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Sample records for dehydrogenase ldh levels

  1. Lactate dehydrogenase (LDH activity in retinoblastoma

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    Maurya OPS

    1987-01-01

    Full Text Available LDH estimation in aqueous and serum was carried out in 10 cases of retinoblastoma and 10 control cases (normal. LDH estimation was done by calorimetric method devised by King-Wooten (1964 (1. LDH levels were quite high in serum and aqueous in retinoblastoma, as compared to control cases LDH aqueous/serum ratio was significantly higher in retinoblastoma as compared to control

  2. Lactate dehydrogenase (LDH isoenzymes patterns in ocular tumours

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    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.

  3. Preliminary Study on Serum Lactate Dehydrogenase (LDH)-Prognostic Biomarker in Carcinoma Breast

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    Gandhe, Mahendra Bhauraoji; Gupta, Dilip; Reddy, M.V.R.

    2016-01-01

    Introduction Serum Lactate Dehydrogenase (LDH) is one of the biochemical markers for breast cancer. Serum LDH is enzyme required for anaerobic glycolysis. One of its isoenzyme is increased in breast cancer due to up-regulation in its gene. It leads to increase in serum LDH level in breast cancer patients. Serum LDH is economical, easily available and easy to estimate. Aim In the present study, we evaluated the LDH levels in circulation of newly diagnosed patients of breast cancer and tried to correlate it with different TNM staging of carcinoma breast before interventions and after adjuvant therapy of these patients. Materials and Methods This prospective study was done on 83 diagnosed patients of breast cancer was conducted among poor patients in rural area. This study was conducted in the Department of Surgery between October 2008 to October 2010, at MGIMS, Sevagram, Maharashtra, a rural medical college located in Central India. Out of total 83 participants, 10 participants were having adverse events following surgery and remaining 73 participants were without adverse events following surgery. The significant difference in serum LDH levels between two groups, with and without adverse surgical outcome was calculated by Mann-Whitney U test. Results Patients with higher clinical TNM staging were having higher serum LDH levels. The serum LDH levels at sixth months following surgery showed a trend of statistically significant difference between patients with and without adverse events. As increased serum LDH levels in breast cancer patients shows poor prognosis, surgical outcome or advanced metastases. Conclusion Serum LDH monitoring can be used as a prognostic biomarker in patients of breast cancer. For confirmation of this finding, we require further more studies on larger sample size and long-term follow-up in patients specifically with higher serum LDH levels. PMID:27134855

  4. Analysis of Quaternary Structure of a [LDH-like] Malate Dehydrogenase of Plasmodium falciparum with Oligomeric Mutants

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    L-Malate dehydrogenase (PfMDH) from Plasmodium falciparum, the causative agent for the most severe form of malaria, has shown remarkable similarities to L-lactate dehydrogenase (PfLDH). PfMDH is more closely related to [LDH-like] MDHs characterized in archea and other prokaryotes. Initial sequence a...

  5. Physical and functional association of lactate dehydrogenase (LDH) with skeletal muscle mitochondria.

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    Elustondo, Pia A; White, Adrienne E; Hughes, Meghan E; Brebner, Karen; Pavlov, Evgeny; Kane, Daniel A

    2013-08-30

    The intracellular lactate shuttle hypothesis posits that lactate generated in the cytosol is oxidized by mitochondrial lactate dehydrogenase (LDH) of the same cell. To examine whether skeletal muscle mitochondria oxidize lactate, mitochondrial respiratory oxygen flux (JO2) was measured during the sequential addition of various substrates and cofactors onto permeabilized rat gastrocnemius muscle fibers, as well as isolated mitochondrial subpopulations. Addition of lactate did not alter JO2. However, subsequent addition of NAD(+) significantly increased JO2, and was abolished by the inhibitor of mitochondrial pyruvate transport, α-cyano-4-hydroxycinnamate. In experiments with isolated subsarcolemmal and intermyofibrillar mitochondrial subpopulations, only subsarcolemmal exhibited NAD(+)-dependent lactate oxidation. To further investigate the details of the physical association of LDH with mitochondria in muscle, immunofluorescence/confocal microscopy and immunoblotting approaches were used. LDH clearly colocalized with mitochondria in intact, as well as permeabilized fibers. LDH is likely localized inside the outer mitochondrial membrane, but not in the mitochondrial matrix. Collectively, these results suggest that extra-matrix LDH is strategically positioned within skeletal muscle fibers to functionally interact with mitochondria.

  6. Physical and Functional Association of Lactate Dehydrogenase (LDH) with Skeletal Muscle Mitochondria*

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    Elustondo, Pia A.; White, Adrienne E.; Hughes, Meghan E.; Brebner, Karen; Pavlov, Evgeny; Kane, Daniel A.

    2013-01-01

    The intracellular lactate shuttle hypothesis posits that lactate generated in the cytosol is oxidized by mitochondrial lactate dehydrogenase (LDH) of the same cell. To examine whether skeletal muscle mitochondria oxidize lactate, mitochondrial respiratory oxygen flux (JO2) was measured during the sequential addition of various substrates and cofactors onto permeabilized rat gastrocnemius muscle fibers, as well as isolated mitochondrial subpopulations. Addition of lactate did not alter JO2. However, subsequent addition of NAD+ significantly increased JO2, and was abolished by the inhibitor of mitochondrial pyruvate transport, α-cyano-4-hydroxycinnamate. In experiments with isolated subsarcolemmal and intermyofibrillar mitochondrial subpopulations, only subsarcolemmal exhibited NAD+-dependent lactate oxidation. To further investigate the details of the physical association of LDH with mitochondria in muscle, immunofluorescence/confocal microscopy and immunoblotting approaches were used. LDH clearly colocalized with mitochondria in intact, as well as permeabilized fibers. LDH is likely localized inside the outer mitochondrial membrane, but not in the mitochondrial matrix. Collectively, these results suggest that extra-matrix LDH is strategically positioned within skeletal muscle fibers to functionally interact with mitochondria. PMID:23873936

  7. The prognostic value of serum LDH levels in patients with hepatocellualr carcinoma after hepatic resection.

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    Hu, Wen-Jie; Fu, Shun-Jun; Diao, Jing-Fang; Wan, Dai-Wei; Tan, Zhi-Jian; Zhi, Qiao-Ming; He, Jun-Ming

    2015-07-16

    Serum lactate dehydrogenase (LDH) is a prognostic marker in many tumor types. The present study is to determine the value of preoperative peripheral LDH in predicting the prognosis of patients with HCC after hepatectomy. Clinicopathological and follow-up data selected 323 HCC patients who underwent hepatectomy. These patients were categorized as high LDH(>240 U/I) and low LDH group (≤ 240 U/I). Significant differences in tumor size, capsulation, tumor number, vascular invasion and TNM stage were observed between these two groups (P 240 U/I group were poorer than those in the LDH ≤ 240 U/I group respectively. Multivariate analysis demonstrated that LDH > 240 U/I served as an independent prognostic indicator of worse disease-free survival [hazard ratio (HR) = 1.711; 95% confidence interval (CI), 1.275-2.297; P < 0.001] and overall survival (HR = 1.568; 95% CI, 1.144-2.149; P = 0.005). Stratification analysis showed that LDH exhibited a greater predictive value for DFS and OS in HCC patients with with AFP < 200 ng/ml. Our results suggested that serum LDH level might be a potential and reliable prognostic biomarker in HCC patients after liver resection.

  8. Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes

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    Morello, Fulvio; Ravetti, Anna; Nazerian, Peiman; Liedl, Giovanni; Veglio, Maria Grazia; Battista, Stefania; Vanni, Simone; Pivetta, Emanuele; Montrucchio, Giuseppe; Mengozzi, Giulio; Rinaldi, Mauro; Moiraghi, Corrado; Lupia, Enrico

    2016-01-01

    Abstract In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far. This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency...

  9. Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances a Pika’s Sprint-Running Capacity in Hypoxic Environment

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

    2015-01-01

    LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000–5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N-isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N-isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in Qinghai

  10. Testis-Specific Lactate Dehydrogenase (LDH-C4 in Skeletal Muscle Enhances Apika’s Sprint-Running Capacity in Hypoxic Environment

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    Yang Wang

    2015-08-01

    Full Text Available LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae, which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000–5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N-isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N-isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in

  11. Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances a Pika's Sprint-Running Capacity in Hypoxic Environment.

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

    2015-08-07

    LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000-5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N-isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N-isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in Qinghai-Tibet plateau

  12. Assessment of three new parasite lactate dehydrogenase (pan-pLDH) tests for diagnosis of uncomplicated malaria.

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    Fogg, Carole; Twesigye, Rogers; Batwala, Vincent; Piola, Patrice; Nabasumba, Carolyn; Kiguli, James; Mutebi, Frederick; Hook, Christa; Guillerm, Martine; Moody, Anthony; Guthmann, Jean-Paul

    2008-01-01

    A study to assess the diagnostic capabilities of three parasite lactate dehydrogenase (pan-pLDH) tests, Vistapan), Carestart and Parabank), was conducted in Uganda. An HRP2 test, Paracheck-Pf), and a Giemsa-stained blood film were performed with the pLDH tests for outpatients with suspected malaria. In total, 460 subjects were recruited: 248 with positive blood films and 212 with negative blood films. Plasmodium falciparum was present in 95% of infections. Sensitivity above 90% was shown by two pLDH tests, Carestart (95.6%) and Vistapan (91.9%), and specificity above 90% by Parabank (94.3%) and Carestart (91.5%). Sensitivity decreased with low parasitaemia (chi(2) trend, P90% with parasitaemia > or =100/microl. All tests had good inter-reader reliability (kappa>0.95). Two weeks after diagnosis, 4-10% of pLDH tests were still positive compared with 69.7% of the HRP2 tests. All tests had similar ease of use. In conclusion, two pLDH tests performed well in diagnosing P. falciparum malaria, and all pLDH tests became negative after treatment more quickly than the HRP2. Therefore the rapid test of choice for use with artemisinin-combination therapies in this area would be one of these new pLDH tests.

  13. [The expression of the sperm-specific lactate dehydrogenase gene Ldh-c in plateau pika (Ochotona curzoniae) cardiac muscle and its effect on the anaerobic glycolysis].

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    Li, Xiao; Wei, Lian; Wang, Yang; Xu, Li-Na; Wei, Lin-Na; Wei, Deng-Bang

    2015-06-25

    The plateau pika (Ochotona curzoniae) has a strong adaptability to hypoxic plateau environment. We found that the sperm-specific lactate dehydrogenase (LDH-C4) gene Ldh-c expressed in plateau pika cardiac muscle. In order to shed light on the effect of LDH-C4 on the anaerobic glycolysis in plateau pika cardiac muscle, 20 pikas were randomly divided into the inhibitor group and the control group, and the sample size of each group was 10. The pikas of inhibitor group were injected with 1 mL 1 mol/L N-isopropyl oxamate, a specific LDH-C4 inhibitor, in biceps femoris muscle of hind legs, each leg with 500 μL. The pikas of control group were injected with the same volume of normal saline (0.9% NaCl). The mRNA and protein expression levels of Ldh-c gene in plateau pika cardiac muscle were determined by real-time PCR and Western blot. The activities of LDH, and the contents of lactate (LD) and ATP in cardiac muscle were compared between the inhibitor group and the control group. The results showed that 1) the expression levels of Ldh-c mRNA and protein were 0.47 ± 0.06 and 0.68 ± 0.08, respectively; 2) 30 min after injection of 1 mL 1 mol/L N-isopropyl oxamate in biceps femoris muscle, the concentration of N-isopropyl oxamate in blood was 0.08 mmol/L; 3) in cardiac muscle of the inhibitor group and the control group, the LDH activities were (6.18 ± 0.48) U/mg and (9.08 ± 0.58) U/mg, the contents of LD were (0.21 ± 0.03) mmol/g and (0.26 ± 0.04) mmol/g, and the contents of ATP were (4.40 ± 0.69) nmol/mg and (6.18 ± 0.73) nmol/mg (P < 0.01); 5) the inhibition rates of N-isopropyl oxamate to LDH, LD and ATP were 31.98%, 20.90% and 28.70%, respectively. The results suggest that Ldh-c expresses in cardiac muscle of plateau pika, and the pika cardiac muscle may get at least 28% ATP for its activities by LDH-C4 catalyzed anaerobic glycolysis, which reduces the dependence on oxygen and enhances the adaptation to the hypoxic environments.

  14. The role of LDH serum levels in predicting global outcome in HCC patients undergoing TACE: implications for clinical management.

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    Mario Scartozzi

    Full Text Available In many tumor types serum lactate dehydrogenase (LDH levels is an indirect marker of tumor hypoxia, neo-angiogenesis and worse prognosis. However data about hepatocellular carcinoma (HCC are lacking in the clinical setting of patients undergoing transarterial-chemoembolization (TACE in whom hypoxia and neo-angiogenesis may represent a molecular key to treatment failure. Aim of our analysis was to evaluate the role of LDH pre-treatment levels in determining clinical outcome for patients with HCC receiving TACE. One hundred and fourteen patients were available for our analysis. For all patients LDH values were collected within one month before the procedure. We divided our patients into two groups, according to LDH serum concentration registered before TACE (first: LDH≤450 U/l 84 patients; second: LDH>450 U/l 30 patients. Patients were classified according to the variation in LDH serum levels pre- and post-treatment (increased: 62 patients vs. decreased 52 patients. No statistically significant differences were found between the groups for all clinical characteristics analyzed (gender, median age, performance status ECOG, staging systems. In patients with LDH values below 450 U/l median time to progression (TTP was 16.3 months, whereas it was of 10.1 months in patients above the cut-off (p = 0.0085. Accordingly median overall survival (OS was 22.4 months and 11.7 months (p = 0.0049. In patients with decreased LDH values after treatment median TTP was 12.4 months, and median OS was 22.1 months, whereas TTP was 9.1 months and OS was 9.5 in patients with increased LDH levels (TTP: p = 0.0087; OS: p<0.0001. In our experience, LDH seemed able to predict clinical outcome for HCC patients undergoing TACE. Given the correlation between LDH levels and tumor angiogenesis we can speculate that patients with high LDH pretreatment levels may be optimal candidates for clinical trial exploring a multimodality treatment approach with TACE and anti

  15. Effects and Mechanism of Atmospheric-Pressure Dielectric Barrier Discharge Cold Plasma on Lactate Dehydrogenase (LDH) Enzyme.

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    Zhang, Hao; Xu, Zimu; Shen, Jie; Li, Xu; Ding, Lili; Ma, Jie; Lan, Yan; Xia, Weidong; Cheng, Cheng; Sun, Qiang; Zhang, Zelong; Chu, Paul K

    2015-01-01

    Proteins are carriers of biological functions and the effects of atmospheric-pressure non-thermal plasmas on proteins are important to applications such as sterilization and plasma-induced apoptosis of cancer cells. Herein, we report our detailed investigation of the effects of helium-oxygen non-thermal dielectric barrier discharge (DBD) plasmas on the inactivation of lactate dehydrogenase (LDH) enzyme solutions. Circular dichroism (CD) and dynamic light scattering (DLS) indicate that the loss of activity stems from plasma-induced modification of the secondary molecular structure as well as polymerization of the peptide chains. Raising the treatment intensity leads to a reduced alpha-helix content, increase in the percentage of the beta-sheet regions and random sequence, as well as gradually decreasing LDH activity. However, the structure of the LDH plasma-treated for 300 seconds exhibits a recovery trend after storage for 24 h and its activity also increases slightly. By comparing direct and indirect plasma treatments, plasma-induced LDH inactivation can be attributed to reactive species (RS) in the plasma, especially ones with a long lifetime including hydrogen peroxide, ozone, and nitrate ion which play the major role in the alteration of the macromolecular structure and molecular diameter in lieu of heat, UV radiation, and charged particles.

  16. Effects and Mechanism of Atmospheric-Pressure Dielectric Barrier Discharge Cold Plasma on Lactate Dehydrogenase (LDH) Enzyme

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    Zhang, Hao; Xu, Zimu; Shen, Jie; Li, Xu; Ding, Lili; Ma, Jie; Lan, Yan; Xia, Weidong; Cheng, Cheng; Sun, Qiang; Zhang, Zelong; Chu, Paul K.

    2015-05-01

    Proteins are carriers of biological functions and the effects of atmospheric-pressure non-thermal plasmas on proteins are important to applications such as sterilization and plasma-induced apoptosis of cancer cells. Herein, we report our detailed investigation of the effects of helium-oxygen non-thermal dielectric barrier discharge (DBD) plasmas on the inactivation of lactate dehydrogenase (LDH) enzyme solutions. Circular dichroism (CD) and dynamic light scattering (DLS) indicate that the loss of activity stems from plasma-induced modification of the secondary molecular structure as well as polymerization of the peptide chains. Raising the treatment intensity leads to a reduced alpha-helix content, increase in the percentage of the beta-sheet regions and random sequence, as well as gradually decreasing LDH activity. However, the structure of the LDH plasma-treated for 300 seconds exhibits a recovery trend after storage for 24 h and its activity also increases slightly. By comparing direct and indirect plasma treatments, plasma-induced LDH inactivation can be attributed to reactive species (RS) in the plasma, especially ones with a long lifetime including hydrogen peroxide, ozone, and nitrate ion which play the major role in the alteration of the macromolecular structure and molecular diameter in lieu of heat, UV radiation, and charged particles.

  17. Alteration of hydrogen metabolism of ldh-deleted Enterobacter aerogenes by overexpression of NAD+-dependent formate dehydrogenase.

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    Lu, Yuan; Zhao, Hongxin; Zhang, Chong; Lai, Qiheng; Wu, Xi; Xing, Xin-Hui

    2010-03-01

    The NAD+-dependent formate dehydrogenase FDH1 gene (fdh1), cloned from Candida boidinii, was expressed in the ldh-deleted mutant of Enterobacter aerogenes IAM1183 strain. The plasmid of pCom10 driven by the PalkB promoter was used to construct the fdh1 expression system and thus introduce a new dihydronicotinamide adenine dinucleotide (NADH) regeneration pathway from formate in the ldh-deleted mutant. The knockout of NADH-consuming lactate pathway affected the whole cellular metabolism, and the hydrogen yield increased by 11.4% compared with the wild strain. Expression of fdh1 in the ldh-deleted mutant caused lower final cell concentration and final pH after 16 h cultivation, and finally resulted in 86.8% of increase in hydrogen yield per mole consumed glucose. The analysis of cellular metabolites and estimated redox state balance in the fdhl-expressed strain showed that more excess of reducing power was formed by the rewired NADH regeneration pathway, changing the metabolic distribution and promoting the hydrogen production.

  18. An alpha-proteobacterial type malate dehydrogenase may complement LDH function in Plasmodium falciparum. Cloning and biochemical characterization of the enzyme.

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    Tripathi, Abhai K; Desai, Prashant V; Pradhan, Anupam; Khan, Shabana I; Avery, Mitchell A; Walker, Larry A; Tekwani, Babu L

    2004-09-01

    Malate dehydrogenase (MDH) may be important in carbohydrate and energy metabolism in malarial parasites. The cDNA corresponding to the MDH gene, identified on chromosome 6 of the Plasmodium falciparum genome, was amplified by RT-PCR, cloned and overexpressed in Escherichia coli. The recombinant Pf MDH was purified to homogeneity and biochemically characterized as an NAD(+)(H)-specific MDH, which catalysed reversible interconversion of malate to oxaloacetate. Pf MDH could not use NADP/NADPH as a cofactor, but used acetylpyridine adenine dinucleoide, an analogue of NAD. The enzyme exhibited strict substrate and cofactor specificity. The highest levels of Pf MDH transcripts were detected in trophozoites while the Pf MDH protein level remained high in trophozoites as well as schizonts. A highly refined model of Pf MDH revealed distinct structural characteristics of substrate and cofactor binding sites and important amino acid residues lining these pockets. The active site amino acid residues involved in substrate binding were conserved in Pf MDH but the N-terminal glycine motif, which is involved in nucleotide binding, was similar to the GXGXXG signature sequence found in Pf LDH and also in alpha-proteobacterial MDHs. Oxamic acid did not inhibit Pf MDH, while gossypol, which interacts at the nucleotide binding site of oxidoreductases and shows antimalarial activity, inhibited Pf MDH also. Treatment of a synchronized culture of P. falciparum trophozoites with gossypol caused induction in expression of Pf MDH, while expression of Pf LDH was reduced and expression of malate:quinone oxidoreductase remained unchanged. Pf MDH may complement Pf LDH function of NAD/NADH coupling in malaria parasites. Thus, dual inhibitors of Pf MDH and Pf LDH may be required to target this pathway and to develop potential new antimalarial drugs.

  19. Comparative characterization of a temperature responsive gene (lactate dehydrogenase-B, ldh-b in two congeneric tropical fish, Lates calcarifer and Lates niloticus

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    Richard C. Edmunds, Lynne van Herwerden, Carolyn Smith-Keune, Dean R. Jerry

    2009-01-01

    Full Text Available The characterization of candidate loci is a critical step in obtaining insight into adaptation and acclimation of organisms. In this study of two non-model tropical (to sub-tropical congeneric perciformes (Lates calcarifer and Lates niloticus we characterized both coding and non-coding regions of lactate dehydrogenase-B (ldh-b, a locus which exhibits temperature-adaptive differences among temperate and sub-tropical populations of the North American killifish Fundulus heteroclitus. Ldh-b was 5,004 and 3,527 bp in length in L. calcarifer and L. niloticus, respectively, with coding regions comprising 1,005 bp in both species. A high level of sequence homology existed between species for both coding and non-coding regions of ldh-b (> 97% homology, corresponding to a 98.5% amino acid sequence homology. All six known functional sites within the encoded protein sequence (LDH-B were conserved between the two Lates species. Ten simple sequence repeat (SSR motifs (mono-, di-, tri- and tetranucleotide and thirty putative microRNA elements (miRNAs were identified within introns 1, 2, 5 and 6 of both Lates species. Five single nucleotide polymorphisms (SNPs were also identified within miRNA containing intron regions. Such SNPs are implicated in several complex human conditions and/or diseases (as demonstrated by extensive genome-wide association studies. This novel characterization serves as a platform to further examine how non-model species may respond to changes in their native temperatures, which are expected to increase by up to 6°C over the next century.

  20. Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes

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    Morello, Fulvio; Ravetti, Anna; Nazerian, Peiman; Liedl, Giovanni; Veglio, Maria Grazia; Battista, Stefania; Vanni, Simone; Pivetta, Emanuele; Montrucchio, Giuseppe; Mengozzi, Giulio; Rinaldi, Mauro; Moiraghi, Corrado; Lupia, Enrico

    2016-01-01

    Abstract In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far. This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality. One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367–557) in patients with AAS and 383 U/L (IQR 331–460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37–51) and the specificity was 73% (95% CI 69–76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH ≥ 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH ≥ 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11–4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH ≥ 450 U/L in elderly, hemodynamically stable

  1. Significance of CSF-LDH in various types of meningitis

    OpenAIRE

    Vekaria, Parul N; Jasani, Jasmin H; Dhruva, Gauravi; Kotadia, Tarun

    2015-01-01

    The cerebrospinal fluid concentration of Lactate dehydrogenase (LDH) was studied in patients with pyogenic and tubercular meningitis. Significant increase in LDH level (P<0.001) were observed in the test group when compared to the control group. LDH may  useful in differentiating viral from other meningitis. It may act as corroborative evidence of meningitis.

  2. Regulation of crayfish, Orconectes virilis, tail muscle lactate dehydrogenase (LDH) in response to anoxic conditions is associated with alterations in phosphorylation patterns.

    Science.gov (United States)

    Green, Stuart R; Storey, Kenneth B

    2016-12-01

    Lactate dehydrogenase (LDH), the terminal enzyme of anaerobic glycolysis, has a crucial role in sustaining ATP production by glycolysis during periods of anoxia via regenerating NAD(+) through the production of lactate. The present study examined the effects of prolonged (20h) anoxic submergence on LDH from the tail muscle of an anoxia-tolerant crayfish (Orconectes virilis). LDH was purified to homogeneity from tail muscle of both aerobic control and anoxic crayfish in a three step process. Analysis of the kinetic parameters and the stability of LDH showed that the Vmax in the pyruvate-reducing direction was significantly higher for the enzyme from anoxic crayfish whereas in the lactate-oxidizing direction the Vmax was significantly higher for the control enzyme. Differential scanning fluorimetry was used to assess thermal unfolding of crayfish LDH. The results showed that the enzyme from control muscle had a significantly higher melting temperature (greater thermal stability) than the anoxic enzyme form, suggesting that there was a structural difference between the two enzyme forms. Immunoblotting of purified LDH implicated post-translational modification as the reason for this difference; purified LDH from aerobic control crayfish showed significantly higher amounts of serine/threonine phosphorylation than did the anoxic enzyme form. This study provides evidence for anoxia-induced modifications of crayfish muscle LDH that may contribute significantly to modulating enzyme function under anoxic conditions.

  3. Study of serum LDH and GGT levels in carcinoma breast

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    Rajeswari, Guddanti; Srinivas, P Satya; Krishna Sai, K. Siva Rama; Suresh, Eadala

    2016-01-01

    Background: Breast cancer is the second most common cancer in women next only to cervical cancer. Multiple factors are associated with an increased risk of developing breast cancer. For the early detection of carcinoma of breast, a number of biochemical markers have been studied to evaluate the malignancy.Aim: To analyse serum Lactate Dehydrogenase, Gamma Glutamyl Transpeptidase, liver enzymes (SGOT, SGPT, & ALP) and total proteins in diagnosis of carcinoma breast patients and compared wi...

  4. Equating salivary lactate dehydrogenase (LDH) with LDH-5 expression in patients with oral squamous cell carcinoma: An insight into metabolic reprogramming of cancer cell as a predictor of aggressive phenotype.

    Science.gov (United States)

    Saluja, Tajindra Singh; Spadigam, Anita; Dhupar, Anita; Syed, Shaheen

    2016-04-01

    Oral squamous cell carcinoma (OSCC) is the sixth most common human malignancy. According to World Health Organization, oral cancer has been reported to have the highest morbidity and mortality and a survival rate of approximately 50 % at 5 years from diagnosis. This is attributed to the subjectivity in TNM staging and histological grading which may result in less than optimum treatment outcomes including tumour recurrence. One of the hallmarks of cancer is aerobic glycolysis also known as the Warburg effect. This glycolytic phenotype (hypoxic state) not only confers immortality to cancer cells, but also correlates with the belligerent behaviour of various malignancies and is reflected as an increase in the expression of lactate dehydrogenase 5 (LDH-5), the main isoform of LDH catalysing the conversion of pyruvate to lactate during glycolysis. The diagnostic role of salivary LDH in assessing the metabolic phenotype of oral cancer has not been studied. Since salivary LDH is mainly sourced from oral epithelial cells, any pathological changes in the epithelium should reflect diagnostically in saliva. Thus in our current research, we made an attempt to ascertain the biological behaviour and aggressiveness of OSCC by appraising its metabolic phenotype as indirectly reflected in salivary LDH activity. We found that salivary LDH can be used to assess the aggressiveness of different histological grades of OSCC. For the first time, an evidence of differing metabolic behaviour in similar histologic tumour grade is presented. Taken together, our study examines the inclusion of salivary LDH as potential diagnostic parameter and therapeutic index in OSCC.

  5. Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with non-metastatic breast cancer.

    Science.gov (United States)

    Liu, Xiaoan; Meng, Qing H; Ye, Yuanqing; Hildebrandt, Michelle A T; Gu, Jian; Wu, Xifeng

    2015-02-01

    Liver function tests (LFTs) have been reported as independent predictors of non-liver disease-related morbidity and mortality in general population and cancer patients. In this study, we evaluated the relationship between pretreatment serum LFTs and overall survival (OS) in non-metastatic Caucasian breast cancer patients. Seven LFTs, including albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase (LDH), total bilirubin and total protein, were measured in pretreatment serum from 2425 female Caucasian patients with newly diagnosed, histologically confirmed non-metastatic invasive breast cancer. Multivariate Cox model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for the association of individual LFTs with 5-year OS while adjusting for age, smoking status, pathological characteristics and treatment regimen. We found that serum albumin, LDH and total bilirubin were significantly associated with 5-year OS in multivariate Cox analyses. Patients with higher albumin level exhibited 45% reduced risk of death (HR = 0.55, 95% CI: 0.40-0.75) compared with those with lower albumin level. Patients with higher total bilirubin level had a nearly 40% reduction in the risk of death (HR = 0.62, 95% CI: 0.45-0.85) and patients with higher LDH levels had a 1.42-fold increased risk of death (HR = 1.42, 95% CI: 1.08-1.88). Furthermore, cumulative analysis showed a significant dose-response trend of significantly increasing risk of death with increasing number of unfavorable LFT levels. Our result highlighted the potential of using pretreatment serum levels of albumin, LDH and total bilirubin as prognostic factors for OS in patients with non-metastatic breast cancer.

  6. EFFECT OF TRIGONELLA FOENUM GRAECUM ON LACTATE DEHYDROGENASE (LDH ACTIVITY OF BLOOD, LIVER AND PANCREAS IN NORMAL AND ALLOXAN- INDUCED DIABETIC MICE

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    Sekaran Sridhar et al.

    2012-02-01

    Full Text Available The effect of aqueous seeds extract of Trigonella foenum graecum Linn was studied on Lactate dehydrogenase (LDH activity of blood, liver and pancreas in normal and alloxan- induced diabetic mice. Our study showed that aqueous seeds extract, Oral administration of 50 mg/animal (0.5 ml of extract in alternative days up to 7 days (1st, 3rd, 5th & 7th day. In alloxan induced diabetic mice, there was a significant increase in LDH activity of all the three tissues. The enzyme Lactate dehydrogenase showed significant decrease in the diabetic group treated with aqueous extract of tested plant when compared with the diabetic group. It is clear from the current data in this study that ginseng aqueous extract was the most efficient of the tested plant.

  7. Prognostic impact of LDH levels in patients with relapsed/refractory seminoma.

    Science.gov (United States)

    Powles, Tom; Bascoul-Mollevi, Caroline; Kramar, Andrew; Lorch, Anja; Beyer, Jörg

    2013-08-01

    To evaluate the impact of age and LDH levels in patients with relapsed seminoma. Data on the 204 seminoma from the International Prognostic Factor Study Group (IPFSG) were analyzed. All patients experienced unequivocal relapse/progression after at least three cisplatin-based chemotherapy cycles. Age and LDH at relapse were assessed in addition to previously identified prognostic factors for all germ cell tumor patients from the database (J Clin Oncol 28:4906, 2010). The impact of the IPFSG score remained highly significant in multivariate analysis. In addition, LDH ≥1.5 times the upper limit of normal (ULN) was significant in univariate (HR 1.96; CI 1.06-3.61) and multivariate analysis (HR 1.90; CI 1.00-3.62). Age, however, was not significant. Therefore, LDH was incorporated into a modified new IPFSG seminoma score by moving patients to the next unfavorable group for patients with LDH values ≥1.5 × ULN. Three prognostic groups were thus generated, which better subdivided seminoma patients than the original IPFSG score. Progression-free survival at 2 years: "very low risk" (n = 23) 85.7% (95% CI 62-95), "low risk" (n = 44) 62.7 % (95% CI 46-75) and "intermediate risk" (n = 36) 35.1% (95% CI 20-51). Overall survival at 3 years: "very low risk" 88.8% (95% CI 62-97), "low risk" 71.3% (95% CI 55-83) and "intermediate risk" 51.3% (95% CI 33-67). The addition of LDH, but not age, improves the impact of the IPFSG prognostic score in seminoma patients relapsing or progressing after cisplatin-based chemotherapy.

  8. PREPARATION OF IgA MONOCLONAL ANTIBODIES TO MURINE LACTIC DEHYDROGENASE-C4 (LDH-C4)

    Institute of Scientific and Technical Information of China (English)

    FENGShu-Lin; BENKun-Long; LIANGZhi-Guo

    1989-01-01

    LDH--C4 is a sperm specific lactic dehydrogcnase in mammals and human, and is consid ered as a model molecule for contraceptive vaccine research. Significant contraceptive effects were observed in female mice, rabbits and baboons immunized with purified

  9. Initial LDH level can predict the survival benefit from bevacizumab in the first-line setting in Chinese patients with metastatic colorectal cancer

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    Yin CX

    2014-08-01

    Full Text Available Chenxi Yin,1,2,* Chang Jiang,1,2,* Fangxin Liao,1,2 Yuming Rong,1,2 Xiuyu Cai,1,2 Guifang Guo,1,2 Huijuan Qiu,1,2 Xuxian Chen,1,2 Bei Zhang,1,2 Wenzhuo He,1,2 Liangping Xia1,2 1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer, Medicine, 2VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this paper Background: Markers to predict the efficacy of bevacizumab treatment have been not fully validated in most cancers, including metastatic colorectal cancer (mCRC. The aim of this study was to investigate the potential role of lactate dehydrogenase (LDH in predicting the survival benefit from first-line bevacizumab treatment, in Chinese patients with mCRC. Methods: All the patients were diagnosed with mCRC at the Sun Yat-sen University Cancer Center from 2003 to 2013. The study group and the control group were classified by receiving bevacizumab or not. The serum LDH value of all the patients had been detected before the first-line treatment. The primary end point was progression-free survival (PFS. Results: The median PFS of the study and the control group (patients who received bevacizumab or not was 11.3 and 9.1 months, respectively (P=0.004. In the control group, the median PFS of the high LDH level and the low LDH level groups was 6.9 and 10.2 months, respectively (P<0.001. However, in the study group, the corresponding median PFS was 9.9 and 11.9 months, respectively (P=0.145. In addition, for the low LDH level group, the median PFS was 11.9 and 10.2 months for patients who received bevacizumab or not, respectively (P=0.066; however, the median PFS of patients receiving bevacizumab or not was significantly different in the high LDH level group (9.9 and 6.9 months, respectively (P=0.012. Conclusion: The addition of bevacizumab in the first-line treatment setting could improve the

  10. Unusually high serum levels of lactate dehydrogenase without perivalvular leakage following double valve replacement: predictor of tetany attack after thyroidectomy.

    Science.gov (United States)

    Ryomoto, Masaaki; Miyamoto, Yuji; Mitsuno, Masataka; Yamamura, Mitsuhiro; Ohata, Toshihiro; Tanaka, Hiroe

    2006-11-01

    A 57-year-old woman who complained of exertional dyspnea was diagnosed as having severe aortic valve stenosis and mitral valve regurgitation. The patient underwent double valve replacement with a mechanical prosthesis. Postoperative laboratory data showed unusually high serum lactate dehydrogenase (LDH) levels, even though no perivalvular leakage was detected by echocardiography. Tetany occurred suddenly owing to hypoparathyroidism, which seemed to be a late complication after thyroidectomy. After calcium administration, the symptoms dramatically diminished, as did the serum LDH levels. Hypoparathyroidism should be doubted if serum LDH levels increase higher than the normal range following valve replacement without obvious perivalvular leakage.

  11. The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy.

    Science.gov (United States)

    Faloppi, Luca; Del Prete, Michela; Casadei Gardini, Andrea; Santini, Daniele; Silvestris, Nicola; Bianconi, Maristella; Giampieri, Riccardo; Valgiusti, Martina; Brunetti, Oronzo; Bittoni, Alessandro; Andrikou, Kalliopi; Lai, Eleonora; Dessì, Alessandra; Cascinu, Stefano; Scartozzi, Mario

    2016-04-11

    LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37-0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54-1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33-0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27-0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy.

  12. Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells.

    Science.gov (United States)

    Rossi, Soledad P; Windschüttl, Stefanie; Matzkin, María E; Rey-Ares, Verónica; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; Levalle, Oscar; Calandra, Ricardo S; Mayerhofer, Artur; Frungieri, Mónica B

    2016-10-15

    Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D2 (PGD2) system in Sertoli cells. Now, we found that PGD2 increases ROS and hydrogen peroxide (H2O2) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H2O2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant N-acetyl-L-cysteine and the PI3K/Akt pathway inhibitor LY 294002. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD2 in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB/ATF-1 pathway.

  13. Effect of HEMADO on Level of CK-MB and LDH Enzymes after Ischemia/Reperfusion Injury in Isolated Rat Heart

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    Mohammad Amani

    2013-01-01

    Full Text Available Introduction: Ischemia/Reperfusion (IR injury mainly causes the increase of enzymes involved in myocytes injury including CK-MB (creatine kinase-MB isoenzyme and LDH (lactate dehydrogenase. Leakage of CK-MB isoenzyme and LDH from myocardial tissues to blood is indicator of acute myocardial infarction. The aim of this study was to assess the effect of HEMADO on IR injury and its relationship with mitochondrial ATP-sensitive K+ channels (mitoKATP in rat heart. Methods: Twenty eight male Wistar rats (250-300g were divided into four groups (seven members in each group: control (without ischemia, I/R (with ischemia+without HEMADO, ischemia received HEMADO (HEMADO, ischemia received HEMADO and 5-HD (5-hydroxydecanoate, specific mitoKATP channel blocker (HEMADO+5-HD. The animals were anesthetized and the hearts were quickly removed and mounted on Langendorff apparatus and perfused by Krebs-Henseleit solution under constant pressure and temperature of 37ºC. After 20 minutes of stabilization, ischemic groups were exposed to 40 minutes of global ischemia and consecutive 90 minutes of reperfusion. Results: IR injury increased the level of LDH and CK-MB in the collected coronary flow during 5 minutes since start of reperfusion. HEMADO reduced the enzymes’ levels and using 5-HD abolished the effect of HEMADO. Conclusion: Our findings indicated that HEMADO could protect the heart against ischemia-reperfusion injury by decreasing the CK-MB and LDH levels. The cardioprotective effect of HEMADO may be mediated in part by mitoKATP.

  14. Impact of Pre-Treatment Lactate Dehydrogenase Levels on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.

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    Alessandro Passardi

    Full Text Available To investigate the impact of pre-treatment lactate dehydrogenase (LDH levels on the outcome of patients with metastatic colorectal cancer treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase III prospective multicentre randomized ITACa (Italian Trial in Advanced Colorectal Cancer trial.Three hundred and seventy patients enrolled onto the ITACa first-line trial were considered for this study, 176 receiving chemotherapy (either FOLFIRI or FOLFOX plus bevacizumab and 194 receiving chemotherapy only. Pre-treatment LDH levels were evaluated to identify a potential correlation with progression-free survival (PFS, overall survival (OS and objective response rate.Information on pre-treatment LDH levels was available for 344 patients. High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001 and median OS (16.1 months vs. 25.2 months, p< 0.0001 in the overall population. In the chemotherapy plus bevacizumab group, median PFS was 9.1 and 9.8 months in patients with high LDH and low LDH, respectively (p= 0.073, whereas in the chemotherapy-only arm it was 6.9 and 9.1 months, respectively (p < 0.0001. In patients with high LDH, the addition of bevacizumab to chemotherapy led to a reduction in the rate of progressive disease (16.4 vs. 30.5%, p= 0.081 and to a prolonged PFS (p= 0.028.A high LDH value was confirmed as a marker of poor prognosis. Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.NCT01878422 ClinicalTrials.gov.

  15. Serum LDH in chronic cough: a potential marker of airway inflammation.

    Science.gov (United States)

    Faruqi, Shoaib; Wilmot, Rachel; Wright, Caroline; Morice, Alyn Hugh

    2012-04-01

    Lactate dehydrogenase (LDH) is found in almost all tissues of the body and five different isoenzymes are known (LDH-1 to LDH-5). LDH can be elevated in many pathological conditions. We have observed serum LDH to be increased in patients with chronic cough. We wanted to confirm this finding, study the reproducibility and determine the origin of the LDH. Patients prospectively seen at the Hull Cough Clinic had total and specific LDH isoenzyme levels in serum determined. A subgroup of patients also had a serum creatine phosphokinase (CK) measured. Patients completed cough symptom scores and the Hull Airway Reflux Questionnaire (HARQ). Spirometry was performed. Eighty-three patients were included. Forty-two percent had LDH values above the reference range and 78% had LDH values in the fourth quartile of the reference range or above. This increase in LDH was predominantly because of a rise in isoenzymes 4 and 5. The increase in LDH was found to be reproducible at 8 weeks. Ten percent had CK values above the normal range. There was no correlation observed between LDH values and the cough scores, HARQ scores or lung function. Serum LDH levels are elevated in a substantial proportion of patients with chronic cough. This rise is likely to be due to airway inflammation known to be associated with chronic cough. © 2011 Blackwell Publishing Ltd.

  16. Baseline Serum Lactate Dehydrogenase Levels for Patients Treated With Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Predictor of Poor Prognosis and Subsequent Liver Metastasis

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    Zhou Guanqun; Tang Linglong; Mao Yanping; Chen Lei; Li Wenfei; Sun Ying [Department of Radiation Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou (China); Liu Lizhi; Li Li [Imaging Diagnosis and Interventional Center, Cancer Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou (China); Lin Aihua [Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou (China); Ma Jun, E-mail: drjunma@hotmail.com [Department of Radiation Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou (China)

    2012-03-01

    Purpose: To evaluate the prognostic value of baseline serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Cases of NPC (n = 465) that involved treatment with IMRT with or without chemotherapy were retrospectively analyzed. Results: The mean ({+-}SD) and median baseline serum LDH levels for this cohort were 172.77 {+-} 2.28 and 164.00 IU/L, respectively. Levels of LDH were significantly elevated in patients with locoregionally advanced disease (p = 0.016). Elevated LDH levels were identified as a prognostic factor for rates of overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), with p values <0.001 in the univariate analysis and p < 0.001, p = 0.004, and p = 0.003, respectively, in the multivariate analysis. Correspondingly, the prognostic impact of patient LDH levels was found to be statistically significant for rates of OS, DFS, and DMFS (p = 0.028, 0.024, and 0.020, respectively). For patients who experienced subsequent liver failure after treatment, markedly higher pretreatment serum LDH levels were detected compared with patients experiencing distant metastasis events at other sites (p = 0.032). Conclusions: Elevated baseline LDH levels are associated with clinically advanced disease and are a poor prognosticator for OS, DFS, and DMFS for NPC patients. These results suggest that elevated serum levels of LDH should be considered when evaluating treatment options.

  17. Pretreatment Serum Lactate Dehydrogenase Level as an Independent Prognostic Factor of Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era.

    Science.gov (United States)

    Chen, Zhuhong; Guo, Qiaojuan; Lu, Tianzhu; Lin, Shaojun; Zong, Jingfeng; Zhan, Shenghua; Xu, Luying; Pan, Jianji

    2017-01-25

    BACKGROUND The aims of this study were to analyze the prognostic value of baseline lactate dehydrogenase (LDH) among nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), and to evaluate the potential application of LDH in monitoring treatment efficacy dynamically. MATERIAL AND METHODS From June 2005 to December 2010, 1188 patients with non-metastatic NPC who underwent IMRT with or without chemotherapy were reviewed. Univariate and multivariate analyses were performed to evaluate the predictive value of baseline LDH. Wilcoxon signed-rank test was used to analyze the difference between baseline and post-radiotherapy LDH, and to compare post-radiotherapy LDH with the LDH in cases of distant failure. RESULTS Patients with elevated LDH had significant inferior survival rates, in terms of overall survival (70.0% vs. 83.2%, p=0.010), disease-specific survival (71.1% vs. 85.7%, p=0.002), and distant metastasis-free survival (71.1% vs. 83.4%, p=0.009), but not correlated with locoregional relapse-free survival (p=0.275) or progression-free survival (p=0.104). Subgroup analysis demonstrated that this predictive effect was more significant with advanced stage. Sixty-five post-radiotherapy LDH levels were available from the 90 patients with high LDH at initial diagnosis, and these levels fell in 65 patients, with 62 cases (95.4%) falling within the normal range. Of the 208 patients who experienced distant metastasis, 87 had an available LDH level at that time. Among them, 69 cases (79.3%) had an increased level compared with the post-radiotherapy LDH level. CONCLUSIONS Pretreatment LDH is a simple, cost-effective biomarker that could predict survival rates and might be used in individualized treatment. It is also a potential biomarker that might reflect tumor burden and be used to monitor therapy efficacy.

  18. Tumor LDH-A expression and serum LDH status are two metabolic predictors for triple negative breast cancer brain metastasis.

    Science.gov (United States)

    Dong, Tieying; Liu, Zhaoliang; Xuan, Qijia; Wang, Zhuozhong; Ma, Wenjie; Zhang, Qingyuan

    2017-07-20

    There are limited therapeutic methods for triple negative breast cancer in the clinic, which is easy to progress into the brain to form metastatic lesions and evolve into the terminal stage. Because both the primary cancer and the brain metastasis have high glycolysis, we hypothesize that lactate dehydrogenase (LDH), which catalyzes the final step of glycolysis, may be a predictor, as well as a treatment target, for breast cancer brain metastasis. Therefore, the expression of LDH-A was detected on 119 triple negative breast cancer tissues with immunohistochemistry, and the serum LDH levels were also measured. Our results showed that the LDH-A expression inside the tumor was significantly higher than the matched normal tissues. Tumor LDH-A expression, serum LDH status, and the slope of serum LDH status were closely associated with triple negative breast cancer brain metastasis and brain metastasis free survival. This study indicates that tumor LDH and serum LDH status are two predictors for triple negative breast cancer brain metastasis.

  19. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408 Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408

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    Thiago Cezar Fujita

    2010-09-01

    Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease.Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed

  20. Effect of Hypoxia on Ldh-c Expression in Somatic Cells of Plateau Pika

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

    2016-01-01

    Sperm specific lactate dehydrogenases (LDH-C4) is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, Ldh-c was originally thought to be expressed only in testes and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia-tolerant mammal living 3000–5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testes and sper...

  1. Is a Plasmodium lactate dehydrogenase (pLDH) enzyme-linked immunosorbent (ELISA)-based assay a valid tool for detecting risky malaria blood donations in Africa?

    Science.gov (United States)

    Atchade, Pascal S; Doderer-Lang, Cécile; Chabi, Nicodème; Perrotey, Sylvie; Abdelrahman, Tamer; Akpovi, Casimir D; Anani, Ludovic; Bigot, André; Sanni, Ambaliou; Candolfi, Ermanno

    2013-08-08

    Malaria is a leading cause of mortality in southern Benin. The main causative agent, Plasmodium falciparum, poses a threat on critical transfusions in pregnant women and children. This study's objective was to compare the performance of different malaria screening methods in blood donors in southern Benin, a malaria-endemic country. Blood from 2,515 voluntary blood donors in Benin was collected over a period of 10 months in ethylenediaminetetraacetic acid (EDTA) tubes, which were then classified according to extraction time: long rainy season, short dry season, short rainy season, and long dry season. Microscopic examination was used to count parasites. Parasite density (PD) was expressed as the number of parasites per μL of blood. Pan Plasmodium pLDH detection was assessed by an ELISA-malaria antigen test. Using crude soluble P. falciparum antigens, an ELISA-malaria antibody test detected anti-Plasmodium antibodies. Among the 2,515 blood donors (2,025 males and 488 females) screened, the rate of asymptomatic Plasmodium carriage was 295/2,515 (11.72%, 95% CI: 10.5-13.1%). Males had a higher infection rate (12.4%) than did females (8.8%). Parasite density was very low: between seven and100 parasites per μL of blood was reported in 80% of donors with parasitaemia. Three Plasmodium species were diagnosed: P. falciparum in 280/295 patients (95.0%), Plasmodium malariae in 14/295 (5.0%), and Plasmodium ovale in 1/295 (0.34%). Malaria prevalence in donors was higher during the rainy seasons (13.7%) compared with the dry seasons (9.9%). The use of a highly sensitive assay enabled pan Plasmodium pLDH detection in 966/2,515 (38.4%, 95% CI: 36.5%-40.3%). Malaria antibody prevalence was 1,859/2,515 (73.9%, 95% CI: 72.16-75.6%). Donors' antigenaemia and antibody levels varied significantly (P Plasmodium can transmit malaria to donation recipients. Malaria diagnostic methods are currently available, but the feasibility criteria for mass screening in endemic areas become

  2. MA和AIHA患者LDH和RET%检测的临床意义%Detection and clinical significance of serum LDH level and reticulocyte percentage in the megaloblastic anemia and autoimmune hemolytic anemia patients

    Institute of Scientific and Technical Information of China (English)

    马丽娜; 李兴; 杨晓阳; 崔晓红; 吴和弟

    2012-01-01

    目的 通过检测巨幼细胞贫血(MA)和自身免疫性溶血性贫血(AIHA)患者血清乳酸脱氢酶(LDH)和网织红细胞百分比(RET%),探讨LDH和RET%在MA和AIHA诊断中的作用.方法 对40例MA组、30例AIHI组以及40例正常对照组LDH、RET%的水平变化作回顾性分析比较.结果 MA组、AIHI组血清LDH水平明显高于正常组,差异有统计学意义(均P<0.01);MA组LDH明显高于AIHI组,差异有统计学意义(P<0.01); AIHI组RET%明显高于MA组和正常组,差异有统计学意义(P<0.01);MA组RET%与正常组对比无差异(P>0.05).结论 血清LDH和RET%水平对临床鉴别MA和AIHA具有临床指导意义.%Objective In older to identify the clinical diagnosis significance of serum lactate dehydrogenase (LDH) and reticulocyte percentage (RET%)in patients of megaloblastic anemia (MA)and autoimmune hemolytic anemia (AIHA). Methods The serum lactate dehydrogenase(LDH)and reticulocyte percentage(RET%)levels of the 40 MA group,30 AIHI group and 40 normal group,were retrospectively compared and analyzed. Results LDH levels were significantly higher in the MA and AIHI group than the normal group's (P<0.0l). Meanwhile,the levels of LDH were also significantly different between the MA group and the AIHA group (P<0.0l). RET% levels were significantly higher in the AIHA group than the levels of MA and normal group (P<0.01) but RET% levels were not different between the MA group and the normal group (P>0.05). Conclusion The levels of Serum LDH and RET% are important for the clinical diagnosis of MA and AIHA patients.

  3. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia = Determinação da lactate desidrogenase (LDH e do transcrito Bcr-Abl em pacientes com leucemia mielóide crônica

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    Roberto Iemitsu Tatakihara

    2010-07-01

    Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease. Leucemia mieloide crônica (LMC é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH,considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentraçãode LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A

  4. Effects of CXCR4 siRNA/dextran-spermine nanoparticles on CXCR4 expression and serum LDH levels in a mouse model of colorectal cancer metastasis to the liver

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    Abedini F

    2011-09-01

    Full Text Available Fatemeh Abedini1, Maznah Ismail1,4, Hossein Hosseinkhani2, Tengku Azmi Tengku Ibrahim1,3, Abdul Rahman Omar1,3, Pei Pei Chong4, Mohd Hair Bejo3, Abraham J Domb51Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 2Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 3Faculty of Veterinary Medicine, 4Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor Darul Ehsan, Malaysia; 5Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University-Hadassah Medical School, Jerusalem, IsraelAbstract: Liver metastasis is the main cause of mortality related to colorectal cancer. CXCR4 is necessary for the outgrowth of colon cancer micrometastases. In oncology, it has been demonstrated that several human tumors release lactate dehydrogenase (LDH into the circulation. CXCR4 gene expression and serum LDH levels are often increased in patients with colorectal cancer. Despite technological advances in cancer therapy, five-year overall survival is still around 50%. Therefore, better treatment needs to be developed. RNA interference (RNAi is a modern and powerful tool for inhibition of gene expression. However, the rate-limiting step in this technology is effective delivery of RNAi agents. We have investigated a novel strategy of CXCR4 siRNA therapy and its effect on serum LDH levels in a BALB/C mouse model of colorectal cancer metastasis to the liver. Hepatic metastasis was established by injecting a CT26.WT mouse colon carcinoma cell line via the tail vein. Our results demonstrated that CXCR4 siRNA/dextran-spermine nanoparticles achieved high silencing efficiency with low toxicity. Favorable localization of the nanoparticles was confirmed with CXCR4 gene expression in the liver, that was correlated with serum LDH levels. More research will be needed to determine the effect of CXCR4

  5. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion

    OpenAIRE

    Verma, Akash; Phua, Chee Kiang; Sim, Wen Yuan; Algoso, Reyes Elmer; Tee, Kuan Sen; Lew, Sennen J. W.; Lim, Albert Y.H.; Goh, Soon Keng; Tai, Dessmon Y. H.; Kor, Ai Ching; Ho, Benjamin; Abisheganaden, John

    2016-01-01

    Abstract To study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis. Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012. Univariate analyses showed lower pleural fluid LDH 667 (313–967) versus 971 (214–3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 ...

  6. The Effects of Heart and Skeletal Muscle Inflammation and Cardiomyopathy Syndrome on Creatine Kinase and Lactate Dehydrogenase Levels in Atlantic Salmon (Salmo salar L.

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    Muhammad Naveed Yousaf

    2012-01-01

    Full Text Available Heart and skeletal muscle inflammation (HSMI and cardiomyopathy syndrome (CMS are putative viral cardiac diseases of Atlantic salmon. This study examined the levels and correlated the serum enzymes creatine kinase (CK and lactate dehydrogenase (LDH to the histopathology of clinical outbreaks of HSMI and chronic CMS in farmed Atlantic salmon. A total of 75 fish from 3 different HSMI outbreaks, 30 chronic CMS fish, and 68 fish from 3 nondiseased fish groups were used as the study population (N=173. Serum CK and LDH levels correlated significantly with the total inflammation and total necrosis scores for HSMI fish (P=0.001. However, no correlation was identified for enzyme levels and histopathology scores for chronic CMS fish. The significantly increased CK and LDH levels and their positive correlations to histopathology differentiate HSMI from CMS clinically suggesting the potential use of enzymes for screening for HSMI is promising.

  7. Impact of probiotic-supplemented diet on the expression level of lactate dehydrogenase in the leukocytes of rabbits.

    Science.gov (United States)

    Ghoneim, Magdy A E; Moselhy, Said S

    2014-04-01

    Probiotics are known as living, nonpathogenic microorganisms that colonize the intestine and provide benefit to the host. The present study aims to measure one important energy metabolism-related enzyme activity in blood of rabbits fed on probiotics of recommended concentration. In addition, it also aims for the evaluation of the expression level of lactate dehydrogenase (LDH) enzyme using reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Two groups of rabbits are used: control group receiving normal standardized diet and the other probiotic-supplemented group receiving the same diet containing probiotic, namely, Mega acidophilus (200 million cfu/kg body weight/day) for 4 weeks. The obtained results revealed that the rabbits supplemented with probiotics showed a significant decrease in the levels of serum total cholesterol (TC), triacylglycerol, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) when compared with control group. Risk factors detected by measuring TC/HDL-c and LDL-c/HDL-c ratios showed statistically significant decrease in probiotic-supplemented rabbits when compared with control group. In addition, blood glucose and total LDH activity were elevated in probiotic-supplemented rabbits when compared with control group. RT-PCR products of LDH-M gene produced two specific amplicons. One amplicon has the expected size of 243 bp from all samples of rabbits as revealed by GelPro software. The level of LDH-M expression was found to be increased in the probiotic-supplemented group. However, unexpected amplicons are produced at 586 bp in all the samples, which may be a dimeric form of the amplified region. It was concluded that this probiotic blend is beneficiary for the metabolic reactions of lipids in the body. Moreover, LDH expression level can be considered as a biomarker for the effect of probiotic and hence monitoring the metabolic changes as reflected from its administration.

  8. Correlation between the Lactate Dehydrogenase Levels with Laboratory Variables in the Clinical Severity of Sickle Cell Anemia in Congolese Patients.

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    Tite Minga Mikobi

    Full Text Available Sickle cell anemia is an inflammatory disease and is characterized by chronic hemolysis. We sought to evaluate the association of lactate dehydrogenase levels with specific clinical phenotypes and laboratory variables in patients with sickle cell anemia.The present cross-sectional study was conducted in Sickle Cell Centre of Yolo in Kinshasa, the Democratic Republic of Congo. Two hundred and eleven patients with Sickle Cell Anemia in steady state were recruited. Seventy-four participants with normal Hb (Hb-AA were selected as a control group.The average rates of hemoglobin, hematocrit, and red blood cells tended to be significantly lower in subjects with Hb-SS (p<0.001. The average rates of white blood cells, platelets, reticulocytes and serum LDH were significantly higher in subjects with Hb-SS (p<0.001. The average rates of Hb, HbF, hematocrit and red blood cells of Hb-SS patients with asymptomatic clinical phenotype were significantly higher than those of the two other phenotypes. However, the average rates of white blood cells, platelets, reticulocytes, and LDH of Hb-SS patients with the severe clinical phenotype are higher than those of two other clinical phenotypes. Significant correlations were observed between Hb and white blood cell in severe clinical phenotype (r3 = -0.37 * between Hb and red blood cells in the three phenotypes (r1 = 0.69 * r2 * = 0.69, r3 = 0.83 *, and finally between Hb and reticulocytes in the asymptomatic clinical phenotype and severe clinical phenotype (r1 = -0.50 * r3 = 0.45 *. A significant increase in LDH was observed in patients with leg ulcer, cholelithiasis and aseptic necrosis of the femoral head.The increase in serum LDH is accompanied by changes in hematological parameters. In our midst, serum LDH may be considered as an indicator of the severity of the disease.

