate levels of lactate concentration emphasizes the importance of avoiding intensities above LT in the early parts of a dominantly aerobic endurance competition. It also emphasizes the importance of a high V[Combining Dot Above]O2max for aerobic endurance athletes and may partly explain the V[Combining Dot Above]O2 slow component as impaired RE. PMID:26817745

  14. Serum lactate as a marker of mortality in patients with hip fracture: A prospective study.

    Science.gov (United States)

    Venkatesan, M; Smith, R P; Balasubramanian, S; Khan, A; Uzoigwe, C E; Coats, T J; Godsiff, S

    2015-11-01

    Outcomes from patients suffering hip fracture remain poor, with 9% mortality at 30 days and 35% at 1 year. Despite robust guidelines these mortality rates have undergone little change. Admission serum lactate in patients with sepsis or suffering general trauma has been shown to be an indicator of adverse clinical outcomes. We investigated whether venous lactate can predict mortality for hip fracture patients. Over a 12-month period the admission venous lactate of all patients presenting to our institution with hip fractures was prospectively collated. Demographic and patient survivorship data were also prospectively recorded. Multivariate binary logistic regression and Cox proportional hazards ratio analysis was used to evaluate the relationship between admission venous lactate and 30-day mortality and early survivorship, whilst adjusting for age and gender. 770 patients were included in the study. The mean age was 80 years. The overall 30-day mortality for this cohort was 9.5%. Admission venous lactate was associated with early death. A 1mmol/L increase in venous lactate resulted in a 1.9 (95% CI 1.5-2.3 p<0.0001) fold increase in the odds of 30-day mortality and a 1.4 (95% CI: 1.2-1.6 p<0.0001) factor increase in the risk of death at any time after hip fracture. Admission venous lactate remained a predictor of mortality despite adjustment for patients American Society of Anesthesiologists (ASA) grade. Those with an admission serum lactate of 3mmol/L or greater were particularly at risk. This cohort had a 30-day mortality odds that was 5-fold higher than those whose level was less than 3mmol/L (p<0.0001) and at any-time risk of death that was 1.9 times higher (p<0.0001). Those with a level of less than 3mmol/L had a 30-day mortality of 6.8%. For those with an admission venous lactate of 3mmol/L or greater this was four times higher at 28%. The difference was statistically significant (p<0.0001). Elevated admission venous lactate following hip fracture is a

  15. Oxidation of Exogenous Lactate by Lactate Dehydrogenase C in the Midpiece of Rat Epididymal Sperm is Essential for Motility and Oxidative Activity

    OpenAIRE

    Hideaki Yamashiro; Masaaki Toyomizu; Akane Kadowaki; Zenya Takeda; Fumiaki Nakazato; Natsuki Toyama; Jin Kobayashi; Eimei Sato

    2009-01-01

    Problem statement: To identify the metabolic reaction-glycolysis or oxidative phosphorylation that is mainly involved in the production of energy required for rat sperm mobilization. Approach: Epididymal sperm were collected from Wistar rats and extended in lactate-containing or lactate-free raffinose-modified Krebs-Ringer Bicarbonate solution (mKRB)-egg yolk medium supplemented with 0, 1, 2, or 3 mM 2-Deoxy-D-Glucose (2 DG) and 1, 2, or 3 mM sodium Oxamate (OX). Sperm motility, straight-line...

  16. Lengthening of the remating interval improves body condition and reproduction efficiency of lactating rabbit does

    OpenAIRE

    Marongiu, Maria Laura; Gulinati, Alessandro; Bomboi, Giovanni Cristoforo; Sechi, Pietro; Floris, Basilio Remo

    2009-01-01

    The requirements of intensively reared rabbit does are very high because of the overlapping of lactation and pregnancy. In this situation, it is important to adopt the most appropriate reproductive system to improve the energy balance of the lactating does and to maximise their productive potential. Previous studies demonstrated that an increase of dietary energy content is often not sufficient to cancel the energy deficit and avoid intense body mobilisation. A negative energy bal...

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

    Directory of Open Access Journals (Sweden)

    Jimena Laporta

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

  18. Management of Lactational Mastitis and Breast Abscesses: Review of Current Knowledge and Practice

    OpenAIRE

    Kataria, Kamal; Srivastava, Anurag; Dhar, Anita

    2012-01-01

    Most breast abscesses develops as a complication of lactational mastitis. The incidence of breast abscess ranges from 0.4 to 11 % of all lactating mothers. The traditional management of breast abscesses involves incision and drainage of pus along with antistaphylococcal antibiotics, but this is associated with prolonged healing time, regular dressings, difficulty in breast feeding, and the possibility of milk fistula with unsatisfactory cosmetic outcome. It has recently been reported that bre...

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

    OpenAIRE

    Picciano, Mary Frances; McGuire, Michelle K.

    2008-01-01

    Nutrient requirements increase during periods of growth and development such as pregnancy and lactation. In response, many clinicians recommend dietary supplements during these important periods of the life cycle. Although there exist some recommendations concerning the need for a limited number of nutrients in supplemental form (eg, iron, folic acid, and iodine), there is a relative paucity of data concerning the use of dietary supplements during pregnancy and lactation. Limited data suggest...

  20. Lactation-induced reduction in hippocampal neurogenesis is reversed by chronic stress exposure

    OpenAIRE

    Hillerer, Katharina M; Neumann, Inga D.; Couillard-Despres, Sebastien; Aigner, Ludwig; Slattery, David A.

    2014-01-01

    The peripartum period is a time of high susceptibility for mood and anxiety disorders, some of which have recently been associated with alterations in hippocampal neurogenesis. Several factors including stress, aging, and, perhaps unexpectedly, lactation have been shown to decrease hippocampal neurogenesis. Intriguingly, lactation is also a time of reduced stress responsivity suggesting that the effect of stress on neurogenic processes may differ during this period. Therefore, the aim of the ...