  9. Correlation between the Lactate Dehydrogenase Levels with Laboratory Variables in the Clinical Severity of Sickle Cell Anemia in Congolese Patients

    Science.gov (United States)

    Mikobi, Tite Minga; Lukusa Tshilobo, Prosper; Aloni, Michel Ntetani; Mvumbi Lelo, Georges; Akilimali, Pierre Zalagile; Muyembe-Tamfum, Jean Jacques; Race, Valérie; Matthijs, Gert; Mbuyi Mwamba, Jean Marie

    2015-01-01

    Background Sickle cell anemia is an inflammatory disease and is characterized by chronic hemolysis. We sought to evaluate the association of lactate dehydrogenase levels with specific clinical phenotypes and laboratory variables in patients with sickle cell anemia. Methods The present cross-sectional study was conducted in Sickle Cell Centre of Yolo in Kinshasa, the Democratic Republic of Congo. Two hundred and eleven patients with Sickle Cell Anemia in steady state were recruited. Seventy-four participants with normal Hb (Hb-AA) were selected as a control group. Results The average rates of hemoglobin, hematocrit, and red blood cells tended to be significantly lower in subjects with Hb-SS (p<0.001). The average rates of white blood cells, platelets, reticulocytes and serum LDH were significantly higher in subjects with Hb-SS (p<0.001). The average rates of Hb, HbF, hematocrit and red blood cells of Hb-SS patients with asymptomatic clinical phenotype were significantly higher than those of the two other phenotypes. However, the average rates of white blood cells, platelets, reticulocytes, and LDH of Hb-SS patients with the severe clinical phenotype are higher than those of two other clinical phenotypes. Significant correlations were observed between Hb and white blood cell in severe clinical phenotype (r3 = -0.37 *) between Hb and red blood cells in the three phenotypes (r1 = 0.69 * r2 * = 0.69, r3 = 0.83 *), and finally between Hb and reticulocytes in the asymptomatic clinical phenotype and severe clinical phenotype (r1 = -0.50 * r3 = 0.45 *). A significant increase in LDH was observed in patients with leg ulcer, cholelithiasis and aseptic necrosis of the femoral head. Conclusion The increase in serum LDH is accompanied by changes in hematological parameters. In our midst, serum LDH may be considered as an indicator of the severity of the disease. PMID:25946088

  10. Effect of Hypoxia on Ldh-c Expression in Somatic Cells of Plateau Pika.

    Science.gov (United States)

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

    2016-08-01

    Sperm specific lactate dehydrogenases (LDH-C₄) is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, Ldh-c was originally thought to be expressed only in testes and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia-tolerant mammal living 3000-5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testes and sperm, but also in the somatic tissues of plateau pika. To reveal the effect of hypoxia on pika Ldh-c expression, we investigated the mRNA and protein level of Ldh-c as well as the biochemical index of anaerobic glycolysis in pika somatic tissues at the altitudes of 2200 m, 3200 m and 3900 m. Our results showed that mRNA and protein expression levels of Ldh-c in the tissues of pika's heart, liver, brain and skeletal muscle were increased significantly from 2200 m to 3200 m, but had no difference from 3200 m to 3900 m; the activities of LDH and the contents of lactate showed no difference from 2200 m to 3200 m, but were increased significantly from 3200 m to 3900 m. Hypoxia up-regulated and maintained the expression levels of Ldh-c in the pika somatic cells. Under the hypoxia condition, plateau pikas increased anaerobic glycolysis in somatic cells by LDH-C₄, and that may have reduced their dependence on oxygen and enhanced their adaptation to the hypoxic environment.

  11. Lactate dehydrogenase test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003471.htm Lactate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Lactate dehydrogenase (LDH) is a protein that helps produce energy ...

  12. Anoxia- and hypoxia-induced expression of LDH-A* in the Amazon Oscar, Astronotus crassipinis

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    Vera Maria Fonseca Almeida-Val

    2011-01-01

    Full Text Available Adaptation or acclimation to hypoxia occurs via the modulation of physiologically relevant genes, such as erythropoietin, transferrin, vascular endothelial growth factor, phosphofructokinase and lactate dehydrogenase A. In the present study, we have cloned, sequenced and examined the modulation of the LDH-A gene after an Amazonian fish species, Astronotus crassipinis (the Oscar, was exposed to hypoxia and anoxia. In earlier studies, we have discovered that adults of this species are extremely tolerant to hypoxia and anoxia, while the juveniles are less tolerant. Exposure of juveniles to acute hypoxia and anoxia resulted in increased LDH-A gene expression in skeletal and cardiac muscles. When exposed to graded hypoxia juveniles show decreased LDH-A expression. In adults, the levels of LDH-A mRNA did not increase in hypoxic or anoxic conditions. Our results demonstrate that, when given time for acclimation, fish at different life-stages are able to respond differently to survive hypoxic episodes.

  13. In vitro effect of some anthelmintics on lactate dehydrogenase activity of Cotylophoron cotylophorum (Digenea: paramphistomidae).

    Science.gov (United States)

    Veerakumari, L; Munuswamy, N

    2000-07-24

    Effects of praziquantel (PZQ), levamisole (LEV), mebendazole (MBZ), fenbendazole (FBZ) and albendazole (ABZ) on the lactate dehydrogenase (LDH) activity of Cotylophoron cotylophorum were studied in vitro. Maximum levels of inhibition of LDH catalysing both oxidation and reduction reactions were observed in PZQ- and LEV-treated worms. Similarly, benzimidazoles - MBZ, FBZ and ABZ - have also significantly inhibited the activity of LDH catalysing the oxidation of lactate; whereas the activity of LDH catalysing the reduction of pyruvate was accelerated. This affects the mitochondrial energy generating process which ultimately proves fatal to the parasite. Therefore, the mode of action of benzimidazoles is primarily on the activation of LDH catalysing the conversion of pyruvate to lactate.

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

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    Yang Wang

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Total LDH and LDH isoenzyme distribution in the serum of normal children

    NARCIS (Netherlands)

    Heiden, C.V.D.; Desplanque, J.; Stoop, J.W.; Wadman, S.K.

    Total LDH activity and LDH isoenzyme distribution were determined in sera of in normal children from 4 to 13 years old and compared to a control group of adult sera. It was found that in children the level of total LDH activity and the isoenzyme distribution did not differ significantly from that in

  17. Total LDH and LDH isoenzyme distribution in the serum of normal children

    NARCIS (Netherlands)

    Heiden, C.V.D.; Desplanque, J.; Stoop, J.W.; Wadman, S.K.

    1968-01-01

    Total LDH activity and LDH isoenzyme distribution were determined in sera of in normal children from 4 to 13 years old and compared to a control group of adult sera. It was found that in children the level of total LDH activity and the isoenzyme distribution did not differ significantly from that in

  18. CcpA-independent glucose regulation of lactate dehydrogenase 1 in Staphylococcus aureus.

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    Adrianne K Crooke

    Full Text Available Lactate Dehydrogenase 1 (Ldh1 is a key enzyme involved in Staphylococcus aureus NO·-resistance. Full ldh1-induction requires the presence of glucose, and mutants lacking the Carbon-Catabolite Protein (CcpA exhibit decreased ldh1 transcription and diminished Ldh1 activity. The redox-regulator Rex represses ldh1 directly by binding to Rex-sites within the ldh1 promoter (P(ldh1. In the absence of Rex, neither glucose nor CcpA affect ldh1 expression implying that glucose/CcpA-mediated activation requires Rex activity. Rex-mediated repression of ldh1 depends on cellular redox status and is maximal when NADH levels are low. However, compared to WT cells, the ΔccpA mutant exhibited impaired redox balance with relatively high NADH levels, yet ldh1 was still poorly expressed. Furthermore, CcpA did not drastically alter Rex transcript levels, nor did glucose or CcpA affect the expression of other Rex-regulated genes indicating that the glucose/CcpA effect is specific for P(ldh1. A putative catabolite response element (CRE is located ∼30 bp upstream of the promoter-distal Rex-binding site in P(ldh1. However, CcpA had no affinity for P(ldh1 in vitro and a genomic mutation of CRE upstream of P(ldh1 in S. aureus had no affect on Ldh1 expression in vivo. In contrast to WT, ΔccpA S. aureus preferentially consumes non-glycolytic carbon sources. However when grown in defined medium with glucose as the primary carbon source, ΔccpA mutants express high levels of Ldh1 compared to growth in media devoid of glucose. Thus, the actual consumption of glucose stimulates Ldh1 expression rather than direct CcpA interaction at P(ldh1.

  19. Elevation of serum GGT and LDH levels, together with higher BCLC staging are associated with poor overall survival from hepatocellular carcinoma: a retrospective analysis.

    Science.gov (United States)

    Yang, Zongguo; Ye, Peiyan; Xu, Qingnian; Lu, Yunfei; Tang, Bozong; Wang, Qiang; Chen, Shishi; Chen, Xiaorong

    2015-06-01

    Serum biomarkers predicting prognosis have not been adequately explored in HCC patients. The aim of this study was to investigate prognostic significance of parameters of liver function, tumor markers, and other clinicopathological features in HCC patients. Medical records of HCC patients were retrospectively extracted and overall survival was evaluated with the Kaplan-Meier method. Significant difference was estimated with the Log rank method. Univariate and multivariate analyses were used for the study of significance of prognostic factor. A total of 273 HCC patients were included in this analysis. According to the Cox regression analysis and Kaplan-Meier event analysis, GGT and LDH levels of liver function tests were significantly associated with HCC overall survival. Elevated serum CEA level was a risk factor related to poor HCC overall survival. And advanced BCLC staging contributed to a lower overall survival in HCC patients. HCC could benefit from surgical resection, TACE, and radiotherapy. ROC curves demonstrated that different from CEA, elevated GGT and LDH could accurately predict HCC overall survival. In conclusion, serum GGT and LDH together with higher BCLC staging should be potential predictive factors for HCC overall survival.

  20. Spinal Fluid Lactate Dehydrogenase Level Differentiates between Structural and Metabolic Etiologies of Altered Mental Status in Children

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    Nahid KHOSROSHAHI

    2015-01-01

    mortality after hemispheric ischemic stroke. Crit care med 2004; 32: 241-5.Teasdale G, Jennett B. Assessment of coma and impaired consciousness: a practical scale. Lancet 1974; 2: 81-4.Wityk RJ, Stern BJ. Ischemic stroke: today and tomorrow. Crit care med 1994; 22: 1278-93.Vázquez Jorge Alejandro, Adducci Maria del Carmen, Monzón Daniel Godoy, Iserson Kenneth V. Lactic dehyrogenase in cerebrospinal fluid may differentiate between structural and non-strucfiular central nervous system lesion in patient with diminished levels of consciousness. The Journal of Emergency Medicine2009; 37(1: 93–97.Kärkelä J, Pasanen M, Kaukinen S, Mörsky P, Harmoinen A. Evaluation of hypoxic brain injury with spinal fluid enzymes, lactate, and pyruvate. Crit Care Med. 1992 Mar; 20(3:378-86. 2007: pp. 835. ISBN 0-7817-7087-4.DV Kamat, BP Chakravorty. Comparative values of CSF-LDH isoenzymes in neurological disorders. Indian Journal of Medical Sciences 1999; 53 (1: 1-6.Pollak AN, Gupton CL. Emergency Care and Transportation of the Sick and Injured. Boston: Jones and Bartlett 2002: pp. 140. ISBN 0-7637-1666-9.Nayak BS, Bhat R. Cerebrospinal fluid lactate dehydrogenase and glutamine in meningitis. Indian J Physiol Pharmacol. 2005 Jan; 49(1:108-10.A Twijnstra, A P van Zanten, A A Hart, et al. al. Serial lumbar and ventricle cerebrospinal fluid lactate dehydrogenase activities in patients with leptomeningeal metastases from solid and haematological tumours. J Neurol Neurosurg Psychiatry 1987 50: 313-320.Nussinovitch M, Finkelstein Y, Politi K, Harel D, Klinger G, Razon Y, Nussinovitch U, Nussinovitch N. Cerebrospinal fluid lactate dehydrogenase isoenzymes in children with bacterial and aseptic meningitis. Translational Research 2009. 154 (4: 214-218.Feldman William E. Cerebrospinal Fluid Lactic Acid Dehydrogenase Activity. Levels in Untreated and Partially Antibiotic-Treated Meningitis. Am J Dis Child. 1975; 129(1: 77-80.Lutsar I, Haldre S, Topman M, Talvik T. Enzymatic changes in the

  1. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion.

    Science.gov (United States)

    Verma, Akash; Phua, Chee Kiang; Sim, Wen Yuan; Algoso, Reyes Elmer; Tee, Kuan Sen; Lew, Sennen J W; Lim, Albert Y H; Goh, Soon Keng; Tai, Dessmon Y H; Kor, Ai Ching; Ho, Benjamin; Abisheganaden, John

    2016-06-01

    To study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis.Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012.Univariate analyses showed lower pleural fluid LDH 667 (313-967) versus 971 (214-3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 (100%) versus 36 (55.3%), P = 0.009, and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy 8 (89%) versus 26 (40%), P = 0.009 to correlate with survival of more than 1.7 year versus less than 1.7 year. In multivariate analysis, low pleural fluid LDH and female gender maintained significance. The pleural LDH level of ≤1500 and >1500 U/L discriminated significantly (P = 0.009) between survival.High pleural LDH (>1500 IU/L) predicts shorter survival (less than a year) in patients with adenocarcinoma lung presenting with MPE at the time of initial diagnosis. This marker may be clinically applied for selecting therapeutic modality directed at prevention of reaccumulation of MPE. Patients with low pleural LDH may be considered suitable for measures that provide more sustained effect on prevention of reaccumulation such as chemical pleurodesis or tunneled pleural catheter.

  2. Stimulation of d- and l-lactate dehydrogenases transcriptional levels in presence of diammonium hydrogen phosphate resulting to enhanced lactic acid production by Lactobacillus strain.

    Science.gov (United States)

    Singhvi, Mamata; Zendo, Takeshi; Iida, Hiroshi; Gokhale, Digambar; Sonomoto, Kenji

    2017-08-08

    The present study revealed the effect of nitrogen sources on lactic acid production and stimulation of d- and l-lactate dehydrogenases (LDH) of parent Lactobacillus lactis NCIM 2368 and its mutant RM2-24 generated after UV mutagenesis. Both the parent and mutant strains were evaluated for d-lactic acid production in control and modified media. The modified media did not show remarkable effect on lactic acid production in case of parent whereas mutant exhibited significant enhancement in d-lactic acid production along with the appearance of l-lactic acid in the broth. Both LDH activities and specific activities were found to be higher in mutant than the parent strain. These results suggested that the diammonium hydrogen phosphate in modified media triggered the expression of LDH genes leading to enhanced lactic acid production. This observation has been proved by studying the expression levels of d- and l-LDH genes of parent and mutant in control and modified media using quantitative RT-PCR technique. In case of mutant, the transcriptional levels of d-LDH and l-LDH increased ∼17 fold and ∼1.38 fold respectively in modified medium compared to the values obtained with control medium. In case of parent, no significant change in transcriptional levels of d- and l-LDH was found when the cells were grown in either control medium or modified medium. This study suggested that the mutant, RM2-24 has l-LDH gene which is expressed in presence of (NH4)2HPO4 resulting in l-lactic acid production. Co-production of l-lactic acid in d-lactic acid fermentation may be detrimental in the PLA production. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  3. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia.

    Science.gov (United States)

    Sun, Jia; Su, Junwei; Xie, Yirui; Yin, Michael T; Huang, Ying; Xu, Lijun; Zhou, Qihui; Zhu, Biao

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R (2) = 0.258), HBDH (P = 0.001, R (2) = 0.335), and Ferritin (P = 0.005, R (2) = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781-1.000, P < 0.001; 95% CI 0.592-0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

  4. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia

    Directory of Open Access Journals (Sweden)

    Jia Sun

    2016-01-01

    Full Text Available Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P=0.008, R2=0.258, HBDH (P=0.001, R2=0.335, and Ferritin (P=0.005, R2=0.237. Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P<0.001; 1.11 ± 0.72, P=0.043, larger AUC (95% CI 0.781–1.000, P<0.001; 95% CI 0.592–0.917, P=0.043, and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

  5. Urinary Lactate Dehydrogenase Activity and Its Isozyme Patterns in Kawasaki Disease

    Science.gov (United States)

    Kawamura, Yoichi; Kanai, Takashi; Takizawa, Mari; Yoshida, Yusuke; Tsujita, Yuki; Nonoyama, Shigeaki

    2017-01-01

    Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD). We investigated the potential significance of urinary lactate dehydrogenase (U-LDH) activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5) levels were compared among 120 patients with KD, 18 patients with viral infection (VI), and 43 patients with upper urinary tract infection (UTI) and additionally compared between intravenous immunoglobulin (IVIG) responders (n = 89) and nonresponders (n = 31) with KD. Total U-LDH activity was higher in KD (35.4 ± 4.8 IU/L, P < 0.05) and UTI patients (66.0 ± 8.0 IU/L, P < 0.01) than in VI patients (17.0 ± 6.2 IU/L). In the isozyme pattern analysis, KD patients had high levels of U-LDH1 and U-LDH2, while UTI patients had high levels of U-LDH3, U-LDH4, and U-LDH5. Furthermore, IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1 ± 4.7 IU/L, P < 0.05), especially U-LDH1 and U-LDH2 (P < 0.05), than IVIG responders (32.0 ± 2.8 IU/L). KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients. PMID:28348604

  6. Urinary Lactate Dehydrogenase Activity and Its Isozyme Patterns in Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Yoichi Kawamura

    2017-01-01

    Full Text Available Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD. We investigated the potential significance of urinary lactate dehydrogenase (U-LDH activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5 levels were compared among 120 patients with KD, 18 patients with viral infection (VI, and 43 patients with upper urinary tract infection (UTI and additionally compared between intravenous immunoglobulin (IVIG responders (n=89 and nonresponders (n=31 with KD. Total U-LDH activity was higher in KD (35.4±4.8 IU/L, P<0.05 and UTI patients (66.0±8.0 IU/L, P<0.01 than in VI patients (17.0±6.2 IU/L. In the isozyme pattern analysis, KD patients had high levels of U-LDH1 and U-LDH2, while UTI patients had high levels of U-LDH3, U-LDH4, and U-LDH5. Furthermore, IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1±4.7 IU/L, P<0.05, especially U-LDH1 and U-LDH2 (P<0.05, than IVIG responders (32.0±2.8 IU/L. KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients.

  7. Cerebrospinal fluid lactate dehydrogenase isoenzymes in children with bacterial and aseptic meningitis.

    Science.gov (United States)

    Nussinovitch, Moshe; Finkelstein, Yaron; Elishkevitz, Keren Politi; Volovitz, Benjamin; Harel, Daniella; Klinger, Gil; Razon, Yaron; Nussinovitch, Udi; Nussinovitch, Naomi

    2009-10-01

    Differentiation of bacterial from aseptic meningitis may be difficult. Our aim was to determine the pattern of distribution of lactate dehydrogenase (LDH) isoenzymes in the cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis. One hundred and fifty-seven patients with suspected meningitis were enrolled in the study. They were divided into 3 groups according to the culture- or bacterial antigen assay-proven diagnosis and CSF findings: bacterial meningitis (n = 31), aseptic meningitis (n = 65), and non-meningitis (n = 61). Total LDH level and percentages of LDH isoenzymes in the CSF were measured in each patient. Each group showed a distinct LDH isoenzyme distribution pattern, with a statistically significant difference among the groups in the percentages of the various isoenzymes. Compared with the non-meningitis group, total LDH activity in the CSF was high in the aseptic meningitis group (49.82+/-35.59 U/L, P < 0.001) and exaggerated in the bacterial meningitis group (944.53+/-112.3 U/L, P < 0.001). Low LDH-2 levels were unique to bacterial meningitis (P < 0.01), whereas high LDH-3 levels were characteristic of aseptic meningitis (P < 0.05). Both groups had low levels of LDH-1 and high levels of LDH-4 and LDH-5. In conclusion, the LDH isoenzyme pattern may be of clinical diagnostic value in meningitis, particularly when culture results are pending.

  8. Cloning and Characterization of Multiple RNA Splicing Variants of LDH-C Gene in Human and Rat

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    Qinglian Zhang

    2013-06-01

    Full Text Available The expression of LDH-C (Lactate dehydrogenase C gene is restricted in mature germ cells; however multiple splice variants of LDH-C expressed in human cancers and yak normal testes were reported recently. In order to know if there are any LDH-C splice variants in human normal testes, we set out to clone the putative variants in human and rat. Four splicing variants in human testes, 1 splicing variant in human spermatozoa, 6 splicing variants in rat testes and 1 splicing variant in rat non-testes tissues (liver, heart and muscle were cloned. The putative polypeptides encoded by these variants were compared with the full-length LDH-C protein, the results showed that these putative polypeptides were truncated LDH-C proteins or truncated LDH-C proteins with a few amino acid residues different at N or C terminal. This suggested that these variants are possibly not used for translation, but targets of nonsense-mediated mRNA decay. Western blotting did not detect any bands with similar molecular weight as the putative polypeptides. RT-PCR showed that the expression levels of the splicing variants were significant during development of rat testes. The results indicate that LDH-C was not silenced by transcriptional repression in non-mature germ cells, but significantly transcripted and alternatively spliced.

  9. Estimation of salivary lactate dehydrogenase in oral leukoplakia and oral squamous cell carcinoma: a biochemical study.

    Science.gov (United States)

    Patel, Shrikant; Metgud, Rashmi

    2015-01-01

    Enzyme Lactate Dehydrogenase (LDH) is found in the cells of almost all body tissues. The profile of salivary total LDH enzymes is similar to that found in oral epithelium, indicating that the major source of salivary LDH is probably the oral epithelium-shedding cells. Consequently, LDH concentration in saliva, as an expression of cellular necrosis, could be a specific indicator for oral lesions that affect the integrity of the oral mucosa. Study comprised of three groups as follows: Group I: Comprised of 25 healthy individuals of comparable age. Group II: 25 otherwise healthy and consenting patients with oral leukoplakia (OL). Group III: 25 otherwise healthy and consenting oral squamous cell carcinoma (OSCC) patients. Biochemical estimation of LDH was done with the help of Semiautomatic Analyzer. Inter comparison of salivary total LDH levels between all the three groups revealed that salivary LDH levels increase from healthy control group to Oral Leukoplakia group to further increase in OSCC group. On comparisons between the histopathological grades of OSCC group the level of LDH were found to increase from well differentiated to moderately differentiated to further increase in poorly differentiated patients. The present salivary analysis for LDH enzyme reveals an overall altered salivary LDH enzyme level in OL and OSCC cases.

  10. Antibodies against Clonorchis sinensis LDH could cross-react with LDHB localizing on the plasma membrane of human hepatocarcinoma cell SMMC-7721 and induce apoptosis.

    Science.gov (United States)

    Song, Tianzhang; Gan, Wenjia; Chen, Jintao; Huang, Lilin; Yin, Hongling; He, Tailong; Huang, Huaiqiu; Hu, Xuchu

    2016-04-01

    Lactate dehydrogenase (LDH) is a terminal enzyme in anaerobic glycolytic pathway. It widely exists in various organisms and is in charge of converting the glycolysis product pyruvic acid to lactic acid. Most parasites, including Clonorchis sinensis, predominantly depend on glycolysis to provide energy. Bioinformatic analysis predicts that the LDHs from many species have more than one transmembrane region, suggesting that it may be a membrane protein. C. sinensis LDH (CsLDH) has been confirmed as a transmembrane protein mainly located in the tegument. The antibodies against CsLDH can inhibit the worm's energy metabolism, kill the worm, and may have the same effects on human cancer cells. In this study, we cloned and characterized human LDHA (HsLDHA), HsLDHB, and CsLDH. Semi-quantitative real-time RCP showed that HsLDHB only existed in hepatocarcinoma cell SMMC-7721. Confocal microscopy and Western blot experiments revealed that HsLDHB was localized in the plasma membrane of SMMC-7721 cells, and the antibodies against CsLDH could cross-react with it. This cross-reaction could inhibit the enzymatic activity of HsLDHB. The cancer cells co-cultured with anti-CsLDH sera showed a significant decrease in cell proliferation rate and increases in caspase 9 and reactive oxygen species (ROS) levels. Therefore, anti-CsLDH antibodies can induce the apoptosis of cancer cells SMMC-7721 and may serve as a new tool to inhibit tumor.

  11. Lactate dehydrogenase as an indicator of liver, muscular and cancer diseases

    Institute of Scientific and Technical Information of China (English)

    Zahraa Qasum Ali; Zahraa Muhammed Noree

    2015-01-01

    Objective: To determine lactate dehydrogenase (LDH) level as an indicator of liver, muscular or cancer diseases in patients of more than 40 years of age. Methods: Ninety-one patients (43 females and 48 males) had been tested forLDH and liver function tests (LFTs).Creatine kinase (CK) levels were measurement only in patients who had high levels ofLDH. Results: As an indicator for liver diseases, high levels ofLDH and one or more ofLFTs, especially alkaline phosphatase, had been observed in 12 patients (8 females and 4 males). For muscular damage, measurement of CK in patients with elevated levels ofLDH and normal levels of LFT revealed that CK values elevated in three males and one female.Whereas high LDH levels, as an indicator for cancer diseases, were found in three males and one female who had normal values ofLFTs and CK. Conclusions:LDH can be regarded as a good biomarker for diagnosis of liver, muscular and cancer diseases. There is little variable between males and females in the elevated value of LDH. Patients who had high values ofLDH, although they had normal levels ofLFTs andCK are proposed to have unidentified cancer disease.

  12. The impact of hypoxia on the activity of lactate dehydrogenase in two different pre-clinical tumour models

    DEFF Research Database (Denmark)

    Lukacova, Slavka; Sørensen, Brita; Alsner, Jan

    2008-01-01

    Aim. To investigate the direct relationship between tumour hypoxia and lactate dehydrogenase (Ldh) levels in serum and tumour in two different pre-clinical murine models. Materials and methods. Experiments were performed in CDF1 or C3H/Km mice implanted with a C3H mammary carcinoma and SCCVII...... carcinoma bearing mice. Reoxygenation for 4 or 24 hours had no additional effect on Ldh activity in any of the models. Discussion. Serum Ldh activity can be a marker for tumour burden in certain types of cancer. The relationship between serum and tumour Ldh and tumour hypoxia has not been confirmed. However...

  13. Mild hypoxia in vivo regulates cardioprotective SUR2A: A role for Akt and LDH.

    Science.gov (United States)

    Mohammed Abdul, Khaja Shameem; Jovanović, Sofija; Du, Qingyou; Sukhodub, Andriy; Jovanović, Aleksandar

    2015-05-01

    High-altitude residents have lower mortality rates for ischaemic heart disease and this is ascribed to cardiac gene remodelling by chronic hypoxia. SUR2A is a cardioprotective ABC protein serving as a subunit of sarcolemmal ATP-sensitive K(+) channels. The purpose of this study was to determine whether SUR2A is regulated by mild hypoxia in vivo and to elucidate the underlying mechanism. Mice were exposed to either 21% (control) or 18% (mild hypoxia) oxygen for 24h. Exposure to 18% oxygen did not affect partial pressure of O(2) (PO(2)) and CO(2) (PCO(2)) in the blood, haematocrit or level of ATP in the heart. However, hypoxia increased myocardial lactate dehydrogenase (LDH) and lactate as well as NAD(+) without affecting total NAD. SUR2A levels were significantly increased as well as myocardial resistance to ischaemia-reperfusion. Exposure to 18% oxygen did not phosphorylate extracellular signal regulated kinases (ERK1/2) or AMP activated protein kinase (AMPK), but it phosphorylated protein kinase B (Akt). An inhibitor of phosphoinositide 3-kinases (PI3K), LY294002 (0.2mg/mouse), abolished all observed effects of hypoxia. LDH inhibitors, galloflavin (50 μM) and sodium oxamate (80 mM) significantly decreased levels of SUR2A in heart embryonic H9c2 cells, while inactive mutant LDH form, gly193-M-LDH increased cellular sensitivity towards stress induced by 2,4-dinitrophenol (10mM). Treatment of H9c2 cells with sodium lactate (30 mM) increased intracellular lactate, but did not affect LDH activity or SUR2A levels. We conclude that PI3K/Akt signalling pathway and LDH play a crucial role in increase of cardiac SUR2A induced by in vivo exposure to 18% oxygen.

  14. The expression of Ldh-c in the skeletal muscle of plateau pika (Ochotona curzoniae enhances adaptation to a hypoxic environment

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    Zhi F. An

    2017-09-01

    Full Text Available The plateau pika (Ochotona curzoniae is a species of sprint-running alpine animals in the Qinghai-Tibet Plateau, which is a harsh highland hypoxic environment. Ldh-c is expressed in the testis, sperm and somatic tissues of plateau pika. To reveal the role and physiological mechanisms of sperm-specific lactate dehydrogenase (LDH-C4, in plateau pika to adapt to hypoxic environment, an adenoviral line of pMultiRNAi-Ldhc was constructed and injected into the bilateral biceps femoris of the hind legs. The swimming times of the pikas, and the Ldh-c expression levels, total LDH activities and ATP levels in skeletal muscle, were measured after the pikas were raised in the trapped site for 5 days. Our results showed that after Ldh-c was silenced, the sprint-running ability (swimming time of the plateau pikas was significant decreased, and the total LDH activities and ATP levels were reduced by 28.21% and 27.88%, respectively. Our results indicated that expression of Ldh-c in the skeletal muscle of plateau pika increased anaerobic glycolysis and enhanced adaptation to highland hypoxic environments.

  15. 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.

  16. High sensitive C-reactive protein as a systemic inflammatory marker and LDH-3 isoenzyme in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Nillawar, Anup N; Bardapurkar, J S; Bardapurkar, S J

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, mainly due to tobacco smoke. Pulmonary function tests (PFTs) are mandatory to diagnose COPD which shows irreversible airway obstruction. This study was aimed at understanding the behavior of biochemical parameters such as high sensitive C-reactive protein (hs-CRP) and lactate dehydrogenase (LDH) isoenzymes in COPD. Cytoplasmic cellular enzymes, such as LDH in the extracellular space, although of no further metabolic function in this space, are of benefit because they serve as indicators suggestive of disturbances of the cellular integrity induced by pathological conditions. The lung pattern is characterized by proportional increases in isoenzymes 3, 4, and 5. Hs-CRP indicates low grade of systemic inflammation. Total (n = 45) patients of COPD (diagnosed on PFTs) were included. We followed the guidelines laid by the institute ethical committee. Investigations performed on the serum were the serum for hs-CRP, LDH isoenzymes on agarose gel electrophoresis. The results obtained showed that the value of hs-CRP was 4.6 ± 0.42 mg/L. The isoenzymes pattern was characterized by an increase in LDH-3 and LDH-4 fractions. This is evident even in those patients with normal LDH (n = 13) levels. This study states that there is a moderate positive correlation in between CRP and LDH-3 (r = 0.33; P = 0.01). Raised LDH-3 levels do not correlate with FEV(1) % (forced expiratory volume in first second) predicted. Moreover, it associates positively with hs-CRP and smoking status and negatively with body mass index. This underlines the potential of these parameters to complement the present system of staging which is solely based upon FEV(1) % predicted.

  17. High sensitive C-reactive protein as a systemic inflammatory marker and LDH-3 isoenzyme in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Anup N Nillawar

    2012-01-01

    Full Text Available Background and Objectives: Chronic obstructive pulmonary disease (COPD is a chronic inflammatory disease, mainly due to tobacco smoke. Pulmonary function tests (PFTs are mandatory to diagnose COPD which shows irreversible airway obstruction. This study was aimed at understanding the behavior of biochemical parameters such as high sensitive C-reactive protein (hs-CRP and lactate dehydrogenase (LDH isoenzymes in COPD. Cytoplasmic cellular enzymes, such as LDH in the extracellular space, although of no further metabolic function in this space, are of benefit because they serve as indicators suggestive of disturbances of the cellular integrity induced by pathological conditions. The lung pattern is characterized by proportional increases in isoenzymes 3, 4, and 5. Hs-CRP indicates low grade of systemic inflammation. Materials and Methods: Total (n = 45 patients of COPD (diagnosed on PFTs were included. We followed the guidelines laid by the institute ethical committee. Investigations performed on the serum were the serum for hs-CRP, LDH isoenzymes on agarose gel electrophoresis. Results: The results obtained showed that the value of hs-CRP was 4.6 ΁ 0.42 mg/L. The isoenzymes pattern was characterized by an increase in LDH-3 and LDH-4 fractions. This is evident even in those patients with normal LDH (n = 13 levels. Interpretation and Conclusion: This study states that there is a moderate positive correlation in between CRP and LDH-3 (r = 0.33; P = 0.01. Raised LDH-3 levels do not correlate with FEV 1 % (forced expiratory volume in first second predicted. Moreover, it associates positively with hs-CRP and smoking status and negatively with body mass index. This underlines the potential of these parameters to complement the present system of staging which is solely based upon FEV 1 % predicted.

  18. Urinary Lactate Dehydrogenase Activity and Its Isozyme Patterns in Kawasaki Disease.

    Science.gov (United States)

    Kawamura, Yoichi; Takeshita, Seiichiro; Kanai, Takashi; Takizawa, Mari; Yoshida, Yusuke; Tsujita, Yuki; Nonoyama, Shigeaki

    2017-01-01

    Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD). We investigated the potential significance of urinary lactate dehydrogenase (U-LDH) activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5) levels were compared among 120 patients with KD, 18 patients with viral infection (VI), and 43 patients with upper urinary tract infection (UTI) and additionally compared between intravenous immunoglobulin (IVIG) responders (n = 89) and nonresponders (n = 31) with KD. Total U-LDH activity was higher in KD (35.4 ± 4.8 IU/L, P IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1 ± 4.7 IU/L, P IVIG responders (32.0 ± 2.8 IU/L). KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients.

  19. Lactic acid production by Rhizopus oryzae transformants with modified lactate dehydrogenase activity.

    Science.gov (United States)

    Skory, C D

    2004-04-01

    Rhizopus oryzae is capable of producing high levels of lactic acid by the fermentation of glucose. Yields typically vary over 60-80%, with the remaining glucose diverted primarily into ethanol fermentation. The goal of this work was to increase lactate dehydrogenase (LDH) activity, so lactic acid fermentation could more effectively compete for available pyruvate. Three different constructs, pLdhA71X, pLdhA48XI, and pLdhA89VII, containing various lengths of the ldhA gene fragment, were transformed into R. oryzae. This fungus rarely integrates DNA used for transformation, but instead relies on extra-chromosomal replication in a high-copy number. Plasmid pLdhA48XI was linearized prior to transformation in order to facilitate integration into the pyrG gene used for selection. Isolates transformed with ldhA containing plasmid were compared with both the wild-type parent strain and the auxotrophic recipient strain containing vector only. All isolates transformed with pLdhA71X or pLdhA48XI had multiple copies of the ldhA gene that resulted in ldhA transcript accumulation, LDH specific activity, and lactic acid production higher than the controls. Integration of plasmid pLdhA48XI increased the stability of the strain, but did not seem to offer any benefit for increasing lactic acid production. Since lactic acid fermentation competes with ethanol and fumaric acid production, it was not unexpected that increased lactic acid production was always concomitant with decreased ethanol and fumaric acid. Plasmid pLdhA71X, containing a large ldhA fragment (6.1 kb), routinely yielded higher levels of lactic acid than the smaller region (3.3 kb) used to construct plasmid pLdhA48XI. The greatest levels of ldhA transcript and enzyme production occurred with isolates transformed with plasmid pLdhA89VII. However, these transformants always produced less lactic acid and higher amounts of ethanol, fumaric, and glycerol compared with the control.

  20. Long term intensive exercise training leads to a higher plasma malate/lactate dehydrogenase (M/L) ratio and increased level of lipid mobilization in horses.

    Science.gov (United States)

    Li, Gebin; Lee, Peter; Mori, Nobuko; Yamamoto, Ichiro; Arai, Toshiro

    2012-06-01

    Continuous high intensity training may induce alterations to enzyme activities related to glucose and lipid metabolism in horses. In our study, five Thoroughbred race horses (3 male and 2 female, avg age=5 yrs old) were compared against five riding horses (1 male, 1 female, 3 gelding, avg age=13 yrs old) in terms of energy metabolism, by examining plasma malate (MDH) and lactate (LDH) dehydrogenase activities and M/L ratio. MDH is involved in NADH and ATP generation, whereas LDH can convert NADH back into NAD(+) for ATP generation. An increase in plasma M/L ratio can reflect heightened energy metabolism in the liver and skeletal muscle of horses adapted to continuous intensive exercise. Moreover, plasma lipid metabolism analytes (adiponectin, NEFA, total cholesterol (T-Cho), and triglycerides (TG)) can reflect changes to lipolysis rate, which can also indicate a change in energy metabolism. Overall, race horses demonstrated increased MDH and LDH activity in plasma (4x and 2x greater, respectively), in addition to a plasma M/L ratio twice as high as that of riding horses (2.0 vs 1.0). In addition, race horses also demonstrated significantly higher levels of plasma NEFA (50% greater), TG (2x greater), and T-Cho (20% greater) as compared to riding horses. Therefore, race horse muscles may have adapted to prolonged high intensity endurance exercise by gaining a higher oxidative capacity and an increased capacity for fat utilization as an energy source, resulting in heightened energy metabolism and increased rate of lipid mobilization.

  1. Serum alcohol dehydrogenase levels in patients with mental disorders.

    Science.gov (United States)

    Kravos, Matej; Malesic, Ivan; Levanic, Suzana

    2005-11-01

    Alcohol dehydrogenase (ADH) was assessed in 81 patients admitted to hospital for treatment for alcohol dependence with or without liver cirrhosis, 20 patients with bipolar disorder treated with lithium carbonate and 41 patients with various mental disorders treated with psychopharmacologic agents. Testing the hypothesis of the arithmetic mean showed that in alcohol dependents the arithmetic mean of ADH activity (12.19 nkat/l+/-5.61) differs significantly from that in healthy subjects (4.45 nkat/l+/-2.31) and in the group with ethanol poisoning (6.24 nkat/l+/-3.65) there is none. In the group with bipolar disorder, treated with lithium (7.39 nkat/l+/-3.11) and, in the group of patients treated with psychiatric drugs because of various mental disorders (7.79 nkat/l+/-8.51), the differences are statistically significant. In our opinion, assessing ADH activity in the sera of alcohol dependents could be an additional marker advantageous to the diagnostics, course and monitoring of therapy in such patients. In the groups of patients with mental disorders treated with psychotropic drugs, the increased ADH activity was found to be a more sensitive marker for the detection of drug hepatotoxicity.

  2. Reduced grain chalkiness and its possible physiological mechanism in transgenic rice overexpressing l-GalLDH

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    Le Yu

    2015-04-01

    Full Text Available Chalkiness is one of the key factors determining rice quality and price. Ascorbic acid (Asc is a major plant antioxidant that performs many functions in plants. l-Galactono-1,4-lactone dehydrogenase (l-GalLDH, EC1.3.2.3 is an enzyme that catalyzes the final step of Asc biosynthesis in plants. Here we show that the l-GalLDH-overexpressing transgenic rice, GO-2, which has constitutively higher leaf Asc content than wild-type (WT plants, exhibits significantly reduced grain chalkiness. Higher foliar ascorbate/dehydroascorbate (Asc/DHA ratios at 40, 60, 80, and 100 days of plant age were observed in GO-2. Further investigation showed that the enhanced level of Asc resulted in a significantly higher ribulose-1,5-bisphosphate (RuBP carboxylase/oxygenase (Rubisco protein level in GO-2 at 80 days. In addition, levels of abscisic acid (ABA and jasmonic acid (JA were lower in GO-2 at 60, 80, and 100 days. The results we present here indicate that the enhanced level of Asc is likely responsible for changing redox homeostasis in key developmental stages associated with grain filling and alters grain chalkiness in the l-GalLDH-overexpressing transgenic by maintaining photosynthetic function and affecting phytohormones associated with grain filling.

  3. Reduced grain chalkiness and its possible physiological mechanism in transgenic rice overexpressing L-GalLDH

    Institute of Scientific and Technical Information of China (English)

    Le; Yu; Yonghai; Liu; Jianhua; Tong; Junhui; Ding; Ruozhong; Wang; Changlian; Peng; Langtao; Xiao

    2015-01-01

    Chalkiness is one of the key factors determining rice quality and price. Ascorbic acid(Asc) is a major plant antioxidant that performs many functions in plants. L-Galactono-1,4-lactone dehydrogenase(L-Gal LDH, EC1.3.2.3) is an enzyme that catalyzes the final step of Asc biosynthesis in plants. Here we show that the L-Gal LDH-overexpressing transgenic rice, GO-2,which has constitutively higher leaf Asc content than wild-type(WT) plants, exhibits significantly reduced grain chalkiness. Higher foliar ascorbate/dehydroascorbate(Asc/DHA)ratios at 40, 60, 80, and 100 days of plant age were observed in GO-2. Further investigation showed that the enhanced level of Asc resulted in a significantly higher ribulose-1,5-bisphosphate(Ru BP) carboxylase/oxygenase(Rubisco) protein level in GO-2 at 80 days. In addition, levels of abscisic acid(ABA) and jasmonic acid(JA) were lower in GO-2 at 60, 80, and100 days. The results we present here indicate that the enhanced level of Asc is likely responsible for changing redox homeostasis in key developmental stages associated with grain filling and alters grain chalkiness in the L-Gal LDH-overexpressing transgenic by maintaining photosynthetic function and affecting phytohormones associated with grain filling.

  4. Effect of anti-parasite drugs on the recombinant lactate dehydrogenase from Clonorchis senensis%4种驱虫药对重组华支睾乳酸脱氢酶(CsLDH)作用研究

    Institute of Scientific and Technical Information of China (English)

    黄灿; 胡旭初; 王乐旬; 吕刚; 余新炳; 徐劲

    2009-01-01

    目的 检测吡喹酮以及苯并咪唑类药物对重组的华支睾吸虫乳酸脱氢酶(CsLDH)酶促功能的影响,探讨其药物作用机制.方法 将不同浓度的吡喹酮、阿苯达唑、芬苯达唑和甲苯咪唑加入CsLDH所催化的丙酮酸还原成乳酸(正反应)以及乳酸氧化成丙酮酸(逆反应)的标准反应体系当中,紫外分光光度法测定NADH在A340处吸光度,SPSS16.0统计软件分析试验数据.结果 相比于对照组,9mmol/L的吡喹酮对正、逆反应的抑制均可达到94%(P<0.01);0.2 mmol/L的阿苯达唑对正、逆反应的抑制分别为84%(P<0.01)和79%(P <0.01),0.06 mmol/L的芬苯达唑对正、逆反应的抑制分别为92%(P<0.01)和86%(P<0.01),0.1 mmol/L的甲苯咪唑对正、逆反应分别为98%(P<0.01)和87%(P<0.01).结论 吡喹酮、阿苯达唑、芬苯达唑和甲苯咪唑可能以CsLDH为作用靶点杀伤华支睾吸虫而发挥治疗作用.

  5. SERUM LACTATE DEHYDROGENASE AS A PROGNOSTIC MARKER IN BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Hardik

    2015-11-01

    Full Text Available : BACKGROUND: Breast cancer a multifactorial disease and one of the most dreaded of human diseases that claims the lives of thousands of women all over the globe every year. This may probably due to the fact that it remains undiagnosed at an early stage perhaps due to lack of awareness amongst the females and the fact that most cancers do not produce any symptoms until the tumour are too large to be removed surgically. Hence there is need to detect cancer at an early stage. AIM: Estimation of diagnostic importance and prognostication of serum Lactate dehydrogenase in cases on breast cancer. SETTINGS AND DESIGN: An observational study was conducted in Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe, Wardha which included 44 confirmed cases of carcinoma breast and 44 normal healthy females admitted in AVBRH in a span of 2 years. METHODS AND MATERIAL: Determination of serum LDH was done using TC matrix analyser. The values of LDH were obtained on presentation, 21 days after intervention, 2 months after intervention and 6 months after intervention. The values of LDH on presentation in both the groups were compared. The decline in the values of LDH were observed with the due course of treatment. Chisquare test and Student’s Unpaired and paired t test were used for statistical analysis. RESULT: The mean Lactate dehydrogenase on presentation was in study group and control group was 564.38±219.41 IU/L and 404.18±101.32 IU/L respectively (p<0.05. The levels of Lactate dehydrogenase decreased with due course of treatment. The levels of LDH were proportionate to the stage of disease. CONCLUSION: The results of the study concludes cost effective usefulness of serum Lactate dehydrogenase in early detection of breast cancer and to assess its prognostic importance which can be done in smaller laboratories. The traditional model of DS-

  6. Renal Cortical Lactate Dehydrogenase: A Useful, Accurate, Quantitative Marker of In Vivo Tubular Injury and Acute Renal Failure.

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    Richard A Zager

    Full Text Available Studies of experimental acute kidney injury (AKI are critically dependent on having precise methods for assessing the extent of tubular cell death. However, the most widely used techniques either provide indirect assessments (e.g., BUN, creatinine, suffer from the need for semi-quantitative grading (renal histology, or reflect the status of residual viable, not the number of lost, renal tubular cells (e.g., NGAL content. Lactate dehydrogenase (LDH release is a highly reliable test for assessing degrees of in vitro cell death. However, its utility as an in vivo AKI marker has not been defined. Towards this end, CD-1 mice were subjected to graded renal ischemia (0, 15, 22, 30, 40, or 60 min or to nephrotoxic (glycerol; maleate AKI. Sham operated mice, or mice with AKI in the absence of acute tubular necrosis (ureteral obstruction; endotoxemia, served as negative controls. Renal cortical LDH or NGAL levels were assayed 2 or 24 hrs later. Ischemic, glycerol, and maleate-induced AKI were each associated with striking, steep, inverse correlations (r, -0.89 between renal injury severity and renal LDH content. With severe AKI, >65% LDH declines were observed. Corresponding prompt plasma and urinary LDH increases were observed. These observations, coupled with the maintenance of normal cortical LDH mRNA levels, indicated the renal LDH efflux, not decreased LDH synthesis, caused the falling cortical LDH levels. Renal LDH content was well maintained with sham surgery, ureteral obstruction or endotoxemic AKI. In contrast to LDH, renal cortical NGAL levels did not correlate with AKI severity. In sum, the above results indicate that renal cortical LDH assay is a highly accurate quantitative technique for gauging the extent of experimental acute ischemic and toxic renal injury. That it avoids the limitations of more traditional AKI markers implies great potential utility in experimental studies that require precise quantitation of tubule cell death.

  7. Epilepsy treatment. Targeting LDH enzymes with a stiripentol analog to treat epilepsy.

    Science.gov (United States)

    Sada, Nagisa; Lee, Suni; Katsu, Takashi; Otsuki, Takemi; Inoue, Tsuyoshi

    2015-03-20

    Neuronal excitation is regulated by energy metabolism, and drug-resistant epilepsy can be suppressed by special diets. Here, we report that seizures and epileptiform activity are reduced by inhibition of the metabolic pathway via lactate dehydrogenase (LDH), a component of the astrocyte-neuron lactate shuttle. Inhibition of the enzyme LDH hyperpolarized neurons, which was reversed by the downstream metabolite pyruvate. LDH inhibition also suppressed seizures in vivo in a mouse model of epilepsy. We further found that stiripentol, a clinically used antiepileptic drug, is an LDH inhibitor. By modifying its chemical structure, we identified a previously unknown LDH inhibitor, which potently suppressed seizures in vivo. We conclude that LDH inhibitors are a promising new group of antiepileptic drugs.

  8. Major Role of NAD-Dependent Lactate Dehydrogenases in the Production of l-Lactic Acid with High Optical Purity by the Thermophile Bacillus coagulans.

    Science.gov (United States)

    Wang, Limin; Cai, Yumeng; Zhu, Lingfeng; Guo, Honglian; Yu, Bo

    2014-12-01

    Bacillus coagulans 2-6 is an excellent producer of optically pure l-lactic acid. However, little is known about the mechanism of synthesis of the highly optically pure l-lactic acid produced by this strain. Three enzymes responsible for lactic acid production-NAD-dependent l-lactate dehydrogenase (l-nLDH; encoded by ldhL), NAD-dependent d-lactate dehydrogenase (d-nLDH; encoded by ldhD), and glycolate oxidase (GOX)-were systematically investigated in order to study the relationship between these enzymes and the optical purity of lactic acid. Lactobacillus delbrueckii subsp. bulgaricus DSM 20081 (a d-lactic acid producer) and Lactobacillus plantarum subsp. plantarum DSM 20174 (a dl-lactic acid producer) were also examined in this study as comparative strains, in addition to B. coagulans. The specific activities of key enzymes for lactic acid production in the three strains were characterized in vivo and in vitro, and the levels of transcription of the ldhL, ldhD, and GOX genes during fermentation were also analyzed. The catalytic activities of l-nLDH and d-nLDH were different in l-, d-, and dl-lactic acid producers. Only l-nLDH activity was detected in B. coagulans 2-6 under native conditions, and the level of transcription of ldhL in B. coagulans 2-6 was much higher than that of ldhD or the GOX gene at all growth phases. However, for the two Lactobacillus strains used in this study, ldhD transcription levels were higher than those of ldhL. The high catalytic efficiency of l-nLDH toward pyruvate and the high transcription ratios of ldhL to ldhD and ldhL to the GOX gene provide the key explanations for the high optical purity of l-lactic acid produced by B. coagulans 2-6. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  9. Opportunities for improving pLDH-based malaria diagnostic tests

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    Choi Young

    2011-08-01

    Full Text Available Abstract Background Monoclonal antibodies to Plasmodium lactate dehydrogenase (pLDH have been previously used to format immunochromatographic tests for the diagnosis of malaria. Using pLDH as an antigen has several advantages as a sensitive measure of the presence of parasites within patient blood samples. However, variable results in terms of specificity and sensitivity among different commercially available diagnostic kits have been reported and it has not been clear from these studies whether the performance of an individual test is due simply to how it is engineered or whether it is due to the biochemical nature of the pLDH-antibody reaction itself. Methods A series of systematic studies to determine how various pLDH monoclonal antibodies work in combination was undertaken. Different combinations of anti-pLDH monoclonal antibodies were used in a rapid-test immunochromatographic assay format to determine parameters of sensitivity and specificity with regard to individual Plasmodium species. Results Dramatic differences were found in both species specificity and overall sensitivity depending on which antibody is used on the immunochromatographic strip and which is used on the colorimetric colloidal-gold used for visual detection. Discussion The results demonstrate the feasibility of different test formats for the detection and speciation of malarial infections. In addition, the data will enable the development of a universal rapid test algorithm that may potentially provide a cost-effective strategy to diagnose and manage patients in a wide range of clinical settings. Conclusion These data emphasize that using different anti-pLDH antibody combinations offers a tractable way to optimize immunochromatographic pLDH tests.

  10. Lactate Dehydrogenase Is an Important Prognostic Indicator for Hepatocellular Carcinoma after Partial Hepatectomy

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    Jing-Ping Zhang

    2015-12-01

    Full Text Available Preoperative serum lactate dehydrogenase (LDH has been used as a prognostic indicator for patients with hepatocellular carcinoma (HCC treated with sorafenib or undergoing transcatheter arterial chemoembolization, but its significance in predicting survival of HCC patients who received curative resection remains undefined. A total of 683 patients with histopathologically confirmed HCC were enrolled in this study. The prognostic significance of preoperative serum LDH was determined by Kaplan-Meier analysis and a Cox proportional hazards regression model. The association between the preoperative serum LDH and clinicopathological parameters was evaluated by the χ2 test or linear regression analysis when appropriate. Higher preoperative serum LDH level was associated with worse prognosis. In a multivariate Cox proportional hazards analysis, the preoperative serum LDH level could predict overall survival and recurrence independently. Higher preoperative serum LDH level is associated with the elevated serum alpha-fetoprotein, the presence of hepatitis B surface antigen, larger tumor size, the presence of macrovascular invasion, the advanced tumor–lymph node–metastasis stage, worse tumor differentiation, and Child-Pugh B. Preoperative serum LDH level was an inexpensive, simple, convenient, and routinely measured biomarker exhibiting a potential to select patients at high risk with poor clinical outcome for appropriate treatment strategies.

  11. 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

    a homolactic pattern of fermentation. Only after lactate dehydrogenase activity was reduced ninefold compared to the wild-type was the growth rate significantly affected, and the ldh mutants started to produce mixed-acid products (formate, acetate, and ethanol in addition to lactate). Flux control coefficients...... were determined and it was found that lactate dehydrogenase exerted virtually no control on the glycolytic flux at the wild-type enzyme level and also not on the flux catalyzed by the enzyme itself, i.e. on the lactate production. As expected, the flux towards the mixed-acid products was strongly...... 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...

  12. 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

    A series of mutant strains of Lactococcus lactis were constructed with lactate dehydrogenase (LDH) activities ranging from below 1% to 133% of the wild-type activity level. The mutants with 59% to 133% of lactate dehydrogenase activity had growth rates similar to the wild-type and showed...... a homolactic pattern of fermentation. Only after lactate dehydrogenase activity was reduced ninefold compared to the wild-type was the growth rate significantly affected, and the ldh mutants started to produce mixed-acid products (formate, acetate, and ethanol in addition to lactate). Flux control coefficients...... were determined and it was found that lactate dehydrogenase exerted virtually no control on the glycolytic flux at the wild-type enzyme level and also not on the flux catalyzed by the enzyme itself, i.e. on the lactate production. As expected, the flux towards the mixed-acid products was strongly...

  13. Utility of NSE, ProGRP and LDH in Diagnosis and Treatment
in Patients with Small Cell Lung Cancer

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    Yan PENG

    2016-09-01

    Full Text Available Background and objective Small cell lung cancer (SCLC is a rapidly growing tumor with characteristic of neuroendocrine cellular function. Neuron specific enolase (NSE, pro-gastrin-releasing peptide (ProGRP and lactic dehydrogenase (LDH are valuable in diagnosis and treatment of SCLC. By analyzing the variation of NSE, ProGRP and LDH before and after treatment, the aim of this study is to investigate the efficacy of tumor markers in diagnostic staging, therapeutic evaluation and prediction of disease relapsing. Methods Patients with SCLC who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic (includes NSE, ProGRP and LDH level before and after 2 cycles chemotherapy, efficacy evaluation, progression-free survival (PFS were analyzed. Results Before treatment, Serum NSE, ProGRP and LDH in patients with extensive disease (ED were significantly higher than those with limited disease (LD(all P4 cycles chemotherapy and with obvious decrease of ProGRP than those who accepted ≤4 cycles chemotherapy and with less obvious decrease of ProGRP in LD group; ED patients with no more than 2 distant metastasis, normal LDH level before treatment and obvious decrease of ProGRP after chemotherapy had lower short term relapse risk. In addition, the types of relapse (sensitive relapse, drug resistance relapse and refractory relapse were negatively correlated with decrease of ProGRP (P=0.044. By multivariate analysis, numbers of chemotherapy cycle was independent prognostic factor for PFS in LD SCLC; numbers of distant metastasis and decrease of ProGRP were independent prognostic factors for PFS in ED SCLC. Conclusion Increase level of serum tumor markers is related to tumor burden. Decrease level of ProGRP after treatment may prognose efficacy and relapse risk.

  14. Cloning of Lactate dehydrogenase Gene and Effect on the Waterlogging Tolerance of Brassica napus L.

    Directory of Open Access Journals (Sweden)

    Ben-bo Xu

    2012-10-01

    Full Text Available To investigate the mechanism on waterlogging tolerance in Brassica napus, 12 B. napus cultivars with different waterlogging tolerance were used in the research and Waterlogging Tolerance Index (WTI was calculated by multiplying relative percentage germination and the relative seedling height. The results indicated that Lactate Dehydrogenase (LDH enzyme activity rapidly increased at 24 h after waterlogging treatment and reached peak between 48-72 h. WTI was correlated with LDH enzyme activity at 24 h after water logging treatment and the correlation coefficient between them was 0.84. Transcription level of the BnLDH had significant difference in the 12 lines after waterlogging treatment. BnLDH expression level was very low before waterlogging treatment and induced by waterlogging treatment and arrived at peak at 48 h. Correlation analysis indicated correlation coefficient between WTI and BnLDH expression at 24 and 48 h after waterlogging treatment was 0.56 and 0.72, respectively. An LDH gene, denoted BnLDH-1, was cloned from oilseeds by the Rapid Amplification of CDNA Ends (RACE from 12 materials and the results indicated all of them had same protein sequence.

  15. Serum lactate dehydrogenase profile as a retrospective indicator of uterine preparedness for labor: a prospective, observational study.

    Science.gov (United States)

    Neal, Jeremy L; Lowe, Nancy K; Corwin, Elizabeth J

    2013-06-08

    Lactate dehydrogenase (LDH) isoenzymes are required for adenosine triphosphate production, with each of five different isoenzymes having varying proficiencies in anaerobic versus aerobic environments. With advancing pregnancy, the isoenzyme profile in uterine muscle shifts toward a more anaerobic profile, speculatively to facilitate uterine efficiency during periods of low oxygen that accompany labor contractions. Profile shifting may even occur throughout labor. Maternal serum LDH levels between 24-48 hours following delivery predominantly originate from uterine muscle, reflecting the enzymatic state of the myometrium during labor. Our purpose was to describe serum LDH isoenzymes 24-30 hours post-delivery to determine if cervical dilation rates following labor admission were associated with a particular LDH profile. We also compared differences in post-delivery LDH isoenzyme profiles between women admitted in pre-active versus established active labor. Low-risk, nulliparous women with spontaneous labor onset were sampled (n = 91). Maternal serum LDH was measured at labor admission and 24-30 hours post-vaginal delivery. Rates of cervical dilation during the first four hours after admission were also measured. Spearman's rho coefficients were used for association testing and t tests evaluated for group and paired-sample differences. More efficient dilation following admission was associated with decreased LDH1 (p = 0.029) and increased LDH3 and LDH4 (p = 0.017 and p = 0.017, respectively) in the post-delivery period. Women admitted in established active labor had higher relative serum levels of LDH3 (t = 2.373; p = 0.023) and LDH4 (t = 2.268; p = 0.029) and lower levels of LDH1 (t = 2.073; p = 0.045) and LDH5 (t = 2.041; p = 0.048) when compared to women admitted in pre-active labor.Despite having similar dilatations at admission (3.4 ± 0.5 and 3.7 ± 0.6 cm, respectively), women admitted in pre-active labor had longer in-hospital labor durations (12.1 ± 4.3 vs. 5

  16. Evaluation on the inhibition of pyrrol-2-yl ethanone derivatives to lactate dehydrogenase and anticancer activities

    Science.gov (United States)

    Lu, Na-Na; Weng, Zhao-Yue; Chen, Qiu-Yun; Boison, Daniel; Xiao, Xin-Xin; Gao, Jing

    2016-08-01

    Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. In order to develop bifunctional compounds as inhibitor of LDH-A and anticancer agents, two pyrrol-2-yl methanone (or ethanone) derivatives (PM1 and PM2) were synthesized and evaluated as inhibitors of LDH-A based on the enzyme assay and cell assay by spectroscopy analysis. Fluorescence and CD spectra results demonstrated that both the change of second structure of LDH-A and the affinity interaction for compounds to LDH-A gave great effect on the activity of LDH-A. In particular, low concentration of compounds (1 μμ-25 μμ) could change the level of pyruvate in cancer cells. Moreover, the in vitro assay results demonstrated that pyrrol-2-yl ethanone derivatives can inhibit the proliferation of cancer cells. Therefore, pyrrol-2-yl ethanone derivatives (PM2) can be both LDH-A inhibitor and anticancer agents.

  17. The negative impact of α-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation.

    Science.gov (United States)

    Kiss, Gergely; Konrad, Csaba; Doczi, Judit; Starkov, Anatoly A; Kawamata, Hibiki; Manfredi, Giovanni; Zhang, Steven F; Gibson, Gary E; Beal, M Flint; Adam-Vizi, Vera; Chinopoulos, Christos

    2013-06-01

    A decline in α-ketoglutarate dehydrogenase complex (KGDHC) activity has been associated with neurodegeneration. Provision of succinyl-CoA by KGDHC is essential for generation of matrix ATP (or GTP) by substrate-level phosphorylation catalyzed by succinyl-CoA ligase. Here, we demonstrate ATP consumption in respiration-impaired isolated and in situ neuronal somal mitochondria from transgenic mice with a deficiency of either dihydrolipoyl succinyltransferase (DLST) or dihydrolipoyl dehydrogenase (DLD) that exhibit a 20-48% decrease in KGDHC activity. Import of ATP into the mitochondrial matrix of transgenic mice was attributed to a shift in the reversal potential of the adenine nucleotide translocase toward more negative values due to diminished matrix substrate-level phosphorylation, which causes the translocase to reverse prematurely. Immunoreactivity of all three subunits of succinyl-CoA ligase and maximal enzymatic activity were unaffected in transgenic mice as compared to wild-type littermates. Therefore, decreased matrix substrate-level phosphorylation was due to diminished provision of succinyl-CoA. These results were corroborated further by the finding that mitochondria from wild-type mice respiring on substrates supporting substrate-level phosphorylation exhibited ~30% higher ADP-ATP exchange rates compared to those obtained from DLST(+/-) or DLD(+/-) littermates. We propose that KGDHC-associated pathologies are a consequence of the inability of respiration-impaired mitochondria to rely on "in-house" mitochondrial ATP reserves.

  18. Supplementation of medium with diammonium hydrogen phosphate enhanced the D-lactate dehydrogenase levels leading to increased D-lactic acid productivity.

    Science.gov (United States)

    Singhvi, Mamata; Jadhav, Akanksha; Gokhale, Digambar

    2013-10-01

    The production of D-lactic acid by Lactobacillus lactis RM2-24 was investigated using modified media to increase the efficiency of the fermentation process. The results indicated that the addition of 5 g/l peptone and 1 g/l (NH4)2HPO4 enhanced D-lactic acid production by 32%, as compared to that obtained from non supplemented media, with a productivity of 3.0 g/l/h. Lactate dehydrogenase (LDH) expression profile in these different media was studied which resulted in appearance of additional LDH isoform produced by cells when they were grown in HSYE supplemented with (NH4)2HPO4. The additional LDH appears to be L-LDH contributing to production of L-lactic acid in the fermented broth. This is totally new information in the lactic acid fermentation and could be very useful to industries engaged in D-lactic acid production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Acute overexpression of lactate dehydrogenase-A perturbs beta-cell mitochondrial metabolism and insulin secretion.

    Science.gov (United States)

    Ainscow, E K; Zhao, C; Rutter, G A

    2000-07-01

    Islet beta-cells express low levels of lactate dehydrogenase and have high glycerol phosphate dehydrogenase activity. To determine whether this configuration favors oxidative glucose metabolism via mitochondria in the beta-cell and is important for beta-cell metabolic signal transduction, we have determined the effects on glucose metabolism and insulin secretion of acute overexpression of the skeletal muscle isoform of lactate dehydrogenase (LDH)-A. Monitored in single MIN6 beta-cells, LDH hyperexpression (achieved by intranuclear cDNA microinjection or adenoviral infection) diminished the response to glucose of both phases of increases in mitochondrial NAD(P)H, as well as increases in mitochondrial membrane potential, cytosolic free ATP, and cystolic free Ca2+. These effects were observed at all glucose concentrations, but were most pronounced at submaximal glucose levels. Correspondingly, adenoviral vector-mediated LDH-A overexpression reduced insulin secretion stimulated by 11 mmol/l glucose and the subsequent response to stimulation with 30 mmol/l glucose, but it was without significant effect when the concentration of glucose was raised acutely from 3 to 30 mmol/l. Thus, overexpression of LDH activity interferes with normal glucose metabolism and insulin secretion in the islet beta-cell type, and it may therefore be directly responsible for insulin secretory defects in some forms of type 2 diabetes. The results also reinforce the view that glucose-derived pyruvate metabolism in the mitochondrion is critical for glucose-stimulated insulin secretion in the beta-cell.

  20. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Fujin [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Ma, Song [Department of Urinary Surgery, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Xue, Yubao [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China); Hou, Jianquan, E-mail: Jianquanhou@aliyun.com [Department of Urinary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu (China); Zhang, Yongjie, E-mail: zhangyj0818@126.com [Department of Medical Oncology, Huai' an Hospital to Xuzhou Medical University, Huai' an, Jiangsu (China)

    2016-01-22

    Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC. - Highlights: • Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. • IHC analysis of 136 MIBC specimens revealed increased LDH-A is correlated with positive Oct4 and negative E-cadherin. • In vitro experiments demonstrated LDH-A promotes MIBC progression by positive regulation of EMT/CSC.

  1. LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer.

    Science.gov (United States)

    Jiang, Fujin; Ma, Song; Xue, Yubao; Hou, Jianquan; Zhang, Yongjie

    2016-01-22

    Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC.

  2. The effect of extracellular alkalinization on lactate metabolism of breast cancer stem cells: Overview of LDH-A, LDH-B, MCT1 and MCT4 gene expression

    Science.gov (United States)

    Neolaka, G. M. G.; Yustisia, I.; Sadikin, M.; Wanandi, S. I.

    2017-08-01

    Changes in the metabolic status of cancer cells are presumed to be correlated with the adjustment of these cells to extracellular changes. Cell glycolysis increases the production of intracellular lactate catalyzed by the lactate dehydrogenases, both LDH-A and LDH-B. An increase in intracellular lactate can affect extracellular pH balance through monocarboxylate transporters, particularly MCT1 and MCT4. This study aimed to analyze the effects of extracellular alkalinization on the lactate metabolism of human breast cancer stem cells (BCSCs). In this study, human primary BCSCs (CD24-/CD44+ cells) were treated with 100 mM sodium bicarbonate for 0.5, 24, and 48 h in DMEM F12/HEPES. After incubation, extracellular pH was measured and cells were harvested to extract the total RNA and protein. The expression of LDH-A, LDH-B, MCT1, and MCT4 mRNA genes were analyzed using qRT-PCR method. Our study shows that administration of sodium bicarbonate in the BCSC culture medium could increase extracellular pH. To balance the increase of extracellular pH, BCSCs regulated the expression of LDH-A, LDH-B, MCT1, and MCT4 genes. As the extracellular pH increases, the expression of LDH-A that converts pyruvate to lactate increased along with the increase of MCT 4 and MCT 1 expression, which act as lactate transporters. As the incubation time increases, the pH decreases, leading to the suppression of LDH-A and increase of LDH-B expression that converts lactate into pyruvate. Therefore, we suggest that the extracellular alkalinization by sodium bicarbonate in BCSCs affected the genes that regulate lactate metabolism.

  3. Ascorbic acid deficiency leads to increased grain chalkiness in transgenic rice for suppressed of L-GalLDH.

    Science.gov (United States)

    Yu, Le; Liu, Yonghai; Lu, Lina; Zhang, Qilei; Chen, Yezheng; Zhou, Liping; Chen, Hua; Peng, Changlian

    2017-04-01

    The grain chalkiness of rice (Oryza sativa L.), which determines the rice quality and price, is a major concern in rice breeding. Reactive oxygen species (ROS) plays a critical role in regulating rice endosperm chalkiness. Ascorbic acid (Asc) is a major plant antioxidant, which strictly regulates the levels of ROS. l-galactono-1, 4-lactone dehydrogenase (L-GalLDH, EC 1.3.2.3) is an enzyme that catalyzes the last step of Asc biosynthesis in higher plants. Here we show that the L-GalLDH-suppressed transgenic rice, GI-1 and GI-2, which have constitutively low (between 30% and 50%) leaf and grain Asc content compared with the wild-type (WT), exhibit significantly increased grain chalkiness. Further examination showed that the deficiency of Asc resulted in a higher lipid peroxidation and H2O2 content, accompanied by a lower hydroxyl radical scavenging rate, total antioxidant capacity and photosynthetic ability. In addition, changes of the enzyme activities and gene transcript abundances related to starch synthesis were also observed in GI-1 and GI-2 grains. The results we presented here suggest a close correlation between Asc deficiency and grain chalkiness in the L-GalLDH-suppressed transgenics. Asc deficiency leads to the accumulation of H2O2, affecting antioxidant capacity and photosynthetic function, changing enzyme activities and gene transcript abundances related to starch synthesis, finally leading to the increased grain chalkiness. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Elevated lactate dehydrogenase activity and increased cardiovascular mortality in the arsenic-endemic areas of southwestern Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Ya-Tang [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Genomics Research Center, Academia Sinica, Taiwan (China); Chen, Chien-Jen [Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Genomics Research Center, Academia Sinica, Taiwan (China); Li, Wan-Fen [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Hsu, Ling-I [Genomics Research Center, Academia Sinica, Taiwan (China); Tsai, Li-Yu; Huang, Yeou-Lih [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Taiwan (China); Sun, Chien-Wen [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Chen, Wei J., E-mail: wjchen@ntu.edu.tw [Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Genetic Epidemiology Core Laboratory, National Taiwan University Center for Genomic Medicine, Taiwan (China); Wang, Shu-Li, E-mail: slwang@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan (China); Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan (China)

    2012-08-01

    Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validated for the evaluation of long-term, chronic arsenic exposure. The present study examined the long-term effect of chronic arsenic exposure on CVD and serum LDH levels, after consideration of arsenic metabolism capacity. A total of 380 subjects from an arseniasis-endemic area and 303 from a non-endemic area of southwestern Taiwan were recruited in 2002. Various urinary arsenic species were analyzed using high-performance liquid chromatography (HPLC) and hydride generation systems. Fasting serum was used for quantitative determination of the total LDH activity. A significant dose–response relationship was observed between arsenic exposure and LDH elevation, independent of urinary arsenic profiles (P < 0.001). Furthermore, abnormal LDH elevation was associated with CVD mortality after adjustment for Framingham risk scores for 10-year CVD and arsenic exposure (hazard ratio, 3.98; 95% confidence interval, 1.07–14.81). LDH was elevated in subjects with arsenic exposure in a dose-dependent manner. LDH is a marker of arsenic toxicity associated with CVD mortality. Results of this study have important implications for use in ascertaining long-term arsenic exposure risk of CVD. -- Highlights: ► We showed that arsenic exposure was correlated with LDH elevation. ► LDH elevation was related to arsenic methylation capacity. ► Abnormal LDH elevation can be a marker of susceptibility to CVD mortality.

  5. Molecular characterization and expression studies during melon fruit development and ripening of L-galactono-1,4-lactone dehydrogenase

    DEFF Research Database (Denmark)

    Pateraki, Irene; Sanmartin, Maite; Kalamaki, Mary S.

    2004-01-01

    The last step of ascorbic acid (AA) biosynthesis is catalysed by the enzyme L-galactono-1,4-lactone dehydrogenase (GalLDH, EC 1.3.2.3), located on the inner mitochondrial membrane. The enzyme converts L-galactono-1,4-lactone to ascorbic acid (AA). In this work, the cloning and characterization...... of a GalLDH full-length cDNA from melon (Cucumis melo L.) are described. Melon genomic DNA Southern analysis indicated that CmGalLDH was encoded by a single gene. CmGalLDH mRNA accumulation was detected in all tissues studied, but differentially expressed during fruit development and seed germination......GalLDH expression is regulated by light. Finally, various stresses and growth regulators resulted in no significant change in steady state levels of CmGalLDH mRNA in 20-d-old melon seedlings. To the authors' knowledge, this is the first report of GalLDH transcript induction in seed germination and differential gene...

  6. Repercussões da L-alanil-glutamina sobre as concentrações de lactato e lactato desidrogenase (LDH em pacientes com isquemia crítica dos membros inferiores submetidos a revascularização distal Repercussions of l-alanyl-glutamine upon the concentrations of lactate and lactate dehydrogenase (LDH in patients with critical ischemia of lower limbs subjected to distal revascularization

    Directory of Open Access Journals (Sweden)

    Wellington Forte Alves

    2003-06-01

    Full Text Available OBJETIVO: Investigar efeitos da L-alanil-glutamina nas concentrações musculares de lactato, e nas concentrações sanguíneas de LDH, em pacientes com isquemia crítica dos membros inferiores submetidos à revascularização distal. MÉTODOS: Dezesseis adultos (12-homens/4-mulheres foram distribuídos em 2 grupos (1-controle/2-estudo. Três horas após injeção endovenosa de 250 ml de L-alanil-glutamina a 20% adicionados a 750 ml de soro fisiológico (Grupo 2, ou 1000 ml de solução salina (Grupo 1, iniciava-se a revascularização, sob raquianestesia. Amostras musculares e de sangue (arterial/venoso foram coletadas no início do procedimento (TI, no final (TF, e 10 e 20 minutos após isquemia (T1/T2. RESULTADOS: Observou-se redução significante (pPURPOSE: Investigate the repercussions of L-alanyl-glutamine in muscular tissue concentrations of lactate, and venous and arterial blood concentrations of LDH, in patients with critical ischemia of the lower limbs submitted to distal revascularization. METHODS: Sixteen adults (12 male/4 female were distributed in 2 groups (1-Control/2-Experiment. Three hours after the intravenous injection of 250 ml of a 20% solution of L-alanyl-glutamine added to 750 ml of saline solution (Group 2; or 1000 ml of saline solution (Group 1, distal bypass was carried out under spinal anesthesia. Muscle and blood samples (arterial/venous were collected at the beginning of the surgical procedure (TI, at the end (TF, and 10 and 20 minutes after re-establishment of blood flow. RESULTS: Significant reduction (p<0,05 of lactate concentration was observed in healthy muscle tissue in L-alanyl-glutamine treated patients in comparison to control group, at all times studied. There was a significant reduction (p <0,05 in venous concentrations of LDH in treated patients at all times studied (TI/TFV/T1V/T2V; and in arterial blood during reperfusion (T1A/T2A. CONCLUSIONS: 1. Decreased lactate concentrations in healthy skeletal

  7. Protein engineering applications of industrially exploitable enzymes: Geobacillus stearothermophilus LDH and Candida methylica FDH.

    Science.gov (United States)

    Karagüler, N G; Sessions, R B; Binay, B; Ordu, E B; Clarke, A R

    2007-12-01

    Enzymes have become important tools in several industries due to their ability to produce chirally pure and complex molecules with interesting biological properties. The NAD(+)-dependent LDH (lactate dehydrogenase) [bsLDH [Geobacillus stearothermophilus (formerly Bacillus stearothermophilus) LDH] from G. stearothermophilus and the NAD(+)-dependent FDH (formate dehydrogenase) [cmFDH (Candida methylica FDH)] enzyme from C. methylica are particularly crucial enzymes in the pharmaceutical industry and are related to each other in terms of NADH use and regeneration. LDH catalyses the interconversion of pyruvate (oxo acid) and lactate (alpha-hydroxy acid) using the NADH/NAD(+) pair as a redox cofactor. Employing LDH to reduce other oxo acids can generate chirally pure alpha-hydroxy acids of use in the production of pharmaceuticals. One important use of FDH is to regenerate the relatively expensive NADH cofactor that is used by NAD(+)-dependent oxidoreductases such as LDH. Both LDH and FDH from organisms of interest were previously cloned and overproduced. Therefore they are available at a low cost. However, both of these enzymes show disadvantages in the large-scale production of chirally pure compounds. We have applied two routes of protein engineering studies to improve the properties of these two enzymes, namely DNA shuffling and site-directed mutagenesis. Altering the substrate specificity of bsLDH by DNA shuffling and changing the coenzyme specificity of cmFDH by site-directed mutagenesis are the most successful examples of our studies. The present paper will also include the details of these examples together with some other applications of protein engineering regarding these enzymes.

  8. 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

  9. Myristica fragrans Suppresses Tumor Growth and Metabolism by Inhibiting Lactate Dehydrogenase A.

    Science.gov (United States)

    Kim, Eun-Yeong; Choi, Hee-Jung; Park, Mi-Ju; Jung, Yeon-Seop; Lee, Syng-Ook; Kim, Keuk-Jun; Choi, Jung-Hye; Chung, Tae-Wook; Ha, Ki-Tae

    2016-01-01

    Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation, rather than by maintaining a comparatively low rate of tricarboxylic acid cycle, i.e., Warburg's effect. In the pathway, the pyruvate produced by glycolysis is converted to lactic acid by lactate dehydrogenase (LDH). Here, we demonstrated that water extracts from the seeds of Myristica fragrans Houtt. (MF) inhibit the in vitro enzymatic activity of LDH. MF effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Although the expression of LDH-A was not changed by MF, both lactate production and LDH activity were decreased in MF-treated cells under both normoxic and hypoxic conditions. In addition, intracellular ATP levels were also decreased by MF treatment, and the uptake of glucose was also reduced by MF treatment. Furthermore, the experiment on tumor growth in the in vivo mice model revealed that MF effectively reduced the growth of allotransplanted Lewis lung carcinoma cells. Taken together, these results suggest that MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. These results implicate MF as a potential candidate for development into a novel drug against cancer through inhibition of LDH activity.

  10. Validity of a New Kit Measuring Salivary Lactate Dehydrogenase Level for Screening Gingivitis

    Science.gov (United States)

    Ekuni, Daisuke; Kataoka, Kota; Yokoi, Aya; Taniguchi-Tabata, Ayano; Mizuno, Hirofumi; Miyai, Hisataka; Uchida, Yoko; Fukuhara, Daiki; Sugiura, Yoshio; Morita, Manabu

    2017-01-01

    Aim. The aim of this study was to determine the usefulness of a new kit that can evaluate salivary lactate dehydrogenase (LD) level in real time for screening gingivitis. Materials and Methods. The study included 70 systemic healthy volunteers [29 males and 41 females; mean age ± SD: 24.1 ± 2.6 years]. Resting saliva was collected from each participant and LD level was evaluated in real time using the kit (a color-changing sheet with an integer scale ranging from 1 to 10). A dentist measured probing pocket depth, clinical attachment level, and the proportion of sites with bleeding on probing (% BOP) at six sites on all teeth. Gingivitis was diagnosed when the BOP value was ≥20%. Results. Salivary LD level was positively correlated with mean % BOP (odds ratio: 1.47, 95% confidence interval: 1.132–1.916, and P gingivitis in young adults, which contributes to early detection of future periodontitis. PMID:28337048

  11. [Effect of Guilingji Capsule on the fertility, liver functions, and serum LDH of male SD rats exposed by 900 mhz cell phone].

    Science.gov (United States)

    Ma, Hui-Rong; Li, Yuan-Yuan; Luo, Ya-Ping; Ma, Xue-Lian; Gong, Zhi-Qiang

    2014-04-01

    To observe the effect of Guilingji Capsule (GC) on the fertility, liver functions, and serum lactate dehydrogenase (LDH) of adult male SD rats exposed by 900 MHz cell phone. Totally 18 adult male SD rats and 36 adult female rats in child-bearing period were selected and randomly divided into three groups according to weight equilibrium principle, i.e., the normal group, the radiated group, and the GC group, 6 males and 12 females in each group. Male rats in the normal group and all female rats were not radiated. Male rats in the radiated group and the GC group received radiation for 4 h per day, lasting for 18 successive days. Rats in the GC group received GC suspension at the daily dose of 0. 15 g/kg by gastrogavage at the same time. Equal volume of normal saline was administrated to other male rats. Then male rats were mated with corresponding female rats from the 14th radiation night to the 18th radiation night in the ratio of 1:2. Male rats were killed following on the next morning of ending the radiation. Female rats were normally fed and then killed before delivery. The pregnant outcomes of female rats in responding groups (the rates of pregnancy and the number of death fetus, birth weight, body length, and tail length) were observed and compared. Serum alanine aminotransferase (ALT), aspartate transferase (AST), AST/ALT, and LDH levels of the male rats were detected by colorimetry. Histological and morphological changes of liver were observed by HE staining. Compared with the normal group, the pregnancy rates of female rats decreased and the number of death fetus increased, the serum LDH level obviously increased in the radiated group (P LDH decreased in the GC group (P LDH level increased by exposure toy GSM 900 MHz cell phone. GC could prevent and treat the aforesaid lesion. But there was no statistical difference in serum ALT or AST levels.

  12. Tear Malate Dehydrogenase,Lactate Dehydrogenase and Their Isoenzymes in Normal Chinese Subjects and Patients of Ocular Surface Disorders

    Institute of Scientific and Technical Information of China (English)

    QingGuo; HanchengZhang

    1995-01-01

    Purose:To determine levels of malate dehydrogenase(MDH),lactate dehydroge-nase(LDH)and their isoenzymes in tears of normal Chinese subjects and patients with ocular surface disorders.Methods:The age range of normal subjects was10-88,with136mal and 128fe-male subjects.123patients suffered from ocular surface disorders.Tears were col-lected from lower fornix on Xinghua filter disc(0.1mm thick,5mm in diameter).The values of tearMDHand LDHwere determined by MONARCH-2000Ana-lyzer(U.S.A)Their isoenzymes were separated by acetate cellulose elec-trophoresis and were determined by Model CDS-200light densitometer.Results:The normal values of tear LDH and MDH were 45.51+23.00-81.35+37.84umol·s-1/Land11.00+5.33-19.50+9.17umol·s-1/Lrespectively,dis-regarding sex or eye distriction(P>0.05).The values of tear LDHandMDH in the group aged10-19were significantly lower than in another groups(P<0.05),95%normal ranges of tearMDHaged below19and above20were3.63-19.90umol·s-1/L.THe MDH isoenzymes comprised MDHs and MDHm,the former accounting for80.0-89.1%.The LDH isoenzymes comprised 5varieties.of which the ratioH/Mof subunit H tosubunit Mwas0.196+0.02.Levels of tear LDH,MDHand their isoenzymes in different diseases were various.Conclusions;Tear LDH/MDHratio reflected sensitively the matabolism of corneae and conjunetival epithelium.The changes in LDH isoenzymes were hel-ful to the differential diagnosis of external eye diseases,and the increase of MDHm reflected sensitively the degree of injury to the corneal epithelium.

  13. Androgen-stimulated UDP-glucose dehydrogenase expression limits prostate androgen availability without impacting hyaluronan levels

    Science.gov (United States)

    Wei, Qin; Galbenus, Robert; Raza, Ashraf; Cerny, Ronald L.; Simpson, Melanie A.

    2009-01-01

    UDP-glucose dehydrogenase (UGDH) oxidizes UDP-glucose to UDP-glucuronate, an essential precursor for production of hyaluronan (HA), proteoglycans, and xenobiotic glucuronides. High levels of HA turnover in prostate cancer are correlated with aggressive progression. UGDH expression is high in the normal prostate even though HA accumulation is virtually undetectable. Thus, its normal role in the prostate may be to provide precursors for glucuronosyltransferase enzymes, which inactivate and solubilize androgens by glucuronidation. In this report, we quantified androgen dependence of UGDH, glucuronosyltransferase, and HA synthase expression. Androgen dependent and independent human prostate cancer cell lines were used to test the effects of UGDH manipulation on tumor cell growth, HA production and androgen glucuronidation. Dihydrotestosterone (DHT) increased UGDH expression ≈2.5-fold in androgen dependent cells. However, upregulation of UGDH did not affect HA synthase expression or enhance HA production. Mass spectrometric analysis showed that DHT was converted to a glucuronide, DHT-G, at a six-fold higher level in androgen dependent cells relative to androgen independent cells. The increased solubilization and elimination of DHT corresponded to slower cellular growth kinetics, which could be reversed in androgen dependent cells by treatment with a UDP-glucuronate scavenger. Collectively, these results suggest that dysregulated expression of UGDH could promote the development of androgen independent tumor cell growth by increasing available levels of intracellular androgen. PMID:19244115

  14. Alcohol Dehydrogenase-1B (rs1229984 and Aldehyde Dehydrogenase-2 (rs671 Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men.

    Directory of Open Access Journals (Sweden)

    Akira Yokoyama

    Full Text Available Elevated serum triglyceride (TG and high-density-lipoprotein cholesterol (HDL-C levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype modify ethanol metabolism and are prevalent (≈90% and ≈40%, respectively in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics.The population consisted of 1806 Japanese alcoholic men (≥40 years who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission.High serum levels of TG (≥150 mg/dl, HDL-C (>80 mg/dl, and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ≥140 mg/dl were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval for a high TG level (2.22 [1.67-2.94] and 1.39 [0.99-1.96], respectively, and decreased the OR for a high HDL-C level (0.37 [0.28-0.49] and 0.51 [0.37-0.69], respectively. The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45-0.80]. The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (≥220 mg/dl and HDL-C (≥100 mg/dl.The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL

  15. Serum lactic dehydrogenase isoenzymes and serum hydroxy butyric dehydrogenase in myocardial infarction

    Directory of Open Access Journals (Sweden)

    Kanekar D

    1979-01-01

    Full Text Available Total serum lactate dehydrogenase activity in cases of myocar-dial infarct is difficult to interpret as abnormal values can occur in diseases of liver, kidney and skeletal muscle. The estimation of its isoenzymes is of better diagnostic help because of its tissue specificity. Serum LDH isoenzymes were studied in patients o f myocardial infarction and results are quantitated by densitometry. As LDH 1 represents serum hydroxybutyric dehydrogenase when 2-oxylbutyrate is used as substrate, serum hydroxybutyric dehydro-genase was also estimated in above patients. Greater specificity in diagnosis is achieved with SHBDH because of its myocardial nature and lower incidence of false positive results.

  16. [Species specificity of the isoenzyme profile of lactate dehydrogenase in organs of rodents of various ecogenesis].

    Science.gov (United States)

    Kozhevnikova, L K; Tiutiunnik, N N; Unzhakov, A R; Meldo, Kh I

    2004-02-01

    Separation of isoenzymes of lactate dehydrogenase (LDH, EC. 1.1.1.27) in extracts of heart, kidney, liver, spleen, lungs of nutrias, chinchillas by agar gel electrophoresis reveals a species specificity in ratio of electrophoretic fractions of the enzyme. The isoenzymes of LDH were seem to play an important role in adaptation of fur animals to environmental conditions. It has been shown that in semiaquatic mammals--nutrias, the relative content of the A-subunits in the isoenzymatic spectrum of LDH in organs was increased as compared with terrestrial animals--chinchillas, whereas relative content of B-subunits in these organs of chinchillas was very high. This is an example of subtle biochemical specialisation of function at molecular level to environmental conditions.

  17. 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. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  18. Lactate dehydrogenase assay for assessment of polycation cytotoxicity

    DEFF Research Database (Denmark)

    Parhamifar, Ladan; Andersen, Helene; Moghimi, Seyed Moien

    2013-01-01

    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...

  19. The impact of hypoxia on the activity of lactate dehydrogenase in two different pre-clinical tumour models

    DEFF Research Database (Denmark)

    Lukacova, Slavka; Sørensen, Brita; Alsner, Jan;

    2008-01-01

    Aim. To investigate the direct relationship between tumour hypoxia and lactate dehydrogenase (Ldh) levels in serum and tumour in two different pre-clinical murine models. Materials and methods. Experiments were performed in CDF1 or C3H/Km mice implanted with a C3H mammary carcinoma and SCCVII...... squamous cell carcinoma, respectively. Low oxygen breathing for 1-72 h was used to increase tumour hypoxia. Ldh activity was measured in the serum and tumour cytosole with a colorimetric method. Tumour Ldha mRNA levels were assessed with RT-PCR. Results. The serum Ldh in non-tumour bearing CDF1 mice and C3......H/km mice was 10.5+/-2 U/ml and 12+/-2 U/ml, respectively. For C3H mammary carcinoma bearing mice, a positive correlation between tumour volume and tumour and serum Ldh was found. Tumour Ldh in SCCVII carcinomas also increased with increasing tumour volume, but no volume dependence of serum Ldh...

  20. The Actual Role of LDH as Tumor Marker, Biochemical and Clinical Aspects.

    Science.gov (United States)

    Jurisic, Vladimir; Radenkovic, Sandra; Konjevic, Gordana

    2015-01-01

    Lactate dehydrogenase (LDH) among many biochemical parameters represents a very valuable enzyme in patients with cancer with possibility for easy routine measurement in many clinical laboratories. Previous studies where mostly based on investigated LDH in serum of patients with cancer with aims to estimate their clinical significance. The new directions in investigation of LDH where based on the principle that tumor cells release intracellular enzymes trough damaged cell membrane, that is mostly consequence in intracellular mitochondrial machinery alteration, and apoptosis deregulation. This consideration can be used not only in-vitro assays, but also in respect to clinical characteristics of tumor patients. Based on new techniques of molecular biology it is shown that intracellular characteristics of LDH enzyme are very sensitive indicators of the cellular metabolic state, aerobic or anaerobic direction of glycolysis, activation status and malignant transformation. Using different molecular analyses it is very useful to analyzed intracellular LDH activity in different cell line and tumor tissues obtained from patients, not only to understanding complexity in cancer biochemistry but also in early clinical diagnosis. Based on understandings of the LDH altered metabolism, new therapy option is created with aims to blocking certain metabolic pathways and stop tumors growth.

  1. LDH Concentration in Nasal-Wash Fluid as a Biochemical Predictor of Bronchiolitis Severity

    Science.gov (United States)

    Laham, Federico R.; Trott, Amanda A.; Bennett, Berkeley L.; Kozinetz, Claudia A.; Jewell, Alan M.; Garofalo, Roberto P.; Piedra, Pedro A.

    2011-01-01

    Objective Because the decision to hospitalize an infant with bronchiolitis is often supported by subjective criteria and objective indicators of bronchiolitis severity are lacking, we tested the hypothesis that lactate dehydrogenase (LDH), which is released from injured cells, is a useful biochemical indicator of bronchiolitis severity. Patients and Methods We retrospectively analyzed a study of children bronchiolitis. Demographic, clinical information, nasal-wash (NW) and serum specimens were obtained. NW samples were analyzed for respiratory viruses, caspase 3/7 activity and a panel of cytokines and chemokines. Total LDH activity was tested in NW samples and sera. Results Of 101 enrolled children (median age, 5.6 months), 98 had NW specimens available. A viral etiology was found in 82 patients (83.6%), with respiratory syncytial virus (RSV) (66%) and rhinovirus (19%) being the most common viruses detected. Concentrations of LDH in NW specimens were independent from those in sera, and were higher in children with RSV infection or with dual infection. Significant correlations were found between NW LDH and NW cytokines/chemokines. Similarly, NW LDH correlated with NW-caspase 3/7 activity (r=0.75; Pbronchiolitis varied according to viral etiology and disease severity. Values in the upper quartile were associated with ~80% risk reduction in hospitalization, likely reflecting a robust antiviral response. NW LDH may be a useful biomarker to assist the clinician in the decision to hospitalize a child with bronchiolitis. PMID:20100751

  2. Analysis of lactate and malate dehydrogenase enzyme profiles of selected major carps of wetland of Calcutta.

    Science.gov (United States)

    Manna, Madhumita; Chakraborty, Priyanka

    2012-07-01

    The East Calcutta Wetland (ECW), a Ramsar site in India, acts as the only sink for both city sewages as well as effluents from the surrounding small-scale industries and is alarmingly polluted with heavy metals. The three best edible major carp species rohu (Labeo rohita,), catla (Catla catla,) and mrigala (Cirrhinus mrigala) were undertaken to monitor lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) by cellulose acetate electrophoresis (CAE) to assess the effects of pollutants, if any. Crude tissue extracts were prepared from brain, eye, heart, skeletal muscle and kidney tissue respectively from each type of fish. No differences were not found in MDH of catla from both sites for all tissues analyzed in this study. Rohu also showed similar mobility for all tissues except for heart tissue which was distinctly different in fishes from ECW site than that of its counterpart from non ECW site. On the other hand, MDH of two tissues of mrigala, eye and muscle respectively showed different migration patterns. LDH profiles for all tissues of three fish species from both the sites were consistently similar, only the expression levels of muscle LDH of mrigala and kidney LDH of rohu varied little.

  3. Molecular and kinetic properties of sperm specific LDH after radiation inactivation.

    Science.gov (United States)

    Gupta, G S; Kang, B P

    2000-03-01

    Radiation inactivation of sperm specific lactate dehydrogenase-C4 (LDH-C4) has been studied and compared with the somatic LDH in aqueous solution. D37 of C isozyme was 470 Gy and that of B isozyme was 520 Gy. Semi-log plots of log N/No versus dose suggested that the inactivation of two LDH isozymes in presence of normal saline follows a single hit kinetics. Target molecular weight calculated by radiation analysis was found as 1.52 x 10(5) gm/mole for LDH-C4 and 1.38 x 10(5) gm/mole for LDH-B4. SDS-PAGE of irradiated enzymes showed a band of 35 kDa but did not indicate the presence of any other extra band, when compared with sham-irradiated enzymes. Chemical kinetics of residual activity following irradiation at D37 showed decrease in Vmax with coenzymes and primary substrates. However, decrease in Km was seen with pyruvate as increasing substrate. Nevertheless, K did not change when NAD+ was the leading substrate for LDH-B4 or LDH-C4. A hyperchromicity in intrinsic fluorescence and a blue shift in lambdamax over sham-irradiated LDH-C4 revealed the exposure of buried tryptophan residues to the surface after radiation inactivation. Results suggest that inspite of presence of variant amino acids, the conformations of two isozymes are stabilized by similar forces which behave in a similar way for radiation inactivation in aqueous phase.

  4. Lactate dehydrogenase inhibitors can reverse inflammation induced changes in colon cancer cells.

    Science.gov (United States)

    Manerba, Marcella; Di Ianni, Lorenza; Govoni, Marzia; Roberti, Marinella; Recanatini, Maurizio; Di Stefano, Giuseppina

    2017-01-01

    The inflammatory microenvironment is an essential component of neoplastic lesions and can significantly impact on tumor progression. Besides facilitating invasive growth, inflammatory cytokines were also found to reprogram cancer cell metabolism and to induce aerobic glycolysis. Previous studies did not consider the possible contribution played in these changes by lactate dehydrogenase (LDH). The A isoform of LDH (LDH-A) is the master regulator of aerobic glycolysis; it actively reduces pyruvate and causes enhanced lactate levels in tumor tissues. In cancer cells, lactate was recently found to directly increase migration ability; moreover, when released in the microenvironment, it can facilitate matrix remodeling. In this paper, we illustrate that treatment of human colon adenocarcinoma cells with TNF-α and IL-17, two pro-inflammatory cytokines, modifies LDH activity, causing a shift toward the A isoform which results in increased lactate production. At the same time, the two cytokines appeared to induce features of epithelial-mesenchymal transition in the treated cells, such as reduction of E-cadherin levels and increased secretion of metalloproteinases. Noteworthy, oxamate and galloflavin, two inhibitors of LDH activity which reduce lactate production in cells, were found to relieve the inflammation-induced effects. These results suggest LDH-A and/or lactate as common elements at the cross-road between cancer cell metabolism, tumor progression and inflammation. At present, LDH inhibitors suitable for clinical use are actively searched as possible anti-proliferative agents; our data lead to hypothesize for these compounds a wider potential in anticancer treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Amplification of LDH gene from Indian strains of Plasmodium vivax

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    Ritu Berwal, N. Gopalan, Kshitij Chandel, Shri Prakash ,K. Sekhar

    2006-09-01

    Full Text Available Background & objectives: Plasmodium vivax is geographically widespread and responsible for >50% of malaria cases in India. Increased drug resistance of the parasite highlights the immediaterequirement of early and accurate diagnosis as well as new therapeutics. In view of this, the presentstudy was undertaken to amplify P. vivax (Indian strains lactate dehydrogenase gene (PvLDHwhich has been identified as a good target for antimalarials as well as diagnostics.Methods: P. vivax infected clinical blood samples were collected from southern part of India andwere tested with established diagnostic parameters (ICT, Giemsa staining. Total DNA was extractedfrom blood samples and subjected to PCR using two sets of primers, one for the amplification of fullPvLDH gene (951bp and the other for a partial PvLDH gene fragment (422bp, covering a variableantigenic region (140aa as compared to other plasmodial species.Results & conclusion: PCRs for both the full and partial gene targets were optimised and found to beconsistent when tested on several P. vivax positive clinical samples. In addition, full gene PCR wasfound to specifically detect only P. vivax DNA and could be used as a specific molecular diagnostictool. These amplified products can be cloned and expressed as a recombinant protein that might beuseful for the development and screening of antimalarials as well as for diagnostic purposes.

  6. Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein

    Science.gov (United States)

    Akagawa, Mitsugu; Minematsu, Kenji; Shibata, Takahiro; Kondo, Tatsuhiko; Ishii, Takeshi; Uchida, Koji

    2016-01-01

    Pyrroloquinoline quinone (PQQ), a redox-active o-quinone, is an important nutrient involved in numerous physiological and biochemical processes in mammals. Despite such beneficial functions, the underlying molecular mechanisms remain to be established. In the present study, using PQQ-immobilized Sepharose beads as a probe, we examined the presence of protein(s) that are capable of binding PQQ in mouse NIH/3T3 fibroblasts and identified five cellular proteins, including l-lactate dehydrogenase (LDH) A chain, as potential mammalian PQQ-binding proteins. In vitro studies using a purified rabbit muscle LDH show that PQQ inhibits the formation of lactate from pyruvate in the presence of NADH (forward reaction), whereas it enhances the conversion of lactate to pyruvate in the presence of NAD+ (reverse reaction). The molecular mechanism underlying PQQ-mediated regulation of LDH activity is attributed to the oxidation of NADH to NAD+ by PQQ. Indeed, the PQQ-bound LDH oxidizes NADH, generating NAD+, and significantly catalyzes the conversion of lactate to pyruvate. Furthermore, PQQ attenuates cellular lactate release and increases intracellular ATP levels in the NIH/3T3 fibroblasts. Our results suggest that PQQ, modulating LDH activity to facilitate pyruvate formation through its redox-cycling activity, may be involved in the enhanced energy production via mitochondrial TCA cycle and oxidative phosphorylation. PMID:27230956

  7. Structure and Function of Plasmodium falciparum malate dehydrogenase: Role of Critical Amino Acids in C-substrate Binding Procket

    Science.gov (United States)

    Malaria parasite thrives on anaerobic fermentation of glucose for energy. Earlier studies from our lab have demonstrated that a cytosolic malate dehydrogenase (PfMDH) with striking similarity to lactate dehydrogenase (PfLDH) might complement PfLDH function in Plasmodium falciparum. The N-terminal g...

  8. 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 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.

  9. Lactate dehydrogenase-B is silenced by promoter methylation in a high frequency of human breast cancers.

    Directory of Open Access Journals (Sweden)

    Nicola J Brown

    Full Text Available OBJECTIVE: Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer. EXPERIMENTAL DESIGN: Lactate Dehydrogenase (LDH isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA. RESULTS: Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/25 cases of breast cancer tissues, but not in 5/5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained, was seen in 23/26 (88% breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O(2, for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002, and T-47D cells (2.9 fold, p = 0.009, but not in MDA-MB-436 (-0.9 fold, p = 0.229, or MCF10AT (1.2 fold, p = 0.09 cells. CONCLUSIONS: Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia.

  10. 'Dual hit' metabolic modulator LDCA selectively kills cancer cells by efficient competitive inhibition of LDH-A.

    Science.gov (United States)

    Ghosh, Monisankar; Saha, Suchandrima; Dutta, Samir Kumar

    2016-02-07

    Herein, we synthesize and elucidate the potential of a novel 'dual hit' molecule, LDCA, to constitutively block lactate dehydrogenase isoform-A (LDH-A) to selectively subvert apoptosis and rigorously attenuate breast tumor progression in a mouse model, comprehensively delineating the therapeutic prospectus of LDCA in the field of cancer metabolics.

  11. AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis.

    Science.gov (United States)

    Theret, Marine; Gsaier, Linda; Schaffer, Bethany; Juban, Gaëtan; Ben Larbi, Sabrina; Weiss-Gayet, Michèle; Bultot, Laurent; Collodet, Caterina; Foretz, Marc; Desplanches, Dominique; Sanz, Pascual; Zang, Zizhao; Yang, Lin; Vial, Guillaume; Viollet, Benoit; Sakamoto, Kei; Brunet, Anne; Chazaud, Bénédicte; Mounier, Rémi

    2017-07-03

    Control of stem cell fate to either enter terminal differentiation versus returning to quiescence (self-renewal) is crucial for tissue repair. Here, we showed that AMP-activated protein kinase (AMPK), the master metabolic regulator of the cell, controls muscle stem cell (MuSC) self-renewal. AMPKα1(-/-) MuSCs displayed a high self-renewal rate, which impairs muscle regeneration. AMPKα1(-/-) MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKα1. LDH, which is a non-limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKα1(-/-) phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKα1(-/-) MuSC self-renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKα1/LDH pathway, emphasizing the importance of metabolism in stem cell fate. © 2017 The Authors.

  12. Relationship between protecitve effect of probucol on endothelial cells and asymmetrical dimethylarginine levels

    Institute of Scientific and Technical Information of China (English)

    Jun-linJIANG; Xiao-hongZHANG; Han-wuDENG; Yuan-JianLI

    2004-01-01

    AIM: To investigate the relationship between protective effect of probucol on endothelial cells and endogenous nitric oxide synthase inhibitor levels. METHODS: Endothelial cells were treated with oxidative-low density lipoprotein (ox-LDL) (100 rag/L) or lysophosphatidyl choline (LPC) (5 mg/L) for 48 h, and the release of lactate dehydrogenase (LDH), levels of nitric oxide (NO),

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

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    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

  14. 白念珠菌与LDH抗体的交叉免疫研究%Cross-reactive immune response of Candida albicans with anti-LDH antibody

    Institute of Scientific and Technical Information of China (English)

    钟毅; 黄怀球; 赵静; 袁立燕; 张静; 张晓辉; 李美荣

    2012-01-01

    To identify the conserved epitopes of Candida albicans malate dehydrogenase (CaMDH), the structure, function and phylogenetic analysis of the CaMDH sequence were predicted by using tools of bioinformatics. The phylogenetic a-nalysis showed the amino acid sequence of Schistosoma japonic um lactic dehydrogenase (SjLDH) had lowest identity (18. 2%) with CaMDH than that of other species (43%). The structure prediction result showed that CaMDH contained LDH conserved domain and 7 main B cell epitopes, in which 3 epitopes displayed high levels of similarity with that of SjI.DH. The MDH active site located at the NAD (P) binding domain. Furthermore, the Sj'LDH recombinant protein immune serum which had lowest i-dentity with CaMDH in study was chosen to make cross-reactive immune response with Candida albicans protein. The positive result with the anti-LDH body identify that the interaction point was highly conserved epitopes of CaMDH homologous sequence and supply new methods for the vaccine, diagnosis and drug target study of the CaMDH.%目的 识别白念珠菌苹果酸脱氢酶(Candida albicans malate dehydrogenase,CaMDH)保守表位结构.方法 本研究利用生物信息学方法,预测CaMDH的结构、功能和进化关系,并选取同源序列中与CaMDH序列一致性较低的日本血吸虫乳酸脱氢酶(Schistosoma japonicum lactate dehydrogenase,SjLDH)免疫血清与白念珠菌总蛋白进行交叉免疫反应.结果 发现CaMDH与常见病原生物的同源序列一致性可达43%,其中与SjLDH一致性最低(18.2%).CaMDH具有乳酸脱氢酶保守区域,7个主要的B细胞表位,其中3处与SjLDH表位相似.苹果酸脱氢酶活化点包含于NAD(P)结合部分中.白念珠菌总蛋白与SjLDH免疫血清交叉免疫反应阳性.结论 交叉免疫反应阳性提示识别结合位点为LDH/MDH同源序列高度保守的表位结构,为进一步从高度保守的抗原决定簇中筛选真菌疫苗表位、诊断特异抗体、抗真菌药物治疗靶点提供了实验基础.

  15. Expression of lactate dehydrogenases A and B during chicken spermatogenesis: characterization of testis specific transcripts.

    Science.gov (United States)

    Arias, W M; Mezquita, C; Mezquita, J

    2000-07-19

    The substrates required for glycolysis change markedly at successive stages of spermatogenesis suggesting a considerable plasticity in the expression of glycolytic enzymes. Lactate dehydrogenase (LDH) isoenzymes, LDH-A and LDH-B, are expressed in premeiotic, meiotic cells, and early spermatids, both in avian and mammalian spermatogenesis. Highly polyadenylated forms, particularly of LDH-A, were detected in chicken testis. While mammals and columbid birds express the testis specific LDH-C gene in meiotic and postmeiotic cells, several LDH-B testis specific transcripts were detected in the corresponding cells during chicken spermatogenesis. These testis specific transcripts and the mRNA of mammalian LDH-C show several properties in common, such as temporal correlation of expression, mRNA stability, and repression of premature translation. These observations suggest that the testis specific transcripts could perform during chicken spermatogenesis the functions of the LDH-C mRNA in mammalian testis. Copyright 2000 Wiley-Liss, Inc.

  16. cDNA Fragment Cloning of L-Galactono-1,4-Lactone Dehydrogenase and It's Expression in Different Organs of R.roxburghii Tratt

    Institute of Scientific and Technical Information of China (English)

    AN Hua-ming; CHEN Li-geng; FAN Wei-guo

    2004-01-01

    A 855 bp cDNA encoding L-galactono-1,4-lactone dehydrogenase (GalLDH) fragment was cloned from fruit of R. roxburghii Tratt by the method of RT-PCR, on the basis of the homologous genes of Arabidopsis thaliana, cauliflower, sweet potato, strawberry, etc. in GenBank. Sequence analysis showed 79-92% identity in nucleotide sequence and 75-87%identity in amino acid sequence to that of strawberry and Arabidopsis thaliana, etc.Northern blot showed that the expression of GalLDH was significantly different in different organs. The transcription level of GalLDH in fruit was significantly higher than that in leaf, stem and root respectively. Furthermore, this expression mode was highly correlated with AsA levels.

  17. High glutamate attenuates S100B and LDH outputs from rat cortical slices enhanced by either oxygen-glucose deprivation or menadione.

    Science.gov (United States)

    Demircan, Celaleddin; Gül, Zülfiye; Büyükuysal, R Levent

    2014-07-01

    One hour incubation of rat cortical slices in a medium without oxygen and glucose (oxygen-glucose deprivation, OGD) increased S100B release to 6.53 ± 0.3 ng/ml/mg protein from its control value of 3.61 ± 0.2 ng/ml/mg protein. When these slices were then transferred to a medium containing oxygen and glucose (reoxygenation, REO), S100B release rose to 344 % of its control value. REO also caused 192 % increase in lactate dehydrogenase (LDH) leakage. Glutamate added at millimolar concentration into the medium decreased OGD or REO-induced S100B release and REO-induced LDH leakage. Alpha-ketoglutarate, a metabolic product of glutamate, was found to be as effective as glutamate in decreasing the S100B and LDH outputs. Similarly lactate, 2-ketobutyrate and ethyl pyruvate, a lipophilic derivative of pyruvate, also exerted a glutamate-like effect on S100B and LDH outputs. Preincubation with menadione, which produces H2O2 intracellularly, significantly increased S100B and LDH levels in normoxic medium. All drugs tested in the present study, with the exception of pyruvate, showed a complete protection against menadione preincubation. Additionally, each OGD-REO, menadione or H2O2-induced mitochondrial energy impairments determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and OGD-REO or menadione-induced increases in reactive oxygen substances (ROS) determined by 2,7-dichlorofluorescin diacetate (DCFH-DA) were also recovered by glutamate. Interestingly, H2O2-induced increase in fluorescence intensity derived from DCFH-DA in a slice-free physiological medium was attenuated significantly by glutamate and alpha-keto acids. All these drug actions support the conclusion that high glutamate, such as alpha-ketoglutarate and other keto acids, protects the slices against OGD- and REO-induced S100B and LDH outputs probably by scavenging ROS in addition to its energy substrate metabolite property.

  18. Correlation of LDH with mosquitoes deltamethrin-resistance%乳酸脱氢酶与蚊虫对溴氰菊酯抗性相关性的研究

    Institute of Scientific and Technical Information of China (English)

    张利; 叶钰亭; 孙林春; 洪善超; 沈波; 朱昌亮

    2012-01-01

    目的 研究乳酸脱氢酶(LDH)与蚊溴氰菊酯抗性之间的关系. 方法 应用RT- PCR及cDNA末端快速扩增(rapid amplification of cDNA end,RACE)技术扩增白纹伊蚊LDH全长基因;用实时荧光定量PCR检测敏感和抗性蚊C6/36细胞中LDH基因的表达水平;用乳酸脱氢酶活性检测试剂盒检测敏感和抗性蚊细胞中LDH酶活性.结果 LDH基因全长共1831 bp,其中ORF为996 bp,共编码331个氨基酸.该基因与埃及伊蚊、黑腹果蝇、小家鼠和人的乳酸脱氢酶的同源性分别为89%、72%、66%和65%.实时荧光定量PCR结果表明,LDH基因在抗性蚊细胞中高表达,为敏感蚊细胞的1.87倍(P<0.05).LDH酶活性检测结果显示,LDH在敏感蚊细胞中的酶活性范围为1~ 95 U/gprot,均值为40 U/gprot;在抗性蚊细胞中的酶活性范围为20 ~ 150 U/gprot,均值为75 U/gprot(n=15,P<0.01).结论 抗性蚊细胞中的LDH表达量和酶活性均高于敏感蚊细胞,提示LDH可能与蚊溴氰菊酯抗性相关.%Objective To investigate the correlation between LDH and deltamethrin( DM) -resistance in mosquitoes. Methods Cloning the full-length of LDH from mosquito C6/36 cell line and cheeking the expression level of LDH between DM-susceptible and resistant mosquito cells using quantitative PCR. Then, assaying the enzyme activities of LDH between DM-susceptible and resistant mosquito cells using lactate dehydrogenase assay kit. Results The full-length of LDH( 1 831 bp) was cloned from Aedes albopictus using RT-PCR and RACE-PCR. An open reading frame ( ORF) of 996 bp was found to encode 331 amino acids. The sequence shared 89% , 72% , 66% and 65% ho-mology with LDH of Aedes aegypti,Drosophila melanogaster,Mus musculus and Homo sapiens. Quantitative PCR demonstrated that the expression level of LDH was 1.87 folds (P<0. 05) higher in DM-resistant cells than that in-susceptible cells. The enzyme activities of LDH in DM-susceptible cells was 1-95 U/gprot,the average level was 40 U

  19. Serum lactate dehydrogenase profile as a retrospective indicator of uterine preparedness for labor: a prospective, observational study

    Science.gov (United States)

    2013-01-01

    Background Lactate dehydrogenase (LDH) isoenzymes are required for adenosine triphosphate production, with each of five different isoenzymes having varying proficiencies in anaerobic versus aerobic environments. With advancing pregnancy, the isoenzyme profile in uterine muscle shifts toward a more anaerobic profile, speculatively to facilitate uterine efficiency during periods of low oxygen that accompany labor contractions. Profile shifting may even occur throughout labor. Maternal serum LDH levels between 24–48 hours following delivery predominantly originate from uterine muscle, reflecting the enzymatic state of the myometrium during labor. Our purpose was to describe serum LDH isoenzymes 24–30 hours post-delivery to determine if cervical dilation rates following labor admission were associated with a particular LDH profile. We also compared differences in post-delivery LDH isoenzyme profiles between women admitted in pre-active versus established active labor. Methods Low-risk, nulliparous women with spontaneous labor onset were sampled (n = 91). Maternal serum LDH was measured at labor admission and 24–30 hours post-vaginal delivery. Rates of cervical dilation during the first four hours after admission were also measured. Spearman’s rho coefficients were used for association testing and t tests evaluated for group and paired-sample differences. Results More efficient dilation following admission was associated with decreased LDH1 (p = 0.029) and increased LDH3 and LDH4 (p = 0.017 and p = 0.017, respectively) in the post-delivery period. Women admitted in established active labor had higher relative serum levels of LDH3 (t = 2.373; p = 0.023) and LDH4 (t = 2.268; p = 0.029) and lower levels of LDH1 (t = 2.073; p = 0.045) and LDH5 (t = 2.041; p = 0.048) when compared to women admitted in pre-active labor. Despite having similar dilatations at admission (3.4 ± 0.5 and 3.7 ± 0.6 cm, respectively

  20. Nicotine promotes Streptococcus mutans extracellular polysaccharide synthesis, cell aggregation and overall lactate dehydrogenase activity.

    Science.gov (United States)

    Huang, R; Li, M; Gregory, R L

    2015-08-01

    Several epidemiology studies have reported a positive relationship between smoking and dental caries. Nicotine, an alkaloid component of tobacco, has been demonstrated to stimulate biofilm formation and metabolic activity of Streptococcus mutans, one of the most important pathogens of dental caries. The first aim of the present study was to explore the possible mechanisms leading to increased biofilm by nicotine treatment from three aspects, extracellular polysaccharides (EPS) synthesis, glucosyltransferase (Gtf) synthesis and glucan-binding protein (Gbp) synthesis at the mRNA and protein levels. The second aim was to investigate how nicotine affects S. mutans virulence, particular in lactate dehydrogenase (LDH) activity. Confocal laser scanning microscopy results demonstrated that both biofilm bacterial cell numbers and EPS were increased by nicotine. Gtf and GbpA protein expression of S. mutans planktonic cells were upregulated while GbpB protein expression of biofilm cells were downregulated by nicotine. The mRNA expression trends of those genes were mostly consistent with results on protein level but not statistically significant, and gtfD and gbpD of biofilm cells were inhibited. Nicotine was not directly involved in S. mutans LDH activity. However, since it increases the total number of bacterial cells in biofilm, the overall LDH activity of S. mutans biofilm is increased. In conclusion, nicotine stimulates S. mutans planktonic cell Gtf and Gbp expression. This leads to more planktonic cells attaching to the dental biofilm. Increased cell numbers within biofilm results in higher overall LDH activity. This contributes to caries development in smokers.

  1. Magnetisme i LDH og produktene etter dekomposisjon

    OpenAIRE

    Glesne, Erik

    2015-01-01

    Oppgaven omfatter studier av strukturelle og magnetiske egenskaper til materialer med lagdelt struktur i klassen lagdelte dobbelthydroksider (LDH). LDHer er lagdelte leirematerialer der det sitter vann og ladningsbalanserende anioner mellom lagene. Mange ulike kombinasjoner kationer med ulik ladning kan danne lagene, og LDHer har derfor en rekke interessante potensielle bruksområder. Dette omfatter blant annet multifunksjonelle nanokompositter med både polymerer og andre lagdelte strukturer i...

  2. Chilling enhances the NAD levels and cytosolic malate dehydrogenase activity in diapause eggs of the silkworm, Bombyx mori%低温冷藏提高家蚕滞育卵 NAD 含量和胞质苹果酸脱氢酶活性

    Institute of Scientific and Technical Information of China (English)

    王启龙; 万华星; 姚金美; 司马杨虎; 赵林川

    2012-01-01

    为了调查5℃低温处理是否改变家蚕Bombyx mori卵滞育NAD代谢,本研究利用HPLC和分光光度法测定了经25℃和5℃分别处理的滞育卵中NADH含量、NAD+含量、乳酸脱氢酶(LDH)活性和胞质苹果酸脱氢酶(cMDH)活性.结果表明:5℃处理的NAD(NADH+NAD+)含量和cMDH活性分别增加了 106%和53%,并且 显著高于25℃处理(P<0.01);但是两种处理的NADH/NAD+比值和LDH活性没有显著差异(P>0.05).据此推测,5℃低温处理加强了家蚕滞育卵NAD+合成和再生能力.%To investigate whether chilling at 5℃ changes the metabolism of NAD in diapause eggs of the silkworm, Bombyx mori, the levels of NADH and NAD+ along with the activities of lactate dehydrogenase (LDH) and cytosolic malate dehydrogenase ( cMDH ) in diapause eggs incubated at 25℃ and 5℃ , respectively, were determined using HPLC and spectrophotometric methods. NAD (NADH + NAD+) levels and the cMDH activity in diapause eggs incubated at 5℃ increased by 106% and 53% , respectively, which were significantly higher than those in diapause eggs incubated at 25℃ (P 0.05 ). It is so inferred that the ability for NAD + synthesis and regeneration in Bombyx diapause eggs is enhanced by chilling.

  3. Identification of yak lactate dehydrogenase B gene variants by gene cloning

    Institute of Scientific and Technical Information of China (English)

    ZHENG YuCai; ZHAO XingBo; ZHOU Jing; PIAO Ying; JIN SuYu; HE QingHua; HONG Jian; LINing; WU ChangXin

    2008-01-01

    Native polyacrylamide gel electrophoresis showed that two types of lactate dehydrogenase (LDH) existed in yaks. Based on the electrophoresis characteristics of LDH isoenzymes, yak LDH variants were speculated to be the gene mutation on H subunit encoded by B gene. According to the mobility in electrophoresis, the fast-band LDH type was named LDH-Hf and the slow-band LDH type LDH-Hs. In order to reveal the gene alteration In yak LDH variants, total RNA was extracted from heart tissues of yaks with different LDH variants, and cDNAs of the two variants were reverse transcripted. Two variants of B genes were cloned by RT-PCR. Sequence analysis revealed that four nucleotides differed between LDH-Bf and LDH-Bs, which resulted in two amino acids alteration. By Deepview software analysis of the conformation of yak LDH1 variants and H subunit, these four nucleotides altered two amino acids that generated new hydrogen bonds to change the hydrogen bonds network, and further caused subtle conformstionsl changes between the two LDH variants.

  4. Identification of yak lactate dehydrogenase B gene variants by gene cloning

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Native polyacrylamide gel electrophoresis showed that two types of lactate dehydrogenase (LDH) existed in yaks. Based on the electrophoresis characteristics of LDH isoenzymes, yak LDH variants were speculated to be the gene mutation on H subunit encoded by B gene. According to the mobility in electrophoresis, the fast-band LDH type was named LDH-Hf and the slow-band LDH type LDH-Hs. In order to reveal the gene alteration in yak LDH variants, total RNA was extracted from heart tissues of yaks with different LDH variants, and cDNAs of the two variants were reverse transcripted. Two variants of B genes were cloned by RT-PCR. Sequence analysis revealed that four nucleotides differed between LDH-Bf and LDH-Bs, which resulted in two amino acids alteration. By Deepview software analysis of the conformation of yak LDH1 variants and H subunit, these four nucleotides altered two amino acids that generated new hydrogen bonds to change the hydrogen bonds network, and further caused subtle conformational changes between the two LDH variants.

  5. Particle-induced artifacts in the MTT and LDH viability assays.

    Science.gov (United States)

    Holder, Amara L; Goth-Goldstein, Regine; Lucas, Donald; Koshland, Catherine P

    2012-09-17

    In vitro testing is a common first step in assessing combustion-generated and engineered nanoparticle-related health hazards. Commercially available viability assays are frequently used to compare the toxicity of different particle types and to generate dose-response data. Nanoparticles, well-known for having large surface areas and chemically active surfaces, may interfere with viability assays, producing a false assessment of toxicity and making it difficult to compare toxicity data. The objective of this study is to measure the extent of particle interference in two common viability assays, the MTT reduction and the lactate dehydrogenase (LDH) release assays. Diesel particles, activated carbon, flame soot, oxidized flame soot, and titanium dioxide particles are assessed for interactions with the MTT and LDH assay under cell-free conditions. Diesel particles, at concentrations as low as 0.05 μg/mL, reduce MTT. Other particle types reduce MTT only at a concentration of 50 μg/mL and higher. The activated carbon, soot, and oxidized soot particles bind LDH to varying extents, reducing the concentration measured in the LDH assay. The interfering effects of the particles explain in part the different toxicities measured in human bronchial epithelial cells (16HBE14o). We conclude that valid particle toxicity assessments can only be assured after first performing controls to verify that the particles under investigation do not interfere with a specific assay at the expected concentrations.

  6. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Partl, Richard, E-mail: richard.partl@medunigraz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria); Richtig, Erika [Department of Dermatology, Medical University of Graz, Graz (Austria); Avian, Alexander; Berghold, Andrea [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz (Austria); Kapp, Karin S. [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria)

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  7. Antibody-mediated rejection: Importance of lactate dehydrogenase and neutrophilia in early diagnosis

    Directory of Open Access Journals (Sweden)

    Taqi Toufeeq Khan

    2011-01-01

    Full Text Available We report the importance of elevated serum lactate dehydrogenase (LDH and neutrophilia (NT in two renal transplant recipients who developed renal impairment in the early post-operative period. One of our recipients developed oliguria and increased serum creatinine with unexplained elevation of LDH and NT. The biopsy was C4d positive with platelet and fibrin thrombi in the glomerular capillaries and arterioles and interpreted as acute vasculitis or thrombotic form of antibody-mediated rejection (VAMR with positive donor-specific antibodies (DSA. Despite intensive treatment, this graft was lost. When another patient developed a similar picture, prompt immunoadsorption was started without waiting for a confirmatory biopsy or DSA, and both were later reported as positive. Improvement in renal function was associated with decreasing levels of LDH and NT. Neither of these was elevated in cases of acute cellular rejection (ACR or antibody mediated rejection (AMR with isolated tubular injury (TAMR. It may therefore be reasonable to assume that LDH and NT are potential diagnostic and prognostic markers of VAMR.

  8. Hepatocyte damage induced by lymphocytes from patients with chronic liver diseases, as detected by LDH release.

    Science.gov (United States)

    Fernandez-Cruz, E; Escartin, P; Bootello, A; Kreisler, M; Segovia de Arana, J M

    1978-01-01

    We have used a cytoplasmic enzyme system in the study of the in vitro cytotoxic activity of human peripheral blood leucocytes against isolated liver cells in patients with chronic liver diseases. Lymphocytes from primary biliary cirrhosis and chronic active liver disease patients were shown to have an in vitro capacity to induce a cytolitic effect on isolated hepatocytes, as demonstrated by the enhanced release of lactate dehydrogenase (LDH), a cytoplasmic marker enzyme. No significant LDH release was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis. Our results corroborate, in a different assay system, by a simple, reproducible and different method, that lymphocyte-mediated liver cell damage "in vitro" occurs in both primary biliary cirrhosis and chronic active liver disease. PMID:657588

  9. [Succinic semialdehyde dehydrogenase deficiency: decrease in 4-OH-butyric acid levels with low doses of vigabatrin].

    Science.gov (United States)

    Escalera, G Iglesias; Ferrer, I; Marina, Ll Carrasco; Sala, P Ruiz; Salomons, G S; Jakobs, C; Pérez-Cerdá, C

    2010-02-01

    Succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disease caused by a deficiency in gamma-aminobutyric degradation, resulting in an increase in gamma-hydroxybutyric acid in biological fluids. The clinical spectrum is heterogeneous, including a variety of neurological manifestations and psychiatric symptoms. The treatment usually used is vigabatrin, but its clinical efficacy is under discussion. We present two affected siblings. The older brother was examined when he was 2.5 years old due to psychomotor and developmental delay, disturbances in motor coordination, axial hypotonia and language disability. His younger brother had mild axial hypotonia when 5 months old. Metabolic studies demonstrated a high plasma and urine concentration of gamma-hydroxybutyric acid. Mutation analysis of the gene ALDH5A1 confirmed the disease. After 1 year of treatment with low-doses of vigabatrin of the older patient, a decrease in gamma-hydroxybutyric acid plasma levels and a slow clinical improvement were observed.

  10. Relationship of lactate dehydrogenase activity with body measeurements of Angus x Charolais cows and calves

    Science.gov (United States)

    Angus x Charolais cows (n = 87) and their Angus-sired, spring-born calves (n = 86) were utilized to examine relationships between lactate dehydrogenase (LDH) activity and body measurements of beef cows; and the relationship between maternal LDH activity in late gestation and subsequent calf birth we...

  11. Optimization, Application, and Interpretation of Lactate Dehydrogenase Measurements in Microwell Determination of Cell Number and Toxicity

    NARCIS (Netherlands)

    Wolterbeek, H.T.; Van der Meer, A.J.G.M.

    2005-01-01

    The lactate dehydrogenase (LDH) assay was addressed for its sensitivity, disturbances by foaming, and cell number and size. Cells were from a U-251 MG grade IV human glioblastoma brain tumor cell line used in 100-µl well volumes. Cells were counted by microscopy and Coulter counting; assays were LDH

  12. PARÁMETROS BIOQUÍMICOS ENZIMÁTICOS (ALT, AST, ALP, Γ-GT, LDH EN NIÑOS CON LEUCEMIA LINFOBLÁSTICA AGUDA ANTES DEL TRATAMIENTO ANTINEOPLÁSICO

    Directory of Open Access Journals (Sweden)

    Jeél Moya S

    2015-12-01

    Full Text Available Objective: To determine the enzymatic biochemical parameters (glutamic pyruvic transaminase (ALT, glutamic oxaloacetic transaminase (AST, alkaline phosphatase (ALP, gamma glutamyltransferase (γ-GT, and lactate dehydrogenase (LDH in children with acute lymphoblastic leukemia (ALL before cancer treatment. Material and Methods: A prospective experimental, observational, cross-sectional study was conducted in 30 children between 2 and 15 years old, from several Neoplastic Centers in Lima. Blood collection was performed in BD red cap Vacutainer tubes, processed in the semi-automated analyzer BIOTEC® EMP-168, with Wiener Lab Group enzyme reagents under the modified method Szaaz and UV-Optimized by IFCC, SSCC and SFBC. Finally, coding and tabulation was performed. Results: 60% were boys and 46.7% are between the ages of 2-6 years. Serum levels of AST were increased by 33.3% in boys and 50% in girls. Serum ALT values were increased in 33.3% of boys and 41.7% of girls; only 25% of girls showed increased levels of γ-GT values; ALP was increased in 44.4% of boys and 66.7% of girls. Moreover LDH levels were increased in 55.6% of boys and 41.7% of girls. Conclusions: The enzymatic tests LDH, AST, ALT and ALP are increased in children with ALL compared to normal values due to tumor lysis syndrome characterized by electrolyte abnormalities, and as a result of the massive destruction of tumor cells and rapid release of large amounts of intracellular elements.

  13. SIGNIFICANCE OF LACTATE DEHYDROGENASE AND ASPARTATE TRANSAMINASE AS BIOCHEMICAL MARKERS AND AS PREDICTORS OF SEVERITY OF PREGNANCY-INDUCED HYPERTENSION AND ITS COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Ramesh Sonowal

    2017-03-01

    Full Text Available BACKGROUND To compare serum Lactate Dehydrogenase (LDH and serum Aspartate Transaminase (AST of normotensive pregnant women with those of preeclamptic and eclamptic women. To determine the relationship of levels of serum lactate dehydrogenase and serum aspartate transaminase with severity of pregnancy-induced hypertension and its complications. MATERIALSAND METHODS The study was carried out on pregnant hypertensive patients attending outpatient department of Obstetrics and Gynaecology department, AMCH, Dibrugarh, Assam from 1 st July 2013 to 30 th June 2014. Normotensive pregnant women were taken as controls. Each serum sample from both the control group as well as study group was estimated for lactate dehydrogenase and aspartate transaminase using standard methods and a comparison is drawn and analysed using t-test and Chi-square test. RESULTS Serum lactate dehydrogenase and serum aspartate transaminase levels were higher in the study group in comparison to the study groups. The mean serum LDH was 198±30.03U/L in control group, whereas in preeclampsia and eclampsia, mean serum levels of LDH were 817±114U/L and 927±108U/L, respectively. The levels of the serum AST were found to be less than 600U/L in normotensive and preeclampsia patients and more than 600 U/L in eclampsia and other complications of PIH. CONCLUSION Serum lactate dehydrogenase and serum aspartate transaminase levels in patients suffering from preeclampsia and its complications are consistently higher compared to the normotensive pregnant patients. To determine the usefulness of inclusion of these enzymes along with other cardiac enzymes in the panel of investigations of pregnant women universally needs further large scale comparative studies.

  14. Polypropylene/Layered Double Hydroxide (LDH) Nanocomposites: Influence of LDH Particle Size on the Crystallization Behavior of Polypropylene.

    Science.gov (United States)

    Nagendra, Baku; Mohan, Kiran; Gowd, E Bhoje

    2015-06-17

    Highly dispersed isotactic polypropylene (iPP) nanocomposites were prepared by incorporating two different sized Mg-Al LDH nanoparticles with different loadings from 1 to 10 wt % using a modified solvent mixing method. Larger sized LDH nanoparticles (∼3-4 μm) were prepared from the gel form of Mg-Al LDH, and the smaller sized nanoparticles (∼50-200 nm) were prepared by sonication of as-synthesized LDH particles. Such obtained LDH nanoparticles were carefully characterized using wide-angle X-ray diffraction (WAXD), transmission electron microscopy, and scanning electron microscopy. WAXD and atomic force microscopy results indicate that the LDH nanoparticles were highly dispersed in the iPP matrix. The influence of LDH nanoparticles size and concentration on the thermal stability, spherulitic morphology, melting behavior, isothermal crystallization kinetics, and lamellar structure of iPP were investigated. Incorporation of low loadings of sonicated LDH particles (e.g., 1-2.5 wt %) show substantial effect on thermal stability, spherulite size, crystallinity, and crystallization half-time and lamellar morphology of iPP compared to the pure iPP and that of nanocomposites with larger LDH particles with same loadings. The better nucleation ability of iPP in the presence of sonicated LDH can be attributed to the high surface area of LDH nanoparticles along with its better dispersibility within the polymer matrix. The incorporation of LDH nanoparticles does not change the crystallization growth mechanism and crystal structure of iPP.

  15. The correlation between aldehyde dehydrogenase-1A1 level and tumor shrinkage after preoperative chemoradiation in locally advanced rectal cancer

    Directory of Open Access Journals (Sweden)

    Rhandyka Rafli

    2015-12-01

    Full Text Available This study was performed to determine the correlation between aldehyde dehydrogenase-1A1 (ALDH1A1 level and tumor shrinkage after chemoradiation in locally advanced rectal cancer. This is a retrospective study of 14 locally advanced rectal cancer patients with long course neoadjuvant chemoradiation. ALDH1A1 level was measured using ELISA from paraffin embedded tissue. Tumor shrinkage was measured from computed tomography (CT scan or magnetic resonance imaging (MRI based on Response Evaluation Criteria in Solid Tumor v1.1 (RECIST v1.1. The mean of ALDH1A1 level was 9.014 ± 3.3 pg/mL and the mean of tumor shrinkage was 7.89 ± 35.7%. Partial response proportion was 28.6%, stable disease proportion was 50% and progressive disease proportion was 21.4%. There was a significant strong negative correlation (r = –0.890, plt; 0.001 between ALDH1A1 and tumor shrinkage. In conclusion, tumor shrinkage in locally advanced rectal cancer after preoperative chemoradiation was influenced by ALDH1A1 level. Higher level of ALDH1A1 suggests decreased tumor shrinkage after preoperative chemoradiation.

  16. 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

    2002-01-01

    procedure were assayed for marker enzymes and lactate dehydrogenase (LDH). The mitochondrial fraction contained no LDH activity (detection limit approximately 0.05 % of the tissue activity) and the distribution of LDH activity among the fractions paralleled that of pyruvate kinase, i.e. LDH was fractionated...... as a cytoplasmic enzyme. Respiratory experiments with the mitochondrial fraction also indicated the absence of LDH. Lactate did not cause respiration, nor did it affect the respiration of pyruvate + malate. The major part of the native cytochrome c was retained in the isolated mitochondria, which, 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....

  17. Down-regulation of lactate dehydrogenase-A by siRNAs for reduced lactic acid formation of Chinese hamster ovary cells producing thrombopoietin.

    Science.gov (United States)

    Kim, Sung Hyun; Lee, Gyun Min

    2007-02-01

    Lactate, one of the major waste products in mammalian cell culture, can inhibit cell growth and affect cellular metabolism at high concentrations. To reduce lactate formation, lactate dehydrogenase-A (LDH-A), an enzyme catalyzing the conversion of glucose-derived pyruvate to lactate, was down-regulated by an expression vector of small interfering RNAs (siRNA) in recombinant Chinese hamster ovary (rCHO) cells producing human thrombopoietin (hTPO). Three clones expressing low levels of LDH-A, determined by reverse transcription-PCR and an enzyme activity test, were established in addition to a negative control cell line. LDH-A activities in the three clones were decreased by 75-89%, compared with that of the control CHO cell line, demonstrating that the effect of siRNA is more significant than that of other traditional methods such as homologous recombination (30%) and antisense mRNA (29%). The specific glucose consumption rates of the three clones were reduced to 54-87% when compared to the control cell line. Similarly, the specific lactate production rates were reduced to 45-79% of the control cell line level. In addition, reduction of LDH-A did not impair either cell proliferation or hTPO productivity. Taken together, these results show that the lactate formation rate in rCHO cell culture can be efficiently reduced through the down-regulation of LDH via siRNA.

  18. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Chihiro Moriya

    2016-01-01

    Full Text Available We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD or a 60% high-fat diet (HFD with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

  19. Can elevated lactate and LDH produce a false positive enzymatic ethanol result in live patients presenting to the emergency department?

    Science.gov (United States)

    Nacca, Nicholas; Hodgman, Michael J; Lao, Kirselle; Elkins, Matthew; Holland, Michael G

    2017-08-16

    There have been allegations in the courtroom that elevated serum lactic acid in trauma victims can yield a falsely elevated serum ethanol assay. Most hospitals utilize an indirect method of ethanol measurement where a serum sample is added to a mix of alcohol dehydrogenase and oxidized nicotinamide adenine dinucleotide (NAD+). This allows any ethanol in the patient's serum to be metabolized to acetaldehyde, and in the process results in the reduction of NAD + to NADH. NADH is then measured using spectrophotometry. The courtroom allegation stems from the concept that oxidation of lactate to pyruvate by lactate dehydrogenase (LDH) results in the same molar-for-molar reduction of NAD + to NADH, and could therefore theoretically cause patients with elevated lactate and LDH to have a falsely elevated ethanol concentration. Patients with elevated lactic acid and LDH concentrations who presented to a university hospital from 20 April 2015 to 13 December 2015 were identified to provide possible test specimens. If a sufficient amount of serum was available, the sample was used to re-run the lactate and LDH concentration simultaneously with an enzymatic ethanol assay. Any samples that had elevated lactic acid and LDH concentrations on this retesting, and also yielded a positive ethanol concentration, were sent for confirmatory gas chromatography testing of ethanol concentrations. A control group of 20 samples with normal lactate and LDH were included. A total of 37 samples were included in the final analysis. Only 4 patients had an elevated enzymatic ethanol concentration, and all 4 also had a measurable GC ethanol concentration. The lactate in this dataset ranged from 2.4 to 24.2 mmol/L, with a mean of 6.53 mmol/L (normal value 0.5-2.2). The LDH ranged from 242 to 8838 U/L with a mean of 1695 U/L (normal value 122-225 U/L). Twenty control samples were run on patients with normal lactate and LDH, none of which yielded a positive enzymatic ethanol result

  20. Androgens enhance the glycolytic metabolism and lactate export in prostate cancer cells by modulating the expression of GLUT1, GLUT3, PFK, LDH and MCT4 genes.

    Science.gov (United States)

    Vaz, Cátia V; Marques, Ricardo; Alves, Marco G; Oliveira, Pedro F; Cavaco, José E; Maia, Cláudio J; Socorro, Sílvia

    2016-01-01

    The present study aims to investigate the role of androgens in controlling the glycolytic metabolism and lactate efflux in prostate cancer (PCa) cells. Androgen-responsive LNCaP cells were treated with 5α-dihydrotestosterone (DHT, 10 nM) for 12-48 h, and their glycolytic metabolism, lactate production and viability were analyzed. Intracellular and extracellular levels of glucose and lactate were determined spectrophotometrically, and the expression of glucose transporters (GLUT1/GLUT3), phosphofructokinase 1, lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT4) was analyzed by real-time PCR and Western blot. The enzymatic activity of LDH was determined by means of a colorimetric assay. Experiments were reproduced in androgen-non-responsive DU145 and PC3 cells. Androgens stimulated glucose consumption in LNCaP cells by increasing the expression of GLUT3, GLUT1 and PFK, which was underpinned by increased cell viability. Accordingly, lactate production by LNCaP cells was enhanced upon DHT stimulation as evidenced by the increased levels of lactate found in cell culture medium. Although LDH enzymatic activity decreased in LNCaP cells treated with DHT, the expression of MCT4 was significantly increased with androgenic treatment, which sustains the increase on lactate export. Glucose consumption and the expression of GLUTs and PFK remained unchanged in DHT-treated DU145 and PC3 cells. The results obtained establish androgens as modulators of glycolytic metabolism in PCa cells by stimulating glucose consumption, as well as the production and export of lactate, which may represent a crucial issue-driven prostate tumor development. These findings also highlight the importance of PCa therapies targeting AR and metabolism-related proteins.

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

    Science.gov (United States)

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

    2017-02-01

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

  2. Cariogenicity of a lactate dehydrogenase-deficient mutant of Streptococcus mutans serotype c in gnotobiotic rats.

    OpenAIRE

    FitzGerald, R.J.; Adams, B. O.; Sandham, H. J.; Abhyankar, S

    1989-01-01

    A lactate dehydrogenase-deficient (Ldh-) mutant of a human isolate of Streptococcus mutans serotype c was tested in a gnotobiotic rat caries model. Compared with the wild-type Ldh-positive (Ldh+) strains, it was significantly (alpha less than or equal to 0.005) less cariogenic in experiments with two different sublines of Sprague-Dawley rats. The Ldh- mutant strain 044 colonized the oral cavity of the test animals to the same extent as its parent strain 041, although its initial implantation ...

  3. Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels.

    Science.gov (United States)

    Parkhomenko, Yulia M; Kudryavtsev, Pavel A; Pylypchuk, Svetlana Yu; Chekhivska, Lilia I; Stepanenko, Svetlana P; Sergiichuk, Andrej A; Bunik, Victoria I

    2011-06-01

    Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability.

  4. Synaptosomal lactate dehydrogenase isoenzyme composition is shifted toward aerobic forms in primate brain evolution.

    Science.gov (United States)

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

    2014-01-01

    With the evolution of a relatively large brain size in haplorhine primates (i.e. tarsiers, monkeys, apes, and humans), there have been associated changes in the molecular machinery that delivers energy to the neocortex. Here we investigated variation in lactate dehydrogenase (LDH) expression and isoenzyme composition of the neocortex and striatum in primates using quantitative Western blotting and isoenzyme analysis of total homogenates and synaptosomal fractions. Analysis of isoform expression revealed that LDH in synaptosomal fractions from both forebrain regions shifted towards a predominance of the heart-type, aerobic isoform LDH-B among haplorhines as compared to strepsirrhines (i.e. lorises and lemurs), while in the total homogenate of the neocortex and striatum there was no significant difference in LDH isoenzyme composition between the primate suborders. The largest increase occurred in synapse-associated LDH-B expression in the neocortex, with an especially remarkable elevation in the ratio of LDH-B/LDH-A in humans. The phylogenetic variation in the ratio of LDH-B/LDH-A was correlated with species-typical brain mass but not the encephalization quotient. A significant LDH-B increase in the subneuronal fraction from haplorhine neocortex and striatum suggests a relatively higher rate of aerobic glycolysis that is linked to synaptosomal mitochondrial metabolism. Our results indicate that there is a differential composition of LDH isoenzymes and metabolism in synaptic terminals that evolved in primates to meet increased energy requirements in association with brain enlargement.

  5. Insights into the Synthesis of Layered Double Hydroxide (LDH) Nanoparticles: Part 2. Formation Mechanisms of LDH

    OpenAIRE

    Sun, Xiaodi; Dey, Sandwip K.

    2015-01-01

    This study demonstrates the effect of (co)intercalated anion compositions on nanostructure evolution to understand the formation mechanisms of layered double hydroxide (LDH) nanoparticles following coprecipitation and hydrothermal treatments (HT). Initially, the room temperature coprecipitation resulted in amorphous primary nanoparticles that agglomerated at the edges due to low surface charge densities. The reversibility of such agglomeration was determined by the crystalline quality upon HT...

  6. Effect of radiation in utero on mouse testes lactate dehydrogenase-X

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, N.; Prasad, R.; Bushong, S.C.

    1976-01-01

    Lactate dehydrogenase-X(LDH-X), a sperm specific isozyme of mammals, can be used as a marker for active spermatogenesis. LDH-X electrophoretic patterns may also be affected in radiation-induced sterility following in utero irradiation. To investigate this relationship pregnant female mice were given 100 rad x radiation on day 10, 13, and 17 following gestation. All male offspring were sacrificed 20 days after birth and testes tissues obtained. The testes were homogenized to obtain crude extracts for starch gel electrophoresis and zymogram staining for LDH-X. Results to date show that the LDH-X is not expressed in the testis when fetal irradiation occurred at 10 and 13 days following gestation. Faint bands of LDH-X were observed in testes homogenates of mice whose mothers were irradiated 17 days following gestation. Pronounced LDH-X bands were present in all control preparations.

  7. Dehydrin, alcohol dehydrogenase, and central metabolite levels are associated with cold tolerance in diploid strawberry (Fragaria spp.).

    Science.gov (United States)

    Davik, Jahn; Koehler, Gage; From, Britta; Torp, Torfinn; Rohloff, Jens; Eidem, Petter; Wilson, Robert C; Sønsteby, Anita; Randall, Stephen K; Alsheikh, Muath

    2013-01-01

    The use of artificial freezing tests, identification of biomarkers linked to or directly involved in the low-temperature tolerance processes, could prove useful in applied strawberry breeding. This study was conducted to identify genotypes of diploid strawberry that differ in their tolerance to low-temperature stress and to investigate whether a set of candidate proteins and metabolites correlate with the level of tolerance. 17 Fragaria vesca, 2 F. nilgerrensis, 2 F. nubicola, and 1 F. pentaphylla genotypes were evaluated for low-temperature tolerance. Estimates of temperatures where 50 % of the plants survived (LT₅₀) ranged from -4.7 to -12.0 °C between the genotypes. Among the F. vesca genotypes, the LT₅₀ varied from -7.7 °C to -12.0 °C. Among the most tolerant were three F. vesca ssp. bracteata genotypes (FDP821, NCGR424, and NCGR502), while a F. vesca ssp. californica genotype (FDP817) was the least tolerant (LT₅₀) -7.7 °C). Alcohol dehydrogenase (ADH), total dehydrin expression, and content of central metabolism constituents were assayed in select plants acclimated at 2 °C. The LT₅₀ estimates and the expression of ADH and total dehydrins were highly correlated (r(adh) = -0.87, r (dehyd) = -0.82). Compounds related to the citric acid cycle were quantified in the leaves during acclimation. While several sugars and acids were significantly correlated to the LT₅₀ estimates early in the acclimation period, only galactinol proved to be a good LT₅₀ predictor after 28 days of acclimation (r(galact) = 0.79). It is concluded that ADH, dehydrins, and galactinol show great potential to serve as biomarkers for cold tolerance in diploid strawberry.

  8. Procalcitonin, C-reactive protein and serum lactate dehydrogenase in the diagnosis of bacterial sepsis, SIRS and systemic candidiasis.

    Science.gov (United States)

    Miglietta, Fabio; Faneschi, Maria Letizia; Lobreglio, Giambattista; Palumbo, Claudio; Rizzo, Adriana; Cucurachi, Marco; Portaccio, Gerolamo; Guerra, Francesco; Pizzolante, Maria

    2015-09-01

    The aim of this study was to evaluate procalcitonin (PCT), C-reactive protein (CRP), platelet count (PLT) and serum lactate dehydrogenase (LDH) as early markers for diagnosis of SIRS, bacterial sepsis and systemic candidiasis in intensive care unit (ICU) patients. Based on blood culture results, the patients were divided into a sepsis group (70 patients), a SIRS group (42 patients) and a systemic candidiasis group (33 patients). PCT, CRP, LDH and PLT levels were measured on day 0 and on day 2 from the sepsis symptom onset. PCT levels were higher in Gram negative sepsis than those in Gram positive sepsis, although the P value between the two subgroups is not significant (P=0.095). Bacterial sepsis group had higher PCT and CRP levels compared with the systemic candidiasis group, whereas PLT and LDH levels showed similar levels in these two subgroups. The AUC for PCT (AUC: 0.892, P SIRS and systemic candidiasis groups (P=0.093 N.S.). In conclusion, PCT can be used as a preliminary marker in the event of clinical suspicion of systemic candidiasis; however, low PCT levels (SIRS groups.

  9. A potato tuber-expressed mNRA with homology to steroid dehydrogenases affects gibberellin levels and plant development

    NARCIS (Netherlands)

    Bachem, C.W.B.; Horvath, B.M.; Trindade, L.M.; Claassens, M.M.J.; Davelaar, E.; Jordi, W.J.R.M.; Visser, R.G.F.

    2001-01-01

    Using cDNA-AFLP RNA fingerprinting throughout potato tuber development, we have isolated a transcript-derived fragment (TDF511) with strong homology to plant steroid dehydrogenases. During in vitro tuberization, the abundance profile of the TDF shows close correlation to the process of tuber formati

  10. A potato tuber-expressed mNRA with homology to steroid dehydrogenases affects gibberellin levels and plant development

    NARCIS (Netherlands)

    Bachem, C.W.B.; Horvath, B.M.; Trindade, L.M.; Claassens, M.M.J.; Davelaar, E.; Jordi, W.J.R.M.; Visser, R.G.F.

    2001-01-01

    Using cDNA-AFLP RNA fingerprinting throughout potato tuber development, we have isolated a transcript-derived fragment (TDF511) with strong homology to plant steroid dehydrogenases. During in vitro tuberization, the abundance profile of the TDF shows close correlation to the process of tuber

  11. Glyceraldehyde-3-phosphate dehydrogenase is largely unresponsive to low regulatory levels of hydrogen peroxide in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Sousa-Lopes Ana

    2010-12-01

    Full Text Available Abstract Background The reversible oxidation of protein SH groups has been considered to be the basis of redox regulation by which changes in hydrogen peroxide (H2O2 concentrations may control protein function. Several proteins become S-glutathionylated following exposure to H2O2 in a variety of cellular systems. In yeast, when using a high initial H2O2 dose, glyceraldehyde-3-phosphate dehydrogenase (GAPDH was identified as the major target of S-glutathionylation which leads to reversible inactivation of the enzyme. GAPDH inactivation by H2O2 functions to reroute carbohydrate flux to produce NADPH. Here we report the effect of low regulatory H2O2 doses on GAPDH activity and expression in Saccharomyces cerevisiae. Results A calibrated and controlled method of H2O2 delivery - the steady-state titration - in which cells are exposed to constant, low, and known H2O2 concentrations, was used in this study. This technique, contrary to the common bolus addition, allows determining which H2O2 concentrations trigger specific biological responses. This work shows that both in exponential- and stationary-phase cells, low regulatory H2O2 concentrations induce a large upregulation of catalase, a fingerprint of the cellular oxidative stress response, but GAPDH oxidation and the ensuing activity decrease are only observed at death-inducing high H2O2 doses. GAPDH activity is constant upon incubation with sub-lethal H2O2 doses, but in stationary-phase cells there is a differential response in the expression of the three GAPDH isoenzymes: Tdh1p is strongly upregulated while Tdh2p/Tdh3p are slightly downregulated. Conclusions In yeast GAPDH activity is largely unresponsive to low to moderate H2O2 doses. This points to a scenario where (a cellular redoxins efficiently cope with levels of GAPDH oxidation induced by a vast range of sub-lethal H2O2 concentrations, (b inactivation of GAPDH cannot be considered a sensitive biomarker of H2O2-induced oxidation in vivo

  12. Lactate dehydrogenase and body mass index are prognostic factors in patients with recurrent small cell lung cancer receiving amrubicin.

    Science.gov (United States)

    Inomata, Minehiko; Hayashi, Ryuji; Tokui, Kotaro; Taka, Chihiro; Okazawa, Seisuke; Kambara, Kenta; Ichikawa, Tomomi; Yamada, Toru; Miwa, Toshiro; Kashii, Tatsuhiko; Matsui, Shoko; Tobe, Kazuyuki

    2016-12-01

    Amrubicin monotherapy can be an effective treatment option for patients with recurrent small cell lung cancer (SCLC). We conducted this retrospective study to investigate the prognostic factors in patients with recurrent SCLC receiving amrubicin monotherapy. The associations between survival and clinical data, including the performance status, body mass index (BMI), plasma lactate dehydrogenase (LDH) level, and plasma neuron-specific enolase level, were evaluated in patients with recurrent SCLC, and a subset analysis of patients with platinum-resistant disease was conducted. In all, 37 patients were evaluated. The median survival from the date of initiation of amrubicin monotherapy was 9.1 months (95% confidence interval 4.7-12.0 months). Multivariate analysis using a Cox proportional hazard model identified the plasma LDH level (p = 0.049), BMI (p = 0.031), and platinum resistance (p = 0.032) as independent factors associated with survival. The same associations were also observed in the subset of patients with platinum-resistant disease. Our findings suggest that the plasma LDH level and BMI may be useful prognostic factors in patients with SCLC receiving amrubicin monotherapy, including patients with platinum-resistant disease.

  13. Serum LDH and CA-125: Markers for Diagnosis of Ovarian Malignancy.

    Science.gov (United States)

    Deeba, F; Khatun, S; Alam, M M; Shahida, S M

    2015-04-01

    This prospective multi-centre study was carried out in the Department of obstetrics and gynaecology of Bangabandhu Sheikh Mujib Medical University, Dhaka Medical College Hospital and Bangladesh Medical College Hospital, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh, during the period of January 2008 to December 2009, to establish the raised level of serum LDH and serum CA-125 in pre-operative discrimination of benign and malignant ovarian cancer to be used as a diagnostic marker and its validity by determining sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPP). A total number of 141 consecutive suspected subjects of ovarian tumour admitted in the above mentioned hospitals and enrolled for surgical management were included in this study. Serum LDH was done in all these subjects and they were followed up from the admission upto the postoperative tissue diagnosis of live tumor in respective pathology departments for histopathological correlation. The patients who were diagnosed as malignant placed in Group I and diagnosed benign ovarian tumor placed in Group II. Serous cystadenoma and mucinous cyst adenoma were more common in benign tumors, which were 38.9% and 20.4% respectively. However, more than a half (57.1%) had serous cyst adenocarcinoma in malignant tumors. In LDH for evaluation of malignancy, true positive 16 and false positive 18, false negative 12 and true negative 95 cases. LDH and serum CA-125 level (combined, i.e. both positive) for evaluation of malignancy, true positive 14 and false positive 0, false negative 14 and true negative 113 cases. LDH/serum CA-125 level (anyone positive) for evaluation of malignancy, true positive 25 and false positive 37, false negative 3 and true negative 76 cases. The validity of LDH were sensitivity 57.1%, specificity 84.1%, accuracy 78.7%, positive predictive values 47.1% and negative predictive values 88.8% for malignancy of ovarian tumour. The

  14. Plasmodium falciparum and Plasmodium vivax specific lactate dehydrogenase: genetic polymorphism study from Indian isolates.

    Science.gov (United States)

    Keluskar, Priyadarshan; Singh, Vineeta; Gupta, Purva; Ingle, Sanjay

    2014-08-01

    Control and eradication of malaria is hindered by the acquisition of drug resistance by Plasmodium species. This has necessitated a persistent search for novel drugs and more efficient targets. Plasmodium species specific lactate dehydrogenase is one of the potential therapeutic and diagnostic targets, because of its indispensable role in endoerythrocytic stage of the parasite. A target molecule that is highly conserved in the parasite population can be more effectively used in diagnostics and therapeutics, hence, in the present study polymorphism in PfLDH (Plasmodiumfalciparum specific LDH) and PvLDH (Plasmodiumvivax specific LDH) genes was analyzed using PCR-single strand confirmation polymorphism (PCR-SSCP) and sequencing. Forty-six P. falciparum and thirty-five P. vivax samples were screened from different states of India. Our findings have revealed presence of a single PfLDH genotype and six PvLDH genotypes among the studied samples. Interestingly, along with synonymous substitutions, nonsynonymous substitutions were reported to be present for the first time in the PvLDH genotypes. Further, through amino acid sequence alignment and homology modeling studies we observed that the catalytic residues were conserved in all PvLDH genotypes and the nonsynonymous substitutions have not altered the enzyme structure significantly. Evolutionary genetics studies have confirmed that PfLDH and PvLDH loci are under strong purifying selection. Phylogenetic analysis of the pLDH gene sequences revealed that P. falciparum compared to P. vivax, has recent origin. The study therefore supports PfLDH and PvLDH as suitable therapeutic and diagnostic targets as well as phylogenetic markers to understand the genealogy of malaria species.

  15. Pathohistological changes in kidney and LDH activity in broiler treated with different doses of ochratoxin A

    Directory of Open Access Journals (Sweden)

    Nedeljković-Trailovć Jelena B.

    2005-01-01

    Full Text Available The three-week long trial was performed on day-old Hybro broilers divided into four groups. After 14 days long preexperimental period, the experimental groups were offered feed contaminated with 0.5, 1.0 and 1.5 ppm OA during 7 respectively. At the end of the trial blood and kidney samples were taken for investigations. In broilers feed with 1.5 ppm of OA histopathological examination of the kidney tissue revealed changes located in proximal tubules. Some cells were dim and swollen. These changes produced particular or total reduction in tubular lumen of kidney. Acute tubular necrosis existed in some of tubulocites in form of small foci. Fragmentation of necrotic mass and presence of fresh red blood cells were also detected. The LDH activity was significantly greater in broilers of experimental groups compared with control group. All presented data indicated that intensity of pathohistological alterations and LDH activity depends upon dietary OTA level. Positive correlation between pathohistological changes and increased LDH activity caused by OTA was noticed. Thus, LDH activity mea- sure could be used as early diagnostic tool in measuring changes caused by OTA.

  16. Predictive value of mid-trimester amniotic fluid high-sensitive C-reactive protein, ferritin, and lactate dehydrogenase for fetal growth restriction

    Directory of Open Access Journals (Sweden)

    Borna Sedigheh

    2009-10-01

    Full Text Available Background: Fetal growth restriction (FGR is surprisingly common with placental dysfunction occurring in about 3% of pregnancies and despite advances in obstetric care, FGR remains a major problem in developed countries. Aim: The purpose of this study is to find out the predictive value of amniotic fluid high sensitive C-reactive protein (hs-CRP, ferritin, and lactate dehydrogenase (LDH for FGR. Materials and Methods: This prospective strategy of this study has been conducted on pregnant women who underwent genetic amniocentesis between 15th and 20th weeks of gestation. All patients were followed up on until delivery. Patients with abnormal karyotype and iatrogenic preterm delivery for fetal and maternal indications were excluded. The samples were immediately sent to laboratory for cytogenetic and biochemical examination. Non-parametric tests and receiver-operator characteristic curve analysis were used for statistical purpose. Results: A significant correlation between incremental amniotic fluid alpha fetoprotein (αFPr and LDH levels and FGR at gestational weeks 15th-20th was found out. We also found an optimum cut-off value> 140 IU/L for the amniotic fluid LDH concentration with a sensitivity of 87.5% and a specificity of 82.4% for the prediction of FGR. Conclusion: Once the LDH value is confirmed, it could serve as a prediction factor for FGR at the time of genetic amniocentesis at gestational weeks 15-20.

  17. LDH inhibition impacts on heat shock response and induces senescence of hepatocellular carcinoma cells.

    Science.gov (United States)

    Manerba, Marcella; Di Ianni, Lorenza; Govoni, Marzia; Roberti, Marinella; Recanatini, Maurizio; Di Stefano, Giuseppina

    2017-07-15

    In normal cells, heat shock response (HSR) is rapidly induced in response to a variety of harmful conditions and represents one of the most efficient defense mechanism. In cancer tissues, constitutive activation converts HSR into a life-threatening process, which plays a major role in helping cell survival and proliferation. Overexpression of heat shock proteins (HSPs) has been widely reported in human cancers and was found to correlate with tumor progression. Hepatocellular carcinoma is one of the conditions in which HSR activation was shown to have the highest clinical significance. Transcription of HSPs is induced by HSF-1, which also activates glycolytic metabolism and increases the expression of LDH-A, the master regulator of the Warburg effect. In this paper, we tried to explore the relationship between HSR and LDH-A. In cultured hepatocellular carcinoma cells, by using two enzyme inhibitors (oxamate and galloflavin), we found that the reduction of LDH-A activity led to decreased level and function of the major HSPs involved in tumorigenesis. Galloflavin (a polyphenol) also inhibited the ATPase activity of two of the examined HSPs. Finally, hindering HSR markedly lowered the alpha-fetoprotein cellular levels and induced senescence. Specific inhibitors of single HSPs are currently under evaluation in different neoplastic diseases. However, one of the effects usually observed during treatment is a compensatory elevation of other HSPs, which decreases treatment efficacy. Our results highlight a connection between LDH and HSR and suggest LDH inhibition as a way to globally impact on this tumor promoting process. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Metabolic Engineering of Mannitol Production in Lactococcus lactis: Influence of Overexpression of Mannitol 1-Phosphate Dehydrogenase in Different Genetic Backgrounds

    NARCIS (Netherlands)

    Wisselink, H.W.; Mars, A.E.; Meer, van der P.; Eggink, G.; Hugenholtz, J.

    2004-01-01

    To obtain a mannitol-producing Lactococcus lactis strain, the mannitol 1-phosphate dehydrogenase gene (mtlD) from Lactobacillus plantarum was overexpressed in a wild-type strain, a lactate dehydrogenase(LDH)-deficient strain, and a strain with reduced phosphofructokinase activity. High-performance l

  19. Metabolic Engineering of Mannitol Production in Lactococcus lactis: Influence of Overexpression of Mannitol 1-Phosphate Dehydrogenase in Different Genetic Backgrounds

    NARCIS (Netherlands)

    Wisselink, H.W.; Mars, A.E.; Meer, van der P.; Eggink, G.; Hugenholtz, J.

    2004-01-01

    To obtain a mannitol-producing Lactococcus lactis strain, the mannitol 1-phosphate dehydrogenase gene (mtlD) from Lactobacillus plantarum was overexpressed in a wild-type strain, a lactate dehydrogenase(LDH)-deficient strain, and a strain with reduced phosphofructokinase activity. High-performance

  20. Differential pulse voltammetric studies on the effects of Al(Ⅲ) on the lactate dehydrogenase activity

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper, differential pulse voltammetry (DPV) was applied to study the effects of aluminum Al(Ⅲ) on the lactate dehydrogenase (LDH) activity. Michaelis-Menten constant (KNADHm) and maximum velocity (vmax) in the enzyme promoting catalytic reaction of "pyruvate(Pyr) + NADH + H+ LDH(=) lactate + NAD+" under different conditions by monitoring DPV reduction current of NAD+ were reported.(C) 2007 Shu Ping Bi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  1. In Situ lactate dehydrogenase activiy-a novel renal cortical imaging biomarker of tubular injury?

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Laustsen, Christoffer; Bertelsen, Lotte Bonde;

    , apoptosis and inflammation. Lactate dehydrogenase (LDH) activity has previously been suggested as a renal tubular injury marker, but has a major limitation in the sense that it can only be measured in terminal kidneys. By the use of a hyperpolarized [1-13C]pyruvate magnetic resonance imaging (MRI) approach...... to monitor metabolic changes, we here investigate LDH activity and renal metabolism after IRI. This procedure gives a novel non-invasive method for investigation renal tissue injury in concern with IRI....

  2. Testis-specific lactate dehydrogenase is expressed in somatic tissues of plateau pikas☆

    Science.gov (United States)

    Wang, Duowei; Wei, Lian; Wei, Dengbang; Rao, Xinfeng; Qi, Xinzhang; Wang, Xiaojun; Ma, Benyuan

    2013-01-01

    LDH-C4 is a lactate dehydrogenase that catalyzes the interconversion of pyruvate with lactate. In mammals the, Ldh-c gene was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae), belonging to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living at 3000–5000 m above sea levelon the Qinghai-Tibet Plateau. We found that the expression pattern of six LDH isoenzymes in the somatic tissues of female and male plateau pikas to be the same as those in testis and sperm, suggesting that LDH-C4 was expressed in somatic tissues of plateau pika. Here we report the detection of LDHC in the somatic tissues of plateau pika using RT-PCR, Western blotting and immunohistochemistry. Our results indicate that Ldh-c mRNA is transcribed in the heart, liver, lung, kidney, brain, skeletal muscle and testis. In somatic tissues LDHC was translated in the cytoplasm, while in testis it was expressed in both cytoplasm and mitochondria. The third band from cathode to anode in LDH isoenzymes was identified as LDH-C4. The finding that Ldh-c is expressed in both somatic tissues and testis of plateau pika provides important implications for more in-depth research into the Ldh-c function in mammals. PMID:23772382

  3. The effects of lanthanoid on the structure–function of lactate dehydrogenase from mice heart.

    Science.gov (United States)

    Li, Na; Duan, Yanmei; Zhou, Min; Liu, Chao; Hong, Fashui

    2009-12-01

    The activity of lactate dehydrogenase (LDH, EC1.1.1.27) is often changed upon inflammatory responses in animals. Lanthanoid (Ln) was shown to provoke various inflammatory responses both in rats and mice; however, the molecular mechanism by which Ln3+ exert its toxicity has not been completely understood, especially that we know little about the mechanism of the interaction between Ln with 4f electron shell and alternation valence and LDH. In this report, we investigated the mechanisms of LaCl3, CeCl3, and NdCl3 on LDH activity in vivo and in vitro. Our results showed that La3+, Ce3+, and Nd3+ could significantly activate LDH in vivo and in vitro; the order of activation was Ce3+>Nd3+> La3+>control. The affinity of LDH for Ce3+ was higher than Nd3+ and La3+; the saturated binding sites for Ce3+ on the LDH protein were 1.2 and for La3+ and Nd3+ 1.55. Ln3+ caused the reduction of exposure degree of cysteine or tryptophan/tyrosine of LDH, the increase of space resistance, and the enhancement of α-helix in secondary structure of LDH, which was greatest in Ce3+ treatment, medium in Nd3+ treatment, and least in La3+ treatment. It implied that the changes of structure-function on LDH caused by Ln3+ were closely related to the characteristics of 4f electron shell and alternation valence in Ln.

  4. (1-3)-beta-D-glucan in association with lactate dehydrogenase as biomarkers of Pneumocystis pneumonia (PcP) in HIV-infected patients.

    Science.gov (United States)

    Esteves, F; Lee, C-H; de Sousa, B; Badura, R; Seringa, M; Fernandes, C; Gaspar, J F; Antunes, F; Matos, O

    2014-07-01

    Pneumocystis pneumonia (PcP) is a major HIV-related illness caused by Pneumocystis jirovecii. Definitive diagnosis of PcP requires microscopic detection of P. jirovecii in pulmonary specimens. The objective of this study was to evaluate the usefulness of two serum markers in the diagnosis of PcP. Serum levels of (1-3)-beta-d-glucan (BG) and lactate dehydrogenase (LDH) were investigated in 100 HIV-positive adult patients and 50 healthy blood donors. PcP cases were confirmed using indirect immunofluorescence with monoclonal anti-Pneumocystis antibodies and nested-PCR to amplify the large subunit mitochondrial rRNA gene of P. jirovecii in pulmonary specimens. BG and LDH levels in serum were measured using quantitative microplate-based assays. BG and LDH positive sera were statistically associated with PcP cases (P ≤ 0.001). Sensitivity, specificity, positive/negative predictive values (PPV/NPV), and positive/negative likelihood ratios (PLR/NLR) were 91.3 %, 61.3 %, 85.1 %, 79.2 %, 2.359, and 0.142, respectively, for the BG kit assay, and 91.3 %, 35.5 %, 75.9 %, 64.7 %, 1.415 and 0.245, respectively, for the LDH test. Serologic markers levels combined with the clinical diagnostic criteria for PcP were evaluated for their usefulness in diagnosis of PcP. The most promising cutoff levels for diagnosis of PcP were determined to be 400 pg/ml of BG and 350 U/l of LDH, which combined with clinical data presented 92.8 % sensitivity, 83.9 % specificity, 92.8 % PPV, 83.9 % NPV, 5.764 PLR and 0.086 NLR (P PcP diagnosis.

  5. 5年生人参出苗期几种脱氢酶活力比较%Comparison of Dehydrogenase Activity in 5-year Ginseng during Seedling Stage

    Institute of Scientific and Technical Information of China (English)

    刘宏; 赵雨; 邢楠楠; 张惠; 刘海龙

    2012-01-01

    OBJECTIVE To compare the activities of malate dehydrogenase (MDH), lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH), glucose-6-phosphate dehydrogenase (G6PDH) and α-Glycerophosphate dehydrogenase (α-GPD) in 5-year Ginseng Radix in seedling stage. METHODS Adopt neutral buffer solution to extract the coarse enzyme. Use spectrophotometry to test the activities of MDH, LDH, ADH, G6PDH, α-GPD. RESULTS In seedling stage of Ginseng Radix, there were different changes trends of these five dehydrogenase in root and sprout. And there were peak values in different stages. CONCLUSION The activities of MDH, LDH, ADH, G6PDH, a-GPD can be used as the evaluation indicators of quality of Ginseng Radix.%目的 对5年生人参出苗期参根和参苗中苹果酸脱氢酶(malate dehydrogenase,MDH)、乳酸脱氢酶(lactate dehydrogenase,LDH)、乙醇脱氢酶(Alcohol dehydrogenase,ADH)、葡萄糖-6-磷酸脱氢酶(glucose-6-phosphate dehydrogenase,G6PDH)、α-磷酸甘油脱氢酶(α-glycerophosphate dehydrogenase,α-GPD)5种脱氢酶的活力进行比较.方法 采用中性缓冲液提取粗酶液,应用分光光度法测定MDH,LDH,ADH,G6PDH,α-GPD的活力.结果 在人参出苗期,参根和参苗中的5种脱氢酶活力变化趋势有所不同,并在不同时期出现峰值.结论 MDH,LDH,ADH,G6PDH,α-GPD的活力可以作为人参生长过程中长势优劣的评价指标.

  6. Regulation of the activity of lactate dehydrogenases from four lactic acid bacteria.

    Science.gov (United States)

    Feldman-Salit, Anna; Hering, Silvio; Messiha, Hanan L; Veith, Nadine; Cojocaru, Vlad; Sieg, Antje; Westerhoff, Hans V; Kreikemeyer, Bernd; Wade, Rebecca C; Fiedler, Tomas

    2013-07-19

    Despite high similarity in sequence and catalytic properties, the l-lactate dehydrogenases (LDHs) in lactic acid bacteria (LAB) display differences in their regulation that may arise from their adaptation to different habitats. We combined experimental and computational approaches to investigate the effects of fructose 1,6-bisphosphate (FBP), phosphate (Pi), and ionic strength (NaCl concentration) on six LDHs from four LABs studied at pH 6 and pH 7. We found that 1) the extent of activation by FBP (Kact) differs. Lactobacillus plantarum LDH is not regulated by FBP, but the other LDHs are activated with increasing sensitivity in the following order: Enterococcus faecalis LDH2 ≤ Lactococcus lactis LDH2 < E. faecalis LDH1 < L. lactis LDH1 ≤ Streptococcus pyogenes LDH. This trend reflects the electrostatic properties in the allosteric binding site of the LDH enzymes. 2) For L. plantarum, S. pyogenes, and E. faecalis, the effects of Pi are distinguishable from the effect of changing ionic strength by adding NaCl. 3) Addition of Pi inhibits E. faecalis LDH2, whereas in the absence of FBP, Pi is an activator of S. pyogenes LDH, E. faecalis LDH1, and L. lactis LDH1 and LDH2 at pH 6. These effects can be interpreted by considering the computed binding affinities of Pi to the catalytic and allosteric binding sites of the enzymes modeled in protonation states corresponding to pH 6 and pH 7. Overall, the results show a subtle interplay among the effects of Pi, FBP, and pH that results in different regulatory effects on the LDHs of different LABs.

  7. The level of glucose-6-phosphate dehydrogenase activity strongly influences xylose fermentation and inhibitor sensitivity in recombinant Saccharomyces cerevisiae strains

    DEFF Research Database (Denmark)

    Jeppsson, M.; Johansson, B.; Jensen, Peter Ruhdal

    2003-01-01

    Disruption of the ZWF1 gene encoding glucose-6-phosphate dehydrogenase (G6PDH) has been shown to reduce the xylitol yield and the xylose consumption in the xylose-utilizing recombinant Saccharomyces cerevisiae strain TMB3255. In the present investigation we have studied the influence of different...... consumption, respectively, compared with the ZWF1-disrupted strain. Both strains exhibited decreased xylitol yields (0.13 and 0.19 g/g xylose) and enhanced ethanol yields (0.36 and 0.34 g/g xylose) compared with the control strain TMB3001 (0.29 g xylitol/g xylose, 0.31 g ethanol/g xylose). Cytoplasmic...... than the strain with wild-type G6PDH-activity, which suggested that the availability of intracellular NADPH correlated with tolerance towards lignocellulose-derived inhibitors. Low G6PDH-activity strains were also more sensitive to H2O2 than the control strain TMB3001....

  8. LDH is an adverse prognostic factor independent of ISS in transplant-eligible myeloma patients receiving bortezomib-based induction regimens.

    Science.gov (United States)

    Chim, Chor Sang; Sim, Joycelyn; Tam, Sidney; Tse, Eric; Lie, Albert Kwok Wai; Kwong, Yok Lam

    2015-04-01

    Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined whether elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT). Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N = 25), PAD (N = 19), VTD (N = 33)], followed by ASCT and thalidomide maintenance. Five-year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, complete remission/near complete remission (CR/nCR rates postinduction or ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS III (P = 0.042) and serum β2-microglobulin (P = 0.040). Univariate analysis showed that elevated LDH, ISS III, high β2-microglobulin, and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (P = 0.007) and EFS (P = 0.008). In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Is Serum Total LDH Evaluation Able to Differentiate between Alimentary Lymphoma and Inflammatory Bowel Disease in a Real World Clinical Setting?

    Science.gov (United States)

    Terragni, Rossella; Morselli-Labate, Antonio M.; Vignoli, Massimo; Bottero, Enrico; Brunetti, Barbara; Saunders, Jimmy H.

    2016-01-01

    Context An increase in enzyme lactate dehydrogenase (LDH) in serum is a negative prognostic factor for survival in cats affected by lymphoma. Measuring LDH at the time of diagnosis has been studied for differentiating neoplastic disease from non-neoplastic disease in dogs. Inflammatory bowel disease (IBD) and alimentary lymphoma are common diseases in cats. Objective The aim of this study was to determine whether elevation of total LDH occurred in cats with alimentary lymphoma and non-neoplastic gastrointestinal disease, such as IBD, and to evaluate whether this enzyme is useful in supporting the differential diagnosis of these specific diseases. Materials and Methods A prospective non-randomized controlled study was carried-out in a real world setting of three Italian private veterinary clinics. Seventy-one client-owned cats with a history of chronic gastrointestinal symptoms were enrolled; 33 cats were histologically diagnosed as having alimentary lymphoma and 38 cats as having IBD. Serum samples of total LDH analysis were measured. Results Gender (P = 0.016) and age (P = 0.046) were found to be significant factors influencing the differentiation of serum total LDH between cats with alimentary lymphoma and those with IBD. Despite low diagnostic accuracy in the overall population (63%), a cut-off value of serum total LDH ranging from 0.85- to 1.04-times the upper reference limit showed good capability (accuracy >80%) of differentiating these two conditions in neutered males and cats younger than 8 years of age (AUC: 0.805, 0.833; sensitivities: 76.9%, 83.3%; specificities: 80.0%, 76.5%; PPV: 76.9%, 55.6%; NPV: 80.0%, 92.9%; respectively). Conclusions Although our study showed that gender and age are significant factors in differentiating serum total LDH between cats with alimentary lymphoma and those with IBD, this test had poor diagnostic accuracy in differentiating between these two conditions in the overall population. PMID:26986208

  10. Is Serum Total LDH Evaluation Able to Differentiate between Alimentary Lymphoma and Inflammatory Bowel Disease in a Real World Clinical Setting?

    Directory of Open Access Journals (Sweden)

    Rossella Terragni

    Full Text Available An increase in enzyme lactate dehydrogenase (LDH in serum is a negative prognostic factor for survival in cats affected by lymphoma. Measuring LDH at the time of diagnosis has been studied for differentiating neoplastic disease from non-neoplastic disease in dogs. Inflammatory bowel disease (IBD and alimentary lymphoma are common diseases in cats.The aim of this study was to determine whether elevation of total LDH occurred in cats with alimentary lymphoma and non-neoplastic gastrointestinal disease, such as IBD, and to evaluate whether this enzyme is useful in supporting the differential diagnosis of these specific diseases.A prospective non-randomized controlled study was carried-out in a real world setting of three Italian private veterinary clinics. Seventy-one client-owned cats with a history of chronic gastrointestinal symptoms were enrolled; 33 cats were histologically diagnosed as having alimentary lymphoma and 38 cats as having IBD. Serum samples of total LDH analysis were measured.Gender (P = 0.016 and age (P = 0.046 were found to be significant factors influencing the differentiation of serum total LDH between cats with alimentary lymphoma and those with IBD. Despite low diagnostic accuracy in the overall population (63%, a cut-off value of serum total LDH ranging from 0.85- to 1.04-times the upper reference limit showed good capability (accuracy >80% of differentiating these two conditions in neutered males and cats younger than 8 years of age (AUC: 0.805, 0.833; sensitivities: 76.9%, 83.3%; specificities: 80.0%, 76.5%; PPV: 76.9%, 55.6%; NPV: 80.0%, 92.9%; respectively.Although our study showed that gender and age are significant factors in differentiating serum total LDH between cats with alimentary lymphoma and those with IBD, this test had poor diagnostic accuracy in differentiating between these two conditions in the overall population.

  11. Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements.

    Science.gov (United States)

    Firth, J D; Ebert, B L; Ratcliffe, P J

    1995-09-08

    The oxygen-regulated control system responsible for the induction of erythropoietin (Epo) by hypoxia is present in most (if not all) cells and operates on other genes, including those involved in energy metabolism. To understand the organization of cis-acting sequences that are responsible for oxygen-regulated gene expression, we have studied the 5' flanking region of the mouse gene encoding the hypoxically inducible enzyme lactate dehydrogenase A (LDH). Deletional and mutational analysis of the function of mouse LDH-reporter fusion gene constructs in transient transfection assays defined three domains, between -41 and -84 base pairs upstream of the transcription initiation site, which were crucial for oxygen-regulated expression. The most important of these, although not capable of driving hypoxic induction in isolation, had the consensus of a hypoxia-inducible factor 1 (HIF-1) site, and cross-competed for the binding of HIF-1 with functionally active Epo and phosphoglycerate kinase-1 sequences. The second domain was positioned close to the HIF-1 site, in an analogous position to one of the critical regions in the Epo 3' hypoxic enhancer. The third domain had the motif of a cAMP response element (CRE). Activation of cAMP by forskolin had no effect on the level of LDH mRNA in normoxia, but produced a magnified response to hypoxia that was dependent upon the integrity of the CRE, indicating an interaction between inducible factors binding the HIF-1 and CRE sites.

  12. Perbandingan Kadar Ldh Antara Penderita Preeklampsia Berat/Eklampsia Dengan Kehamilan Normal

    OpenAIRE

    Asroel, Edwin Martin

    2016-01-01

    Purpose of study :to analyze level of LDH between patients with preeclampsia / severe preeclampsia and normal pregnancy. Study design :this study is held with analytical observation study with cross sectional study to pregnant woman with preeclampsia / severe preeclampsia and pregnant woman with normal blood pressure. Results :this study was held since March 2014, and got 30 pastients with severe preeclampsia and eclampsia with 5 persons dead (16,7%).Character of pregnant mother mostl...

  13. Insights into the synthesis of layered double hydroxide (LDH) nanoparticles: Part 2. Formation mechanisms of LDH.

    Science.gov (United States)

    Sun, Xiaodi; Dey, Sandwip K

    2015-11-15

    This study demonstrates the effect of (co)intercalated anion compositions on nanostructure evolution to understand the formation mechanisms of layered double hydroxide (LDH) nanoparticles following coprecipitation and hydrothermal treatments (HT). Initially, the room temperature coprecipitation resulted in amorphous primary nanoparticles that agglomerated at the edges due to low surface charge densities. The reversibility of such agglomeration was determined by the crystalline quality upon HT and consequent surface charge density, which in turn were strongly influenced by the composition of the intercalated anions. Upon crystallization, the agglomerated Zn2Al(OH)6(NO3)0.3(CO3)0.35⋅xH2O primary nanoparticles re-dispersed, but the Zn2Al(OH)6(NO3)⋅xH2O nanoparticles with much lower stability and higher disorder (especially at the edges) exhibited irreversible agglomeration, and transformed into secondary nanoparticles via aggregational growth. Additionally, the stability studies on Zn2Al(OH)6(NO3)y(CO3)0.5(1-y)⋅xH2O nanoparticles (y=0-1) showed that the size difference between the cointercalated anions caused phase separation when 0.9⩾y⩾0.6, leading to bimodal size distributions. Moreover, the coarsening rates were controlled through the cointercalated anion compositions. By gradually varying the ratio of cointercalated NO3(-) to CO3(2-), monodispersed Zn2Al(OH)6(NO3)y(CO3)0.5(1-y)⋅xH2O (0.5⩾y⩾0) nanoparticles with systematic variation in the particle size of ∼200-400nm were obtained after HT at 85°C for 12h.

  14. Investigation of the stabilizing effects of hydroxyethyl cellulose on LDH during freeze drying and freeze thawing cycles.

    Science.gov (United States)

    Al-Hussein, Anas; Gieseler, Henning

    2015-01-01

    The objective of this study was to investigate both the cryoprotective and lyoprotective effects of the polymer hydroxyethyl cellulose (HEC) on the model protein lactate dehydrogenase (LDH) during freeze thawing and freeze drying cycles. The effect of annealing on both protein stability and the physical state of HEC was evaluated. HEC was used as a sole excipient in the protein formulations, and its stabilizing was compared to that of other excipients which are commonly used in freeze dried protein formulations. Furthermore, other quality aspects of the freeze dried samples containing solely HEC were investigated, such as, reconstitution time and product elegance. Protein stability was evaluated functionally by measuring the activity recovery of the model protein LDH. The physical state of HEC after freeze drying was investigated and compared to this of other studied solutes using differential scanning calorimetry and X-ray powder diffractometry. HEC showed superior cryoprotective effects on LDH during freeze thawing, and considerable lyoprotective effects during the freeze drying process. Annealing had limited influence on the stabilizing effect of HEC. The extensive reconstitution times of the HEC lyophilisates could be greatly improved by incorporation of the surfactant Tween 80 into the formulations prior to freeze drying.

  15. ZnO nanoparticles augment ALT, AST, ALP and LDH expressions in C2C12 cells.

    Science.gov (United States)

    Pandurangan, Muthuraman; Kim, Doo Hwan

    2015-11-01

    The present study aimed to investigate the effect of ZnO nanoparticles on alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) enzyme expressions in C2C12 cells. ZnO nanoparticles are widely used in the several cosmetic lotions and other biomedical products. Several studies report on ZnO nanoparticle mediated cytotoxicity. However, there are no reports on the effect of ZnO nanoparticles on ALT, AST, ALP and LDH enzyme expressions in C2C12 cells. A cytotoxicity assay was carried out to determine the effect of ZnO nanoparticles (1-5 mg/ml) on C2C12 cell viability at 48 and 72 h. ZnO nanoparticles increased ALT, AST, ALP and LDH enzyme mRNA expression and their activities in C2C12 cells. In conclusion, the present study showed that ZnO nanoparticles increased these enzyme activities and its mRNA expression in C2C12 cells in a dose-dependent manner.

  16. L-lactate metabolism can occur in normal and cancer prostate cells via the novel mitochondrial L-lactate dehydrogenase.

    Science.gov (United States)

    De Bari, Lidia; Chieppa, Gabriella; Marra, Ersilia; Passarella, Salvatore

    2010-12-01

    Both normal (PTN1A) and cancer (PC3) prostate cells produce high levels of L-lactate because of a low energy supply via the citric cycle and oxidative phosphorylation. Since some mammalian mitochondria possess a mitochondrial L-lactate dehydrogenase (mLDH), we investigated whether prostate cells can take up L-lactate and metabolize it in the mitochondria. We report here that externally added L-lactate can enter both normal and cancer cells and mitochondria, as shown by both the oxygen consumption and by the increase in fluorescence of NAD(P)H which occur as a result of L-lactate addition. In both cell types L-lactate enters mitochondria in a carrier-mediated manner, as shown by the inhibition of swelling measurements due to the non-penetrant thiol reagent mersalyl. An L-lactate dehydrogenase exists in mitochondria of both cell types located in the inner compartment, as shown by kinetic investigation and by immunological analysis. The mLDHs proved to differ from the cytosolic enzymes (which themselves differ from one another) as functionally investigated with respect to kinetic features and pH profile. Normal and cancer cells were found to differ from one another with respect to mLDH protein level and activity, being the enzyme more highly expressed and of higher activity in PC3 cells. Moreover, the kinetic features and pH profiles of the PC3 mLDH also differ from those of the PNT1A enzyme, this suggesting the occurrence of separate isoenzymes.

  17. The behaviour of LDH-3 in patients with malignant diseases during therapy with cytostatic drugs and prednisone, studied by LDH-isoenzyme electrophoresis on cellulose acetate

    NARCIS (Netherlands)

    Gennip, A.H. van; Tabak-van Gorcum, J.A.; Taminiau, J.A.J.M.; Wadman, S.K.

    1975-01-01

    A modified method used for the quantitative estimation of LDH-isoenzymes in serum after electrophoresis on cellulose acetate is described. Total LDH-activity and isoenzyme distribution in serum samples of capillary blood are compared to those in samples collected by venipuncture. Total LDH-values

  18. Hybridizability of gamma-irradiated lactic dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Saito, M.

    1976-03-01

    The hybridizabilities of the gamma-irradiated chicken heart and pig muscle lactic dehydrogenases were estimated by hybridizing the irradiated enzymes with the unirradiated pig heart lactic dehydrogenase. The disc gel electrophoretic patterns of the inter- and intraspecific hybrids showed that the LDH activity of the pig heart isozyme band increased as a function of dose. This observation was analyzed upon the binomial redistribution pattern of the recombined subunits. The result shows that the hybridizabilities of both the chicken heart and pig muscle isozymes decreased along with the loss of catalytic activity and the release from substrate inhibition. The titration of free SH groups of the irradiated chicken isozyme suggested that the unfolding of the peptide chain destroyed the specific tertiary structure needed for the binding of subunits. (auth)

  19. Isocitrate dehydrogenase 1 (IDH1) mutation in breast adenocarcinoma is associated with elevated levels of serum and urine 2-hydroxyglutarate.

    Science.gov (United States)

    Fathi, Amir T; Sadrzadeh, Hossein; Comander, Amy H; Higgins, Michaela J; Bardia, Aditya; Perry, Ashley; Burke, Meghan; Silver, Regina; Matulis, Christina R; Straley, Kimberly S; Yen, Katharine E; Agresta, Sam; Kim, Hyeryun; Schenkein, David P; Borger, Darrell R

    2014-06-01

    Mutations in the IDH1 and IDH2 (isocitrate dehydrogenase) genes have been discovered across a range of solid-organ and hematologic malignancies, including acute myeloid leukemia, glioma, chondrosarcoma, and cholangiocarcinoma. An intriguing aspect of IDH-mutant tumors is the aberrant production and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which may play a pivotal oncogenic role in these malignancies. We describe the first reported case of an IDH1 p.R132L mutation in a patient with hormone receptor-positive (HR+) breast adenocarcinoma. This patient was initially treated for locally advanced disease, but then suffered a relapse and metastasis, at which point an IDH1-R132 mutation was discovered in an affected lymph node. The mutation was subsequently found in the primary tumor tissue and all metastatic sites, but not in an uninvolved lymph node. In addition, the patient's serum and urine displayed marked elevations in the concentration of 2-HG, significantly higher than that measured in six other patients with metastatic HR+ breast carcinoma whose tumors were found to harbor wild-type IDH1. In summary, IDH1 mutations may impact a rare subgroup of patients with breast adenocarcinoma. This may suggest future avenues for disease monitoring through noninvasive measurement of 2-HG, as well as for the development and study of targeted therapies against the aberrant IDH1 enzyme.

  20. [Effects of the histamine H2 receptor antagonist roxatidine acetate on stomach and liver alcohol dehydrogenase and serum alcohol level].

    Science.gov (United States)

    Beil, W; Sewing, K F

    1993-11-01

    Some histamine-H2-receptor antagonists block gastric first-pass metabolism of ethanol and lead to increased blood alcohol concentrations after ingestion of a low dose (0.15 and 0.3 g/kg) of alcohol. To investigate whether the histamine-H2-receptor antagonist roxatidine acetate has a similar effect, we administered a low dose (0.3 g/kg) of ethanol to eleven volunteers before and after seven days treatment with roxatidine acetate (150 mg once daily). No effect of the drug on mean peak serum alcohol concentrations or on areas under the serum alcohol curves was found. In vitro, roxatidine acetate and its active metabolite roxatidine had almost no effect on guinea-pig gastric alcohol dehydrogenase activity. We conclude that roxatidine acetate does not block gastric first-pass metabolism of ethanol and can be considered as a safe histamine-H2-receptor antagonist in individuals who do not refrain from alcohol consumption under treatment for gastric or duodenal ulcer disease.

  1. Purification and properties of a monomeric lactate dehydrogenase from yak Hypoderma sinense larva.

    Science.gov (United States)

    Li, Pengfei; Jin, Suyu; Huang, Lin; Liu, Haohao; Huang, Zhihong; Lin, Yaqiu; Zheng, Yucai

    2013-06-01

    The objective of the present study was to study the characteristics of lactate dehydrogenase (LDH) from Hypoderma sinense larva. H. sinense larvae were collected from yak (Bos grunniens) and identified by a PCR-RFLP method. Analysis of LDH activity showed that the total LDH activity in H. sinense larva was negatively correlated with the length of larva. Polyacrylamide gel electrophoresis of the extracts of H. sinense larvae revealed one band of LDH, which was then purified by affinity chromatography and gel filtration. This enzyme showed an approximately 36 kDa band on SDS-gel under both reducing and non-reducing conditions, in addition, size exclusion chromatography analysis showed that its molecular weight was smaller than bovine serum albumin (67 kDa), indicating that it contains only one subunit. Michaelis constants (Km) values assay revealed that LDH from H. sinense larva showed significantly lower Km for lactate than other animals. LDH of H. sinense larva was stable at 60 °C for 15 min, and also exhibited high catalytic efficiency in a wide range of pH. HgCl₂ at the concentration of 0.1mM significantly decreased the activity of LDH from H. sinense larva but not at the concentration of 0.01 mM. The results of the present study demonstrate that LDH from H. sinense larva is a thermal stable and pH insensitive enzyme suitable for catalyzing both forward and reverse reactions.

  2. What is the acceptable hemolysis index for the measurements of plasma potassium, LDH and AST?

    Science.gov (United States)

    Rousseau, Nathalie; Pige, Raphaëlle; Cohen, Richard; Pecquet, Matthieu

    2016-06-01

    Hemolysis is a cause of variability in test results for plasma potassium, LDH and AST and is a non-negligible part of measurement uncertainty. However, allowable levels of hemolysis provided by reagent suppliers take neither analytical variability (trueness and precision) nor the measurand into account. Using a calibration range of hemolysis, we measured the plasma concentrations of potassium, LDH and AST, and hemolysis indices with a Cobas C501 analyzer (Roche Diagnostics(®), Meylan, France). Based on the allowable total error (according to Ricós et al.) and the expanded measurement uncertainty equation we calculated the maximum allowable bias for two concentrations of each measurand. Finally, we determined the allowable hemolysis indices for all three measurands. We observed a linear relationship between the observed increases of concentration and hemolysis indices. The LDH measurement was the most sensitive to hemolysis, followed by AST and potassium measurements. The determination of the allowable hemolysis index depends on the targeted measurand, its concentration and the chosen level of requirement of allowable total error.

  3. Inhibitory effects of ionic liquids on the lactic dehydrogenase activity.

    Science.gov (United States)

    Dong, Xing; Fan, Yunchang; Zhang, Heng; Zhong, Yingying; Yang, Yang; Miao, Juan; Hua, Shaofeng

    2016-05-01

    Ionic liquids (ILs) were widely used in scientific and industrial application and have been reported to possess potential toxicity to the environment and human health. The effects of six typical N-methylimidazolium-based ILs ([Cnmim]X, n=4, 6, 8; X=Br(-), Cl(-), BF4(-), CF3SO3(-)) on the lactic dehydrogenase (LDH) activity and the molecular interaction mechanism of ILs and the LDH were investigated with the aid of spectroscopic techniques. Experimental results showed that the LDH activity was inhibited in the presence of ILs. For the ILs with the same anion but different cations, their inhibitory ability on the LDH activity increased with increasing the alkyl chain length on the IL cation. Thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were obtained by analyzing the fluorescence behavior of LDH with the addition of ILs. Both positive ΔH and ΔS suggested that hydrophobicity was the major driven force in the interaction process as expected.

  4. Creatine Kinase and Lactate Dehydrogenase Responses after Different Resistance and Aerobic Exercise Protocols.

    Science.gov (United States)

    Callegari, Gustavo A; Novaes, Jefferson S; Neto, Gabriel R; Dias, Ingrid; Garrido, Nuno D; Dani, Caroline

    2017-09-01

    The aim of this study was to investigate the responses of creatine kinase (CK) and lactate dehydrogenase (LDH) after performing different resistance and aerobic exercise protocols. Twelve recreationally trained men (age, 23.2 ± 5.6 years; body mass, 84.3 ± 9.3 kg; body height, 178.9 ± 4.5 cm; and BMI, 26.3 ± 2.3 kg·m2) volunteered to participate in this study. All subjects were randomly assigned to four experimental protocols (crossover): (a) aerobic training at 60% of VO2max, (b) aerobic training at 80% of VO2max, (c) a resistance exercise (RE) session with a bi-set protocol, and (d) an RE session with a multiple sets protocol. Blood samples were collected before, immediately after and 24 hours following the experimental protocols. After 24 hours, there was a significant increase in CK for the 80% of VO2max protocol vs. the bi-set RE session (p = 0.016). Immediately after the protocols, we observed a significant increase in LDH among certain groups compared to others, as follows: multiple sets RE session vs. 60% of VO2max, bi-set RE session vs. 60% of VO2max, multiple sets RE session vs. 80% of VO2max, and bi-set RE session vs. 80% of VO2max (p = 0.008, p = 0.013; p = 0.002, p = 0.004, respectively). In conclusion, aerobic exercise performed at 80% of VO2max appears to elevate plasma CK levels more than bi-set RE sessions. However, the bi-set and multiple sets RE sessions appeared to trigger greater levels of blood LDH compared to aerobic protocols performed at 60% and 80% of VO2max.

  5. Creatine Kinase and Lactate Dehydrogenase Responses After Different Resistance and Aerobic Exercise Protocols

    Directory of Open Access Journals (Sweden)

    Callegari Gustavo A.

    2017-08-01

    Full Text Available The aim of this study was to investigate the responses of creatine kinase (CK and lactate dehydrogenase (LDH after performing different resistance and aerobic exercise protocols. Twelve recreationally trained men (age, 23.2 ± 5.6 years; body mass, 84.3 ± 9.3 kg; body height, 178.9 ± 4.5 cm; and BMI, 26.3 ± 2.3 kg·m2 volunteered to participate in this study. All subjects were randomly assigned to four experimental protocols (crossover: (a aerobic training at 60% of VO2max, (b aerobic training at 80% of VO2max, (c a resistance exercise (RE session with a bi-set protocol, and (d an RE session with a multiple sets protocol. Blood samples were collected before, immediately after and 24 hours following the experimental protocols. After 24 hours, there was a significant increase in CK for the 80% of VO2max protocol vs. the bi-set RE session (p = 0.016. Immediately after the protocols, we observed a significant increase in LDH among certain groups compared to others, as follows: multiple sets RE session vs. 60% of VO2max, bi-set RE session vs. 60% of VO2max, multiple sets RE session vs. 80% of VO2max, and bi-set RE session vs. 80% of VO2max (p = 0.008, p = 0.013; p = 0.002, p = 0.004, respectively. In conclusion, aerobic exercise performed at 80% of VO2max appears to elevate plasma CK levels more than bi-set RE sessions. However, the bi-set and multiple sets RE sessions appeared to trigger greater levels of blood LDH compared to aerobic protocols performed at 60% and 80% of VO2max.

  6. Development of L-lactate dehydrogenase biosensor based on porous silicon resonant microcavities as fluorescence enhancers.

    Science.gov (United States)

    Jenie, S N Aisyiyah; Prieto-Simon, Beatriz; Voelcker, Nicolas H

    2015-12-15

    The up-regulation of L-lactate dehydrogenase (LDH), an intracellular enzyme present in most of all body tissues, is indicative of several pathological conditions and cellular death. Herein, we demonstrate LDH detection using porous silicon (pSi) microcavities as a luminescence-enhancing optical biosensing platform. Non-fluorescent resazurin was covalently attached onto the pSi surface via thermal hydrocarbonisation, thermal hydrosylilation and acylation. Each surface modification step was confirmed by means of FTIR and the optical shifts of the resonance wavelength of the microcavity. Thermal hydrocarbonisation also afforded excellent surface stability, ensuring that the resazurin was not reduced on the pSi surface. Using a pSi microcavity biosensor, the fluorescence signal upon detection of LDH was amplified by 10 and 5-fold compared to that of a single layer and a detuned microcavity, respectively, giving a limit of detection of 0.08 U/ml. The biosensor showed a linear response between 0.16 and 6.5 U/ml, covering the concentration range of LDH in normal as well as damaged tissues. The biosensor was selective for LDH and did not produce a signal upon incubation with another NAD-dependant enzyme L-glutamic dehydrogenase. The use of the pSi microcavity as a sensing platform reduced reagent usage by 30% and analysis time threefold compared to the standard LDH assay in solution.

  7. Targeting lactate dehydrogenase-A inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor initiating cells

    Science.gov (United States)

    Xie, Han; Hanai, Jun-ichi; Ren, Jian-Guo; Kats, Lev; Burgess, Kerri; Bhargava, Parul; Signoretti, Sabina; Billiard, Julia; Duffy, Kevin J.; Grant, Aaron; Wang, Xiaoen; Lorkiewicz, Pawel K.; Schatzman, Sabrina; Bousamra, Michael; Lane, Andrew N.; Higashi, Richard M.; Fan, Teresa W.M.; Pandolfi, Pier Paolo; Sukhatme, Vikas P.; Seth, Pankaj

    2014-01-01

    Summary The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the inter-conversion of pyruvate and lactate, is upregulated in human cancers and is associated with aggressive tumor outcomes. Here we use a novel inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo. This was accompanied by re-activation of mitochondrial function in vitro but not in vivo or ex vivo. Finally, using a specific small molecule LDH-A inhibitor, we demonstrated that LDH-A is essential for cancer initiating cell survival and proliferation. Thus, LDH-A can be a viable therapeutic target for NSCLC including cancer stem cell-dependent drug resistant tumors. PMID:24726384

  8. Cationic surfactant-based colorimetric detection of Plasmodium lactate dehydrogenase, a biomarker for malaria, using the specific DNA aptamer.

    Directory of Open Access Journals (Sweden)

    Seonghwan Lee

    Full Text Available A simple, sensitive, and selective colorimetric biosensor for the detection of the malarial biomarkers Plasmodium vivax lactate dehydrogenase (PvLDH and Plasmodium falciparum LDH (PfLDH was demonstrated using the pL1 aptamer as the recognition element and gold nanoparticles (AuNPs as probes. The proposed method is based on the aggregation of AuNPs using hexadecyltrimethylammonium bromide (CTAB. The AuNPs exhibited a sensitive color change from red to blue, which could be seen directly with the naked eye and was monitored using UV-visible absorption spectroscopy and transmission electron microscopy (TEM. The reaction conditions were optimized to obtain the maximum color intensity. PvLDH and PfLDH were discernible with a detection limit of 1.25 pM and 2.94 pM, respectively. The applicability of the proposed biosensor was also examined in commercially available human serum.

  9. Modification of Rhizopus lactate dehydrogenase for improved resistance to fructose 1,6-bisphosphate

    Science.gov (United States)

    Rhizopus oryzae is frequently used for fermentative production of lactic acid. We determined that one of the key enzymes, lactate dehydrogenase (LDH), involved in synthesis of lactic acid by R. oryzae was significantly inhibited by fructose 1,6-bisphosphate (FBP) at physiological concentrations. Thi...

  10. [Effect of sectioning the celiac and vagus nerves on the activity and isoenzymatic composition of rat liver lactate dehydrogenase].

    Science.gov (United States)

    Shanygina, K I; Parfernova, N S

    1977-01-01

    Total activity of lactate dehydrogenase (LDH) was increased in rat liver cytoplasm after dissection of nervus celiacus; the enzyme activity was, however, decreased after section of nervus vagus. As showen by polyacrylamide gel electrophoresis the alterations in the enzyme activity occurred mainly due to changes in the isoenzyme LDH5, prevailing in this liver fraction. Administration of insulin did not restore the LDH activity, decreased after vagotomy. The suggestion is corroborated that the regulatory effects of sympathetic and parasympathetic nervous systems on glycolysis are of oppositely directed character.

  11. Co-expression of two heterologous lactate dehydrogenases genes in Kluyveromyces marxianus for l-lactic acid production.

    Science.gov (United States)

    Lee, Jae Won; In, Jung Hoon; Park, Joon-Bum; Shin, Jonghyeok; Park, Jin Hwan; Sung, Bong Hyun; Sohn, Jung-Hoon; Seo, Jin-Ho; Park, Jin-Byoung; Kim, Soo Rin; Kweon, Dae-Hyuk

    2017-01-10

    Lactic acid (LA) is a versatile compound used in the food, pharmaceutical, textile, leather, and chemical industries. Biological production of LA is possible by yeast strains expressing a bacterial gene encoding l-lactate dehydrogenase (LDH). Kluyveromyces marxianus is an emerging non-conventional yeast with various phenotypes of industrial interest. However, it has not been extensively studied for LA production. In this study, K. marxianus was engineered to express and co-express various heterologous LDH enzymes that were reported to have different pH optimums. Specifically, three LDH enzymes originating from Staphylococcus epidermidis (SeLDH; optimal at pH 5.6), Lactobacillus acidophilus (LaLDH; optimal at pH 5.3), and Bos taurus (BtLDH; optimal at pH 9.8) were functionally expressed individually and in combination in K. marxianus, and the resulting strains were compared in terms of LA production. A strain co-expressing SeLDH and LaLDH (KM5 La+SeLDH) produced 16.0g/L LA, whereas the strains expressing those enzymes individually produced only 8.4 and 6.8g/L, respectively. This co-expressing strain produced 24.0g/L LA with a yield of 0.48g/g glucose in the presence of CaCO3. Our results suggest that co-expression of LDH enzymes with different pH optimums provides sufficient LDH activity under dynamic intracellular pH conditions, leading to enhanced production of LA compared to individual expression of the LDH enzymes. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. L(+) lactate dehydrogenase activity from the electric organ of Electrophorus electricus (L.).

    Science.gov (United States)

    Torres-da Matta, J; Nery da Matta, A; Hassón-Voloch, A

    1976-01-01

    Properties of L(+) lactate dehydrogenase (LDH) of Electrophorus electricus (L.) electric organ were studied, comparing the substrates pyruvate and lactate. Electric organ LDH is a soluble enzyme with a pH optimum of 7.4 for pyruvate and 9.0 for lactate. The apparent Km was lower for pyruvate (Km = 2.5 X 10(-4) M) than for lactate (Km = 1.5 X 10(-2) M). With lactate as a substrate at pH 7.4, malonate, oxalate and pyruvate inhibited competitively. For pyruvate as substrate at pH 9.0 malonate inhibited non-competitively and oxalate shiwed uncompetitive inhibition. The different effects of the carboxylic acids on LDH activity suggest different stereospecificities of the two enzyme-coenzyme complexes in the forward and reserve reactions. The reactions of electric organ LDH with substrates and inhibitors are consistent with electrophoretic analysis suggesting that the enzyme is of the M-type.

  13. Quantification of Lactate Dehydrogenase for Cell Viability Testing Using Cell Lines and Primary Cultured Astrocytes.

    Science.gov (United States)

    Kaja, Simon; Payne, Andrew J; Naumchuk, Yuliya; Koulen, Peter

    2017-05-02

    Drug discovery heavily relies on cell viability studies to assess the potential toxicity of drug candidates. L-Lactate dehydrogenase (LDH) is a cytoplasmic enzyme that catalyzes the concomitant interconversions of pyruvate to L-lactate and NADH to NAD(+) during glycolysis, and the reverse reactions during the Cori cycle. In response to cellular damage, induced by endogenous cellular mechanisms or as a result of exogenously applied insults, LDH is released from the cytoplasm into the extracellular environment. Its stability in cell culture medium makes it a well-suited correlate for the presence of damage and toxicity in tissues and cells. We herein present protocols for a reproducible and validated LDH assay optimized for several cell types. In contrast to commercially available LDH assays, often associated with proprietary formulations and high cost, our protocols provide ample opportunities for experiment-specific optimization with low variability and cost. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  14. Distribution & diagnostic efficacy of cardiac markers CK-MB & LDH in pericardial fluid for postmortem diagnosis of ischemic heart disease.

    Science.gov (United States)

    Ghormade, Pankaj Suresh; Kumar, Narendra Baluram; Tingne, Chaitanya Vidyadhar; Keoliya, Ajay Narmadaprasad

    2014-11-01

    The aim of the present study is to evaluate the diagnostic efficacy of biochemical markers creatine kinase-MB (CK-MB) and LDH in pericardial fluid for postmortem diagnosis of ischemic heart disease (IHD). We studied 119 medico-legal autopsies selected during a period of 2 years. Subjects were assigned into diagnostic groups upon final cause of death as follows: (1) sudden cardiac death due to IHD's (n = 52), (2) violent asphyxia (n = 24); (3) polytraumatic deaths (n = 20); (4) natural deaths excluding cardiac causes (n = 23). Pericardial fluid samples were tested for estimating enzyme levels. Histological examination was performed with hematoxylin and eosin (H&E) stain on myocardial tissue samples. We observed highest levels of CK-MB & LDH in deaths due to IHD's. Kruskal-Wallis test revels significant differences in activities of CK-MB (P = 0.0001) and LDH (P = 0.0065) amongst all diagnostic groups. Mann-Whitney test showed highly significant (P MB in group 1 as compared to other diagnostic groups. However, LDH levels were non-discriminatory (P = 0.0827) between cases of IHD's and cases of other natural deaths. CK-MB levels were statistically non-significant between cases divided as myocardial infarction (MI) and severe coronary artery disease in group 1, hence its role for postmortem detection of MI is somewhat limiting. However, sensitivity and negative predictive values of its cut off level obtained in cases of IHD's are nearly equal to diagnostic efficacy in clinical settings. Hence, it can be useful additional diagnostic tool for autopsy diagnosis of IHD's. Whereas, LDH is not useful for postmortem diagnosis in these cases. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  15. Glucose-6-phosphate dehydrogenase

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that helps red ...

  16. G-CSF therapy and catheter-related Gram-positive sepsis increase serum IL-2 receptor α level and may falsely suggest a relapse in children with soft tissue sarcomas unless serum beta2-microglobulin, lactate dehydrogenase and C-reactive protein levels are determined concomitantly.

    Science.gov (United States)

    Bien, Ewa; Balcerska, Anna; Niedzwiecki, Maciej; Krawczyk, Malgorzata; Rapala, Malgorzata; Trzonkowski, Piotr; Stepinski, Jan

    2011-09-01

    Many components of oncologic treatment increase serum sIL-2Rα level, which may falsely suggest a relapse. We tried to establish whether granulocyte colony stimulating factor (G-CSF) and central vein catheter (CVC)-related sepsis increase serum sIL-2Rα level to values on relapse of childhood soft tissue sarcomas (STS) and how to distinguish real relapse from a "false" one. Serum sIL-2Rα, B2-M, LDH, CRP and ESR levels and rates of markers' elevated values were determined prospectively in 18 STS children: pre-treatmently (ST1), in complete remission (CR; ST2), in CR during G-CSF therapy (ST3), in CR during CVC-related sepsis (ST4), on relapse (ST5) and after treatment (ST6) and once in 50 healthy pediatric controls. It appeared that pre-treatment serum sIL-2Rα, LDH, CRP and ESR but not B2-M declined significantly with remission (ST2) achievement. At ST5 sIL-2Rα, B2-M, LDH and CRP increased from ST2 to ST1 values. SIL-2Rα levels at ST3 and ST4 rose significantly in all patients from ST2 to ST1 and ST5 values. At ST3 also serum LDH and B2-M increased to values at ST1 and ST5 and exceeded significantly those at ST2 and ST4. At ST4 CRP but not B2-M and LDH, rose significantly in most patients to values at ST1 and ST5. Thus, serum sIL-2Rα monitoring in pediatric STS reflects well response to chemotherapy unless samples are collected during G-CSF therapy or CVC-related sepsis. Determination of serum B2-M, LDH and CRP together with sIL-2Rα may help to distinguish between "real" relapse and "false" sIL-2Rα increase due to G-CSF administration or CVC-related sepsis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. [Value of combined measurement of C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase and serum ferritin in etiological diagnosis of fever of unknown origin in children].

    Science.gov (United States)

    Xie, Ting; Pan, Jia-Hua; Zhang, Xue

    2015-09-01

    To study the clinical value of combined measurement of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and serum ferritin (SF) in the etiological diagnosis of fever of unknown origin (FUO) in children. The clinical data of 154 hospitalized children who had FUO for at least two weeks were retrospectively analyzed, and they were classified into infection (n=54), rheumatism (n=67), and tumor (n=33) groups according to the diagnosis at discharge. The levels of CRP, ESR, LDH, and SF were compared between the three groups, and the diagnostic values of the four indices alone or together were analyzed using the receiver operating characteristic (ROC) curve. Serum CRP and ESR levels were elevated in all the three groups, and increased most significantly in the rheumatism group. Serum LDH level was increased most significantly in the tumor group. SF level was significantly increased in the rheumatism and tumor groups. The area under the ROC curve (AUC) of LDH for diagnosing rheumatism and the AUC of ESR and CRP for diagnosing tumors were lower than 0.7 (P>0.05). The AUC of CRP for diagnosing infection and rheumatism was 0.861 and 0.782, respectively. The AUC of ESR for diagnosing infection and rheumatism was 0.770 and 0.743, respectively. LDH had relatively low AUC, sensitivity, specificity, and Youden's index in diagnosing infection and tumors. SF had the highest AUC, sensitivity, and Youden's index in diagnosing infection, but had the lowest specificity. SF had relatively high AUC, sensitivity, specificity, and Youden's index in diagnosing rheumatism, but had relatively low AUC in diagnosing tumor. The four indices had higher AUC, sensitivity, and specificity in diagnosing rheumatism and tumors when measured together than when measured alone. In the etiological diagnosis of FUO in children, CRP, ESR, LDH, and SF have certain clinical significance in the preliminary diagnosis of rheumatic diseases, but have limited value in the

  18. Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy

    Directory of Open Access Journals (Sweden)

    Ishikawa Masashi

    2008-07-01

    Full Text Available Abstract Bckground A number of studies have investigated whether the activity levels of enzymes involved in 5-fluorouracil (5-FU metabolism are prognostic factors for survival in patients with colorectal carcinoma. Most reports have examined thymidylate synthetase (TS and dihydropyrimidine dehydrogenase (DPD in unresectable or metastatic cases, therefore it is unclear whether the activity of these enzymes is of prognostic value in colorectal cancer patients treated with radical resection and adjuvant chemotherapy with 5-FU. Methods This study examined fresh frozen specimens of colorectal carcinoma from 40 patients who had undergone curative operation and were orally administered adjuvant tegafur/uracil (UFT chemotherapy. TS, DPD and orotate phosphoribosyl transferase (OPRT activities were assayed in cancer tissue and adjacent normal tissue and their association with clinicopathological variables was investigated. In addition, the relationships between TS, DPD and OPRT activities and patient survival were examined to determine whether any of these enzymes could be useful prognostic factors. Results While there was no clear relationship between pathological findings and TS or DPD activity, OPRT activity was significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis. Postoperative survival was significantly better in the groups with low TS activity and/or high OPRT activity. Conclusion TS and OPRT activity levels in tumor tissue may be important prognostic factors for survival in Dukes' B and C colorectal carcinoma with radical resection and adjuvant chemotherapy with UFT.

  19. Isoniazid acetylating phenotype in patients with paracoccidioidomycosis and its relationship with serum sulfadoxin levels, glucose-6-phosphate dehydrogenase and glutathione reductase activities

    Directory of Open Access Journals (Sweden)

    Benedito Barraviera

    1991-06-01

    Full Text Available The authors evaluated the isoniazid acetylating phenotype and measured hematocrit, hemoglobin, glucose-6-phosphate dehydrogenase and glutathione reductase activities plus serum sulfadoxin levels in 39 patients with paracoccidioidomycosis (33 males and 6 females aged 17 to 58 years. Twenty one (53.84% of the patients presented a slow acetylatingphenotype and 18(46.16% a fast acetylating phenotype. Glucose-6-phosphate- dehydrogenase (G6PD acti vity was decreased in 5(23.80% slow acetylators and in 4(22.22% fast acetylators. Glutathione reductase activity was decreased in 14 (66.66% slow acetylators and in 12 (66.66% fast acetylators. Serum levels of free and total sulfadoxin Were higher in slow acetylator (p Os autores avaliaram o fenótipo acetilador da isoniazida, hematócrito, hemoglobina, atividade da glicose-6- fosfato desidrogenase, glutationa redutase e os níveis séricos de sulfadoxina de 39 doentes com paracoccidíoidomicose, senão 33 do sexo masculino e 6 do feminino, com idades compreendidas entre 17 e 58 anos. Vinte e um (53,84% doentes apresentaram fenótipo acetilador lento e 18 (46,16% rápido. A atividade da glicose-6-fosfato desidrogenase (G6PD esteve diminuída em 5 (23,80% acetiladores lentos e 4 (22,22% rápidos. A atividade da glutationa redutase esteve diminuída em 14 (66,66% acetiladores lentos e 12 (66,66% rápidos. Os níveis séricos de sulfadoxina livre e total foram maiores nos acetiladores lentos (p < 0,02. A análise dos resultados permite concluir que os níveis séricos de sulfadoxina relaciona-se com o fenótipo acetilador. Além disso, os níveis estiveram sempre acima de 50 µg/ml, níveis estes considerados terapêuticos. Por outro lado, a deficiência de glutationa redutase pode estar relacionada com a má absorção intestinal de nutrientes, entre eles riboflavina, vitamina precursora de FAD.

  20. 研究乳酸脱氢酶在小儿贫血中的变化及诊断价值%Study of Lactate Dehydrogenase in Pediatric Anemia and Diagnostic Value

    Institute of Scientific and Technical Information of China (English)

    王静; 李亚蕊; 郝国平

    2013-01-01

    Objective:Comparison of children with anemia,various change of lactic dehydrogenase activity(LDH)in children with anemia,discuss its diagnostic value.Method:Using the international standard enzyme assay for the detection of 96 cases of various types of children with anemia and serum LDH activity,and a comparative analysis.Result:The(newly diagnosed leukemia cases)(AL),hemolytic anemia(HA)and megaloblastic anemia(MA)LDH levels increased significantly,compared with healthy controls,the difference was statistically significant(P0.05).Conclusion:Lactate dehydrogenase determination in anemia diagnosis have a higher clinical value.%  目的:比较各种贫血患儿乳酸脱氢酶(LDH)活性的变化,探讨其在小儿贫血性疾病中的诊断价值.方法:采用国际标准酶法检测96例各类贫血患儿血清中的LDH活性,并进行比较分析.结果:白血病(AL)(初诊病例)、溶血性贫血(HA)及巨幼细胞贫血(MA)的LDH水平均明显增高,与健康对照组比较差异有统计学意义(P0.05).结论:乳酸脱氢酶测定在贫血的辅助诊断中有较高的临床价值.

  1. Glutamate dehydrogenase and Na+-K+ ATPase expression and growth response of Litopenaeus vannamei to different salinities and dietary protein levels

    Science.gov (United States)

    Li, Erchao; Arena, Leticia; Lizama, Gabriel; Gaxiola, Gabriela; Cuzon, Gerard; Rosas, Carlos; Chen, Liqiao; van Wormhoudt, Alain

    2011-03-01

    Improvement in the osmoregulation capacity via nutritional supplies is vitally important in shrimp aquaculture. The effects of dietary protein levels on the osmoregulation capacity of the Pacific white shrimp ( L. vannamei) were investigated. This involved an examination of growth performance, glutamate dehydrogenase (GDH) and Na+-K+ ATPase mRNA expression,, and GDH activity in muscles and gills. Three experimental diets were formulated, containing 25%, 40%, and 50% dietary protein, and fed to the shrimp at a salinity of 25. After 20 days, no significant difference was observed in weight gain, though GDH and Na+-K+ ATPase gene expression and GDH activity increased with higher dietary protein levels. Subsequently, shrimp fed diets with 25% and 50% dietary protein were transferred into tanks with salinities of 38 and 5, respectively, and sampled at weeks 1 and 2. Shrimp fed with 40% protein at 25 in salinity (optimal conditions) were used as a control. Regardless of the salinities, shrimp fed with 50% dietary protein had significantly higher growth performance than other diets; no significant differences were found in comparison with the control. Shrimp fed with 25% dietary protein and maintained at salinities of 38 and 5 had significantly lower weight gain values after 2 weeks. Ambient salinity change also stimulated the hepatosomatic index, which increased in the first week and then recovered to a relatively normal level, as in the control, after 2 weeks. These findings indicate that in white shrimp, the specific protein nutrient and energy demands related to ambient salinity change are associated with protein metabolism. Increased dietary protein level could improve the osmoregulation capacity of L. vannamei with more energy resources allocated to GDH activity and expression.

  2. Ebselen protects against behavioral and biochemical toxicities induced by 3-nitropropionic acid in rats: correlations between motor coordination, reactive species levels, and succinate dehydrogenase activity.

    Science.gov (United States)

    Wilhelm, Ethel A; Bortolatto, Cristiani F; Jesse, Cristiano R; Luchese, Cristiane

    2014-12-01

    The protective effect of ebselen was investigated against 3-nitropropionic acid (3-NP)-induced behavioral and biochemical toxicities in rats. Ebselen (10 or 25 mg/kg, intragastrically) was administered to rats 30 min before 3-NP (20 mg/kg, intraperitoneally) once a day for a period of 4 days. Locomotor activity, motor coordination, and body weight gain were determined. The striatal content of reactive oxygen species (ROS), reduced glutathione (GSH), ascorbic acid (AA), and protein carbonyl as well as catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) activities was determined 24 h after the last dose of 3-NP. Na(+)/ K(+)-ATPase, succinate dehydrogenase (SDH), and δ-aminolevulinic dehydratase (δ-ALA-D) activities were also determined. The results demonstrated that ebselen at a dose of 25 mg/kg, but not at 10 mg/kg, protected against (1) a decrease in locomotor activity, motor coordination impairment, and body weight loss; (2) striatal oxidative damage, which was characterized by an increase in ROS levels, protein carbonyl content, and GR activity, an inhibition of CAT and GPx activities, and a decrease in GSH levels; and (3) an inhibition of SDH and Na(+)/K(+)-ATPase activities, induced by 3-NP. GST activity and AA levels were not modified by ebselen or 3-NP. Ebselen was not effective against the inhibition of δ-ALA-D activity induced by 3-NP. The results revealed a significant correlation between SDH activity and ROS levels, and SDH activity and latency to fall (rotarod test). The present study highlighted the protective effect of ebselen against 3-NP-induced toxicity in rats.

  3. Glutamate dehydrogenase and Na+-K+ ATPase expression and growth response of Litopenaeus vannamei to different salinities and dietary protein levels

    Institute of Scientific and Technical Information of China (English)

    LI Erchao; Leticia ARENA; Gabriel LIZAMA; Gabriela GAXIOLA; Gerard CUZON; Carlos ROSAS; CHEN Liqiao; Alain VAN WORMHOUD

    2011-01-01

    Improvement in the osmoregulation capacity via nutritional supplies is vitally important in shrimp aquaculture. The effects of dietary protein levels on the osmoregulation capacity of the Pacific white shrimp (L. vannamei) were investigated. This involved an examination of growth performance, glutamate dehydrogenase (GDH) and Na+-K+ ATPase mRNA expression,, and GDH activity in muscles and gills. Three experimental diets were formulated, containing 25%, 40~/5, and 50% dietary protein, and fed to the shrimp at a salinity of 25. After 20 days, no significant difference was observed in weight gain, though GDH and Na+-K+ ATPase gene expression and GDH activity increased with higher dietary protein levels. Subsequently, shrimp fed diets with 25% and 50% dietary protein were transferred into tanks with salinities of 38 and 5, respectively, and sampled at weeks 1and 2. Shrimp fed with 40% protein at 25 in salinity (optimal conditions) were used as a control.Regardless of the salinities, shrimp fed with 50% dietary protein had significantly higher growth performance than other diets; no significant differences were found in comparison with the control.Shrimp fed with 25% dietary protein and maintained at salinities of 38 and 5 had significantly lower weight gain values after 2 weeks. Ambient salinity change also stimulated the hepatosomatic index,which increased in the first week and then recovered to a relatively normal level, as in the control,after 2 weeks. These findings indicate that in white shrimp, the specific protein nutrient and energy demands related to ambient salinity change are associated with protein metabolism. Increased dietary protein level could improve the osmoregnlation capacity of L. vannamei with more energy resources allocated to GDH activity and expression.

  4. Introducing a single secondary alcohol dehydrogenase into butanol-tolerant Clostridium acetobutylicum Rh8 switches ABE fermentation to high level IBE fermentation

    Directory of Open Access Journals (Sweden)

    Dai Zongjie

    2012-06-01

    Full Text Available Abstract Background Previously we have developed a butanol tolerant mutant of Clostridium acetobutylicum Rh8, from the wild type strain DSM 1731. Strain Rh8 can tolerate up to 19 g/L butanol, with solvent titer improved accordingly, thus exhibiting industrial application potential. To test if strain Rh8 can be used for production of high level mixed alcohols, a single secondary alcohol dehydrogenase from Clostridium beijerinckii NRRL B593 was overexpressed in strain Rh8 under the control of thl promoter. Results The heterogenous gene sADH was functionally expressed in C. acetobutylicum Rh8. This simple, one-step engineering approach switched the traditional ABE (acetone-butanol-ethanol fermentation to IBE (isopropanol-butanol-ethanol fermentation. The total alcohol titer reached 23.88 g/l (7.6 g/l isopropanol, 15 g/l butanol, and 1.28 g/l ethanol with a yield to glucose of 31.42%. The acid (butyrate and acetate assimilation rate in isopropanol producing strain Rh8(psADH was increased. Conclusions The improved butanol tolerance and the enhanced solvent biosynthesis machinery in strain Rh8 is beneficial for production of high concentration of mixed alcohols. Strain Rh8 can thus be considered as a good host for further engineering of solvent/alcohol production.

  5. Introducing a single secondary alcohol dehydrogenase into butanol-tolerant Clostridium acetobutylicum Rh8 switches ABE fermentation to high level IBE fermentation

    Science.gov (United States)

    2012-01-01

    Background Previously we have developed a butanol tolerant mutant of Clostridium acetobutylicum Rh8, from the wild type strain DSM 1731. Strain Rh8 can tolerate up to 19 g/L butanol, with solvent titer improved accordingly, thus exhibiting industrial application potential. To test if strain Rh8 can be used for production of high level mixed alcohols, a single secondary alcohol dehydrogenase from Clostridium beijerinckii NRRL B593 was overexpressed in strain Rh8 under the control of thl promoter. Results The heterogenous gene sADH was functionally expressed in C. acetobutylicum Rh8. This simple, one-step engineering approach switched the traditional ABE (acetone-butanol-ethanol) fermentation to IBE (isopropanol-butanol-ethanol) fermentation. The total alcohol titer reached 23.88 g/l (7.6 g/l isopropanol, 15 g/l butanol, and 1.28 g/l ethanol) with a yield to glucose of 31.42%. The acid (butyrate and acetate) assimilation rate in isopropanol producing strain Rh8(psADH) was increased. Conclusions The improved butanol tolerance and the enhanced solvent biosynthesis machinery in strain Rh8 is beneficial for production of high concentration of mixed alcohols. Strain Rh8 can thus be considered as a good host for further engineering of solvent/alcohol production. PMID:22742819

  6. Reduced levels of NADH-dependent glutamate dehydrogenase decrease the glutamate content of ripe tomato fruit but have no effect on green fruit or leaves.

    Science.gov (United States)

    Ferraro, Gisela; D'Angelo, Matilde; Sulpice, Ronan; Stitt, Mark; Valle, Estela M

    2015-06-01

    Glutamate (Glu) is a taste enhancer that contributes to the characteristic flavour of foods. In fruit of tomato (Solanum lycopersicum L.), the Glu content increases dramatically during the ripening process, becoming the most abundant free amino acid when the fruit become red. There is also a concomitant increase in NADH-dependent glutamate dehydrogenase (GDH) activity during the ripening transition. This enzyme is located in the mitochondria and catalyses the reversible amination of 2-oxoglutarate to Glu. To investigate the potential effect of GDH on Glu metabolism, the abundance of GDH was altered by artificial microRNA technology. Efficient silencing of all the endogenous SlGDH genes was achieved, leading to a dramatic decrease in total GDH activity. This decrease in GDH activity did not lead to any clear morphological or metabolic phenotype in leaves or green fruit. However, red fruit on the transgenic plants showed markedly reduced levels of Glu and a large increase in aspartate, glucose and fructose content in comparison to wild-type fruit. These results suggest that GDH is involved in the synthesis of Glu in tomato fruit during the ripening processes. This contrasts with the biological role ascribed to GDH in many other tissues and species. Overall, these findings suggest that GDH has a major effect on the control of metabolic composition during tomato fruit ripening, but not at other stages of development.

  7. Total lactate dehydrogenase activity of tail muscle is not cold-adapted in nocturnal lizards from cool-temperate habitats.

    Science.gov (United States)

    Hare, K M; Miller, J H; Clark, A G; Daugherty, C H

    2005-12-01

    The dependence of metabolic processes on temperature constrains the behavior, physiology and ecology of many ectothermic animals. The evolution of nocturnality in lizards, especially in temperate regions, requires adaptations for activity at low temperatures when optimal body temperatures are unlikely to be obtained. We examined whether nocturnal lizards have cold-adapted lactate dehydrogenase (LDH). LDH was chosen as a representative metabolic enzyme. We measured LDH activity of tail muscle in six lizard species (n=123: three nocturnal, two diurnal and one crepuscular) between 5 and 35 degrees C and found no differences in LDH-specific activity or thermal sensitivity among the species. Similarly, the specific activity and thermal sensitivity of LDH were similar between skinks and geckos. Similar enzyme activities among nocturnal and diurnal lizards indicate that there is no selection of temperature specific LDH enzyme activity at any temperature. As many nocturnal lizards actively thermoregulate during the day, LDH may be adapted for a broad range of temperatures rather than adapted specifically for the low temperatures encountered when the animals are active. The total activity of LDH in tropical and temperate lizards is not cold-adapted. More data are required on biochemical adaptations and whole animal thermal preferences before trends can be established.

  8. Enzymatic urea adaptation: lactate and malate dehydrogenase in elasmobranchs.

    Science.gov (United States)

    Laganà, G; Bellocco, E; Mannucci, C; Leuzzi, U; Tellone, E; Kotyk, A; Galtieri, A

    2006-01-01

    Lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) electrophoretic tissue patterns of two different orders of Elasmobranchii: Carchariniformes (Galeus melanostomus and Prionace glauca) and Squaliformes (Etmopterus spinax and Scymnorinus licha) were studied. The number of loci expressed for these enzymes was the same of other elasmobranch species. Differences in tissue distribution were noted in LDH from G. melanostomus due to the presence of an additional heterotetramer in the eye tissue. There were also differences in MDH. In fact, all the tissues of E. spinax and G. melanostomus showed two mitochondrial bands. Major differences were noted in the number of isozymes detected in the four compared elasmobranchs. The highest polymorphism was observed in E. spinax and G. melanostomus, two species that live in changeable environmental conditions. The resistance of isozymes after urea treatment was examined; the resulting patterns showed a quite good resistance of the enzymes, higher for LDH than MDH, also at urea concentration much greater than physiological one. These results indicated that the total isozyme resistance can be considered higher in urea accumulators (such as elasmobranchs) than in the non-accumulators (such as teleosts).

  9. Decreased 11β-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression.

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    Subrata Chowdhury

    Full Text Available We have reported a high expression of IGF-I in pancreatic islet β-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1, which is responsible for the conversion of inert cortisone (11-dehydrocorticosterone, DHC in rodents to active cortisol (corticosterone in the liver and adipose tissues, has not been identified previously as an IGF-I target in pancreatic islets. We characterized the changes in its protein level, enzyme activity and glucose-stimulated insulin secretion. In freshly isolated islets, the level of 11β-HSD1 protein was significantly lower in MT-IGF mice. Using dual-labeled immunofluorescence, 11β-HSD1 was observed exclusively in glucagon-producing, islet α-cells but at a lower level in transgenic vs. wild-type animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone (DEX and DHC inhibited glucose-stimulated insulin secretion from freshly isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre-incubation of DEX caused a significant decrease in insulin release, while the effect of DHC was largely blunted consistent with diminished 11β-HSD1 activity. In order to establish the function of intracrine glucocorticoids, we overexpressed 11β-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC caused apoptosis and a significant decrease in proliferation. Both effects were abolished with the treatment of an 11β-HSD1 inhibitor. Our results demonstrate an inhibitory effect of IGF-I on 11β-HSD1 expression and activity within the pancreatic islets, which may mediate part of the IGF-I effects on cell proliferation, survival and insulin secretion.

  10. Phytophenols in whisky lower blood acetaldehyde level by depressing alcohol metabolism through inhibition of alcohol dehydrogenase 1 (class I) in mice.

    Science.gov (United States)

    Haseba, Takeshi; Sugimoto, Junichi; Sato, Shigeo; Abe, Yuko; Ohno, Youkichi

    2008-12-01

    We recently reported that the maturation of whisky prolongs the exposure of the body to a given dose of alcohol by reducing the rate of alcohol metabolism and thus lowers the blood acetaldehyde level (Alcohol Clin Exp Res. 2007;31:77s-82s). In this study, administration of the nonvolatile fraction of whisky was found to lower the concentration of acetaldehyde in the blood of mice by depressing alcohol metabolism through the inhibition of liver alcohol dehydrogenase (ADH). Four of the 12 phenolic compounds detected in the nonvolatile fraction (caffeic acid, vanillin, syringaldehyde, ellagic acid), the amounts of which increase during the maturation of whisky, were found to strongly inhibit mouse ADH 1 (class I). Their inhibition constant values for ADH 1 were 0.08, 7.9, 15.6, and 22.0 mumol/L, respectively, whereas that for pyrazole, a well-known ADH inhibitor, was 5.1 mumol/L. The 2 phenolic aldehydes and ellagic acid exhibited a mixed type of inhibition, whereas caffeic acid showed the competitive type. When individually administered to mice together with ethanol, each of these phytophenols depressed the elimination of ethanol, thereby lowering the acetaldehyde concentration of blood. Thus, it was demonstrated that the enhanced inhibition of liver ADH 1 due to the increased amounts of these phytophenols in mature whisky caused the depression of alcohol metabolism and a consequent lowering of blood acetaldehyde level. These substances are commonly found in various food plants and act as antioxidants and/or anticarcinogens. Therefore, the intake of foods rich in them together with alcohol may not only diminish the metabolic toxicity of alcohol by reducing both the blood acetaldehyde level and oxidative stress, but also help limit the amount of alcohol a person drinks by depressing alcohol metabolism.

  11. Effect of Follicular Fluid and Platelet-Activating Factor on Lactate Dehydrogenase C Expression in Human Asthenozoospermic Samples

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    Tahereh Esmaeilpour

    2014-01-01

    Full Text Available Background: Application of follicular fluid (FF and platelet-activating factor (PAF in artificial insemination improves sperm motility. Lactate dehydrogenase C (LDH-C is a key enzyme for sperm motility. In this study, the effects of FF and PAF on the sperm motility index and LDH-C expression were investigated. Moreover, LDH-C expression was compared between asthenozoospermic and normozoospermic samples. Methods: The expression of LDH-C was examined by quantitative real-time polymerase chain reaction (q-RT PCR and western blotting after it was treated with optimized concentrations of FF and PAF in twenty asthenozoospermic samples. Also, LDH-C expression was evaluated in five normozoospermic samples. Results: Samples with 75% FF and 100 nM of PAF had an increase in their percentages of progressive and slowly motile sperms and a decrease in their percentages of non-progressive and non-motile sperms. Moreover, LDH-C mRNA transcripts were not changed following PAF and FF treatment, and LDH-C protein was detected in highly progressive motile specimens treated with FF in the asthenozoospermic samples. Furthermore, LDH-C expression was more detectable in the normal sperms. Conclusion: Our results indicated that PAF had more beneficial effects than FF on sperm motility in the asthenozoospermic samples (P=0.0001, although the LDH-C expressions of the sperms were not changed significantly in both groups. We found no association between LDH-C expression and sperm motility after FF and PAF actions. This finding, however, requires further investigation. The fact that LDH-C protein was detected in the normozoospermic, but not asthenozoospermic, samples could be cited as a reason for the infertility in these patients.

  12. PfHRP2 and PfLDH antigen detection for monitoring the efficacy of artemisinin-based combination therapy (ACT in the treatment of uncomplicated falciparum malaria

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    Deloron Philippe

    2009-09-01

    Full Text Available Abstract Background An assessment of the accuracy of two malaria rapid diagnostic tests (RDT for the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2 or Pf lactate dehydrogenase (PfLDH was undertaken in children aged between six and 59 months included in an anti-malarial efficacy study in Benin. Methods In Allada (Benin, 205 children aged 6-59 months with falciparum malaria received either artesunate-amodiaquine (ASAQ, artemether-lumefantrine (AL, or sulphadoxine-pyrimethamine (SP. Children included in the study were simultaneously followed by both RDT and high-quality microscopy for up to 42 days. Results At the time of inclusion, PfHRP2-based tests were positive in 203 children (99% and PfLDH-based tests were positive in 204 (99.5%. During follow-up, independent of the treatment received, only 17.3% (28/162 of children effectively cured were negative with the PfHRP2 RDT at day 3, with a gradual increase in specificity until day 42. The specificity of antigen detection with the PfLDH test was 87% (141/162 on day 3, and between 92% and 100% on days 7 to 42. A statistical difference was observed between the persistence of PfHRP2 and PfLDH antigenaemia during follow-up in children treated with artemisinin-based combination therapy (ACT but not with SP. Conclusion Although both RDTs are as sensitive as microscopy in detecting true malaria cases, the PfHRP2 RDT had very low specificity during follow-up until day 28. On the other hand, the PfLDH test could be used to detect failures and, therefore, to assess anti-malarial efficacy.

  13. NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies effects of cigarette smoking on risk of elevated levels of serum liver enzyme in male Japanese health check-up examinees: a cross-sectional study

    OpenAIRE

    Kokaze, Akatsuki; Yoshida, Masao; Ishikawa, Mamoru; Matsunaga, Naomi; Karita, Kanae; Ohtsu, Tadahiro; Ochiai, Hirotaka; Shirasawa, Takako; Nanri, Hinako; Baba, Yuta; HOSHINO, Hiromi; Takashima, Yutaka

    2014-01-01

    Background NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism reportedly influences the effects of cigarette smoking on respiratory function, risk of dyslipidemia, serum non-high-density lipoprotein cholesterol levels, hematological parameters and intraocular pressure. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of cigarette smoking on serum liver enzyme levels in male Japanese health check-up examine...

  14. Cariogenicity of a lactate dehydrogenase-deficient mutant of Streptococcus mutans serotype c in gnotobiotic rats.

    Science.gov (United States)

    Fitzgerald, R J; Adams, B O; Sandham, H J; Abhyankar, S

    1989-03-01

    A lactate dehydrogenase-deficient (Ldh-) mutant of a human isolate of Streptococcus mutans serotype c was tested in a gnotobiotic rat caries model. Compared with the wild-type Ldh-positive (Ldh+) strains, it was significantly (alpha less than or equal to 0.005) less cariogenic in experiments with two different sublines of Sprague-Dawley rats. The Ldh- mutant strain 044 colonized the oral cavity of the test animals to the same extent as its parent strain 041, although its initial implantation was slightly but not significantly (P greater than or equal to 0.2) less. Multiple oral or fecal samples plated on 2,3,5-triphenyltetrazolium indicator medium revealed no evidence of back mutation from Ldh- to Ldh+ in vivo. Both Ldh+ strain 041 and Ldh- strain 044 demonstrated bacteriocinlike activity in vitro against a number of human strains of mutans streptococci representing serotype a (S. cricetus) and serotypes c and e (S. mutans). Serotypes b (S. rattus) and f (S. mutans) and strains of S. mitior, S. sanguis, and S. salivarius were not inhibited. Thus, Ldh mutant strain 044 possesses a number of desirable traits that suggest it should be investigated further as a possible effector strain for replacement therapy of dental caries. These traits include its stability and low cariogenicity in the sensitive gnotobiotic rat caries model, its bacteriocinlike activity against certain other cariogenic S. mutans (but not against more inocuous indigenous oral streptococci), and the fact that it is a member of the most prevalent human serotype of cariogenic streptococci.

  15. Antimalarial activity of potential inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies.

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    Julia Penna-Coutinho

    Full Text Available The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2. The IC(50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use.

  16. Evolutionary factors affecting Lactate dehydrogenase A and B variation in the Daphnia pulex species complex

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    Cristescu Melania E

    2011-07-01

    Full Text Available Abstract Background Evidence for historical, demographic and selective factors affecting enzyme evolution can be obtained by examining nucleotide sequence variation in candidate genes such as Lactate dehydrogenase (Ldh. Two closely related Daphnia species can be distinguished by their electrophoretic Ldh genotype and habitat. Daphnia pulex populations are fixed for the S allele and inhabit temporary ponds, while D. pulicaria populations are fixed for the F allele and inhabit large stratified lakes. One locus is detected in most allozyme surveys, but genome sequencing has revealed two genes, LdhA and LdhB. Results We sequenced both Ldh genes from 70 isolates of these two species from North America to determine if the association between Ldh genotype and habitat shows evidence for selection, and to elucidate the evolutionary history of the two genes. We found that alleles in the pond-dwelling D. pulex and in the lake-dwelling D. pulicaria form distinct groups at both loci, and the substitution of Glutamine (S for Glutamic acid (F at amino acid 229 likely causes the electrophoretic mobility shift in the LDHA protein. Nucleotide diversity in both Ldh genes is much lower in D. pulicaria than in D. pulex. Moreover, the lack of spatial structuring of the variation in both genes over a wide geographic area is consistent with a recent demographic expansion of lake populations. Neutrality tests indicate that both genes are under purifying selection, but the intensity is much stronger on LdhA. Conclusions Although lake-dwelling D. pulicaria hybridizes with the other lineages in the pulex species complex, it remains distinct ecologically and genetically. This ecological divergence, coupled with the intensity of purifying selection on LdhA and the strong association between its genotype and habitat, suggests that experimental studies would be useful to determine if variation in molecular function provides evidence that LDHA variants are adaptive.

  17. Structure and Function of Lactate Dehydrogenase from Hagfish

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    Mitsumasa Okada

    2010-03-01

    Full Text Available The lactate dehydrogenases (LDHs in hagfish have been estimated to be the prototype of those in higher vertebrates. The effects of high hydrostatic pressure from 0.1 to 100 MPa on LDH activities from three hagfishes were examined. The LDH activities of Eptatretus burgeri, living at 45–60 m, were completely lost at 5 MPa. In contrast, LDH-A and -B in Eptatretus okinoseanus maintained 70% of their activities even at 100 MPa. These results show that the deeper the habitat, the higher the tolerance to pressure. To elucidate the molecular mechanisms for adaptation to high pressure, we compared the amino acid sequences and three-dimensional structures of LDHs in these hagfish. There were differences in six amino acids (6, 10, 20, 156, 269, and 341. These amino acidresidues are likely to contribute to the stability of the E. okinoseanus LDH under high-pressure conditions. The amino acids responsible for the pressure tolerance of hagfish are the same in both human and hagfish LDHs, and one substitution that occurred as an adaptation during evolution is coincident with that observed in a human disease. Mutation of these amino acids can cause anomalies that may be implicated in the development of human diseases.

  18. The influence of oxygen on radiation-induced structural and functional changes in glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase

    Science.gov (United States)

    Rodacka, Aleksandra; Serafin, Eligiusz; Bubinski, Michal; Krokosz, Anita; Puchala, Mieczyslaw

    2012-07-01

    Proteins are major targets for oxidative damage due to their abundance in cells and high reactivity with free radicals. In the present study we examined the influence of oxygen on radiation-induced inactivation and structural changes of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase (LDH). We chose these two enzymes because they occur at high concentrations and participate in the most important processes in organisms; furthermore, they show considerable similarity in their structure. Protein solutions were irradiated with X-rays in doses ranging from 0.1 to 0.7 kGy, in air and N2O. The much higher radiation inactivation of GAPDH as compared to LDH is correlated with substantially greater structural changes in this protein, mainly involving the loss of free thiol groups (-SH). Of lesser importance in the differentiation of the radiosensitivity of the studied enzymes are tryptophan residues. Molecular oxygen, present during irradiation, increased to a significantly greater extent the inactivation and structural changes of GAPDH than that of LDH. The results suggest that the greater effect of oxygen on GAPDH is due to the higher efficiency of the superoxide radical, the higher amount of hydroperoxides generated, and the higher degree of unfolding of this protein.

  19. Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma

    DEFF Research Database (Denmark)

    Kelderman, Sander; Heemskerk, Bianca; van Tinteren, Harm;

    2014-01-01

    OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK. In both...... the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection...

  20. The Clinicopathologic Importance of Serum Lactic Dehydrogenase in Patients with Gastric Cancer

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    Zhi Zhao

    2014-01-01

    Full Text Available Background. To explore possible correlation between serum lactate dehydrogenase (SLDH levels and gastric cancer. Materials and Methods. We retrospectively reviewed 365 patients with gastric cancer. The correlation of SLDH levels with clinicopathologic features and survival rate was studied. Results. SLDH levels were closely associated with the pathological (p T stage (P=0.011, metastasis (P=0.012, pTNM stage (P=0.001, and recurrence (P=0.012. Moreover, we found a significant SLDH level difference among Borrmann type (P=0.027, pT stage (P=0.004, lymph node metastasis (P=0.027, metastasis (P<0.001, pTNM stage (P=0.006, and recurrence (P=0.002. In addition, we detected a significant SLDH level difference between alive and dead subgroups (P=0.001. In addition, both univariate analysis and multivariate analysis showed that high SLDH levels were independent prognostic factor. For the subgroup with normal LDH (median point of 157.0 U/L, we detected that the subset with SLDH levels ≥157 U/L (158–245 U/L showed poorer OS (P=0.005 and DFS (P=0.01 than that of ≤157 subgroup. Conclusions. Our results suggest that high SLDH level could be an independent poor prognostic biomarker. Gastric cancer patients with relative high SLDH level (158–245 U/L were prone to develop a shorter OS and DFS.

  1. Lactic dehydrogenase and cancer: an overview.

    Science.gov (United States)

    Gallo, Monica; Sapio, Luigi; Spina, Annamaria; Naviglio, Daniele; Calogero, Armando; Naviglio, Silvio

    2015-01-01

    Despite the intense scientific efforts made, there are still many tumors that are difficult to treat and the percentage of patient survival in the long-term is still too low. Thus, new approaches to the treatment of cancer are needed. Cancer is a highly heterogeneous and complex disease, whose development requires a reorganization of cell metabolism. Most tumor cells downregulate mitochondrial oxidative phosphorylation and increase the rate of glucose consumption and lactate release, independently of oxygen availability (Warburg effect). This metabolic rewiring is largely believed to favour tumor growth and survival, although the underlying molecular mechanisms are not completely understood. Importantly, the correlation between the aerobic glycolysis and cancer is widely regarded as a useful biochemical basis for the development of novel anticancer strategies. Among the enzymes involved in glycolysis, lactate dehydrogenase (LDH) is emerging as a very attractive target for possible pharmacological approaches in cancer therapy. This review addresses the state of the art and the perspectives concerning LDH both as a useful diagnostic marker and a relevant molecular target in cancer therapy and management.

  2. CHARACTERIZATION OF LACTATE DEHYDROGENASE ISOZYME PATTERN AND MORPHOLOGY OF THREE MARINE FISH CELL LINES

    Institute of Scientific and Technical Information of China (English)

    郭华荣; 张士璀; 李红岩; 童裳亮; 相建海

    2002-01-01

    Three continuous marine fish cell lines of FG (i. e., Hounder Gill) from flounder (Paralichthys olivaceus) gill, SPH (i. e. , Sea Perch Heart) from sea perch (Lateolabrax japonicus) heart and RSBF (i.e., Red Sea Bream Fin) from red sea bream (Pagrosomus major) fin, were characterized by lactate dehydrogenase (LDH) isozyme and morphological analysis. The LDH isozyme patterns of these three cell lines and their corresponding tissues of origin were investigated and compared. The results showed: (1) No difference was found in the LDH isozyme patterns of FG and flounder gill tissue. However, the LDH isozyme patterns of SPH and RSBF were significantly different from their corresponding tissues of origin; (2) LDH isozyme patterns of FG, SPH and RSBF were markedly different from each other and could serve as genetic markers for species identification and detection of cross contamination. Morphological change analysis of these three cell lines in comparison to their original tissues indicated that FG cells still appeared epithelioid without morphological transformation. However, morphological changes were found in SPH and RSBF compared to their original tissues. Therefore, the cellular morphology was still plastic in the relatively stable culture conditions, and it was possible that change of LDH patterns wasrelated to morphological changes of fish cells in vitro.

  3. CHARACTERIZATION OF LACTATE DEHYDROGENASE ISOZYME PATTERN AND MORPHOLOGY OF THREE MARINE FISH CELL LINES

    Institute of Scientific and Technical Information of China (English)

    郭华荣; 张士璀; 李红岩; 童裳亮; 相建海

    2002-01-01

    Three continuous marine fish cell lines of FG (i.e. , Flounder Gill) from flounder (Paralichthys olivaceus) gill, SPH (i.e., Sea Perch Heart) fro m sea perch (Lateolabrax japonicus) heart and RSBF (i.e., Red Sea Bream Fin) from red se a bream (Pagrosomus major) fin, were characterized by lactate dehydrogenase (LDH) is ozyme and morphological analysis. The LDH isozyme patterns of these three cell lines and their corresponding tissues of origin were investigated and compared. The results sho wed: (1) No difference was found in the LDH isozyme patterns of FG and flounder gill tissue. However, the LDH isozyme patterns of SPH and RSBF were significantly different from their cor responding tissues of origin; (2) LDH isozyme patterns of FG, SPH and RSBF were markedly di fferent from each other and could serve as genetic markers for species identification and de tection of cross contamination. Morphological change analysis of these three cell lines in compa rison to their original tissues indicated that FG cells still appeared epithelioid without mor phological transformation. However, morphological changes were found in SPH and RSBF compa red to their original tissues. Therefore, the cellular morphology was still plastic in the relatively stable culture conditions, and it was possible that change of LDH patterns was related to morphological changes of fish cells in vitro.

  4. Lactate dehydrogenase isoenzyme patterns upon chronic exposure to cigarette smoke: Protective effect of bacoside A.

    Science.gov (United States)

    Anbarasi, Kothandapani; Sabitha, Kuruvimalai Ekambaram; Devi, Chennam Srinivasulu Shyamala

    2005-09-01

    Despite a strong association between cigarette smoking and alarming increase in mortality rate from smoking-related diseases, around 35-40% of the world's population continues to smoke and many more are being exposed to environmental tobacco smoke. Since the role of free radicals and oxidative damage in the pathogenesis of smoking-related diseases has been suggested, bacoside A, a potent antioxidant was tested for its ability to protect against cigarette smoking-induced toxicity in terms of lactate dehydrogenase (LDH) and its isoenzymes. Rats were exposed to cigarette smoke and simultaneously administered with bacoside A, for a period of 12 weeks. Total LDH activity was assayed in serum, lung, heart, brain, liver and kidney, and serum LDH isoforms were separated electrophoretically. Cigarette smoke exposure resulted in significant increase in serum LDH and its isoenzymes with a concomitant decrease in these organs. These alterations were prevented by administration of bacoside A. Excessive oxidants from cigarette smoke is known to cause peroxidation of membrane lipids leading to cellular damage, thereby resulting in the leakage of LDH into the circulation. Bacoside A could have rendered protection to the organs by stabilizing their cell membranes and prevented the release of LDH, probably through its free radical scavenging and anti-lipid peroxidative effect.

  5. Purification and Electrophoretic Characterization of Lactate Dehydrogenase from Mammalian Blood: A Different Twist on a Classic Experiment

    Science.gov (United States)

    Brunauer, Linda S.

    2016-01-01

    A multiweek protein purification suite, suitable for upper-division biochemistry or biotechnology undergraduate students, is described. Students work in small teams to isolate the enzyme lactate dehydrogenase (LDH) from a nontraditional tissue source, mammalian blood, using a sequence of three column chromatographic procedures: ion-exchange, size…

  6. 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells

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    Shihab Deiab

    2015-01-01

    Full Text Available A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH- A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill. gallnut (RCG (also known as Galla Chinensis extract as a potent (IC50 < 1 µg/mL inhibitor of human LDH-A (hLDH-A. In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC50 = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC50 = 94.18 µM, parallel to attenuated lactic acid production (IC50 = 97.81 µM. In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC50 = 1.2 µM relative to paclitaxel (IC50 < 100 nM. In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.

  7. 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Deiab, Shihab; Mazzio, Elizabeth; Eyunni, Suresh; McTier, Oshlii; Mateeva, Nelly; Elshami, Faisel; Soliman, Karam F A

    2015-01-01

    A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH-) A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill.) gallnut (RCG) (also known as Galla Chinensis) extract as a potent (IC50 < 1 µg/mL) inhibitor of human LDH-A (hLDH-A). In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG) was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC50 = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC50 = 94.18 µM), parallel to attenuated lactic acid production (IC50 = 97.81 µM). In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC50 = 1.2 µM) relative to paclitaxel (IC50 < 100 nM). In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.

  8. An alternative allosteric regulation mechanism of an acidophilic l-lactate dehydrogenase from Enterococcus mundtii 15-1A

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    Yasuyuki Matoba

    2014-01-01

    Full Text Available A plant-derived Enterococcus mundtii 15-1A, that has been previously isolated from Brassica rapa L. subsp. nipposinica (L.H. Bailey Hanelt var. linearifolia by our group, possesses two kinds of l-lactate dehydrogenase (l-LDH: LDH-1 and LDH-2. LDH-1 was activated under low concentration of fluctose-1,6-bisphosphate (FBP at both pH 5.5 and 7.5. Although LDH-2 was also activated under the low concentration of FBP at pH 5.5, a high concentration of FBP is necessary to activate it at pH 7.5. The present study shows the crystal structures of the acidophilic LDH-2 in a complex with and without FBP and NADH. Although the tertiary structure of the ligands-bound LDH-2 is similar to that of the active form of other bacterial l-LDHs, the structure without the ligands is different from that of any other previously determined l-LDHs. Major structural alterations between the two structures of LDH-2 were observed at two regions in one subunit. At the N-terminal parts of the two regions, the ligands-bound form takes an α-helical structure, while the form without ligands displays more disordered and extended structures. A vacuum-ultraviolet circular dichroism analysis showed that the α-helix content of LDH-2 in solution is approximately 30% at pH 7.5, which is close to that in the crystal structure of the form without ligands. A D241N mutant of LDH-2, which was created by us to easily form an α-helix at one of the two parts, exhibited catalytic activity even in the absence of FBP at both pH 5.5 and 7.5.

  9. Characterization of the Saffron Derivative Crocetin as an Inhibitor of Human Lactate Dehydrogenase 5 in the Antiglycolytic Approach against Cancer.

    Science.gov (United States)

    Granchi, Carlotta; Fortunato, Serena; Meini, Serena; Rizzolio, Flavio; Caligiuri, Isabella; Tuccinardi, Tiziano; Lee, Hyang Yeon; Hergenrother, Paul J; Minutolo, Filippo

    2017-07-19

    Inhibition of lactate dehydrogenase (LDH) represents an innovative approach to tackle cancer because this peculiar glycolytic metabolism is characteristic of most invasive tumor cells. An investigation into the biological properties of saffron extracts led to the discover of their LDH-inhibition properties. In particular, the most important saffron components, crocetin, was found to inhibit LDH (IC50 = 54.9 ± 4.7 μM). This carotenoid was independently produced by chemical synthesis, and its LDH-inhibition properties manifested via its antiproliferative activity against two glycolytic cancer cell lines (A549 and HeLa, IC50 = 114.0 ± 8.0 and 113.0 ± 11.1 μM, respectively). The results described in this article suggest that saffron may be a helpful alimentary component in the prevention of cancer that potentially contributes to the efficacy of approved cancer therapies.

  10. Potential Applications of Hybrid Layered Double Hydroxide (LDH Particles in Pulp and Paper Production

    Directory of Open Access Journals (Sweden)

    Sophia von Haartman

    2014-03-01

    Full Text Available Functionalization of papermaking pulp fibers using inorganic particles was investigated as a novel approach. Different layered double hydroxide (LDH particles were used in peroxide bleaching of thermomechanical pulp (TMP and in oxygen bleaching of eucalyptus kraft pulp. LDH particles were also tested as binding sites for optical brightening agents (OBA that are commonly used in paper production. The surface chemistry of LDH-treated pulps was examined using X-ray photoelectron spectroscopy (XPS and apparent contact angle with water. Adsorbed LDH was not detected by XPS on the fiber surfaces after the bleaching trials, but it had a clear impact on the processes. LDH particles modified with terephthalate anions decreased the consumption of hydrogen peroxide and increased opacity by 3 units in TMP. Unmodified LDH particles enhanced the selectivity in oxygen delignification of kraft pulp, leading to 10% gain in ISO brightness and reduction of 2 units in Kappa number in comparison with conventional processes. Paper strength properties were unaffected in the presented system. After bleaching with LDH, the amount of anionic groups on pulp surfaces was increased. Also, the retention of OBA onto TMP fibers was improved with modified LDH particles. LDH proved to have great potential for current and prospective applications in pulp and paper manufacture.

  11. Pharmacokinetics of 5-fluorouracil and increased hepatic dihydropyrimidine dehydrogenase activity levels in 1,2-dimethylhydrazine-induced colorectal cancer model rats.

    Science.gov (United States)

    Kobuchi, Shinji; Ito, Yukako; Okada, Kae; Imoto, Kazuki; Takada, Kanji

    2013-09-01

    To investigate the hepatic dihydropyrimidine dehydrogenase (DPD) activity in colorectal cancer (CRC), which is critically important to create a patient-specific dosing regimen, we performed 5-FU pharmacokinetic studies in 1,2-dimethylhydrazine-induced CRC model rats (CRC rats). After rats received 5-FU intravenous (IV) bolus injections, the area under the plasma concentration-time curve (AUC) and elimination half-life (t 1/2) in CRC rats (10.02 ± 0.37 μg h mL(-1), 0.30 ± 0.02 h, respectively) were significantly lower than that in control rats (13.46 ± 1.20 μg h mL(-1), 0.52 ± 0.05 h, respectively), whereas total plasma clearance (CLtot) in CRC rats (2.01 ± 0.07 L h(-1) kg(-1)) was significantly increased compared with that in control rats (1.54 ± 0.14 L h(-1) kg(-1)). Conversely, the avoidance ratio of the hepatic first-pass effect was approximately 20 % lower than that in control rats. Of interest is that hepatic DPD activity levels and the dihydrouracil-uracil ratio (UH2/Ura ratio) in plasma, which may act as a potential biomarker to evaluate hepatic DPD activity levels, were significantly increased in CRC rats. These results suggest that the decrease of hepatic availability in CRC rats is brought about by the increase in intrinsic clearance induced by the increase in DPD activity, resulting in a decrease in AUC and t 1/2 and an increase in CLtot after 5-FU IV bolus injection. Along with a proper dosing regimen for patients with CRC, a hepatic DPD activity monitoring system, such as the determination of UH2/Ura ratio in plasma, is desirable.

  12. Disruption of lactate dehydrogenase and alcohol dehydrogenase for increased hydrogen production and its effect on metabolic flux in Enterobacter aerogenes.

    Science.gov (United States)

    Zhao, Hongxin; Lu, Yuan; Wang, Liyan; Zhang, Chong; Yang, Cheng; Xing, Xinhui

    2015-10-01

    Hydrogen production by Enterobacter aerogenes from glucose was enhanced by deleting the targeted ldhA and adh genes responsible for two NADH-consuming pathways which consume most NADH generated from glycolysis. Compared with the wild-type, the hydrogen yield of IAM1183-ΔldhA increased 1.5 fold. Metabolic flux analysis showed both IAM1183-ΔldhA and IAM1183-Δadh exhibited significant changes in flux, including enhanced flux towards the hydrogen generation. The lactate production of IAM1183-ΔldhA significantly decreased by 91.42%, while the alcohol yield of IAM1183-Δadh decreased to 30%. The mutant IAM1183-ΔldhA with better hydrogen-producing performance was selected for further investigation in a 5-L fermentor. The hydrogen production of IAM1183-ΔldhA was 2.3 times higher than the wild-type. Further results from the fermentation process showed that the pH decreased to 5.39 levels, then gradually increased to 5.96, indicating that some acidic metabolites might be degraded or uptaken by cells.

  13. Lactate dehydrogenase A as a highly abundant eye lens protein in platypus (Ornithorhynchus anatinus): upsilon (upsilon)-crystallin.

    Science.gov (United States)

    van Rheede, Teun; Amons, Reinout; Stewart, Niall; de Jong, Wilfried W

    2003-06-01

    Vertebrate eye lenses mostly contain two abundant types of proteins, the alpha-crystallins and the beta/gamma-crystallins. In addition, certain housekeeping enzymes are highly expressed as crystallins in various taxa. We now observed an unusual approximately 41-kd protein that makes up 16% to 18% of the total protein in the platypus eye lens. Its cDNA sequence was determined, which identified the protein as muscle-type lactate dehydrogenase A (LDH-A). It is the first observation of LDH-A as a crystallin, and we designate it upsilon (upsilon)-crystallin. Interestingly, the related heart-type LDH-B occurs as an abundant lens protein, known as epsilon-crystallin, in many birds and crocodiles. Thus, two members of the ldh gene family have independently been recruited as crystallins in different higher vertebrate lineages, suggesting that they are particularly suited for this purpose in terms of gene regulatory or protein structural properties. To establish whether platypus LDH-A/upsilon-crystallin has been under different selective constraints as compared with other vertebrate LDH-A sequences, we reconstructed the vertebrate ldh-a gene phylogeny. No conspicuous rate deviations or amino acid replacements were observed.

  14. Insights into the Synthesis of Layered Double Hydroxide (LDH) Nanoparticles: Part 1. Optimization and Controlled Synthesis of Chloride-Intercalated LDH

    OpenAIRE

    Sun, Xiaodi; Neuperger, Erica; Dey, Sandwip K.

    2015-01-01

    Layered double hydroxide (LDH) nanoparticles have excellent anion-intercalating property, and their potential as theranostic nanovectors is high. However, understanding of the control of the mean particle size (MPS) and achievement of monodispersed particle size distribution (PSD) remains elusive. Herein, with the aid of statistical design of experiments on a model system of Cl−-intercalated (Zn, Al)-LDH, controlled synthesis of single crystalline nanoparticles using the coprecipitation metho...

  15. Role of lactate dehydrogenase in metmyoglobin reduction and color stability of different bovine muscles.

    Science.gov (United States)

    Kim, Y H; Keeton, J T; Smith, S B; Berghman, L R; Savell, J W

    2009-11-01

    The role of lactate dehydrogenase (LDH) in metmyoglobin reducing activity (MRA) and color stability of different bovine muscles was studied in two consecutive experiments. In experiment 1, three different bovine muscles -M. longissimus lumborum (LL), M. semimembranosus (SM), and M. psoas major (PM) - were obtained (n=7, respectively), cut into steaks, PVC packaged, and then displayed for 7days at 1°C. The LL was the most red over display time and had more (PLDH-B activity (catalyzing toward NADH generation), LDH1 isoform expression, NADH, and higher (PLDH-B activity, NADH, and a* values after 10days display at 1°C. These results suggest that variation in color stability of physiologically different muscles is regulated by different replenishment rates of NADH via different LDH isozymes.

  16. 肺腺癌中LDH-V、AKT1及Glut1的表达及其与18氟-2-脱氧葡萄糖摄取的相关性研究%Expression of LDH-V, AKT1, Glut1 and Their Relationships with the Uptake of 18F-FDG in Lung Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    李倩; 黄钢; 刘建军; 孙晓光

    2013-01-01

    目的:探讨肺腺癌中乳酸脱氢酶-V(lactate dehydrogenase V,LDH-V)、丝氨酸/苏氨酸蛋白激酶1(serine-threonine kinase 1,AKT1)及葡萄糖转运蛋白1(glucose transporter 1,Glut1)的表达及它们与18氟-2-脱氧葡萄糖(18F-FDG)摄取的关系.方法:54名肺腺癌患者,术前1周进行PET-CT显像.采用免疫组织化学SP法对LDH-V、AKT1、Glut1的表达进行半定量分析,并与术前PET-CT所得的18 F-FDG最大标准化摄取值(maximal standardized uptake value,SUVmax)进行相关性分析.结果:在肺腺癌中,LDH-V、AKT1及Glut1表达的阳性率为88.89%、88.89%、68.52%,LDH-V表达与AKT1及Glut1表达呈正相关(r分别为0.381和0.270,P<0.01和0.05);SUVmax与肿瘤最大直径(maximal diameter,Dmax)呈正相关(r=0.524,P<0.01),Dmax>2 cm患者(n=30)的SUVmax与Glut1表达呈正相关(r=0.407,P<0.05);SUVmax与病理分级、LDH-V及AKT1表达无关.结论:LDH-V、AKT1及Glut1在肺腺癌中广泛表达且LDH-V表达与AKT1及Glut1表达密切相关,Glut1在肺腺癌18F-FDG摄取中发挥重要作用.

  17. Metallocene supported core@LDH catalysts for slurry phase ethylene polymerisation.

    Science.gov (United States)

    Buffet, Jean-Charles; Byles, Coral F H; Felton, Ryan; Chen, Chunping; O'Hare, Dermot

    2016-03-14

    We report the synthesis of solid catalysts based on a zirconocene supported on either silica@AMO-LDH or zeolite@AMO-LDH for the slurry phase polymerisation of ethylene. The hybrid catalysts demonstrate synergistic effects in which the polymerisation activity is up to three times higher than the zirconocene supported on analogous single phase silica or zeolite supports.

  18. Structural Evolvement of Heating Treatment of Mg/Al-LDH and Preparation of Mineral Mesoporous Materials

    Institute of Scientific and Technical Information of China (English)

    CHEN Tianhu; XU Huifang; WANG Yifeng; QING Chengsong; FAN Mingde; CHEN Gang

    2006-01-01

    Although hydrotalcite, or layered double hydroxides (LDHs), is not a common mineral, it is an important material that can be easily synthesized in laboratory. In this study, structural evolvement and BET surface area changes of heat treated Mg/Al-LDH is evaluated by XRD, TEM and N2-BET analyses. The results indicate that the magnesium-aluminum LDH with carbonate as interlayer anion,periclase-like oxides was formed at temperatures of 400-800℃. Meanwhile, 2-3 nanometer mesoporous were formed during decomposition of LDH. However, the heat treated samples still preserve the morphology of the original LDH plates. Periclase-like formed from LDH heat treatment may re-hydrolyze and recover the structure of LDH. However, crystallinity of the recovered LDH is lower than that of the original LDH. This heat treatment will result in formation of (Mg, Al)-oxide nano-crystals and nanopores among the nano-crystals. When heating temperature exceeds 1000, the periclase-like (Mg, Al)-oxide is transformed into a composite with periclase (MgO) and spinel phases.The periclase can be re-hydrolyzed and dissolved in HCl solution. After acid treatment, the sample with a high surface area is composed of spinel nano-crystals and nanopores among them. Our results will provide a new and economic way to synthesize mesoporous materials through pathways of phase transformation of precursor materials with different composition.

  19. Efficient production of L-Lactic acid by metabolically engineered Saccharomyces cerevisiae with a genome-integrated L-lactate dehydrogenase gene.

    Science.gov (United States)

    Ishida, Nobuhiro; Saitoh, Satoshi; Tokuhiro, Kenro; Nagamori, Eiji; Matsuyama, Takashi; Kitamoto, Katsuhiko; Takahashi, Haruo

    2005-04-01

    We developed a metabolically engineered yeast which produces lactic acid efficiently. In this recombinant strain, the coding region for pyruvate decarboxylase 1 (PDC1) on chromosome XII is substituted for that of the l-lactate dehydrogenase gene (LDH) through homologous recombination. The expression of mRNA for the genome-integrated LDH is regulated under the control of the native PDC1 promoter, while PDC1 is completely disrupted. Using this method, we constructed a diploid yeast transformant, with each haploid genome having a single insertion of bovine LDH. Yeast cells expressing LDH were observed to convert glucose to both lactate (55.6 g/liter) and ethanol (16.9 g/liter), with up to 62.2% of the glucose being transformed into lactic acid under neutralizing conditions. This transgenic strain, which expresses bovine LDH under the control of the PDC1 promoter, also showed high lactic acid production (50.2 g/liter) under nonneutralizing conditions. The differences in lactic acid production were compared among four different recombinants expressing a heterologous LDH gene (i.e., either the bovine LDH gene or the Bifidobacterium longum LDH gene): two transgenic strains with 2microm plasmid-based vectors and two genome-integrated strains.

  20. Novel biohybrids of layered double hydroxide and lactate dehydrogenase enzyme: Synthesis, characterization and catalytic activity studies

    Science.gov (United States)

    Djebbi, Mohamed Amine; Braiek, Mohamed; Hidouri, Slah; Namour, Philippe; Jaffrezic-Renault, Nicole; Ben Haj Amara, Abdesslem

    2016-02-01

    The present work introduces new biohybrid materials involving layered double hydroxides (LDH) and biomolecule such as enzyme to produce bioinorganic system. Lactate dehydrogenase (Lac Deh) has been chosen as a model enzyme, being immobilized onto MgAl and ZnAl LDH materials via direct ion-exchange (adsorption) and co-precipitation methods. The immobilization efficiency was largely dependent upon the immobilization methods. A comparative study shows that the co-precipitation method favors the immobilization of great and tunable amount of enzyme. The structural behavior, chemical bonding composition and morphology of the resulting biohybrids were determined by X-ray diffraction (XRD) study, Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM), respectively. The free and immobilized enzyme activity and kinetic parameters were also reported using UV-Visible spectroscopy. However, the modified LDH materials showed a decrease in crystallinity as compared to the unmodified LDH. The change in activity of the immobilized lactate dehydrogenase was considered to be due, to the reduced accessibility of substrate molecules to the active sites of the enzyme and the partial conformational change of the Lac Deh molecules as a result of the immobilization way. Finally, it was proven that there is a correlation between structure/microstructure and enzyme activity dependent on the immobilization process.

  1. Metabolic engineering of lactate dehydrogenase rescues mice from acidosis.

    Science.gov (United States)

    Acharya, Abhinav P; Rafi, Mohammad; Woods, Elliot C; Gardner, Austin B; Murthy, Niren

    2014-06-05

    Acidosis causes millions of deaths each year and strategies for normalizing the blood pH in acidosis patients are greatly needed. The lactate dehydrogenase (LDH) pathway has great potential for treating acidosis due to its ability to convert protons and pyruvate into lactate and thereby raise blood pH, but has been challenging to develop into a therapy because there are no pharmaceutical-based approaches for engineering metabolic pathways in vivo. In this report we demonstrate that the metabolic flux of the LDH pathway can be engineered with the compound 5-amino-2-hydroxymethylphenyl boronic acid (ABA), which binds lactate and accelerates the consumption of protons by converting pyruvate to lactate and increasing the NAD(+)/NADH ratio. We demonstrate here that ABA can rescue mice from metformin induced acidosis, by binding lactate, and increasing the blood pH from 6.7 to 7.2 and the blood NAD(+)/NADH ratio by 5 fold. ABA is the first class of molecule that can metabolically engineer the LDH pathway and has the potential to have a significant impact on medicine, given the large number of patients that suffer from acidosis.

  2. Effects of silver nanoparticle on lactate dehydrogenase activity and histological changes of heart tissue in male wistar rats

    Directory of Open Access Journals (Sweden)

    Noushin Naghsh

    2013-03-01

    Full Text Available Background & Objective: The silver nanoparticles are important in many applications of nanoparticles on human health . The toxicity of silver nanoparticles are not well documented yet. The aim of this study was to investigate the effect of silver nanoparticles on lactate dehydrogenase activity and histological changes in heart tissue.   Materials &Methods: In this study, 40 adult male wistar rats of 220±20gr were divided in to five groups including control and four experimental groups. The latter groups were injected intraperitoneally spherical nano silver particles of 50, 100, 200 and 400 ppm respectively for five consecutive days. Then three, eight and twelve days after the last injection, blood samples were collected and lactate dehydrogenase (LDH activity was assayed . Also, tissue samples from the heart muscle were prepared and studied after staining with Hematoxiline-Eosine. Data of LDH activity was analyzed by One way- ANOVA- test and P-value of ≤ 0.05 were considered as significant.   Results : The result showed that different concentrations of silver nanoparticles have no significant effect on the lactate dehydrogenase (p=0.192 . T he histological study of the tissue after exposure to 400 ppm concentration of silver nanoparticles showed the start of primary apoptosis in heart tissue.   Conclusion: The LDH activity was not changed significantly after exposure to different concentration of silver nanoparticles, which shows the safety of these particles on LDH activity.

  3. Comparative enzymology-new insights from studies of an "old" enzyme, lactate dehydrogenase.

    Science.gov (United States)

    Storey, Kenneth B

    2016-09-01

    Comparative enzymology explores the molecular mechanisms that alter the properties of enzymes to best fit and adapt them to the biotic demands and abiotic stresses that affect the cellular environment in which these protein catalysts function. For many years, comparative enzymology was primarily concerned with analyzing enzyme functional properties (e.g. substrate affinities, allosteric effectors, responses to temperature or pH, stabilizers, denaturants, etc.) in order to determine how enzyme properties were optimized to function under changing conditions. More recently it became apparent that posttranslational modifications of enzymes play a huge role in metabolic regulation. At first, such modifications appeared to target just crucial regulatory enzymes but recent work is showing that many dehydrogenases are also targets of posttranslational modification leading to substantial changes in enzyme properties. The present article focuses in particular on lactate dehydrogenase (LDH) showing that stress-induced changes in enzyme properties can be linked with reversible posttranslational modifications; e.g. changes in the phosphorylation state of LDH occur in response to dehydration stress in frogs and anoxia exposure of turtles and snails. Furthermore, these studies show that LDH is also a target of other posttranslational modifications including acetylation, methylation and ubiquitination that change in response to anoxia or dehydration stress. Selected new methods for exploring posttranslational modifications of dehydrogenases are discussed and new challenges for the future of comparative enzymology are presented that will help to achieve a deeper understanding of biochemical adaptation through enzyme regulation.

  4. A highly sensitive aptasensor towards Plasmodium lactate dehydrogenase for the diagnosis of malaria.

    Science.gov (United States)

    Lee, Seonghwan; Song, Kyung-Mi; Jeon, Weejeong; Jo, Hunho; Shim, Yoon-Bo; Ban, Changill

    2012-05-15

    Finding a highly sensitive diagnostic technique for malaria has challenged scientists for the last century. In the present study, we identified versatile single-strand DNA aptamers for Plasmodium lactate dehydrogenase (pLDH), a biomarker for malaria, via the Systematic Evolution of Ligands by EXponential enrichment (SELEX). The pLDH aptamers selectively bound to the target proteins with high sensitivity (K(d)=16.8-49.6 nM). The selected aptamers were characterized using an electrophoretic mobility shift assay, a quartz crystal microbalance, a fluorescence assay, and circular dichroism spectroscopy. We also designed a simple aptasensor using electrochemical impedance spectroscopy; both Plasmodium vivax LDH and Plasmodium falciparum LDH were selectively detected with a detection limit of 1 pM. Furthermore, the pLDH aptasensor clearly distinguished between malaria-positive blood samples of two major species (P. vivax and P. falciparum) and a negative control, indicating that it may be a useful tool for the diagnosis, monitoring, and surveillance of malaria.

  5. 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.

  6. Interaction between nanoparticulate anatase TiO2 and lactate dehydrogenase.

    Science.gov (United States)

    Duan, Yanmei; Li, Na; Liu, Chao; Liu, Huiting; Cui, Yaling; Wang, Han; Hong, Fashui

    2010-09-01

    In order to study the mechanisms underlying the effects of TiO(2) nanoparticles on lactate dehydrogenase (LDH, EC1.1.1.27), Institute of Cancer Research region mice were injected with nanoparticulate anatase TiO(2) (5 nm) of various doses into the abdominal cavity daily for 14 days. We then examined LDH activity in vivo and in vitro and direct evident for interaction between nanoparticulate anatase TiO(2) and LDH using spectral methods. The results showed that nanoparticulate anatase TiO(2) could significantly activate LDH in vivo and in vitro; the kinetics constant (Km) and Vmax were 0.006 microM and 1,149 unit mg(-1) protein min(-1), respectively, at a low concentration of nanoparticulate anatase TiO(2), and 3.45 and 0.031 microM and 221 unit mg(-1) protein min(-1), respectively, at a high concentration of nanoparticulate anatase TiO(2). By fluorescence spectral assays, the nanoparticulate anatase TiO(2) was determined to be directly bound to LDH, and the binding constants of the binding site were 1.77 x 10(8) L mol(-1) and 2.15 x 10(7) L mol(-1), respectively, and the binding distance between nanoparticulate anatase TiO(2) and the Trp residue of LDH was 4.18 nm, and nanoparticulate anatase TiO(2) induced the protein unfolding. It was concluded that the binding of nanoparticulate anatase TiO(2) altered LDH structure and function.

  7. 常规方法测定LDH测量不确定度的评定%Evaluation of Uncertainty in Measurement of Detecting of LDH in Serum by Routine Method

    Institute of Scientific and Technical Information of China (English)

    郭玉红

    2014-01-01

    目的探讨测量不确定度评定在临床检验常规测量中的应用。方法以常规方法测定乳酸脱氢酶(LDH-L)为列,按测量不确定度评定过程,分析不确定度的来源并分别按A类和B类进行评定,合成标准不确定度,计算拓展不确定度。结果当LDH浓度为水平1时,A类不确定度UA=1.09,B类不确定度UB=3.32,合成标准不确定度UC=3.49,拓展不确定度U=6.84。当LDH浓度为水平2时,A类不确定度UA=0.58,B类不确定度UB=3.32,合成标准不确定度UC=3.37,拓展不确定度U=6.61。结论该研究只评估测量过程的不确定度,各实验室应参照叶测量不确定度表示指南》建立本实验室各项检测项目不确定度评定程序并进行评定,以确保实验结果的可靠性。%Objective To explore the application of evaluation for measurement uncertainty in routine clinical laboratory. Methods The routine test of lactate dehydrogenase (LDH) in serum was chosen as the example to evaluate the process of measurement uncertainty. The sources of uncertainty were identified, and the components of uncertainty were evaluated as type A and B respectively, combined standard uncertainty and calculating the expanded uncertainty. Results When the concentration of LDH is level one, the uncertainty of type A is 1.09, the uncertainty of type B is 3.32, the standard uncertainty is 3.49,the expanded uncertainty is 6.84. When the concentration of LDH is level two, the uncertainty of type A is 0.58, the uncertainty of type B is 3.32, the standard uncertainty is 3.37,the expanded uncertainty is 6.61. Conclusion This study only evaluates the measurement uncertainty during detection process, each laboratory should refer to the "Guide to the expression of uncertainty in measurement" established in their own test content's assessment procedures of measurement uncertainty and assessment it to ensure the reliability of the experimental results.

  8. Effects of budC gene knockout and ldhA overexpression on D-lactic acid production by Klebsiella pneumoniae%budC敲除及ldhA过表达对Klebsiella pneumoniae合成D-乳酸的影响

    Institute of Scientific and Technical Information of China (English)

    王凤寰; 孟青青

    2012-01-01

    为了提高K.pneumoniae中D-乳酸的合成效率,本文以BUD和LDH为改造目标,扩增丁二醇脱氢酶基因budC,并在其中插入四环素抗性基因tet,构建了基因敲除载体pTBT,转化K.pneumoniae,利用同源重组技术,敲除K.pneumoniae染色体上的budC基因,得到重组菌K.pneumoniae B-;在此基础上,构建了表达载体pKP-ldhA,转化K.pneumoniae B-,过量表达乳酸脱氢酶基因ldhA,得到重组菌Kpneumoniae B-L+.摇瓶发酵结果显示,重组菌K.pneumoniae B-L+的丁二醇合成浓度比原始菌降低了90%以上,D-乳酸合成浓度比K.pneumoniae B-和原始菌分别提高了77.1%和41.4%,发酵罐实验D-乳酸产量68.4 g/L,转化率0.78,生产强度1.22 g/(L·h).结果表明,敲除budC及过表达ldhA有利于改善克雷伯肺炎杆菌中D-乳酸的合成.%In the metabolic pathway of Klebsiella pneumoniae, 2,3-butanediol is a byproduct and its accumulation decreases the yield of main product, D-lactic acid. Butanediol dehydrogenase (BUD) is one of the key enzymes for butanediol biosynthesis, which competes with lactate dehydrogenase (LDH) for reducing equivalents of nicotinam-ide adenine dinueleotide (NADH). In order to reduce the butanediol accumulation and improve the D-lactic acid production, in this study, a homologous recombination vector pTBT was constructed and transformed into K. pneumoniae, resulting in K. pneumoniae B-, in which the budC gene encoding butanediol dehydrogenase was disrupted by inserting a tetracycline resistant gene (tet). Simultaneously, the expression vector pKP-ldhA harboring the ldhA gene was constructed and transformed into K. pneumoniae B- to overexpress lactate dehydrogenase. The resulting recombinant strain K. pneumoniae B-L + exhibited a nearly abolished butanediol formation ( decreased by 90% ) but a significantly improved NADH availability and D-lactic acid production. In flask culture, the D-lactic acid concentrations were 77. 1% and 41.4% , respectively, higher than those of

  9. Synthesis and Characterization of PE-g-MA/MgAI-LDH Exfoliation Nanocomposite via Solution Intercalation

    Institute of Scientific and Technical Information of China (English)

    陈伟; 瞿保钧

    2003-01-01

    An organo-modified MgAl-layered double hydroxide (OMgAl-LDH) was mecessfully exfoliated in the xyleue solution of polyethylene-grafted-malelc anhydride (PE-g-MA) under refluxing condition. A PE-g-MA/MgAI-LDH exfoliaUon nanocomposite was formed after the precipitaUon of PE-g-MA from the dispersion system. The structure and thermal property of the PE-g-MA/MgAI-LDH exfoliaUon nanocomposite were characterizd by X-ray diffraction(XRD),transmission electron microscopy(TEM),and thermogravimetry analysis(TGA).The disappearance of d001 XRD peak of OMgAl-LDH at 2θ=3.2° suggests that the MgAl hydroxide sheets are exfoliated in the nanocomposite.The TEM image shows that the MgAl hydroxide sheets of less than 70nm in length or width are exfoliated and dispersed disorderly in PE-g-MA matrix.TGA profiles indicate that the PE-g-MA/MgAl-LDH nanocomposite with 5wt% OMgAl-LDH loading shows a faster charring process in temperature range from 210 to 390℃ and a greater thermal stability beyond 390℃ than PE-g-MA does.The decompostion temperature of the nanocomposite is 25℃ higher than that of PE-g-MA as measured at 50% weight loss.The PE-g-MA/MgAl-LDH nanocomposite is promising for application of flame-retardant polymeric materials.

  10. Preparation and enhanced properties of polyaniline/grafted intercalated ZnAl-LDH nanocomposites

    Science.gov (United States)

    Hu, Jinlong; Gan, Mengyu; Ma, Li; Zhang, Jun; Xie, Shuang; Xu, Fenfang; Shen, JiYue Zheng Xiaoyu; Yin, Hui

    2015-02-01

    The polymeric nanocomposites (PANI/AD-LDH) were prepared by in situ polymerization based on polyaniline (PANI) and decavanadate-intercalated and γ-aminopropyltriethoxysilane (APTS)-grafted ZnAl-layered double hydroxide (AD-LDH). FTIR and XRD studies confirm the grafting of APTS with decavanadate-intercalated LDH (D-LDH). The extent of grafting (wt%) has also been estimated on the basis of the residue left in nitrogen atmosphere at 800 °C in TGA. SEM and XPS studies show the partial exfoliation of grafted LDH in the PANI matrix and the interfacial interaction between PANI and grafted LDH, respectively. The grafted intercalated layered double hydroxide in reinforcing the properties of the PANI nanocomposites has also been investigated by open circuit potential (OCP), tafel polarization curves (TAF), electrochemical impendence spectroscopy (EIS), salt spray test and TGA-DTA. The experimental results indicate that the PANI/AD-LDH has a higher thermal stability and anticorrosion properties relative to the PANI.

  11. [Role of layered double hydroxide (LDH) in the protection of herring testis DNA from heavy metals].

    Science.gov (United States)

    Tang, Yi-Ni; Wu, Ping-Xiao; Zhu, Neng-Wu

    2012-10-01

    The role of layered double hydroxide (LDH) in the protection of herring testis DNA from heavy metals Cd2+ and Pb2+ was studied by X-ray diffraction ( XRD) spectra, Fourier transform infrared (FTIR) spectra, Scanning Electron Microscopy (SEM), Cyclic Voltammetry and Ultraviolet Spectrometry. Size expansion of the basal spacing (003) from 0. 76 nm in LDH to 2. 30 nm was observed in the resulting DNA-LDH nanohybrids and it gave peaks corresponding to C=O (1 534 cm(-1) and 1488 cm(-1)) in skeleton and bases, C-O stretching vibration (1228 cm(-1)), and P-O symmetrical stretching vibration (1096 cm(-1)) in functional groups of DNA, indicating that DNA were intercalated into the LDH by the ion exchange. However, the displacement of NO3(-) was not fully complete (partial intercalation of DNA). The DNA outside LDH interlayers was absorbed on the surface of LDH. The cyclic voltammetric curves showed that DNA in the composites exhibited a very similar peaks, which corresponded to the two reduction current peaks (E(P) = - 1.2 mV and E(P) = -2.4 mV) of free DNA. Also there was no cathode sag emerging in cyclic voltammetric curves, suggesting that both Cd2+ and Pb2+ cannot insert into the groove of DNA to associate with base pairs or other groups when DNA was bound on LDH. The results showed that, on the one hand, both Cd2+ and Pb2+ were absorbed on the external surface of LDH for immobilization, on the other hand, the layer of LDH provided ideal space for DNA by the action of protecting DNA molecules from Cd2+ and Pb2+.

  12. In vivo regulation of alcohol dehydrogenase and lactate dehydrogenase in Rhizopus oryzae to improve L-lactic acid fermentation.

    Science.gov (United States)

    Thitiprasert, Sitanan; Sooksai, Sarintip; Thongchul, Nuttha

    2011-08-01

    Rhizopus oryzae is becoming more important due to its ability to produce an optically pure L: -lactic acid. However, fermentation by Rhizopus usually suffers from low yield because of production of ethanol as a byproduct. Limiting ethanol production in living immobilized R. oryzae by inhibition of alcohol dehydrogenase (ADH) was observed in shake flask fermentation. The effects of ADH inhibitors added into the medium on the regulation of ADH and lactate dehydrogenase (LDH) as well as the production of cell biomass, lactic acid, and ethanol were elucidated. 1,2-diazole and 2,2,2-trifluroethanol were found to be the effective inhibitors used in this study. The highest lactic acid yield of 0.47 g/g glucose was obtained when 0.01 mM 2,2,2-trifluoroethanol was present during the production phase of the pregrown R. oryzae. This represents about 38% increase in yield as compared with that from the simple glucose fermentation. Fungal metabolism was suppressed when iodoacetic acid, N-ethylmaleimide, 4,4'-dithiodipyridine, or 4-hydroxymercury benzoic acid were present. Dramatic increase in ADH and LDH activities but slight change in product yields might be explained by the inhibitors controlling enzyme activities at the pyruvate branch point. This showed that in living R. oryzae, the inhibitors regulated the flux through the related pathways.

  13. Effects of the suppression of lactate dehydrogenase A on the growth and invasion of human gastric cancer cells.

    Science.gov (United States)

    Liu, Xiaojun; Yang, Zhongxia; Chen, Zhaofeng; Chen, Rui; Zhao, Da; Zhou, Yongning; Qiao, Liang

    2015-01-01

    Lactate dehydrogenase A (LDH-A), which regulates glycolytic flux by catalyzing pyruvate to lactate in the cytoplasm, is believed to be one of the highly attractive therapeutic targets for cancers. Firstly, we detected the expression of LDH-A in gastric cancer (GC) cells. LDH-A inhibitor oxamate was then used to suppress the LDH-A activity in GC cells. Cell proliferation, lactic acid production, Transwell migration assay and apoptosis were assessed, respectively. The results showed that inhibition of LDH-A by oxamate decreased the lactate production. In the presence of glucose, oxamate inhibited cell proliferation in a dose-dependent manner. Flow cytometry assay further confirmed a pro-apoptotic effect of oxamate, and this was likely through increased expression of Bax, activated caspase-3, and decreased expression of Bcl-2. Therefore, we believe that oxamate inhibits cell growth, suppresses tumor invasion, and induces apoptosis in GC cells. LDH-A may be a potential therapeutic target for GC.

  14. The predictive value of cumulative lactate dehydrogenase release within the first 72 h of acute myocardial infarction in patients treated with primary angioplasty

    NARCIS (Netherlands)

    Elsman, Peter; Zijlstra, F.; Miedema, Kor; Hoorntje, J.C.; Dikkeschei, L.D.; Slingerland, R.J.; Reiffers, S.; de Boer, M.J.; Suryapranata, H.

    2004-01-01

    Background: In patients with acute myocardial infarction, estimation of infarct size by cumulative lactate dehydrogenase release at 72 h (LDHQ72) is a simple and widely used method. Our objective was to study the value of estimating infarct size, by the cumulative release of LDH over 72, 60, 48 and

  15. Effect of surfactant alkyl chain length on the dispersion, and thermal and dynamic mechanical properties of LDPE/organo-LDH composites

    Directory of Open Access Journals (Sweden)

    2011-05-01

    Full Text Available Low density polyethylene/layered double hydroxide (LDH composites were prepared via melt compounding using different kinds of organo-LDHs and polyethylene-grafted maleic anhydride as the compatibilizer. The organo-LDHs were successfully prepared by converting a commercial MgAl-carbonate LDH into a MgAl-nitrate LDH, which was later modified by anion exchange with linear and branched sodium alkyl sulfates having different alkyl chain lengths (nc = 6, 12 and 20. It was observed that, depending on the size of the surfactant alkyl chain, different degrees of polymer chain intercalation were achieved, which is a function of the interlayer distance of the organo-LDHs, of the packing level of the alkyl chains, and of the different interaction levels between the surfactant and the polymer chains. In particular, when the number of carbon atoms of the surfactant alkyl chain is larger than 12, the intercalation of polymer chains in the interlayer space and depression of the formation of large aggregates of organo-LDH platelets are favored. A remarkable improvement of the thermal-oxidative degradation was evidenced for all of the composites; whereas only a slight increase of the crystallization temperature and no significant changes of both melting temperature and degree of crystallinity were achieved. By thermodynamic mechanical analysis, it was evidenced that a softening of the matrix is may be due to the plasticizing effect of the surfactant.

  16. Diagnostic Value of Serum Lactate Dehydrogenase Isoenzyme and Amino Acid Patterns in Several Schistosomal and Non-Schistosomal Disorders as Compared to other Biochemical Parameters

    Directory of Open Access Journals (Sweden)

    Samia A. Ahmed

    1996-01-01

    Full Text Available Serum lactate dehydrogenase (LDH isoenzyme and amino acid (a. a patterns were evaluated in comparison to several other biochemical parameters for liver and renal function with the objective of clarifying the differential diagnosis of hepatic disorders and predicting the outcome of schistosomal infection in Egyptian patients. Patients examined included those with complicated hepatic disorders and others with different stages of schistosomal infestation, hepatoma or bladder cancer, in addition to a normal control group. Several biochemical parameters appeared to be useful in establishing consistent differences or similarities between the studied groups. Examples are; elevated serum AST/ AL T ratio and methionine content in chronic schistosomiasis, elevated serum urea/creatinine ratio and leucine content in all schistosomal patients and extremely high levels of N-acetyl-β-D-glucosaminidase (NAG in the urine of non-schistosomal bladder cancer patients. In addition, characteristic LDH isoenzyme profiles distinguish between the studied groups, in particular separating chronic schistosomiasis from schistosomal bladder cancer and hepatoma from other hepatic disorders.

  17. Effects of Sesame (Sesamum indicum L.) Supplementation on Creatine Kinase, Lactate Dehydrogenase, Oxidative Stress Markers, and Aerobic Capacity in Semi-Professional Soccer Players.

    Science.gov (United States)

    Barbosa, Carlos V da Silva; Silva, Alexandre S; de Oliveira, Caio V C; Massa, Nayara M L; de Sousa, Yasmim R F; da Costa, Whyara K A; Silva, Ayice C; Delatorre, Plínio; Carvalho, Rhayane; Braga, Valdir de Andrade; Magnani, Marciane

    2017-01-01

    Nutritional intervention with antioxidants rich foods has been considered a strategy to minimize the effects of overtraining in athletes. This experimental, randomized, and placebo-controlled study evaluated the effects of consumption of sesame (Sesamum indicum L.) on muscle damage markers, oxidative stress, systemic inflammation, and aerobic performance in male semi-professional soccer players. Twenty athletes were randomly assigned to groups that received 40 g (two tablespoons) per day of sesame or a placebo during 28 days of regular training (exposed to routine training that includes loads of heavy training in the final half of the season). Before and after intervention, creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (hs-CRP), and aerobic capacity were evaluated. Before intervention, a physiologic imbalance was noted in both groups related to CK and LDH levels. Sesame intake caused a reduction of CK (19%, p sesame consumption may reduce muscle damage and oxidative stress while improving the aerobic capacity in soccer players.

  18. Investigation of the electrochemical and photoelectrochemical properties of Ni-Al LDH photocatalysts.

    Science.gov (United States)

    Iguchi, Shoji; Kikkawa, Soichi; Teramura, Kentaro; Hosokawa, Saburo; Tanaka, Tsunehiro

    2016-05-18

    Layered double hydroxide (LDH) photocatalysts, including Ni-Al LDH, are active for the photocatalytic conversion of CO2 in water under UV light irradiation. In this study, we found that a series of LDHs exhibited anodic photocurrent which is a characteristic feature corresponding to n-type materials. Also, we estimated the potentials of photogenerated electrons and holes for LDHs, which are responsible for the photocatalytic reactions, using electrochemical techniques. The flat band potential of the Ni-Al LDH photocatalyst was estimated to be -0.40 V vs. NHE (pH = 0), indicating that the potential of the photogenerated electron is sufficient to reduce CO2 to CO. Moreover, we revealed that the flat band potentials of M(2+)-M(3+) LDH are clearly influenced by the type of trivalent metal (M(3+)) components.

  19. Misconceptions regarding basic thermodynamics and enzyme kinetics have led to erroneous conclusions regarding the metabolic importance of lactate dehydrogenase isoenzyme expression

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne

    2017-01-01

    Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate involving the coenzyme NAD(+) . Part of the foundation for the proposed shuttling of lactate from astrocytes to neurons during brain activation is the differential distribution of LDH isoenzymes between the two cell...... types. In this short review, we outline the basic kinetic properties of the LDH isoenzymes expressed in neurons and astrocytes, and argue that the distribution of LDH isoenzymes does not in any way govern directional flow of lactate between the two cellular compartments. The two main points...... which cells are producing and which are consuming lactate. Second, the thermodynamic equilibrium of the reaction is toward the reduced substrate (i.e., lactate), which is reflected in the concentrations measured in brain tissue, suggesting that the reaction is at near-equilibrium at steady state...

  20. Utility of NSE, ProGRP and LDH in Diagnosis and Treatment in Patients with Small Cell Lung Cancer%血清NSE、ProGRP和LDH在小细胞肺癌诊断治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    彭彦; 王燕; 李峻岭; 郝学志; 胡兴胜

    2016-01-01

    Background and objective Small cell lung cancer (SCLC) is a rapidly growing tumor with character-istic of neuroendocrine cellular function. Neuron speciifc enolase (NSE), pro-gastrin-releasing peptide (ProGRP) and lactic dehydrogenase (LDH) are valuable in diagnosis and treatment of SCLC. By analyzing the variation of NSE, ProGRP and LDH before and atfer treatment, the aim of this study is to investigate the effcacy of tumor markers in diagnostic staging, therapeu-tic evaluation and prediction of disease relapsing.Methods Patients with SCLC who receiving the ifrst line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic (includes NSE, ProGRP and LDH level before and atfer 2 cycles chemotherapy), effcacy evaluation, progression-free survival (PFS) were analyzed.Results Before treatment, Serum NSE, ProGRP and LDH in patients with extensive disease (ED) were signiifcantly higher than those with limited disease (LD)(allP4 cycles chemotherapy and with obvious decrease of ProGRP than those who accepted ≤4 cycles chemotherapy and with less obvious decrease of ProGRP in LD group; ED patients with no more than 2 distant metastasis, normal LDH level before treat-ment and obvious decrease of ProGRP atfer chemotherapy had lower short term relapse risk. In addition, the types of relapse (sensitive relapse, drug resistance relapse and refractory relapse) were negatively correlated with decrease of ProGRP (P=0.044). By multivariate analysis, numbers of chemotherapy cycle was independent prognostic factor for PFS in LD SCLC; numbers of distant metastasis and decrease of ProGRP were independent prognostic factors for PFS in ED SCLC.Conclusion Increase level of serum tumor markers is related to tumor burden. Decrease level of ProGRP atfer treatment may prognose effcacy and relapse risk.%背景与目的小细胞肺癌(small cell lung cancer, SCLC)是一种生长迅速、具有神经内分泌

  1. Effect of interlayer anions on [NiFe]-LDH nanosheet water oxidation activity

    OpenAIRE

    Hunter, B. M.; Hieringer, W.; Winkler, J.R.; Gray, H B; Müller, A. M.

    2016-01-01

    We synthesized nickel–iron layered double hydroxide ([NiFe]-LDH) nanosheets with different interlayer anions to probe their role in water oxidation catalysis. In alkaline electrolyte in ambient air, carbonate rapidly replaced other interlayer anions and catalytic activity was highest. Electrocatalytic water oxidation in virtually carbonate-free alkaline electrolyte revealed that activity was a function of anion basicity. Our [NiFe]-LDH nanosheets, prepared by pulsed laser ablation in liquids,...

  2. Glucose-6-phosphate dehydrogenase deficiency

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000528.htm Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition in which ...

  3. Synthesis and morphological modification of semiconducting Mg(Zn)Al(Ga)–LDH/ITO thin films

    Energy Technology Data Exchange (ETDEWEB)

    Valente, Jaime S., E-mail: jsanchez@imp.mx [Instituto Mexicano del Petróleo, Eje Central # 152, 07730 México D.F. (Mexico); López-Salinas, Esteban [Instituto Mexicano del Petróleo, Eje Central # 152, 07730 México D.F. (Mexico); Prince, Julia [Universidad Anáhuac México Norte, Av. Universidad Anáhuac # 46, Huixquilucan, Edo. de México 52786 (Mexico); González, Ignacio; Acevedo-Peña, Prospero [Universidad Autónoma Metropolitana-Iztapalapa, Departamento de Química, Apdo. Postal 55-534, 09340 México D.F. (Mexico); Ángel, Paz del [Instituto Mexicano del Petróleo, Eje Central # 152, 07730 México D.F. (Mexico)

    2014-09-15

    Layered double hydroxide (LDH) thin films with different chemical compositions (MgZnAl, MgZnGa, MgGaAl) and varying thicknesses were easily prepared by sol–gel method followed by dip-coating. Films were chemically uniform, transparent and well adhered to a conductive indium tin oxide (ITO) substrate. Structure, chemical composition and morphology of the thin films were characterized by XRD-GADDS, SEM-EDS and AFM. Additionally, the semiconducting properties of all the prepared films were studied through the Mott–Schottky relationship; such properties were closely related to the chemical compositions of the film. The films were characterized after electrochemical treatment and important modifications regarding surface morphology, particle and crystal sizes were observed. An in-depth study was conducted in order to investigate the effect of several different electrochemical treatments on the morphology, particle size distribution and crystal size of LDH thin films. Upon electrochemical treatment, the films' surface became smooth and the particles forming the films were transformed from flaky open LDH platelets to uniformly distributed close-packed LDH nanoparticles. - Highlights: • Semiconducting Mg(Zn)Al(Ga)–LDH/ITO thin films prepared by sol–gel. • LDH thin films show a turbostratic morphology made up of porous flakes. • Electrochemical treatments change the flaky structure into a nanoparticle array.

  4. Stable Suppression of Lactate Dehydrogenase Activity during Anoxia in the Foot Muscle of Littorina littorea and the Potential Role of Acetylation as a Novel Posttranslational Regulatory Mechanism.

    Science.gov (United States)

    Shahriari, Ali; Dawson, Neal J; Bell, Ryan A V; Storey, Kenneth B

    2013-01-01

    The intertidal marine snail, Littorina littorea, has evolved to withstand extended bouts of oxygen deprivation brought about by changing tides or other potentially harmful environmental conditions. Survival is dependent on a strong suppression of its metabolic rate and a drastic reorganization of its cellular biochemistry in order to maintain energy balance under fixed fuel reserves. Lactate dehydrogenase (LDH) is a crucial enzyme of anaerobic metabolism as it is typically responsible for the regeneration of NAD(+), which allows for the continued functioning of glycolysis in the absence of oxygen. This study compared the kinetic and structural characteristics of the D-lactate specific LDH (E.C. 1.1.1.28) from foot muscle of aerobic control versus 24 h anoxia-exposed L. littorea. Anoxic LDH displayed a near 50% decrease in V max (pyruvate-reducing direction) as compared to control LDH. These kinetic differences suggest that there may be a stable modification and regulation of LDH during anoxia, and indeed, subsequent dot-blot analyses identified anoxic LDH as being significantly less acetylated than the corresponding control enzyme. Therefore, acetylation may be the regulatory mechanism that is responsible for the suppression of LDH activity during anoxia, which could allow for the production of alternative glycolytic end products that in turn would increase the ATP yield under fixed fuel reserves.

  5. Stable Suppression of Lactate Dehydrogenase Activity during Anoxia in the Foot Muscle of Littorina littorea and the Potential Role of Acetylation as a Novel Posttranslational Regulatory Mechanism

    Directory of Open Access Journals (Sweden)

    Ali Shahriari

    2013-01-01

    Full Text Available The intertidal marine snail, Littorina littorea, has evolved to withstand extended bouts of oxygen deprivation brought about by changing tides or other potentially harmful environmental conditions. Survival is dependent on a strong suppression of its metabolic rate and a drastic reorganization of its cellular biochemistry in order to maintain energy balance under fixed fuel reserves. Lactate dehydrogenase (LDH is a crucial enzyme of anaerobic metabolism as it is typically responsible for the regeneration of NAD+, which allows for the continued functioning of glycolysis in the absence of oxygen. This study compared the kinetic and structural characteristics of the D-lactate specific LDH (E.C. 1.1.1.28 from foot muscle of aerobic control versus 24 h anoxia-exposed L. littorea. Anoxic LDH displayed a near 50% decrease in Vmax (pyruvate-reducing direction as compared to control LDH. These kinetic differences suggest that there may be a stable modification and regulation of LDH during anoxia, and indeed, subsequent dot-blot analyses identified anoxic LDH as being significantly less acetylated than the corresponding control enzyme. Therefore, acetylation may be the regulatory mechanism that is responsible for the suppression of LDH activity during anoxia, which could allow for the production of alternative glycolytic end products that in turn would increase the ATP yield under fixed fuel reserves.

  6. Studies on lipoamide dehydrogenase.

    NARCIS (Netherlands)

    Benen, J.A.E.

    1992-01-01

    At the onset of the investigations described in this thesis progress was being made on the elucidation of the crystal structure of the Azotobactervinelandii lipoamide dehydrogenase. Also the gene encoding this enzyme was cloned in our laboratory. By this, a firm basis was laid to start site directed

  7. Exfoliation and dispersion of LDH modified with N-tetrabromophthaloyl-glutamic in poly(vinyl alcohol): Morphological and thermal studies

    Indian Academy of Sciences (India)

    Shadpour Mallakpour; Mohammad Dinari; Meysam Talebi

    2015-03-01

    In this study, modified LDH (M-LDH) was synthesized by the co-precipitation reaction of Al(NO3)3.9H2O, Mg(NO3)2.6H2O and N-tetrabromophthaloyl-glutamic (Br-Gl) in short time. M-LDH nanofillers were embedded into poly(vinyl alcohol) (PVA) matrix via ultrasonic irradiation technique which provided PVA/M-LDH NCs. The morphology and structure of the prepared samples were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis (TGA), field emission scanning electron microscopy and X-ray diffraction techniques TGA of the PVA/M-LDH NCs showed that the thermal stability was improved. The enhancement of thermal properties was ascribed to the homogeneous and good dispersion of M-LDH sheets in the PVA matrix by hydrogen bonding between O–H groups of PVA and the M-LDH.

  8. Parasite-specific lactate dehydrogenase for the diagnosis of Plasmodium falciparum infection in an endemic area in west Uganda.

    Science.gov (United States)

    Jelinek, T; Kilian, A H; Henk, M; Mughusu, E B; Nothdurft, H D; Löscher, T; Knobloch, J; Van Sonnenburg, F

    1996-04-01

    The measurement of parasite lactate dehydrogenase (pLDH) has been presented as an easy and rapid method for the diagnosis of malaria in humans. In order to evaluate the sensitivity and specificity of such a test we examined blood samples from 429 Ugandan patients. While pLDH activity was significantly linked to parasitaemia, sensitivity and specificity were found to be rather low at 58.8 and 62.2% respectively. The positive and negative predictive values failed to meet necessary standards. We conclude that the methods of measurement of pLDH activity in malaria infection, although potentially useful for the fast diagnosis of malaria, need to be improved to be of true value in endemic areas.

  9. Cellulase and alcohol dehydrogenase immobilized in Langmuir and Langmuir-Blodgett films and their molecular-level effects upon contact with cellulose and ethanol.

    Science.gov (United States)

    Rodrigues, Dilmer; Camilo, Fernanda Ferraz; Caseli, Luciano

    2014-02-25

    The key challenges for producing devices based on nanostructured films with control over the molecular architecture are to preserve the catalytic activity of the immobilized biomolecules and to provide a reliable method for determining the intermolecular interactions and the accommodation of molecules at very small scales. In this work, the enzymes cellulase and alcohol dehydrogenase (ADH) were coimmobilized with dipalmitoylphosphatidylcholine (DPPC) as Langmuir-Blodgett (LB) films, and their biological activities were assayed by accommodating the structure formed in contact with cellulose. For this purpose, the polysaccharide was dissolved in an ionic liquid, 1-buthyl-3-methylimidazolium chloride (BMImCl), and dropped on the top of the hybrid cellulase-ADH-DPPC LB film. The interactions between cellulose and ethanol, which are the catalytic substrates of the enzymes as well as important elements in the production of second-generation fuels, were then investigated using polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS). Investigation of the secondary structures of the enzymes was performed using PM-IRRAS, through which the presence of ethanol and cellulose was observed to highly affect the structures of ADH and cellulase, respectively. The detection of products formed from the catalyzed reactions as well as the changes of secondary structure of the enzymes immobilization could be carried out, which opens the possibility to produce a means for producing second-generation ethanol using nanoscale arrangements.

  10. Upregulation of metallothionein and glucose-6-phosphate dehydrogenase expression in silver sea bream, Sparus sarba exposed to sublethal levels of cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Man, Angel K.Y. [Department of Biology, Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Woo, Norman Y.S. [Department of Biology, Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)], E-mail: normanwoo@cuhk.edu.hk

    2008-09-29

    In this study, the induction of metallothionein (MT) and glucose-6-phosphate dehydrogenase (G6PDH) gene expression in response to exposure to cadmium (Cd{sup 2+}) was investigated in silver sea bream (Sparus sarba) in vivo. In addition, a primary hepatocyte culture has been developed from silver sea bream liver in order to assess the changes in gene expression of MT and G6PDH in hepatocytes directly exposed to Cd{sup 2+} in vitro. The sea bream metallothionein gene was cloned and characterized for the development of real-time PCR assays for quantification of MT transcript abundance. G6PDH gene expression was quantified using a real-time PCR assay developed using sequence information from a previously cloned silver sea bream G6PDH gene. In both in vivo and in vitro experiments, MT mRNA was highly inducible following Cd{sup 2+} treatment. In addition, Cd{sup 2+} exposure caused the upregulation of G6PDH mRNA expression and this suggests the possibility of the involvement of G6PDH in the defense against Cd{sup 2+}-induced oxidative stress in cells. It is likely that the defense system of silver sea bream to Cd{sup 2+} stress includes upregulation of G6PDH in addition to metallothionein.

  11. Stable shRNA Silencing of Lactate Dehydrogenase A (LDHA) in Human MDA-MB-231 Breast Cancer Cells Fails to Alter Lactic Acid Production, Glycolytic Activity, ATP or Survival.

    Science.gov (United States)

    Mack, Nzinga; Mazzio, Elizabeth A; Bauer, David; Flores-Rozas, Hernan; Soliman, Karam F A

    2017-03-01

    In the US, African Americans have a high death rate from triple-negative breast cancer (TNBC), characterized by lack of hormone receptors (ER, PR, HER2/ERRB2) which are otherwise valuable targets of chemotherapy. There is a need to identify novel targets that negatively impact TNBC tumorigenesis. TNBCs release an abundance of lactic acid, under normoxic, hypoxic and hyperoxic conditions; this referred to as the Warburg effect. Accumulated lactic acid sustains peri-cellular acidity which propels metastatic invasion and malignant aggressive transformation. The source of lactic acid is believed to be via conversion of pyruvate by lactate dehydrogenase (LDH) in the last step of glycolysis, with most studies focusing on the LDHA isoform. In this study, LDHA was silenced using long-term MISSION® shRNA lentivirus in human breast cancer MDA-MB-231 cells. Down-regulation of LDHA transcription and protein expression was confirmed by western blot, immunocytochemistry and qPCR. A number of parameters were measured in fully viable vector controls versus knock-down (KD) clones, including levels of lactic acid produced, glucose consumed, ATP and basic metabolic rates. The data show that lentivirus V-165 generated a knock-down clone most effective in reducing both gene and protein levels to less than 1% of vector controls. Stable KD showed absolutely no changes in cell viability, lactic acid production, ATP, glucose consumption or basic metabolic rate. Given the complete absence of impact on any observed parameter by LDH-A KD and this being somewhat contrary to findings in the literature, further analysis was required to determine why. Whole-transcriptome analytic profile on MDA-MB-231 for LDH subtypes using Agilent Human Genome 4×44k microarrays, where the data show the following component breakdown. Transcripts: 30.47 % LDHA, 69.36% LDHB, 0.12% LDHC and 0.05% LDHD. These findings underscore the importance of alternative isoforms of LDH in cancer cells to produce lactic acid

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

    Science.gov (United States)

    Dave, Khyati K; Punekar, Narayan S

    2015-01-01

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

  13. A pH-responsive layered double hydroxide (LDH)-phthalocyanine nanohybrid for efficient photodynamic therapy.

    Science.gov (United States)

    Li, Xing-Shu; Ke, Mei-Rong; Huang, Wei; Ye, Chun-Hong; Huang, Jian-Dong

    2015-02-16

    A pH-responsive nanohybrid (LDH-ZnPcPS4 ), in which a highly hydrophilic zinc(II) phthalocyanine tetra-α-substituted with 4-sulfonatophenoxy groups (ZnPcPS4 ) is incorporated with a cationic layered double hydroxide (LDH) based on electrostatic interaction, has been specially designed and prepared through a facile co-precipitation approach. ZnPcPS4 is an excellent singlet-oxygen generator with strong absorption at the near-infrared region (692 nm) in cellular culture media, whereas the photoactivities of ZnPcPS4 were remarkably inhibited after incorporation with the LDH. The nanohybrid is essentially stable in aqueous media at pH 7.4; nevertheless, in slightly acidic media of pH 6.5 or 5.0, ZnPcPS4 can be efficiently released from the LDH matrix, thus leading to restoration of the photoactivities. The nanohybrid shows a high photocytotoxicity against HepG2 cells as a result of much more efficient cellular uptake and preferential accumulation in lysosomes, whereby the acidic environment leads to the release of ZnPcPS4 . The IC50 value of LDH-ZnPcPS4 is as low as 0.053 μM, which is 24-fold lower than that of ZnPcPS4 . This work provides a facile approach for the fabrication of photosensitizers with high photocytotoxicity, potential tumor selectivity, and rapid clearance character.

  14. Preparation, characterization and antimicrobial applications of Zn-Fe LDH against MRSA.

    Science.gov (United States)

    Moaty, S A Abdel; Farghali, A A; Khaled, Rehab

    2016-11-01

    Facile and simple processes to get Zn-Fe layered double hydroxide (LDH) with nitrate as the interlayer anion are reported. The method of co-precipitation produced high crystallinity LDH that is marked by XRD, SEM, TEM and FT-IR. Results showed that 99.8% of Cd(+2) removals were at pH11 and 4h. To get the adsorption isotherms, the concentration of metal ions extending from 6 to 18mg/L was utilized. Results supported the Langmuir adsorption model. In contrary, the adsorption process followed the pseudo-second-order reaction kinetics. Interestingly, the prepared LDH shows durable antimicrobial activities against Gram-negative (Proteous vulgaris, Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pyogenes and MRSA) and fungi (Candida albicans, Aspergillus fumigatus, Geotricumcandidum, and Trichophyton mentagrophytes). The minimum inhibitory concentration (MIC) of Zn-Fe LDH varied from 0.49 to 15.60μg/mL according to the types of microorganisms. The prepared LDH achieved 90% at pH8.50 which is the pH of wastewater and at the same time exhibited durable antimicrobial activities against MRSA, Gram-negative, Gram-positive and fungi. Results have significant implications in the field of bioremediation of water with little cost, simple operation, high productivity and easiness of the equipment.

  15. Expressão do Mg+2, CK, AST e LDH em equinos finalistas de provas de enduro Endurance horses finalists: expression of Mg+2, CK, AST and LDH in horse finalists of endurance race

    Directory of Open Access Journals (Sweden)

    Juliana V.F. Sales

    2013-01-01

    ção de permeabilidade das células musculares estriadas esqueléticas, sugerindo o estabelecimento de um processo inflamatório agudo. Devido à expressão da atividade enzimática da CK (p≤0,001, por sua especificidade em relação à ocorrência de danos na musculatura estriada esquelética, juntamente com o íon magnésio (p=0,0004 que participa de várias reações celulares. Houve alterações na concentração de proteína plasmática total (p=0,0009 e hematócrito (p=0,0001, entre os momentos avaliados. Portanto estes resultados servem como valores de referência de equinos finalistas de provas de enduro de 90 km, auxiliando na prevenção da ocorrência de possíveis danos musculares e processos inflamatórios severos.In recent years, due to rising competitive demands, the equine athlete is being increasingly required. Thus, the demands for high performance have fostered interest in the study of pathophysiology of various horse diseases. The relationship between magnesium and exercise has received significant attention because this ion is closely related with the skeletal muscle tissue. Moreover, among the main strategies for the detection and monitoring of clinical muscle damage, features the evaluation of the activity of the enzymes creatine kinase (CK, lactate dehydrogenase (LDH and aspartate aminotransferase (AST. The search for the establishment of parameters that relate to each other is a determining factor in understanding the physiological changes found on athletic horses in effort. Thus, this study aimed to determine how the blood concentrations of magnesium ion and the enzymatic activities of the enzymes CK, LDH and AST behave in Arabian finalist horses in endurance races of 90km and to relate possible changes to the type of physical effort played by animals. It was evaluated the enzymatic activities of the enzymes CK, LDH, AST e the concentration of the ion magnesium in exercise in relation to the rest state of 14 clinically healthy Arabian horses, 9

  16. Inactivation of Lactate Dehydrogenase from Pig Heart by o-Phthalaldehyde

    Institute of Scientific and Technical Information of China (English)

    郑延斌; 王政; 陈宝玉; 王希成

    2003-01-01

    Treatment of lactate dehydrogenase (LDH) with o-phthalaldehyde resulted in a time-dependent loss of enzyme activity.The inactivation followed pseudo first-order kinetics over a wide range of the inhibitor.The second-order rate constant for the inactivation of LDH was estimated to be 1.52 (mol/L)-1·s-1.The modified enzyme showed a characteristic fluorescence emission spectrum with a maximum at 405 nm upon excitation at 337 nm, consistent with the formation of isoindole derivatives by the cross-linking of proximal cysteine and lysine residues.The loss of enzyme activity was concomitant with the increase in absorbance at 337 nm.Stoichiometric study of the reaction showed that complete loss of activity was accompanied by formation of approximately four moles of isoindole derivatives per mole of LDH subunits.One of the substrates, NADH, partially prevented the enzyme from reacting with o-phthalaldehyde, whereas the other substrate, pyruvate, did not provide any protection.Protection experiments suggest that one of the cysteine-lysine pairs modified by o-phthalaldehyde is near the NADH binding site of LDH.

  17. Free energy landscape of the Michaelis complex of lactate dehydrogenase: A network analysis of atomistic simulations

    Science.gov (United States)

    Pan, Xiaoliang; Schwartz, Steven

    2015-03-01

    It has long been recognized that the structure of a protein is a hierarchy of conformations interconverting on multiple time scales. However, the conformational heterogeneity is rarely considered in the context of enzymatic catalysis in which the reactant is usually represented by a single conformation of the enzyme/substrate complex. Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of two forms of the cofactor nicotinamide adenine dinucleotide (NADH and NAD+). Recent experimental results suggest that multiple substates exist within the Michaelis complex of LDH, and they are catalytic competent at different reaction rates. In this study, millisecond-scale all-atom molecular dynamics simulations were performed on LDH to explore the free energy landscape of the Michaelis complex, and network analysis was used to characterize the distribution of the conformations. Our results provide a detailed view of the kinetic network the Michaelis complex and the structures of the substates at atomistic scale. It also shed some light on understanding the complete picture of the catalytic mechanism of LDH.

  18. Insights into the synthesis of layered double hydroxide (LDH) nanoparticles: Part 1. Optimization and controlled synthesis of chloride-intercalated LDH.

    Science.gov (United States)

    Sun, Xiaodi; Neuperger, Erica; Dey, Sandwip K

    2015-12-01

    Layered double hydroxide (LDH) nanoparticles have excellent anion-intercalating property, and their potential as theranostic nanovectors is high. However, understanding of the control of the mean particle size (MPS) and achievement of monodispersed particle size distribution (PSD) remains elusive. Herein, with the aid of statistical design of experiments on a model system of Cl(-)-intercalated (Zn, Al)-LDH, controlled synthesis of single crystalline nanoparticles using the coprecipitation method followed by hydrothermal treatment (HT) was achieved in three steps. First, a 2(4-1) design enabled the identification of influential parameters for MPS (i.e., salt concentration, molar ratio of carbonate to aluminum, solution addition rate, and interaction between salt concentration and stirring rate) and PSD (i.e., salt concentration and stirring rate), as well as the optimum coprecipitation conditions that result in a monodispersed PSD (i.e., low salt concentration and high stirring rate). Second, a preliminary explanation of the HT was suggested and the optimum HT conditions for obtaining ideal Gaussian PSD with chi-squared (χ(2))<3 were found to be 85°C for 5 h. Third, using a central composite design, a quantitative MPS model, expressed in terms of the significant factors, was developed and experimentally verified to synthesize nearly monodispersed LDH nanoparticles with MPS ∼200-500 nm.

  19. New way for iron introduction in LDH matrix used as catalysts for Friedel–Crafts reactions

    Directory of Open Access Journals (Sweden)

    S. Kerchiche

    2017-02-01

    Full Text Available The alkylation of toluene, reaction employing benzyl chloride as the alkylating agent over basic hydrotalcite materials: Fe–Mg–Al-LDH prepared by different synthesis methods, including the method of co-precipitation, impregnation and a new method called the method of intercalation by anion exchange in the lamellar space of the host structure LDH. Our prepared solids were characterized by chemical analysis, XRD analysis, BET method and thermogravimetric analysis (TGA and tested in the alkylation of toluene by benzyl chloride reaction. Fe–Mg–Al-LDH clay without or with calcination (at 773 K has been investigated. The catalyst derived from the hydrotalcite by its calcination at 773 K shows high catalytic activity for the alkylation of toluene and other aromatic compounds. The catalytically active species present in the catalyst in its most active form are the oxides of iron on the catalyst surface.

  20. Design of experiments reveals critical parameters for pilot-scale freeze-and-thaw processing of L-lactic dehydrogenase.

    Science.gov (United States)

    Roessl, Ulrich; Humi, Sebastian; Leitgeb, Stefan; Nidetzky, Bernd

    2015-09-01

    Freezing constitutes an important unit operation of biotechnological protein production. Effects of freeze-and-thaw (F/T) process parameters on stability and other quality attributes of the protein product are usually not well understood. Here a design of experiments (DoE) approach was used to characterize the F/T behavior of L-lactic dehydrogenase (LDH) in a 700-mL pilot-scale freeze container equipped with internal temperature and pH probes. In 24-hour experiments, target temperature between -10 and -38°C most strongly affected LDH stability whereby enzyme activity was retained best at the highest temperature of -10°C. Cooling profile and liquid fill volume also had significant effects on LDH stability and affected the protein aggregation significantly. Parameters of the thawing phase had a comparably small effect on LDH stability. Experiments in which the standard sodium phosphate buffer was exchanged by Tris-HCl and the non-ionic surfactant Tween 80 was added to the protein solution showed that pH shift during freezing and protein surface exposure were the main factors responsible for LDH instability at the lower freeze temperatures. Collectively, evidence is presented that supports the use of DoE-based systematic analysis at pilot scale in the identification of F/T process parameters critical for protein stability and in the development of suitable process control strategies.

  1. Assessment of lactate dehydrogenase, alkaline phosphatase and aspartate aminotransferase activities in cow's milk as an indicator of subclinical mastitis.

    Science.gov (United States)

    Babaei, H; Mansouri-Najand, L; Molaei, M M; Kheradmand, A; Sharifan, M

    2007-05-01

    This study examined the activities of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) in the milk of lactating Holstein cows in association with subclinical mastitis (SCM). A total of 94 milk samples were collected from 58 lactating dairy cows representing stages of lactation from the second to the tenth week after calving. Those which were classified as positive by California mastitis test (CMT) were deemed to have subclinical mastitis. All the milk samples were skimmed by centrifugation at 10 000g at 0 degrees C and were used for enzyme activities estimations. The mean activities of LDH and ALP were higher in the milk from udders with SCM than in the milk from healthy udders (p CMT results and LDH and ALP values were seen at thresholds of > 180 IU/L and > 40 IU/L respectively (kappa values 0.65 and 0.79, respectively). However, the sensitivity of the tests for identifying SCM at these thresholds was higher for ALP (96.4%) than for LDH (68.5%). In this study, LDH and ALP tests were standardized for cow's milk and results showed that only the ALP test was reliable in the early diagnosis of subclinical mastitis.

  2. Aniosotropically organized LDH on PVDF: a geometrically templated electrospun substrate for advanced anion conducting membranes.

    Science.gov (United States)

    Sailaja, G S; Zhang, Peilin; Anilkumar, Gopinathan M; Yamaguchi, Takeo

    2015-04-01

    A bioinspired geometric templating of an electrospun PVDF substrate with hexagonal platelets of Mg-Al layered double hydroxide (LDH), an intrinsic anion conductor, is presented. The distinctive morphology restructures the internal pore geometry and modulates the dynamic wetting profile of PVDF, transforming it into a highly functional substrate for SAFC anion conducting membranes. The membrane fabricated with PVDF-LDH substrate exhibited exceptionally high durability (>140 °C), high anionic conductivity, ion exchange capacity (IEC), restricted swelling, and improved tensile strength, overcoming critical challenges associated with PVDF electrospun substrates and validating its immense potential as a high-temperature-stable and durable substrate for advanced fuel cell membrane applications.

  3. Detection of serum lactic dehydrogenase of infants with bronchiolitis and its clinical significance.%毛细支气管炎患儿血清乳酸脱氢酶水平的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    代东伶; 王缨; 何柳芳; 刘晓红

    2012-01-01

    Objective To investigate the level of serum lactic dehydrogenase( LDH )of infants with bronchiolitis and its clinical significance. Methods According to the clinical manifestation, 131 infant cases with bronchiolitis were divided into two groups, severe case group ( group S ) and mild case group ( group M ). Serum lactic dehydrogenase was detected by automatic biochemistry analyzer and compared between bronchiolitis cases and control subjects. Results Compared with control group, the infants with bronchiolitis had higher LDH level ( P <0.05 ). On admission, LDH was 316. 3 ±84.6 IU/L in group M and 567. 8 ±101.5 IU/L in group S( P <0.05 ),and it was 188.6 ±59.5 IU/L and 195. 4 ±63.3 IU/L respectively after one week treatment ( P <0.05 ). Moreover, all cases in group M had remission,but 7 cases in group S did not have remission or even aggravated and accompanied by further elevated LDH. Conclusion The changes of LDH level in infants with bronchiolitis may indicate the severity of clinical symptoms, and it makes a significant contribution to evaluate the prognosis of bronchiolitis.%目的 探讨毛细支气管炎患儿血清乳酸脱氢酶(LDH)水平及其临床意义.方法 将131例毛细支气管炎患儿按临床症状分为重症组和轻症组两组,并与正常对照组进行比较.结果 与正常对照组比较,毛细支气管炎患儿LDH显著升高(P<0.05);入院时,轻症组与重症组LDH分别为316.3±84.6 IU/L、567.8±101.5 IU/L(P<0.05),经过1周治疗后轻症组与重症组LDH分别为188.6±59.5 IU/L、195.4±63.3 IU/L(P<0.05);而且治疗1周后轻症组临床症状均缓解,而重症组有7例患儿临床症状无缓解甚至加重,LDH水平进一步升高.结论 毛细支气管炎患儿血清LDH的改变可以提示临床症状轻重,对预后判断也具有临床意义.

  4. Ageing behaviour of unary hydroxides in trivalent metal salt solutions: Formation of layered double hydroxide (LDH)-like phases

    Indian Academy of Sciences (India)

    Michael Rajamathi; P Vishnu Kamath

    2000-10-01

    The hydroxides of Mg, Ni, Cu and Zn transform into layered double hydroxide (LDH)-like phases on ageing in solutions of Al or Cr salts. This reaction is similar to acid leaching and proceeds by a dissolution–reprecipitation mechanism offering a simple method of LDH synthesis, with implications for the accepted theories of formation of LDH minerals in the earth’s crust.

  5. Creatine kinase and lactate dehydrogenase responses after upper-body resistance exercise with different rest intervals.

    Science.gov (United States)

    Rodrigues, Bernardo M; Dantas, Estélio; de Salles, Belmiro Freitas; Miranda, Humberto; Koch, Alexander J; Willardson, Jeffrey M; Simão, Roberto

    2010-06-01

    The purpose of the current study was to compare serum creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations at multiple time points after resistance exercise sessions that incorporated different rest intervals between sets and exercises. Twenty untrained men (18.65+/-0.49 years, 68.30+/-7.98 kg, and 174.4+/-4.80 cm) performed 2 resistance exercise sessions (i.e., 3 sets with 80% 1 repetition maximum for 5 upper-body exercises) with either 1-minute (SEQ1) or 3-minute (SEQ3) rest between sets and exercises. For each session, CK and LDH concentrations were measured before exercise (PRE) and 24, 48, and 72 hours after exercise (24P, 48P, and 72P). Subjects lifted a 24% greater (presistance exercise may invoke greater muscle damage.

  6. ATIVIDADE DA LACTATO DESIDROGENASE (LDH SÉRICA EM CÃES SUBMETIDOS À OXIGENAÇÃO EXTRACORPÓREA POR MEMBRANA (ECMO POR UM PERÍODO DE TRÊS HORAS

    Directory of Open Access Journals (Sweden)

    FELIPP SILVEIRA FERREIRA

    2011-09-01

    Full Text Available The extracorporeal membrane oxygenation (ECMO is a prolonged cardiopulmonary support technique, which aims to help the lungs and the heart when they do not respond to conventional non-invasive treatments. This research was carried out to determine the behavior oflactate dehydrogenase (LDH of five mongrel dogs undergoing ECMO for three hours. Under controlled ventilation, positive end-expiratory pressure (PEEP at 10mmHg and FiO2 at 21%, the animals were submitted to femoral cannulation for ECMO (artery and vein, by the arterial-venous (AV deviation. The LDH was measured and evaluated every thirty minutes for an uninterrupted period of three hours. The results were tabulated and statistically analyzed with ANOVA and Tukey tests, with p<0.05. The results showed an increase of serum LDH,featuring a muscle injury during the procedure due to a physiological response, similar to that caused by a hypovolemic shock. We concluded that ECMO is a viable technique for prolonged ventilatory support, but it needs some adjustments for clinical use in dogs.

  7. Evolução molecular adaptativa dos genes da família LDH em teleósteos

    OpenAIRE

    Castro, Nayara Sousa

    2015-01-01

    A L-Lactato Desidrogenase (LDH) é uma enzima chave nos processos do metabolismo glicolítico anaeróbico e possui três genes codificadores em peixes (ldh-a, ldh-b e ldh-c). A regulação desses genes é independente, resultando em especificidade tecidual nos vertebrados. Esses genes foram originados por eventos sucessivos de duplicação do genoma e sua evolução mostra-se intimamente relacionada com o desenvolvimento de mecanismos adaptativos térmicos e de condições fisiológicas distintas, as quais ...

  8. L-lactate dehydrogenase and N-acetyl-beta-D-glucosaminidase activities in bovine milk as indicators of non-specific mastitis.

    Science.gov (United States)

    Chagunda, Mizeck Gg; Larsen, Torben; Bjerring, Martin; Ingvartsen, Klaus L

    2006-11-01

    Systematic factors affecting the activities of L-lactate dehydrogenase (LDH) and N-acetyl-beta-D-glucosaminidase (NAGase) and somatic cell count (SCC), the association between the activities of LDH and NAGase and SCC with respect to udder health status, and the ability of LDH and NAGase to classify cows in udder health categories for early detection of mastitis were studied. A dataset of records from 74 Danish Holstein, 76 Danish Red and 47 Jersey cows on one research farm was used. Cows were grouped into healthy and clinically mastitic. A healthy cow was defined as having no veterinary treatment and SCCmastitis and SCC >800,000 cells/ml. Breed, month of production, and days in milk significantly influenced (Pmastitis. NAGase activity had numerically higher variation in healthy cows than in clinically mastitic cows (CV=56.2% v. CV=53.5%). The relationship between LDH activity and SCC was stronger in milk from clinically mastitic than from healthy cows (r=0.76 v. r=0.48 and r=0.67 v. r=0.44 for correlation of observed values and residuals, respectively). LDH activity had higher sensitivity than NAGase activity (73-95% v. 35-77%) while specificities were in a similar range (92-99%). Further, sensitivities for LDH activity were more robust to changes in the threshold value than those for NAGase activity. Opportunities for automated, in-line real-time mastitis detection are discussed.

  9. LDH-C can be differentially expressed during fermentation of CHO cells

    Directory of Open Access Journals (Sweden)

    Szperalski Berthold

    2011-11-01

    Full Text Available Abstract Expression of CHO mRNA was measured with special microarrays from the Consortium for Chinese Hamster Ovary (CHO Cell Genomics led by Prof. Wei-Shou Hu of the University of Minnesota and Prof. Miranda Yap of the Bioprocess Technology Institute of A*STAR, Singapore (http://hugroup.cems.umn.edu/CHO/cho_index.html. Cultivation experiments were performed in small scale 2L stirred tank bioreactors. During fermentation a temperature shift of -3°C was performed. This was accompanied by a reduction of the cell specific lactate production rate. The analysis of transcriptome samples before and after the temperature shift with microarrays showed several changes in the expression of available gene markers. LDH-C expression raised about 2 fold after temperature shift. LDH-A did not change. As LDH-C is known to be a specialized isoenzyme in sperm cells for consuming lactate in a lactate containing milieu, LDH-C could be proposed as a target for genetic engineering, facilitating lactate consumption in the late phase of high cell density cultures and prolonging longevity of CHO production cultures by reducing lactate and base accumulation.

  10. MMT and LDH organo-modification with surfactants tailored for PLA nanocomposites

    Directory of Open Access Journals (Sweden)

    S. Coiai

    2017-03-01

    Full Text Available Low molecular weight polyesters were end-functionalized with ammonium and carboxylate salts and used in ionic exchange reactions with respectively cationic (MMT and anionic (LDH clays. The hybrid organic-inorganic substrates were structurally analysed to determine the ester oligomers’ modification degree and their thermal behaviour owing to confinement effects. The dispersion of such hybrids in polylactic acid (PLA matrix was performed and the ultimate structural, morphological and thermal properties of the collected nanocomposites were investigated and correlated to the tailored interfacial properties with the different inorganic substrates. While the composites with MMT proved to be stable under thermo-oxidative conditions, the samples obtained by dispersing the LDH hybrid suffered from poor final thermostability owing to molecular weights decrease. Deeper insights about the effect of the interactions at interface (polymer chain-surfactant and polymer chain- inorganic surface evidenced that by promoting an intimate contact between PLA chains and LDH surface (through oligoester used as inorganic substrate modifier a certain extent of PLA hydrolysis triggered by both surfactant and inorganic surface (LDH occurred and cannot completely avoided.

  11. L-lactic acid production from D-xylose with Candida sonorensis expressing a heterologous lactate dehydrogenase encoding gene.

    Science.gov (United States)

    Koivuranta, Kari T; Ilmén, Marja; Wiebe, Marilyn G; Ruohonen, Laura; Suominen, Pirkko; Penttilä, Merja

    2014-08-08

    Bioplastics, like polylactic acid (PLA), are renewable alternatives for petroleum-based plastics. Lactic acid, the monomer of PLA, has traditionally been produced biotechnologically with bacteria. With genetic engineering, yeast have the potential to replace bacteria in biotechnological lactic acid production, with the benefits of being acid tolerant and having simple nutritional requirements. Lactate dehydrogenase genes have been introduced to various yeast to demonstrate this potential. Importantly, an industrial lactic acid producing process utilising yeast has already been implemented. Utilisation of D-xylose in addition to D-glucose in production of biochemicals such as lactic acid by microbial fermentation would be beneficial, as it would allow lignocellulosic raw materials to be utilised in the production processes. The yeast Candida sonorensis, which naturally metabolises D-xylose, was genetically modified to produce L-lactic acid from D-xylose by integrating the gene encoding L-lactic acid dehydrogenase (ldhL) from Lactobacillus helveticus into its genome. In microaerobic, CaCO3-buffered conditions a C. sonorensis ldhL transformant having two copies of the ldhL gene produced 31 g l-1 lactic acid from 50 g l-1 D-xylose free of ethanol.Anaerobic production of lactic acid from D-xylose was assessed after introducing an alternative pathway of D-xylose metabolism, i.e. by adding a xylose isomerase encoded by XYLA from Piromyces sp. alone or together with the xylulokinase encoding gene XKS1 from Saccharomyces cerevisiae. Strains were further modified by deletion of the endogenous xylose reductase encoding gene, alone or together with the xylitol dehydrogenase encoding gene. Strains of C. sonorensis expressing xylose isomerase produced L-lactic acid from D-xylose in anaerobic conditions. The highest anaerobic L-lactic acid production (8.5 g l-1) was observed in strains in which both the xylose reductase and xylitol dehydrogenase encoding genes had been

  12. Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity.

    Science.gov (United States)

    Mehta, Reena; Scheffler, Margaret; Tapia, Lorena; Aideyan, Letisha; Patel, Kirtida D; Jewell, Alan M; Avadhanula, Vasanthi; Mei, Minghua; Garofalo, Roberto P; Piedra, Pedro A

    2014-11-01

    Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  13. Automated High Throughput Protein Crystallization Screening at Nanoliter Scale and Protein Structural Study on Lactate Dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fenglei [Iowa State Univ., Ames, IA (United States)

    2006-08-09

    , evaporation rate can be controlled or adjusted in this method during the crystallization process to favor either nucleation or growing processes for optimizing crystallization process. The protein crystals gotten by this method were experimentally proven to possess high x-ray diffraction qualities. Finally, we crystallized human lactate dehydrogenase 1 (H4) complexed with NADH and determined its structure by x-ray crystallography. The structure of LDH/NADH displays a significantly different structural feature, compared with LDH/NADH/inhibitor ternary complex structure, that subunits in LDH/NADH complex show open conformation or two conformations on the active site while the subunits in LDH/NADH/inhibitor are all in close conformation. Multiple LDH/NADH crystals were obtained and used for x-ray diffraction experiments. Difference in subunit conformation was observed among the structures independently solved from multiple individual LDH/NADH crystals. Structural differences observed among crystals suggest the existence of multiple conformers in solution.

  14. Genetics Home Reference: lactate dehydrogenase deficiency

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions lactate dehydrogenase deficiency lactate dehydrogenase deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Lactate dehydrogenase deficiency is a condition that affects how the ...

  15. 15 Hypoxyprostaglandin dehydrogenase. A review

    DEFF Research Database (Denmark)

    Hansen, Harald S.

    1976-01-01

    A review is given on the enzyme 15 hydroxyprostaglandin dehydrogenase. The determination, activity, distribution, purification, properties and physiological aspects are discussed. 128 references.......A review is given on the enzyme 15 hydroxyprostaglandin dehydrogenase. The determination, activity, distribution, purification, properties and physiological aspects are discussed. 128 references....

  16. Correlation of urinary lactic dehydrogenase with polymorphonuclear leukocytes in urinary tract infections in patients with spinal cord injuries.

    Science.gov (United States)

    Malik, G M; Canawati, H N; Keyser, A J; Ibrahim, M Z; Montgomerie, J Z

    1983-01-01

    A number of indirect methods have been developed to determine the site of urinary tract infection, including the measurement of LDH in urine [1]. Although LDH has been thought to be from the kidneys, it has also been noted that leukocytes could contribute LDH isoenzymes 4 and 5 [2]. Seventeen patients with injured spinal cords and significant bacteriuria were included in this study. Urine specimens obtained by urethral catheter were cultured, and PMNLs identified with Sternheimer-Malbin stain were counted in a hemacytometer. A positive test for antibody-coated bacteria and the lack of patient response to five to 10 days of antibiotic therapy were used as an indication of upper urinary tract infection. Levels of LDH isoenzymes 4 and 5 (cathodal) correlated with the number of PMNLs in the urine (r = 0.63, P less than 0.01). There was no correlation of PMNLs with LDH isoenzymes 1 and 2 (r = 0.18). In addition, there was no correlation of LDH isoenzymes 4 and 5 with the level of urinary tract infection. These results suggest that the PMNLs in the urine are the source of the LDH isoenzymes 4 and 5.

  17. A Review on Molecular Physiology of Malate and Lactate Dehydrogenases in Fishes

    Institute of Scientific and Technical Information of China (English)

    G.TRIPATHI

    1993-01-01

    The malate(EC1.1.1.37)and lactate(EC1.1.1.27)dehydrogenases are the metaboliic enzymes directly or indirectly involved in energy production,gluconeogenesis and lipogenesis.Malate dehydrogenase(MDH)exists in two isoenzymic forms,cytoplasmic(cMDH)and mitochondrial(mMDH),composed of A and /or B subunits(dimeric molecule:MW 40,000-120,000).Lactate dehydrogenase(LDH)has tetrameric(W 35,000-110,000)structure made up of either A and/or B,or C(,C,E,F)subunits,They catalyze an ordered bisubstrate(substrate and coenzyme) reaction in cytosol(cMDH and LDH)and mitochondrion(mMDH)for specific purposes.The cMDH,mMDHand LDH generally exhibit the maxium velocity(Vmax)of 50-500,0.5-15,and 80-400 units/g wet wt.respectively at an optimum pH(6.5-8.0)and temperature(20-30℃).The several folds higher activity of cMDH as compared to mMDH is to carry out three different(energy production,gluconeogenesis,lipogenesis)metabolic functions rather catalysin only Krebs cycle as mMDH does.Kinetic constant(Km)of cMDH,mMDH and LDH for substrate and coenzyme varies within the rage of 0.06-0.30,0.04-0.20,and 0.04-0.50 mmol·L-1 respectively reflecting their affinities for the substrates.Activiities of these enzymes are inhibited by substrates and coenzymes both.A number of environmental and physiological signals considerably influence the enzyme activities.The extreme pH of the medium decreases the activities of cMDH,mMDH and LDH.Seasonal changes in environmental factors(temperature,photoperiod,rainfall,food availability etc.)alter enzyme activities and may affect the expression of subunits.Thermal acclimation exerts tissue and species-spectific changes in Km,activity and subunit expression of cMDH,mMDH and LDH.Activities of these enzymes substantially deline duuring starvation periods.Enzyme scaling shows a decrease in cMDH and an increase in mMDH and LDH activities as a function of increasing body-size.Metabolic hormones may either decrease or increase the activities of enzymes or they do not

  18. A prospective study to assess role of serum lactate dehydrogenase in prediction of adverse outcomes of pre-eclampsia and eclampsia

    Directory of Open Access Journals (Sweden)

    Jyoti Jharia

    2016-08-01

    Results: Higher grades of proteinuria, higher BP and serum LDH levels >600 IU/L are significantly associated with adverse maternal and fetal outcome. Conclusions: LDH co-relates with adversity of maternal and fetal outcome in eclampsia and pre-eclampsia. [Int J Reprod Contracept Obstet Gynecol 2016; 5(8.000: 2522-2529

  19. White shrimp Litopenaeus vannamei recombinant lactate dehydrogenase: Biochemical and kinetic characterization.

    Science.gov (United States)

    Fregoso-Peñuñuri, Ambar A; Valenzuela-Soto, Elisa M; Figueroa-Soto, Ciria G; Peregrino-Uriarte, Alma B; Ochoa-Valdez, Manuel; Leyva-Carrillo, Lilia; Yepiz-Plascencia, Gloria

    2017-09-01

    Shrimp lactate dehydrogenase (LDH) is induced in response to environmental hypoxia. Two protein subunits deduced from different transcripts of the LDH gene from the shrimp Litopenaeus vannamei (LDHvan-1 and LDHvan-2) were identified. These subunits are expressed by alternative splicing. Since both subunits are expressed in most tissues, the purification of the enzyme from the shrimp will likely produce hetero LDH containing both subunits. Therefore, the aim of this study was to overexpress, purify and characterize only one subunit as a recombinant protein, the LDHvan-2. For this, the cDNA from muscle was cloned and overexpressed in E. coli as a fusion protein containing an intein and a chitin binding protein domain (CBD). The recombinant protein was purified by chitin affinity chromatography column that retained the CBD and released solely the full and active LDH. The active protein appears to be a tetramer with molecular mass of approximately 140 kDa and can use pyruvate or lactate as substrates, but has higher specific activity with pyruvate. The enzyme is stable between pH 7.0 to 8.5, and between 20 and 50 °C with an optimal temperature of 50 °C. Two pKa of 9.3 and 6.6, and activation energy of 44.8 kJ/mol°K were found. The kinetic constants Km for NADH was 23.4 ± 1.8 μM, and for pyruvate was 203 ± 25 μM, while Vmax was 7.45 μmol/min/mg protein. The shrimp LDH that is mainly expressed in shrimp muscle preferentially converts pyruvate to lactate and is an important enzyme for the response to hypoxia. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Validity of pleural lactate dehydrogenase measurements in assessment of pleural effusions

    Directory of Open Access Journals (Sweden)

    Elisna Syahruddin

    2012-08-01

    Full Text Available Background Pleural effusions are classified into transudates and exudates based on Light’s criteria, but the main disadvantage of Light’s criteria is the misclassification of transudates as exudates in about 20% of cases. The aim of this study was to determine the validity of various biochemical parameters to differentiate pleural exudates and transudates. Methods An observational study to evaluate diagnostics tests was conducted at the emergency department of Persahabatan Hospital, Jakarta, from September 2010 until December 2011. In total, 119 patients with pleural effusion were evaluated. Simultaneous pleural effusion and blood samples were examined for lactate dehydrogenase (LDH, total protein, cholesterol and albumin, with the clinical diagnosis as the gold standard. Results There were 104 exudative and 15 transudative pleural effusions. Light’s criteria achieved a higher overall accuracy (sensitivity 97%, specificity 80%, accuracy 95%. The optimum cut off values were pleural fluid to serum ratio of LDH 0.4 (sensitivity 95%, specificity 87%, accuracy 94% and pleural fluid LDH of 178 IU/L (sensitivity 92%, specificity 87%, accuracy 92%. Pleural fluid cholesterol was 50 mg/dL (sensitivity 89%, specificity 53%, accuracy 85%, pleural fluid to serum cholesterol ratio 0.41 (sensitivity 75%, specificity 53%, accuracy 72% and serum-effusion albumin gradient 1.3 g/dL (sensitivity 91%, specificity 73%, accuracy 89%. Combination of biochemical tests did not improve sensitivity or accuracy. Conclusions Light’s criteria remain superior to other biochemical tests, but the new cut off values of LDH pleural fluid to serum ratio of 0.4 and pleural fluid LDH of 178 IU/L appears to yield a slight improvement in diagnostic accuracy.

  1. Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Mohammad S Alzahri

    2015-01-01

    Full Text Available Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.

  2. Higher thermostability of l-lactate dehydrogenases is a key factor in decreasing the optical purity of d-lactic acid produced from Lactobacillus coryniformis.

    Science.gov (United States)

    Gu, Sol-A; Jun, Chanha; Joo, Jeong Chan; Kim, Seil; Lee, Seung Hwan; Kim, Yong Hwan

    2014-05-10

    Lactobacillus coryniformis is known to produce d-lactic acid as a dominant fermentation product at a cultivation temperature of approximately 30°C. However, the considerable production of l-lactic acid is observed when the fermentation temperature is greater than 40°C. Because optically pure lactates are synthesized from pyruvate by the catalysis of chiral-specific d- or l-lactate dehydrogenase, the higher thermostability of l-LDHs is assumed to be one of the key factors decreasing the optical purity of d-lactic acid produced from L. coryniformis at high temperature. To verify this hypothesis, two types of d-ldh genes and six types of l-ldh genes based on the genomic information of L. coryniformis were synthesized and expressed in Escherichia coli. Among the LDHs tested, five LDHs showed activity and were used to construct polyclonal antibodies. d-LDH1, l-LDH2, and l-LDH3 were found to be expressed in L. coryniformis by Western blotting analysis. The half-life values (t1/2) of the LDHs at 40°C were estimated to be 10.50, 41.76, and 2311min, and the T50(10) values were 39.50, 39.90, and 58.60°C, respectively. In addition, the Tm values were 36.0, 41.0, and 62.4°C, respectively, which indicates that l-LDH has greater thermostability than d-LDH. The higher thermostability of l-LDHs compared with that of d-LDH1 may be a major reason why the enantiopurity of d-lactic acid is decreased at high fermentation temperatures. The key enzymes characterized will suggest a direction for the design of genetically modified lactic acid bacteria to produce optically pure d-lactic acid. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Production of optically pure L-phenyllactic acid by using engineered Escherichia coli coexpressing L-lactate dehydrogenase and formate dehydrogenase.

    Science.gov (United States)

    Zheng, Zhaojuan; Zhao, Mingyue; Zang, Ying; Zhou, Ying; Ouyang, Jia

    2015-08-10

    L-Phenyllactic acid (L-PLA) is a novel antiseptic agent with broad and effective antimicrobial activity. In addition, L-PLA has been used for synthesis of poly(phenyllactic acid)s, which exhibits better mechanical properties than poly(lactic acid)s. However, the concentration and optical purity of L-PLA produced by native microbes was rather low. An NAD-dependent L-lactate dehydrogenase (L-nLDH) from Bacillus coagulans NL01 was confirmed to have a good ability to produce L-PLA from phenylpyruvic acid (PPA). In the present study, l-nLDH gene and formate dehydrogenase gene were heterologously coexpressed in Escherichia coli. Through two coupled reactions, 79.6mM l-PLA was produced from 82.8mM PPA in 40min and the enantiomeric excess value of L-PLA was high (>99%). Therefore, this process suggested a promising alternative for the production of chiral l-PLA. Copyright © 2015. Published by Elsevier B.V.

  4. Level of PAX5 in differential diagnosis of non-Hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Brij Bharti

    2016-01-01

    Full Text Available Background & objectives: The PAX5, a paired box transcription factor and B-cell activator protein (BSAP, activates B-cell commitment genes and represses non-B-cell lineage genes. About 14 transcript variants of PAX5 have been observed in human. Any alteration in its expression pattern leads to lymphogenesis or associated diseases and carcinogenesis in non-lymphoid tissues. Its mechanisms of function in pathophysiology of non-Hodgkin′s lymphoma (NHL are unclear. This study was intended to explore influence of PAX5 in cascade of NHL pathogenesis and diagnosis. Methods: Samples of 65 patients were evaluated by immunohistochemical staining for cellular localization of PAX5, CD19, CD3, cABL, p53, Ras and Raf and by TUNEL assay, RNA-isolation and reverse transcriptase (RT-PCR, w0 estern blot analysis, and lactate dehydrogenase (LDH specific staining. Results: B-cell type NHL patients were positive for PAX5, p53, Ras, CD19, Raf and CD3. All of them showed TUNEL-positive cells. The differential expression pattern of PAX5, CD19, p53, CD3, Zap700 , HIF 1α, Ras, Raf and MAPK (mitogen-activated protein kinase at the levels of transcripts and proteins was observed. The LDH assay showed modulation of LDH4 and LDH5 isoforms in the lymph nodes of NHL patients. Interpretation & conclusions: The histological observations suggested that the patients represent diverse cases of NHL like mature B-cell type, mature T-cell type and high grade diffuse B-cell type NHL. The findings indicate that patients with NHL may also be analyzed for status of PAX5, CD19 and ZAP70, and their transcriptional and post-translational variants for the differential diagnosis of NHL and therapy.

  5. Expression of lactate dehydrogenase C correlates with poor prognosis in renal cell carcinoma.

    Science.gov (United States)

    Hua, Yibo; Liang, Chao; Zhu, Jundong; Miao, Chenkui; Yu, Yajie; Xu, Aimin; Zhang, Jianzhong; Li, Pu; Li, Shuang; Bao, Meiling; Yang, Jie; Qin, Chao; Wang, Zengjun

    2017-03-01

    Lactate dehydrogenase C is an isoenzyme of lactate dehydrogenase and a member of the cancer-testis antigens family. In this study, we aimed to investigate the expression and functional role of lactate dehydrogenase C and its basic mechanisms in renal cell carcinoma. First, a total of 133 cases of renal cell carcinoma samples were analysed in a tissue microarray, and Kaplan-Meier survival curve analyses were performed to investigate the correlation between lactate dehydrogenase C expression and renal cell carcinoma progression. Lactate dehydrogenase C protein levels and messenger RNA levels were significantly upregulated in renal cell carcinoma tissues, and the patients with positive lactate dehydrogenase C expression had a shorter progression-free survival, indicating the oncogenic role of lactate dehydrogenase C in renal cell carcinoma. In addition, further cytological experiments demonstrated that lactate dehydrogenase C could prompt renal cell carcinoma cells to produce lactate, and increase metastatic and invasive potential of renal cell carcinoma cells. Furthermore, lactate dehydrogenase C could induce the epithelial-mesenchymal transition process and matrix metalloproteinase-9 expression. In summary, these findings showed lactate dehydrogenase C was associated with poor prognosis in renal cell carcinoma and played a pivotal role in the migration and invasion of renal cell carcinoma cells. Lactate dehydrogenase C may act as a novel biomarker for renal cell carcinoma progression and a potential therapeutic target for the treatment of renal cell carcinoma.

  6. Comparative analysis of glucose-6-phosphate dehydrogenase levels in pre-term and term babies delivered at University of Ilorin Teaching Hospital, Nigeria

    Directory of Open Access Journals (Sweden)

    Temitope Olorunsola Obasa

    2012-03-01

    Full Text Available Glucose-6-phosphate (G6P is an enzyme in the hexose monophosphate shunt required for the production of reducing equivalents needed to mop up free radicals. thereby keeping hemoglobin in its free state. Deficiency of the enzyme can cause severe neonatal jaundice. The aim of this study was to compare G6PD levels in pre-term and term babies, and evaluate the extent to which G6PD deficiency determines the severity of jaundice in various gestational age groups. Samples of cord blood collected from consecutively delivered babies in the University of Ilorin Teaching Hospital, Nigeria, were assayed for G6PD levels, and the babies were observed for jaundice during the first week of life. Those who developed jaundice had serial serum bilirubin measured. Nine hundred and thirty-three babies had G6PD assayed, with 348 being G6PD deficient, giving a hospital based prevalence of 37.3%. Of the 644 who were followed up, 143 (22.2% were pre-term and 501(77.8% were term babies. Babies with gestational age (GA 27-29 weeks had the highest G6PD levels. However, there was no significant variation among the different gestational age groups (F=0.64, P=0.64. Jaundice occurred more in pre-term compared to term babies with a relative risk of 2.41 (χ2=60.95, P=0.00001. Occurrence of jaundice in pre-term babies was irrespective of G6PD status (χ2=0.2, P=0.66, RR=1.09, CI=0.83

  7. Identification and bioinformatics analysis of lactate dehydrogenase genes fromEchinococcus granulosus

    Institute of Scientific and Technical Information of China (English)

    Gang Lu; Yajun Lu; Lihua Li; Lixian Wu; Zhigang Fan; Dazhong Shi; Hu Wang; Xiumin Han

    2010-01-01

    Objective:To identify full length cDNA sequence of lactate dehydrogenase(LDH) from adultEchinococcus granulosus (E. granulosus) and to predict the structure and function of its encoding protein using bioinformatics methods.Methods: With the help ofNCBI, EMBI, Expasy and other online sites, the open reading frame (ORF), conserved domain, physical and chemical parameters, signal peptide, epitope, topological structures of the protein sequences were predicted and a homology tertiary structure model was created; VectorNTI software was used for sequence alignment, phylogenetic tree construction and tertiary structure prediction. Results: The target sequence was1 233 bp length with a996 bp biggestORFencoding331 amino acids protein with typicalL-LDH conserved domain. It was confirmed as full length cDNA of LDH fromE. granulosus and named asEgLDH (GenBank accession number:HM748917). The predicted molecular weight and isoelectric point of the deduced protein were3 5516.2Da and6.32 respectively. Compared withLDHs fromTaenia solium, Taenia saginata asiatica, Spirometra erinaceieuropaei, Schistosoma japonicum, Clonorchis sinensis and human, it showed similarity of 86%, 85%, 55%, 58%, 58% and 53%, respectively. EgLDH contained3putative transmembrane regions and4 major epitopes (54aa-59aa,81aa-87aa,97aa-102aa,307aa-313aa), the latter were significant different from the corresponding regions of humanLDH. In addition, someNAD and substrate binding sites located on epitopes54aa-59aa and97aa-102aa, respectively. Tertiary structure prediction showed that3 key catalytic residues105R, 165D and192H forming a catalytic center near the epitope97aa-102aa, mostNAD and substrate binding sites located around the center.Conclusions: The full length cDNA sequences of EgLDH were identified. It encoded a putative transmembrane protein which might be an ideal target molecule for vaccine and drugs.

  8. ZnCr layered double hydroxide (LDH) nanosheets assisted formation of hierarchical flower-like CdZnS@LDH microstructures with improved visible-light-driven H2 production.

    Science.gov (United States)

    Yao, Lihua; Wei, Ding; Yan, Dongpeng; Hu, Changwen

    2015-03-01

    The development of new semiconductor photocatalysts toward splitting water has supplied a promising way to obtain sustainable and clean hydrogen energy. Herein, CdZnS@layered double hydroxide (LDH) composites with a hierarchical flower-like microstructure have been fabricated with the aid of ZnCr-LDH nanosheets as templates. XRD, SEM and HRTEM show that the ZnCr-LDH nanosheets are uniformly dispersed within the composites. The surface of the hierarchical structures is rough and composed of numerous nanocrystals of CdZnS. The HRTEM images indicate that the surface of CdZnS nanocrystals is mainly composed of the (111) plane. Moreover, the visible-light-driven H2 production performance of the CdZnS in the presence and absence of ZnCr-LDH nanosheets has been measured. The results show that ZnCr-LDH nanosheets play an important role in the hierarchical morphology and photocatalytic activity of the as-prepared samples. In the water-splitting process, the visible-light-driven H2 -production rate of hierarchical flower-like CdZnS@LDH is 4.03 times and nearly 10 times higher than that of pristine CdZnS microsphere and pure commercial CdS, respectively. Therefore, this work not only achieves enhanced catalytic performance of the CdZnS by the introduction of ZnCr-LDH nanosheets, but also supplies an insight into the relationship between the hierarchical morphology and the semiconductor photocatalytic activity.

  9. LDH dye hybrid material as coloured filler into polystyrene: Structural characterization and rheological properties

    Science.gov (United States)

    Taviot-Gueho, C.; Illaik, A.; Vuillermoz, C.; Commereuc, S.; Verney, V.; Leroux, F.

    2007-05-01

    The organic inorganic hybrid assembly composed of a dye molecule of large size, direct yellow®50, as interleaved anionic molecule and layered double hydroxide host was investigated by X-ray diffraction. Upon hydrothermal post-synthesis treatment, the basal spacing is strongly decreased, explained by a drastic change in the orientation of the organic molecule against the LDH sheets, from perpendicular to parallel. The interactions were studied by 13C CPMAS NMR technique. Dispersed into polystyrene, the coloured filler was found to behave better in the viscoelastic domain than conventional surfactant LDH filler, maintaining similar rheological properties to filler-free PS. We demonstrate here that an intercalated nanocomposite polymer structure, providing an additional function as colour, is not preposterous.

  10. Intercalation of sulfonated melamine formaldehyde polycondensates into a hydrocalumite LDH structure

    Science.gov (United States)

    von Hoessle, F.; Plank, J.; Leroux, F.

    2015-05-01

    A series of sulfonated melamine formaldehyde (SMF) polycondensates possessing different anionic charge amounts and molecular weights was synthesized and incorporated into a hydrocalumite type layered double hydroxide structure using the rehydration method. For this purpose, tricalcium aluminate was dispersed in water and hydrated in the presence of these polymers. Defined inorganic-organic hybrid materials were obtained as reaction products. All SMF polymers tested intercalated readily into the hydrocalumite structure, independent of their different molecular weights (chain lengths) and anionic charge amounts. X-ray diffraction revealed typical patterns for weakly ordered, highly polymer loaded LDH materials which was confirmed via elemental analysis and thermogravimetry. IR spectroscopy suggests that the SMF polymers are interleaved between the [Ca2Al(OH)6]+ main sheets via electrostatic interaction, and that no chemical bond between the host matrix and the guest anion is formed. The SMF polymers well ensconced within the LDH structure exhibit significantly slower thermal degradation.

  11. MOF membrane synthesis in the confined space of a vertically aligned LDH network.

    Science.gov (United States)

    Liu, Yi; Wang, Nanyi; Diestel, Lisa; Steinbach, Frank; Caro, Jürgen

    2014-04-25

    MOF membranes have gained widespread attention due to their unprecedented gas separation performance. Relying on physical interactions, we successfully deposited MOF seeds on a substrate modified with a network of vertically aligned LDH walls before secondary growth of the MOF layer. ZIF-8 membranes thus prepared show considerable H2 permeance with high H2-CH4 selectivity. This approach is in general suitable for the deposition of nanoparticles on solid surface and their subsequent growth into a dense layer.

  12. MMT and LDH organo-modification with surfactants tailored for PLA nanocomposites

    OpenAIRE

    S. Coiai; F. Cicogna; Santi, A.; L. Perez Amaro; R. Spiniello; F. Signori; Fiori, S.; W. Oberhauser; Passaglia, E.

    2017-01-01

    Low molecular weight polyesters were end-functionalized with ammonium and carboxylate salts and used in ionic exchange reactions with respectively cationic (MMT) and anionic (LDH) clays. The hybrid organic-inorganic substrates were structurally analysed to determine the ester oligomers’ modification degree and their thermal behaviour owing to confinement effects. The dispersion of such hybrids in polylactic acid (PLA) matrix was performed and the ultimate structural, morphological and thermal...

  13. Glyphosate and glufosinate detection at electrogenerated NiAl-LDH thin films

    Energy Technology Data Exchange (ETDEWEB)

    Khenifi, Aicha [Laboratoire des Materiaux Inorganiques, UMR CNRS 6002, Universite Blaise Pascal, Clermont-Ferrand (France); Laboratoire de physico-chimie des materiaux, catalyse et environnement Usto, Oran, El M' nouar (Algeria); Derriche, Zoubir [Laboratoire de physico-chimie des materiaux, catalyse et environnement Usto, Oran, El M' nouar (Algeria); Forano, Claude; Prevot, Vanessa [Laboratoire des Materiaux Inorganiques, UMR CNRS 6002, Universite Blaise Pascal, Clermont-Ferrand (France); Mousty, Christine, E-mail: Christine.Mousty@univ-bpclermont.fr [Laboratoire des Materiaux Inorganiques, UMR CNRS 6002, Universite Blaise Pascal, Clermont-Ferrand (France); Scavetta, Erika, E-mail: scavetta@fci.unibo.it [Laboratorio di Chimica Analitica, Dipartimento di Chimica Fisica ed Inorganica, Universita degli Studi di Bologna (Italy); Ballarin, Barbara; Guadagnini, Lorella; Tonelli, Domenica [Laboratorio di Chimica Analitica, Dipartimento di Chimica Fisica ed Inorganica, Universita degli Studi di Bologna (Italy)

    2009-11-10

    An amperometric sensor based on Ni{sub 1-x}Al{sub x}(OH){sub 2}NO{sub 3x}.nH{sub 2}O layered double hydroxide (LDH) has been developed for the electrochemical analysis in one step of two herbicides: glyphosate (N-(phosphonomethyl)glycine, Glyp) and glufosinate ((DL-homoalanine-4-yl)-methylphosphinic acid, Gluf). NiAl-LDH was prepared by coprecipitation or by electrodeposition at the Pt electrode surface. Inorganic films were fully characterized by X-ray diffraction, Raman spectroscopy and scanning electron microscopy. Adsorption isotherms of Glyp onto this inorganic lamellar material have been established. Electrocatalytic oxidation of Glyp and Gluf is possible at the Ni{sup 3+} centres of the structure. The electrochemical responses of the NiAl-LDH modified electrode were obtained by cyclic voltammetry and chronoamperometry at 0.49 V/SCE as a function of herbicide concentration in 0.1 M NaOH solution. The electrocatalytic response showed a linear dependence on the Glyp concentration ranging between 0.01 and 0.9 mM with a detection limit of 1 {mu}M and sensitivity 287 mA/M cm{sup 2}. The sensitivity found for Gluf was lower (178 mA/M cm{sup 2}).

  14. Use of inline measures of l-lactate dehydrogenase for classification of posttreatment mammary Staphylococcus aureus infection status in dairy cows

    DEFF Research Database (Denmark)

    Jørgensen, Carina; Kristensen, Anders Ringgaard; Østergaard, Søren

    2016-01-01

    An automated method for determining whether dairy cows with subclinical mammary infections recover after antibiotic treatment would be a useful tool in dairy production. For that purpose, online . l-lactate dehydrogenase (LDH) measurements was modeled using a dynamic linear model; the variance...... of the treatment, this test data set consisted of 25 cows that still had a subclinical infection and 23 cows that were recovered. Model sensitivity was 36.0% and specificity was 82.6%. To a large extent, . l-lactate dehydrogenase reflected the cow's immune response to the presence of pathogens in the udder...

  15. Lactate dehydrogenase-elevating virus

    Science.gov (United States)

    This book chapter describes the taxonomic classification of Lactate dehydrogenase-elevating virus (LDV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biologic...

  16. Synthesis of new Tb-doped Zn-Al LDH/tryptophan hybrids and their fluorescent property

    Institute of Scientific and Technical Information of China (English)

    陈玉凤; 王肖庆; 罗世地; 鲍垚

    2016-01-01

    A series of hybrids based on Tb-doped Zn-Al layered double hydroxides (Tb-LDHs) combined with tryptophan (hereafter shortened as Try) were synthesized by soft-chemical method. The composition, structure, and fluorescence of the Tb-LDH/Try hy-brids were analyzed by various characterizations. Compositional analysis indicated that the content of tryptophan present in the hybrids gradually increased while the Tb-LDH reacted with 0.05, 0.1, and 0.25 mol/L Try solution, respectively. XRD results revealed that new reflections appeared in the Tb-LDH/Try hybrids. TGA curves of the Tb-LDH/Try hybrids were different from that of Tb-LDH and Try. IR spectra manifested that the IR spectra of the hybrids were characteristic of the Try and Tb-LDH. Fluorescent spectra sug-gested that the green emission due to5D4→7F5 transition of Tb3+ greatly decreased but not quenched, and the emission attributed to Try obviously increased. Meanwhile the fluorescent spectra of Tb-LDH/Try hybrids presented broad continuous bands in visible region.

  17. Self-assembling organomodified Co/Al based layered double hydroxides (LDH) via one-step route

    Institute of Scientific and Technical Information of China (English)

    WANG De-yi; A.LEUTERITZ; U.WAGENKNECHT; G.HEINRICH

    2009-01-01

    The preparation of self-assembling organomodified Co/Al-layered double hydroxide (LDH) via one-step route was studied.A common surfactant,sodium dodecylbenzenesulfonate (DBS),was employed as an organic modifier.The behavior and structure of self-assembled intercalated organic Co/Al-LDH were investigated by FTIR,SEM,WAXS,element analysis and TGA.Based upon the WAXS results and calculation by Bragg equation,the interlayer distance (d value) for organic Co/Al-LDH is enlarged from 0.75 nm to 3.10 nm,showing that the self-assembling behavior has been carried out successfully.Considering the observation from SEM,the product shows the morphology of organic Co/Al-LDH of a layered structure.In addition,FTIR,element analysis and TGA analysis show that the modifier is intercalated into the gallery of the Co/Al-LDH.Since organic modification for nanofiller is deemed to be necessary before applying it into polymer,the successful preparation of organomodified Co/Al-LDH will be significantly beneficial to the preparation and investigation of novel polymer/LDH nanocomposite.

  18. Histochemical activity of 5-4-isomerase-3-B hydroxy steroid dehydrogenase in the ovary of the viviparous mexican lizardSceloporus mucronatus (Reptilia:Prhynosomatidae) and interelationship with progesterone levels during pregnancy

    Institute of Scientific and Technical Information of China (English)

    Martn Martnez-torres; E Martha Prez-armendariz; M Elena Hernndez Caballero; Juana luis; guadalupe ortz-Lpez

    2012-01-01

    Objective:To relate the histological characteristics and histochemicalΔ5-4-isomerase-3 beta hydroxy steroid dehydrogenase(Δ5-43β-HSD) activity of the corpora lutea(CL) and the atresic vitellogenic follicles(AVF) with progesterone(P4) plasma concentrations in three different times of gestation (early, medium and late) in the viviparous lizardSceloporus mucronatus (S. mucronatus).Methods:The histological characteristics as well as histochemical activity ofΔ5-43β-HSD of theCL andAVF and their relationship with plasmaP4 levels were studied during three different times of pregnancy of the viviparous lizardS. mucronatus.Results:Corpora lutea develops during the first third of gestation.In second third, the luteal tissue reaches maturity and starts the first regressive changes.The last third of gestation was characterized by a considerably advance in the luteolysis.Activity ofΔ5-43β-HSD was observed in he luteal cell mas.The activity of this enzyme were high during the first third and scantle activity was detected in the last third.Even though atresic vitellogenic follicles are found throughout the whole period of gestation,Δ5-43β-HSD activity is very low in relation with showed byCL and does not change significantly in the studied period of time.Another hand, we observed a direct relationship among the histological aspect of the corpus luteum,Δ5-43β-HSD activity and progesterone levels. Conclusions:These observations suggests that the corpus luteum is the most important source of ovarian progesterone(P4) during pregnancy and that the participation of theAVF in the production of this hormone is little or non-existent.

  19. Prognostic value of ferritin, neuron-specific enolase, lactate dehydrogenase, and urinary and plasmatic catecholamine metabolites in children with neuroblastoma

    Directory of Open Access Journals (Sweden)

    Cangemi G

    2012-11-01

    localized disease without MYCN amplification the significant positive associations between urinary and plasmatic vanillylmandelic acid (VMA/homovanillic acid (HVA ratio and a better prognosis remained significant (P < 0.05 and P < 0.01, respectively, as well as, the positive association between high lactate dehydrogenase (LDH values and a worse prognosis (P < 0.001. Moreover, in stage 4 patients without MYCN amplification, neuron-specific enolase levels above 200 ng/mL and LDH levels above 2500 IU/mL maintained their significant association with a worse outcome (P = 0.01 and P = 0.0001, respectively. In conclusion, LDH had an independent prognostic value in patients of all stages without MYCN amplification. Moreover, the urinary and plasmatic VMA/HVA ratio was an independent predictor of prognosis in patients with localized disease without MYCN amplification. Since LDH and catecholamine metabolites are measured in all patients at diagnosis, these findings may be helpful for an easy, cost-effective, patient risk stratification.Keywords: neuroblastoma, markers, prognosis

  20. Degradability Enhancement of Poly(Lactic Acid by Stearate-Zn3Al LDH Nanolayers

    Directory of Open Access Journals (Sweden)

    Mahboobeh Eili

    2012-06-01

    Full Text Available Recent environmental problems and societal concerns associated with the disposal of petroleum based plastics throughout the world have triggered renewed efforts to develop new biodegradable products compatible with our environment. This article describes the preparation, characterization and biodegradation study of poly(lactic acid/layered double hydroxide (PLA/LDH nanocomposites from PLA and stearate-Zn3Al LDH. A solution casting method was used to prepare PLA/stearate-Zn3Al LDH nanocomposites. The anionic clay Zn3Al LDH was firstly prepared by co-precipitation method from a nitrate salt solution at pH 7.0 and then modified by stearate anions through an ion exchange reaction. This modification increased the basal spacing of the synthetic clay from 8.83 Å to 40.10 Å. The morphology and properties of the prepared PLA/stearate-Zn3Al LDH nanocomposites were studied by X-ray diffraction (XRD, transmission electron microscope (TEM, scanning electron microscope (SEM, thermogravimetric analysis (TGA, tensile tests as well as biodegradation studies. From the XRD analysis and TEM observation, the stearate-Zn3Al LDH lost its ordered stacking-structure and was greatly exfoliated in the PLA matrix. Tensile test results of PLA/stearate-Zn3Al LDH nanocomposites showed that the presence of around 1.0–3.0 wt % of the stearate-Zn3Al LDH in the PLA drastically improved its elongation at break. The biodegradation studies demonstrated a significant biodegradation rate improvement of PLA in the presence of stearate-Zn3Al LDH nanolayers. This effect can be caused by the catalytic role of the stearate groups in the biodegradation mechanism leading to much faster disintegration of nanocomposites than pure PLA.

  1. Electric organ lactate dehydrogenase:physical and kinetic properties of the purified enzyme from Electrophorus electricus (L.).

    Science.gov (United States)

    Torres-da Matta, J; da Matta, A N; Hassón-Voloch, A

    1983-04-01

    L(+)lactate dehydrogenase (LDH) from the electric organ of Electrophorus electricus (L.) was purified by ammonium sulfate precipitation, ion-exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-200. Purified LDH was homogeneous when examined by polyacrylamide gel electrophoresis under nondenaturing conditions. Both LDH activity and protein were demonstrable in the same band. The mobility of the LDH-5 isozyme is characteristic of the muscle type enzyme. Isoelectric focusing showed a single molecular species of pIO 6.5 +/- 0.4. The apparent molecular weight was 140,000 (+/- 10%) on the basis of gel filtration of Sephadex G-200. The effect of organic acids on the enzyme activity towards pyruvate (NADH) and lactate (NAD) was determined spectrophotometrically at 340 nm. Sodium oxamate behaved as a mixed inhibitor when lactate (NAD) was the substrate, whereas ethyl oxamate was an uncompetitive inhibitor. Both the sodium salt and the ester of oxamic acid were competitive inhibitors when pyruvate (NADH) was the substrate.

  2. Development and validation of a docking-based virtual screening platform for the identification of new lactate dehydrogenase inhibitors.

    Science.gov (United States)

    Granchi, Carlotta; Capecchi, Alice; Del Frate, Gianluca; Martinelli, Adriano; Macchia, Marco; Minutolo, Filippo; Tuccinardi, Tiziano

    2015-05-15

    The human muscle isoform of lactate dehydrogenase (hLDH5) is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying new hLDH5 inhibitors, a fully automated docking-based virtual screening platform was developed by considering different protein conformations and the consensus docking strategy. In order to verify the reliability of the reported platform, a small database of about 10,000 compounds was filtered by using this method, and the top-ranked compounds were tested for their hLDH5 inhibition activity. Enzymatic assays revealed that, among the ten selected compounds, two proved to efficiently inhibit enzyme activity with IC50 values in the micromolar range. These results demonstrate the validity of the methodologies we followed, encouraging the application of larger virtual screening studies and further refinements of the platform. Furthermore, the two active compounds herein described may be considered as interesting leads for the development of new and more efficient LDH inhibitors.

  3. Semi-Rational Design of Geobacillus stearothermophilus L-Lactate Dehydrogenase to Access Various Chiral α-Hydroxy Acids.

    Science.gov (United States)

    Aslan, Aşkın Sevinç; Birmingham, William R; Karagüler, Nevin Gül; Turner, Nicholas J; Binay, Barış

    2016-06-01

    Chiral α-hydroxy acids (AHAs) are rapidly becoming important synthetic building blocks, in particular for the production of pharmaceuticals and other fine chemicals. Chiral compounds of a variety of functionalities are now often derived using enzymes, and L-lactate dehydrogenase from the thermophilic organism Geobacillus stearothermophilus (bsLDH) has the potential to be employed for the industrial synthesis of chiral α-hydroxy acids. Despite the thorough characterization of this enzyme, generation of variants with high activity on non-natural substrates has remained difficult and therefore limits the use of bsLDH in industry. Here, we present the engineering of bsLDH using semi-rational design as a method of focusing screening in a small and smart library for novel biocatalysts. In this study, six mutant libraries were designed in an effort to expand the substrate range of bsLDH. The eight variants identified as having enhanced activity toward the selected α-keto acids belonged to the same library, which targeted two positions simultaneously. These new variants now may be useful biocatalysts for chiral synthesis of α-hydroxy acids.

  4. Development and Validation of a Docking-Based Virtual Screening Platform for the Identification of New Lactate Dehydrogenase Inhibitors

    Directory of Open Access Journals (Sweden)

    Carlotta Granchi

    2015-05-01

    Full Text Available The human muscle isoform of lactate dehydrogenase (hLDH5 is one of the key enzymes of the glycolytic process. It is overexpressed in metastatic cancer cells and is linked to the vitality of tumors in hypoxic conditions. With the aim of identifying new hLDH5 inhibitors, a fully automated docking-based virtual screening platform was developed by considering different protein conformations and the consensus docking strategy. In order to verify the reliability of the reported platform, a small database of about 10,000 compounds was filtered by using this method, and the top-ranked compounds were tested for their hLDH5 inhibition activity. Enzymatic assays revealed that, among the ten selected compounds, two proved to efficiently inhibit enzyme activity with IC50 values in the micromolar range. These results demonstrate the validity of the methodologies we followed, encouraging the application of larger virtual screening studies and further refinements of the platform. Furthermore, the two active compounds herein described may be considered as interesting leads for the development of new and more efficient LDH inhibitors.

  5. Impact of high pyruvate concentration on kinetics of rabbit muscle lactate dehydrogenase.

    Science.gov (United States)

    Eggert, Matthew Warren; Byrne, Mark E; Chambers, Robert P

    2011-09-01

    In order to evaluate the effectiveness of L: -lactate dehydrogenase (LDH) from rabbit muscle as a regenerative catalyst of the biologically important cofactor nicotinamide adenine dinucleotide (NAD), the kinetics over broad concentrations were studied to develop a suitable kinetic rate expression. Despite robust literature describing the intricate complexations, the mammalian rabbit muscle LDH lacks a quantitative kinetic rate expression accounting for simultaneous inhibition parameters, specifically at high pyruvate concentrations. Product inhibition by L: -lactate was observed to reduce activity at concentrations greater than 25 mM, while expected substrate inhibition by pyruvate was significant above 4.3 mM concentration. The combined effect of ternary and binary complexes of pyruvate and the coenzymes led to experimental rates as little as a third of expected activity. The convenience of the statistical software package JMP allowed for effective determination of experimental kinetic constants and simplification to a suitable rate expression: [formula: see text] where the last three terms represent the inhibition complex terms for lactate, pyruvate, and pyruvate-NAD, respectively. The corresponding values of K (I-Lac), K (I-Pyr), and K (I-Pyr-NAD) for rabbit muscle LDH are 487.33 mM(-1) and 29.91 mM and 97.47 mM at 22 °C and pH 7.8.

  6. An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases

    Science.gov (United States)

    Boucher, Jeffrey I; Jacobowitz, Joseph R; Beckett, Brian C; Classen, Scott; Theobald, Douglas L

    2014-01-01

    Malate and lactate dehydrogenases (MDH and LDH) are homologous, core metabolic enzymes that share a fold and catalytic mechanism yet possess strict specificity for their substrates. In the Apicomplexa, convergent evolution of an unusual LDH from MDH produced a difference in specificity exceeding 12 orders of magnitude. The mechanisms responsible for this extraordinary functional shift are currently unknown. Using ancestral protein resurrection, we find that specificity evolved in apicomplexan LDHs by classic neofunctionalization characterized by long-range epistasis, a promiscuous intermediate, and few gain-of-function mutations of large effect. In canonical MDHs and LDHs, a single residue in the active-site loop governs substrate specificity: Arg102 in MDHs and Gln102 in LDHs. During the evolution of the apicomplexan LDH, however, specificity switched via an insertion that shifted the position and identity of this ‘specificity residue’ to Trp107f. Residues far from the active site also determine specificity, as shown by the crystal structures of three ancestral proteins bracketing the key duplication event. This work provides an unprecedented atomic-resolution view of evolutionary trajectories creating a nascent enzymatic function. DOI: http://dx.doi.org/10.7554/eLife.02304.001 PMID:24966208

  7. Effects of iodonium-class flavin dehydrogenase inhibitors on growth, reactive oxygen production, cell cycle progression, NADPH oxidase 1 levels, and gene expression in human colon cancer cells and xenografts.

    Science.gov (United States)

    Doroshow, James H; Gaur, Shikha; Markel, Susan; Lu, Jiamo; van Balgooy, Josephus; Synold, Timothy W; Xi, Bixin; Wu, Xiwei; Juhasz, Agnes

    2013-04-01

    Iodonium-class flavoprotein dehydrogenase inhibitors have been demonstrated to possess antiproliferative potential and to inhibit reactive oxygen production in human tumor cells, although the mechanism(s) that explains the relationship between altered cell growth and the generation of reactive oxygen species (ROS) remains an area of active investigation. Because of the ability of these compounds to inhibit the activity of flavoprotein-containing epithelial NADPH oxidases, we chose to examine the effects of several iodonium-class flavoprotein inhibitors on human colon cancer cell lines that express high, functional levels of a single such oxidase (NADPH oxidase 1, or Nox1). We found that diphenyleneiodonium (DPI), di-2-thienyliodonium (DTI), and iodonium diphenyl inhibited the growth of Caco2, HT-29, and LS-174T colon cancer cells at concentrations (10-250nM for DPI, 0.5-2.5μM for DTI, and 155nM to 10μM for iodonium diphenyl) substantially lower than needed for DU145 human prostate cancer cells, which do not possess functional NADPH oxidase activity. Drug treatment was associated with decreased H2O2 production and diminished intracellular ROS levels, lasting up to 24h, after short-term (1-h) exposure to the iodonium analogs. Decreased tumor cell proliferation was caused, in part, by a profound block in cell cycle progression at the G1/S interface in both LS-174T and HT-29 cells exposed to either DPI or DTI; and the G1 block was produced, for LS-174T cells, by upregulation of p27 and a drug concentration-related decrease in the expression of cyclins D1, A, and E that was partially prevented by exogenous H2O2. Not only did DPI and DTI decrease intracellular ROS, they both also significantly decreased the mRNA expression levels of Nox1, potentially contributing to the prolonged reduction in tumor cell reactive oxygen levels. We also found that DPI and DTI significantly decreased the growth of both HT-29 and LS-174T human tumor xenografts, at dose levels that produced

  8. An atypical distribution of lactate dehydrogenase isoenzymes in the hooded seal (Cystophora cristata) brain may reflect a biochemical adaptation to diving.

    Science.gov (United States)

    Hoff, Mariana Leivas Müller; Fabrizius, Andrej; Folkow, Lars P; Burmester, Thorsten

    2016-04-01

    The brains of some diving mammals can withstand periods of severe hypoxia without signs of deleterious effects. This may in part be due to an enhanced cerebral capacity for anaerobic energy production. Here, we have tested this hypothesis by comparing various parameters of the lactate dehydrogenase (LDH) in the brain of the hooded seal (Cystophora cristata) with those in the brains of the ferret (Mustela putorius furo) and mouse (Mus musculus). We found that mRNA and protein expression of lactate dehydrogenase a (LDHA) and lactate dehydrogenase b (LDHB), and also the LDH activity were significantly higher in the ferret brain than in brains of the hooded seal and the mouse (p diving mammals. Moreover, immunofluorescence studies showed more pronounced co-localization of LDHB and glial fibrillary acidic protein in the cortex of the hooded seal. Since LDHB isoenzymes primarily catalyze the conversion of lactate to pyruvate, this finding suggests that the contribution of astrocytes to the brain aerobic metabolism is higher in the hooded seal than in non-diving species. The cerebral tolerance of the hooded seal to hypoxia may therefore partly rely on different LDH isoenzymes distribution.

  9. Does corticosteroid treatment cause prolonged recovery and increased total bilirubin level in severe ADAMTS-13-deficient TTP patient?

    Science.gov (United States)

    Sayiner, Zeynel Abidin; Acik, Didar Yanardag; Yilmaz, Mehmet; Subari, Salih; Mete, Ayse Ozlem; Dai, M Sinan

    2015-10-01

    A 41-year-old female patient complaining of fatigue, headache, mild confusion, and rush on her lower extremities was admitted to our emergency department. Laboratory tests revealed that he had anemia, thrombocytopenia, and increased levels of indirect bilirubin and lactic dehydrogenase (LDH) in blood tests. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP). The best supportive care was provided. Therapeutic plasma exchange (TPE) and 1 mg/kg methylprednisolone treatments were administered. On the 10th day of treatment, LDH level and fragmented red blood cells in peripheral blood smear were decreased, but his direct and indirect bilirubin levels increased despite the fact that he was treated with 1 mg/kg methylprednisolone and TPE. The patient had severe ADAMTS-13 deficiency. After discontinued steroids treatment, his bilirubin level normalized within 4 days. On the 4th day after bilirubin level normalized, vincristine treatment was administered. TPE was also continued. There was no consensus about the optimal schedule for discontinuing plasmapheresis therapy, and also we observed total bilirubin level improvement with discontinued corticosteroid treatment. In this case, corticosteroid treatment was linked with the increase of total bilirubin level in severe ADAMTS-13-deficient TTP patient.

  10. Rationally re-designed mutation of NAD-independent l-lactate dehydrogenase: high optical resolution of racemic mandelic acid by the engineered Escherichia coli

    Directory of Open Access Journals (Sweden)

    Jiang Tianyi

    2012-11-01

    Full Text Available Abstract Background NAD-independent l-lactate dehydrogenase (l-iLDH from Pseudomonas stutzeri SDM can potentially be used for the kinetic resolution of small aliphatic 2-hydroxycarboxylic acids. However, this enzyme showed rather low activity towards aromatic 2-hydroxycarboxylic acids. Results Val-108 of l-iLDH was changed to Ala by rationally site-directed mutagenesis. The l-iLDH mutant exhibited much higher activity than wide-type l-iLDH towards l-mandelate, an aromatic 2-hydroxycarboxylic acid. Using the engineered Escherichia coli expressing the mutant l-iLDH as a biocatalyst, 40 g·L-1 of dl-mandelic acid was converted to 20.1 g·L-1 of d-mandelic acid (enantiomeric purity higher than 99.5% and 19.3 g·L-1 of benzoylformic acid. Conclusions A new biocatalyst with high catalytic efficiency toward an unnatural substrate was constructed by rationally re-design mutagenesis. Two building block intermediates (optically pure d-mandelic acid and benzoylformic acid were efficiently produced by the one-pot biotransformation system.

  11. Advanced treatment of stabilized landfill leachate after biochemical process with hydrocalumite chloride (Ca/Al-Cl LDH).

    Science.gov (United States)

    Chen, Hua; Sun, Ying; Ruan, Xiuxiu; Yu, Ying; Zhu, Minying; Zhang, Jia; Zhou, Jizhi; Xu, Yunfeng; Liu, Jianyong; Qian, Guangren

    2016-06-01

    This study investigated the effectiveness of Ca/Al-Cl LDH for the treatment of stabilized landfill leachate. Experiments were performed including different dosage of Ca/Al-Cl LDH and comparison with different reagents, such as CaCl2 and AlCl3. As a result, Ca/Al-Cl LDH efficiently removed organic matters in stabilized landfill leachate with the maximum removal (59.41% COD, 62.06% DOC and 70.56% UV254) at the dose of 30g/L. According to UV254 and EEM, it is remarkable that the formation of Ca/Al-LDH has a greater beneficial to organic removal than other reagents, especially for fulvic acid-like and humic acid-like compounds. Moreover, the removal of fulvic acid-like compounds was much better than humic acid-like compounds. The previous compounds had more carboxylic groups, thus had a better removal selectivity.

  12. Formation of Hierarchical Structure Composed of (Co/Ni)Mn-LDH Nanosheets on MWCNT Backbones for Efficient Electrocatalytic Water Oxidation.

    Science.gov (United States)

    Jia, Gan; Hu, Yingfei; Qian, Qinfeng; Yao, Yingfang; Zhang, Shiying; Li, Zhaosheng; Zou, Zhigang

    2016-06-15

    Active, stable, and cost-effective electrocatalysts are attractive alternatives to the noble metal oxides that have been used in water splitting. The direct nucleation and growth of electrochemically active LDH materials on chemically modified MWCNTs exhibit considerable electrocatalytic activity toward oxygen evolution from water oxidation. CoMn-based and NiMn-based hybrids were synthesized using a facile chemical bath deposition method and the as-synthesized materials exhibited three-dimensional hierarchical configurations with tunable Co/Mn and Ni/Mn ratio. Benefiting from enhanced electrical conductivity with MWCNT backbones and LDH lamellar structure, the Co5Mn-LDH/MWCNT and Ni5Mn-LDH/MWCNT could generated a current density of 10 mA cm(-2) at overpotentials of ∼300 and ∼350 mV, respectively, in 1 M KOH. In addition, the materials also exhibited outstanding long-term electrocatalytic stability.

  13. Empirical evaluation of a virtual laboratory approach to teach lactate dehydrogenase enzyme kinetics.

    Science.gov (United States)

    Booth, Christine; Cheluvappa, Rajkumar; Bellinson, Zack; Maguire, Danni; Zimitat, Craig; Abraham, Joyce; Eri, Rajaraman

    2016-06-01

    Personalised instruction is increasingly recognised as crucial for efficacious learning today. Our seminal work delineates and elaborates on the principles, development and implementation of a specially-designed adaptive, virtual laboratory. We strived to teach laboratory skills associated with lactate dehydrogenase (LDH) enzyme kinetics to 2nd-year biochemistry students using our adaptive learning platform. Pertinent specific aims were to:(1)design/implement a web-based lesson to teach lactate dehydrogenase(LDH) enzyme kinetics to 2nd-year biochemistry students(2)determine its efficacious in improving students' comprehension of enzyme kinetics(3)assess their perception of its usefulness/manageability(vLab versus Conventional Tutorial). Our tools were designed using HTML5 technology. We hosted the program on an adaptive e-learning platform (AeLP). Provisions were made to interactively impart informed laboratory skills associated with measuring LDH enzyme kinetics. A series of e-learning methods were created. Tutorials were generated for interactive teaching and assessment. The learning outcomes herein were on par with that from a conventional classroom tutorial. Student feedback showed that the majority of students found the vLab learning experience "valuable"; and the vLab format/interface "well-designed". However, there were a few technical issues with the 1st roll-out of the platform. Our pioneering effort resulted in productive learning with the vLab, with parity with that from a conventional tutorial. Our contingent discussion emphasises not only the cornerstone advantages, but also the shortcomings of the AeLP method utilised. We conclude with an astute analysis of possible extensions and applications of our methodology.

  14. Stability and activity of lactate dehydrogenase on biofunctional layers deposited by activated vapor silanization (AVS) and immersion silanization (IS)

    Science.gov (United States)

    Calvo, Jorge Nieto-Márquez; Elices, Manuel; Guinea, Gustavo V.; Pérez-Rigueiro, José; Arroyo-Hernández, María

    2017-09-01

    The interaction between surfaces and biological elements, in particular, proteins is critical for the performance of biomaterials and biosensors. This interaction can be controlled by modifying the surface in a process known as biofunctionalization. In this work, the enzyme lactate dehydrogenase (LDH) is used to study the stability of the interaction between a functional protein and amine-functionalized surfaces. Two different functionalization procedures were compared: Activated Vapor Silanization (AVS) and Immersion Silanization (IS). Adsorption kinetics is shown to follow the Langmuir model for AVS-functionalized samples, while IS-functionalized samples show a certain instability if immersed in an aqueous medium for several hours. In turn, the enzymatic activity of LDH is preserved for longer times by using glutaraldehyde as crosslinker between the AVS biofunctional surface and the enzyme.

  15. Local diffusion homogeneity (LDH): an inter-voxel diffusion MRI metric for assessing inter-subject white matter variability.

    Science.gov (United States)

    Gong, Gaolang

    2013-01-01

    Many diffusion parameters and indices (e.g., fractional anisotropy [FA] and mean diffusivity [MD]) have been derived from diffusion magnetic resonance imaging (MRI) data. These parameters have been extensively applied as imaging markers for localizing white matter (WM) changes under various conditions (e.g., development, degeneration and disease). However, the vast majority of the existing parameters is derived from intra-voxel analyses and represents the diffusion properties solely within the voxel unit. Other types of parameters that characterize inter-voxel relationships have been largely overlooked. In the present study, we propose a novel inter-voxel metric referred to as the local diffusion homogeneity (LDH). This metric quantifies the local coherence of water molecule diffusion in a model-free manner. It can serve as an additional marker for evaluating the WM microstructural properties of the brain. To assess the distinguishing features between LDH and FA/MD, the metrics were systematically compared across space and subjects. As an example, both the LDH and FA/MD metrics were applied to measure age-related WM changes. The results indicate that LDH reveals unique inter-subject variability in specific WM regions (e.g., cerebral peduncle, internal capsule and splenium). Furthermore, there are regions in which measurements of age-related WM alterations with the LDH and FA/MD metrics yield discrepant results. These findings suggest that LDH and FA/MD have different sensitivities to specific WM microstructural properties. Taken together, the present study shows that LDH is complementary to the conventional diffusion-MRI markers and may provide additional insights into inter-subject WM variability. Further studies, however, are needed to uncover the neuronal mechanisms underlying the LDH.

  16. Local diffusion homogeneity (LDH: an inter-voxel diffusion MRI metric for assessing inter-subject white matter variability.

    Directory of Open Access Journals (Sweden)

    Gaolang Gong

    Full Text Available Many diffusion parameters and indices (e.g., fractional anisotropy [FA] and mean diffusivity [MD] have been derived from diffusion magnetic resonance imaging (MRI data. These parameters have been extensively applied as imaging markers for localizing white matter (WM changes under various conditions (e.g., development, degeneration and disease. However, the vast majority of the existing parameters is derived from intra-voxel analyses and represents the diffusion properties solely within the voxel unit. Other types of parameters that characterize inter-voxel relationships have been largely overlooked. In the present study, we propose a novel inter-voxel metric referred to as the local diffusion homogeneity (LDH. This metric quantifies the local coherence of water molecule diffusion in a model-free manner. It can serve as an additional marker for evaluating the WM microstructural properties of the brain. To assess the distinguishing features between LDH and FA/MD, the metrics were systematically compared across space and subjects. As an example, both the LDH and FA/MD metrics were applied to measure age-related WM changes. The results indicate that LDH reveals unique inter-subject variability in specific WM regions (e.g., cerebral peduncle, internal capsule and splenium. Furthermore, there are regions in which measurements of age-related WM alterations with the LDH and FA/MD metrics yield discrepant results. These findings suggest that LDH and FA/MD have different sensitivities to specific WM microstructural properties. Taken together, the present study shows that LDH is complementary to the conventional diffusion-MRI markers and may provide additional insights into inter-subject WM variability. Further studies, however, are needed to uncover the neuronal mechanisms underlying the LDH.

  17. Adsorption study of anionic reactive dye from aqueous solution to Mg-Fe-CO3 layered double hydroxide (LDH)

    Science.gov (United States)

    Ahmed, I. M.; Gasser, M. S.

    2012-10-01

    Mg-Fe-Cl Layered double hydroxides (LDHs) have been prepared using a method involving separate nucleation and aging steps with Mg/Fe = 3. The interlayer anions readily replaced by carbonate are characterized by X-ray diffraction (XRD) and FTIR. The effects of different parameters, such as pH, contact time, concentration of dye and temperature on the capacity and adsorption mechanism of Mg-Fe-CO3-LDH in removing an anionic dye (congo red, CR) from aqueous solution were separately investigated. The results show that Mg-Fe-CO3-LDH is particularly efficient in removing CR and the dye removal increases with decreasing pH. The adsorption of CR on Mg-Fe-CO3-LDH reached equilibrium after 15 min where 100 mg/L CR was removed. The equilibrium isotherm indicates that the adsorption of CR onto Mg-Fe-CO3-LDH fits to Langmuir and Freundlich equation as well. The adsorption data obtained from the Langmuir model gave good values of the determination coefficient and the saturated adsorption capacity of Mg-Fe-CO3-LDH for CR was found to be 104.6 mg/g. The regeneration study indicates that the prepared LDH could be used for several cycles. The thermodynamic parameters have been calculated, and the adsorption process was found to be spontaneous, endothermic in nature and follows a pseudo-second-order kinetic model.

  18. Deposition of LDH on plasma treated polylactic acid to reduce water permeability

    KAUST Repository

    Bugatti, Valeria

    2013-04-01

    A simple and scalable deposition process was developed to prepare polylactic acid (PLA) coatings with enhanced water barrier properties for food packaging applications. This method based on electrostatic interactions between the positively charged layers of layered double hydroxides (LDHs) modified with ionic liquids (ILs) and the negatively charged plasma treated polylactic acid leads to homogeneous, stable, and highly durable coatings. Deposition of the LDH coatings increases the surface hydrophobicity of the neat PLA, which results to a decrease in water permeability by about 35%. © 2013 Elsevier Inc.

  19. Effect of Ultraviolet Aging on Rheology and Chemistry of LDH-Modified Bitumen

    OpenAIRE

    Xing Liu; Shaopeng Wu; Gang Liu; Liping Li

    2015-01-01

    Layered double hydroxides (LDHs) are an ultravioletlight (UV)-resistant material. In this study, two types of LDHs (Mg-Al-LDHs and Zn-Al-LDHs) were applied to modify bitumen by melt-blending. The effect of ultraviolet aging on the rheology and chemistry of LDH-modified bitumen was studied by means of dynamic shear rheometer (DSR), thin-layer chromatography with flame ionization detection (TLC-FID), Fourier transform infrared spectroscopy (FTIR), and Ultraviolet-Visible (UV-Vis) spectrophotome...

  20. CELL DAMAGE, ANTIOXIDANT STATUS, AND CORTISOL LEVELS RELATED TO NUTRITION IN SKI MOUNTAINEERING DURING A TWO-DAY RACE

    Directory of Open Access Journals (Sweden)

    Elena Diaz

    2010-06-01

    Full Text Available The aim of this study was to measure the effect of nutrition on cell damage, antioxidant enzymes, and cortisol during a two-day ski mountaineering competition. Twenty-one male skiers participated in the study. Creatine kinase (CK, aspartate aminotransferase (AST, alanine aminotransferase (ALT, ?-glutamyl transpeptidase (GGT, lactate dehydrogenase (LDH, alkaline phosphatase (AP, cortisol and C-reactive protein (CRP, glutathione peroxidase (GPx and reductase activities (GR and C-reactive protein (CRP levels, total antioxidant status, and cortisol levels were measured in serum the day before and immediately after the race. Their diet was also analysed during the competition. Enzymes and cortisol levels significantly increased after the competition. CK and LDH and cortisol levels were negatively correlated to total energy, protein, and fat intake. Intake of vitamin A, B1, B2, B6 and niacin was negatively correlated to LDH and AP. A negative correlation was also found between CK activity and Na, Fe, and Zn intake. Cortisol levels were negatively correlated to the intake of vitamins C, B1 and B2, and niacin. A positive correlation was found between serum GPx and intake of energy, carbohydrates, proteins, A and B vitamins, and folic acid. Skiers with the lowest nutrient intake during the competition were the ones who showed greater cell damage and lower antioxidant enzyme activity and cortisol levels, which may impair performance and also cause injuries and accidents. Particularly, skiers should have high intakes of total energy, macronutrients, vitamins A and B, Na, Zn, and Fe in order to decrease the deleterious effect of strenuous exercise

  1. Effects of vitamin-mineral supplementation on cardiac marker and radical scavenging enzymes, and MDA levels in young swimmers.

    Science.gov (United States)

    Cavas, Levent; Tarhan, Leman

    2004-04-01

    The relationship among the enzyme activities of cardiac markers, the antioxidant defense system, and erythrocyte membrane malonyldialdehyde (MDA) levels related to vitamin-mineral supplementation in swim exercise was investigated. Swimmers aged 11 - 13 years were divided into 2 separate groups as control and vitamin-mineral supplemented. Swimmers participated in a monthly swimming program (4 times/wk) and swam approximately 2- 2.5 km/d. Cardiac markers such as creatine kinase (CK), creatine kinase-MB (CK - MB), glutamic oxaloacetic transaminase [GOT (AST)], lactate dehydrogenase (LDH), and anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in post-training samples were found to be significantly (p<.05) higher than in pre-training samples. Except for GOT (AST), the activity increases in CK, CK-MB, and LDH in female and male supplemented groups were significantly (p<.05) lower than those of control groups during the 1-month period of swim training. Antioxidant enzyme activity increases in the male vitamin-mineral group were significantly (p <.05) higher when compared with the other groups. Post-training MDA levels were significantly (p <.001) higher than pre-training MDA levels in the control groups, whereas no significant (p<.05) differences were found between the vitamin-mineral supplemented groups. Vitamin-mineral supplementation was found to attenuate cardiac and muscle damage markers while also enhancing antioxidant levels and reducing membrane LPO levels in response to 1 month of swim training.

  2. 层状双羟基氢氧化物(LDH)的表面有机化研究%Surface Organizing of Layered Double Hydroxide (LDH)

    Institute of Scientific and Technical Information of China (English)

    杨巧珍; 李峰; 段雪

    2003-01-01

    采用成核晶化隔离法合成MgAl-CO32-型层状双羟基氢氧化物(LDH),并用不同偶联剂对其进行了表面有机化改性研究.通过X射线衍射(XRD)、红外光谱(IR)、X光电子能谱(XPS)、激光粒度分析和透射电镜(TEM)等手段探讨了偶联剂与LDH表面作用的原理.结果表明:硅烷偶联剂和铝钛复合偶联剂均可实现LDH的表面有机化,其中硅烷偶联剂AG-102的改性效果最好,而且用它改性的LDH在PVC中的团聚小,并具有较好的分散性,是一种理想的LDH表面改性剂.

  3. Structure and function of Plasmodium falciparum malate dehydrogenase: role of critical amino acids in co-substrate binding pocket.

    Science.gov (United States)

    Pradhan, Anupam; Tripathi, Abhai K; Desai, Prashant V; Mukherjee, Prasenjit K; Avery, Mitchell A; Walker, Larry A; Tekwani, Babu L

    2009-01-01

    The malaria parasite thrives on anaerobic fermentation of glucose for energy. Earlier studies from our laboratory have demonstrated that a cytosolic malate dehydrogenase (PfMDH) with striking similarity to lactate dehydrogenase (PfLDH) might complement PfLDH function in Plasmodium falciparum. The N-terminal glycine motif, which forms a characteristic Rossman dinucleotide-binding fold in the co-substrate binding pocket, differentiates PfMDH (GlyXGlyXXGly) from other eukaryotic and prokaryotic malate dehydrogenases (GlyXXGlyXXGly). The amino acids lining the co-substrate binding pocket are completely conserved in MDHs from different species of human, primate and rodent malaria parasites. Based on this knowledge and conserved domains among prokaryotic and eukaryotic MDH, the role of critical amino acids lining the co-substrate binding pocket was analyzed in catalytic functions of PfMDH using site-directed mutagenesis. Insertion of Ala at the 9th or 10th position, which converts the N-terminal GlyXGlyXXGly motif (characteristic of malarial MDH and LDH) to GlyXXGlyXXGly (as in bacterial and eukaryotic MDH), uncoupled regulation of the enzyme through substrate inhibition. The dinucleotide fold GlyXGlyXXGly motif seems not to be responsible for the distinct affinity of PfMDH to 3-acetylpyridine-adenine dinucleotide (APAD, a synthetic analog of NAD), since Ala9 and Ala10 insertion mutants still utilized APADH. The Gln11Met mutation, which converts the signature glycine motif in PfMDH to that of PfLDH, did not change the enzyme function. However, the Gln11Gly mutant showed approximately a 5-fold increase in catalytic activity, and higher susceptibility to inhibition with gossypol. Asn119 and His174 participate in binding of both co-substrate and substrate. The Asn119Gly mutant exhibited approximately a 3-fold decrease in catalytic efficiency, while mutation of His174 to Asn or Ala resulted in an inactive enzyme. These studies provide critical insights into the co

  4. Michael hydratase alcohol dehydrogenase or just alcohol dehydrogenase?

    NARCIS (Netherlands)

    Resch, V.A.; Jin, J.; Chen, B.S.; Hanefeld, U.

    2014-01-01

    The Michael hydratase – alcohol dehydrogenase (MhyADH) from Alicycliphilus denitrificans was previously identified as a bi-functional enzyme performing a hydration of α,β-unsaturated ketones and subsequent oxidation of the formed alcohols. The investigations of the bi-functionality were based on a

  5. Michael hydratase alcohol dehydrogenase or just alcohol dehydrogenase?

    NARCIS (Netherlands)

    Resch, V.A.; Jin, J.; Chen, B.S.; Hanefeld, U.

    2014-01-01

    The Michael hydratase – alcohol dehydrogenase (MhyADH) from Alicycliphilus denitrificans was previously identified as a bi-functional enzyme performing a hydration of α,β-unsaturated ketones and subsequent oxidation of the formed alcohols. The investigations of the bi-functionality were based on a s

  6. Effect of Ultraviolet Aging on Rheology and Chemistry of LDH-Modified Bitumen

    Directory of Open Access Journals (Sweden)

    Xing Liu

    2015-08-01

    Full Text Available Layered double hydroxides (LDHs are an ultravioletlight (UV-resistant material. In this study, two types of LDHs (Mg-Al-LDHs and Zn-Al-LDHs were applied to modify bitumen by melt-blending. The effect of ultraviolet aging on the rheology and chemistry of LDH-modified bitumen was studied by means of dynamic shear rheometer (DSR, thin-layer chromatography with flame ionization detection (TLC-FID, Fourier transform infrared spectroscopy (FTIR, and Ultraviolet-Visible (UV-Vis spectrophotometry to reveal the mechanisms of action for LDHs and bitumen. The results showed that within the UV spectra (220–400 nm, the reflectance of Zn-Al-LDHs was larger than that of Mg-Al-LDHs. These two LDHs have different influences on the performance of bitumen. Mg-Al-LDHs had a more obvious influence on the physical and dynamic rheological properties of bitumen than Zn-Al-LDHs. Zn-Al-LDHs improved the UV-aging resistance of bitumen more. The reason can be that the reflectance of the Zn-Al-LDHs to the UV light is larger than that of the Mg-Al-LDHs. The Zn-Al-LDH-modified bitumen had more potential to improve the UV-aging resistance during the service life of asphalt pavement.

  7. INFLUENCE OF LACTATE DEHYDROGENASE ISOENZYME IN GINGIVAL CREVICULAR FLUID AFTER NI-CR ALLOY DENTAL RESTORATION%镍铬合金修复体对龈沟液中LDH同工酶谱的影响

    Institute of Scientific and Technical Information of China (English)

    周俊红; 周立社; 秦文斌; 雎天林; 李利

    2016-01-01

    目的:探讨镍铬合金修复牙体后龈沟液( gingival crevicular fluid, GCF )中乳酸脱氢酶( lactate dehydrogenase,LDH)同工酶的变化。方法:选择镍铬合金修复1~2a的牙位58个,健康牙位54个,用滤纸条法采集GCF,醋酸纤维薄膜电泳结合光密度扫描法测定GCF-LDH同工酶的相对含量。结果:金属修复牙组与健康对照组比较,两组间GCF中LDH1、LDH2、LDH3和LDH5的相对含量均无显著性差异(t1、t2、t3、t5分别为0.49、1.56、0.12、0.37;P>0.05),但镍铬合金修复组GCF-LDH4相对含量明显高于健康组(t4=2.03,P40. 05 ), but the GCF-LDH4 content in the prothetic teeth group was significantly higher than it in the healthy teeth group(t4=2. 03,P4<0. 05). Conclusion:The GCF-LDH isoenzyme-gram of Ni-Cr alloy prothetic teeth is changed. It indicates that Ni-Cr alloy dental prosthesis is likely to have a stimulation or injury to periodontium.

  8. Levels of interleukin-16 in peripheral blood of 52 patients with multiple myeloma and its clinical significance

    Science.gov (United States)

    Long, Shi-Feng; Chen, Guo-An; Fang, Mu-Shui

    2015-01-01

    Purpose: To explore the role of serum interleukin-16 (IL-16) in the occurrence of multiple myeloma (MM) and after the success chemotherapy and its clinical significance. Methods: 52 cases of MM patients, 30 cases of AML patients and 30 healthy volunteers from Jan. 2011 to Jan. 2015 were collected in this study. There was 39 MM patients received chemotherapy. Among those, 24 patients received VAD regimen chemotherapy and 15 patients received BD regimen chemotherapy. Serum IL-16, cystatin C (Cys-C), lactate dehydrogenase (LDH) and levels of β2-microglobulin (β2-MG) were detected before and after the therapy of MM patients. And those results were compared to that of patients with acute myelogenous leukemia (AML) and normal people respectively. Results: The levels of serum IL-16, Cys-C, LDH and β2-MG in MM group were remarkably higher than that of normal control. It was of statistical significance of this difference (P<0.05). Levels of serum IL-16, Cys-C and LDH of MM patients who received therapy were all lower than that of patients before therapy. The serum IL-16 and β2-MG of 52 patients by preliminary diagnosis were analyzed through Pearson correlation analysis before they received therapy. The results showed that there was positive correlation between levels of IL-16 and β2-MG (r=0.782, P<0.01). Conclusions: A high serum IL-16 level detected in newly diagnosed MM patients and its correlation with known factors of disease activity as well as the decrease of IL-16 after chemotherapy suggest that IL-16 may be implicated and a potential therapeutic target for MM. PMID:26885237

  9. Controlled leaching with prolonged activity for Co-LDH supported catalyst during treatment of organic dyes using bicarbonate activation of hydrogen peroxide.

    Science.gov (United States)

    Jawad, Ali; Li, Yibing; Lu, Xiaoyan; Chen, Zhuqi; Liu, Weidong; Yin, Guochuan

    2015-05-30

    The effluents from industries are commonly non-biodegradable and produce various hazardous intermediate products by chemical reactions that have direct impact on environment. In the present investigation, a series of Co-Mg/AL ternary LDH catalysts with fixed Mg/Al ratio were prepared by co-precipitation method. The effect of Co on the activity of the catalyst was monitored on the degradation of methylene blue (MB) as model compound at batch level using bicarbonate activation of H2O2 (BAP) system. On bench level, the best CoMgAl-4 catalyst can completely decolorize both methylene blue (MB) and methylene orange (MO) in short time, while in fixed bed, the catalyst was found stable for over 300 h with nearly 100% decolorization and excellent chemical oxygen demand (COD) removal. No leaching of Co was detected for the entire fixed experiment which may be accounted for long life stability and good activity of the catalyst. The ternary LDH catalysts were characterized by AES, XRD, FTIR, BET, and SEM for its compositional, phase structure, optical properties, textural, and surface morphology respectively. The XRD analysis confirmed characteristic pattern of hydrotalcite like structures without impurity phases. The formation of superoxide and hydroxyl radical as ROS was proposed with CoMgAl-4 by radical's scavengers.

  10. 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

  11. Ni adsorption and Ni-Al LDH precipitation in a sandy aquifer: an experimental and mechanistic modeling study.

    Science.gov (United States)

    Regelink, Inge C; Temminghoff, Erwin J M

    2011-03-01

    Mining activities and industries have created nickel (Ni) contaminations in many parts of the world. The objective of this study is to increase our understanding of Ni adsorption and Nickel-Aluminium Layered Double Hydroxide (Ni-Al LDH) precipitation to reduce Ni mobility in a sandy soil aquifer. At pH ≥ 7.2 both adsorption and Ni-Al LDH precipitation occurred. In batch experiments with the sandy soil up to 70% of oxalate-extractable Al was taken up in LDH formation during 56 days. In a long term column experiment 99% of influent Ni was retained at pH 7.5 due to Ni adsorption (≈ 34%) and Ni-Al LDH precipitation (≈ 66%) based on mechanistic reactive transport modeling. The subsequent leaching at pH 6.5 could be largely attributed to desorption. Our results show that even in sandy aquifers with relatively low Al content, Ni-Al LDH precipitation is a promising mechanism to immobilize Ni.

  12. 弓形虫乳酸脱氢酶LDH2基因启动子的克隆及鉴定%Cloning of Toxoplasma gondii LDH2 gene promoter and evaluation of its promoting activity

    Institute of Scientific and Technical Information of China (English)

    张加勤; 侯香华; 宋秀宇

    2013-01-01

    To clone promoter fragment of Toxoplasma gondii LDH2 gene and to evaluate the promoting activity, a series of fragments of 5 UTR of Toxoplasma gondii LDH2 gene were amplified by PCR, and then inserted into pTX3-basic via Kpn I and Xhol I to construct luciferase reporter plasmids. Forty eight hours after tachyzoites being co-transfected by luciferase reporter plasmids and reference plasmid pRL-Tg, dual-lucif erase assays were carried out to determinate activities of the fragments to initiate luciferase transcription. Results showed that the sequence of the 5 UTR of Toxoplasma gondii LDH2 gene fragments was proved to be correct by sequencing, and a series of luciferase reporter plasmids were verified by PCR, restrictive endonuclease digest, and sequencing. The luciferase activities of all the luciferase reporter plasmids with 5 UTR of Toxoplasma gondii LDH2 in tachyzoites were similar with the negative control pTX3-basic. While in bradyzoites, all the plasmids yielded 40 to 50 folds of luciferase activity to the negative control, and 1. 2 to 1. 5 folds to the positive control of pTX3-basic, excepting for the plasmids pTX3-293 and pTX3-193. In conclusion, the promoter region of Toxoplasma gondii LDH2 was located and cloned successfully. Our results provide evidence for investigation of the mechanism on regulation of the LDH2 gene.%目的 克隆弓形虫乳酸脱氢酶LDH2基因启动子并进行初步鉴定.方法 PCR扩增出LDH2基因5′侧翼序列系列截短突变体,定向插入载体pTX3–basic的Kpn I / Xhol I酶切位点之间,转化大肠埃希菌Top 10,氨苄西林筛选,建立重组LDH2基因5′侧翼序列系列截短突变体荧光素酶表达载体.转染刚地弓形虫速殖子,利用荧光素酶检测试剂盒测定所克隆片段的启动转录活性.结果 成功扩增出LDH2基因5′侧翼序列系列突变体;系列重组荧光素酶表达质粒经PCR、酶切及测序鉴定正确无误;系列重组荧光素酶表达质粒在弓形虫速殖

  13. Optical and UV-Aging Properties of LDH-Modified Bitumen

    Directory of Open Access Journals (Sweden)

    Xing Liu

    2015-07-01

    Full Text Available Layered double hydroxides (LDHs are an ultraviolet-light (UV resistant material. In this study, LDHs were used to modify bitumen. The optical and UV aging properties of LDHs modified bitumen were investigated. Firstly, the thin films of bitumen, with and without LDHs, were prepared. By using the UV-Vis spectrophotometer, absorbance, reflectance, and transmittance of bituminous thin film were evaluated. The morphology of LDHs-modified bitumen was observed by using fluorescence microscopy (FM. Finally, the aging resistance of LDH-modified bitumen was investigated by using the UV-aging oven. Results indicated that the LDHs, especially with 5 wt % in the bitumen, can effectively absorb and reflect the UV light and improve the UV-aging resistance of bitumen. This implied that the addition of LDHs into bitumen had the potential to prolong the service life of asphalt pavement.

  14. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci.

    Science.gov (United States)

    Peralta, Guillermo Hugo; Bergamini, Carina Viviana; Hynes, Erica Rut

    2016-01-01

    Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor.

  15. In situ synthesis of MOF membranes on ZnAl-CO3 LDH buffer layer-modified substrates.

    Science.gov (United States)

    Liu, Yi; Wang, Nanyi; Pan, Jia Hong; Steinbach, Frank; Caro, Jürgen

    2014-10-15

    We develop here a urea hydrolysis method to in situ prepare asymmetric ZnAl-CO3 layered double hydroxide (LDH) buffer layers with various stable equilibrium morphology on porous Al2O3 substrates. In particular it is found that well-intergrown ZIF-8 membranes can be directly synthesized on the ZnAl-CO3 LDH buffer layer-modified substrates, owing to the specific metal-imidazole interaction between ZnAl-CO3 LDHs and ZIF-8. Other Zn-based MOF membranes, like ZIF-7 and ZIF-90, can also be synthesized with this method. Our finding demonstrates that LDH buffer layer represents a new concept for substrate modification.

  16. The activity of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in the sera of patients with brain cancer.

    Science.gov (United States)

    Jelski, Wojciech; Laniewska-Dunaj, Magdalena; Orywal, Karolina; Kochanowicz, Jan; Rutkowski, Robert; Szmitkowski, Maciej

    2014-12-01

    Human brain tissue contains various alcohol dehydrogenase (ADH) isoenzymes and possess also aldehyde dehydrogenase (ALDH) activity. In our last experiments we have shown that ADH and ALDH are present also in the brain tumour cells. Moreover the activities of total ADH and class I isoenzymes were significantly higher in cancer tissue than healthy cells. It can suggests that these changes may be reflected by enzyme activity in the serum of patients with brain cancer. Serum samples were taken for routine biochemical investigation from 62 patients suffering from brain cancer (36 glioblastoma, 26 meningioma). For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity, the fluorometric methods were used. The total ADH activity and activity of class III and IV isoenzymes were measured by the photometric method. A statistically significant increase of class I alcohol dehydrogenase isoenzymes was found in the sera of patients with brain cancer. The median activity of this class isoenzyme in the patients group increased about 24 % in the comparison to the control level. The total alcohol dehydrogenase activity was also significantly higher (26 %) among patients with brain tumour than healthy ones. The activities of other tested ADH isoenzymes and total ALDH were unchanged. The increase of the activity of total ADH and class I alcohol dehydrogenase isoenzyme in the sera of patients with brain cancer seems to be caused by the release of this isoenzyme from tumour's cells.

  17. Increased IMP dehydrogenase gene expression in solid tumor tissues and tumor cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Collart, F.R.; Chubb, C.B.; Mirkin, B.L.; Huberman, E.

    1992-07-10

    IMP dehydrogenase, a regulatory enzyme of guanine nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To assess this possibility, we examined IMP dehydrogenase expression in a series of human solid tumor tissues and tumor cell lines in comparison with their normal counterparts. Increased IMP dehydrogenase gene expression was observed in brain tumors relative to normal brain tissue and in sarcoma cells relative to normal fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines, elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in comparison with the levels in peripheral blood lymphocytes. These results are consistent with an association between increased IMP dehydrogenase expression and either enhanced cell proliferation or malignant transformation.

  18. Characterization of the galactono-1,4-lactone dehydrogenase from pepper fruits and its modulation in the ascorbate biosynthesis. Role of nitric oxide

    Directory of Open Access Journals (Sweden)

    Marta Rodríguez-Ruiz

    2017-08-01

    We also report that an NO (nitric oxide-enriched atmosphere enhanced ascorbate content in pepper fruits about 40% parallel to increased GalLDH gene expression and enzyme activity. This is the first report on the stimulating effect of NO treatment on the vitamin C concentration in plants. Accordingly, the modulation by NO of GalLDH was addressed. In vitro enzymatic assays of GalLDH were performed in the presence of SIN-1 (peroxynitrite donor and S-nitrosoglutahione (NO donor. Combined results of in vivo NO treatment and in vitro assays showed that NO provoked the regulation of GalLDH at transcriptional and post-transcriptional levels, but not post-translational modifications through nitration or S-nitrosylation events promoted by reactive nitrogen species (RNS took place. These results suggest that this modulation point of the ascorbate biosynthesis could be potentially used for biotechnological purposes to increase the vitamin C levels in pepper fruits.

  19. ANTS-anchored Zn-Al-CO3-LDH particles as fluorescent probe for sensing of folic acid

    Science.gov (United States)

    Liu, Pengfei; Liu, Dan; Liu, Yanhuan; Li, Lei

    2016-09-01

    A novel fluorescent nanosensor for detecting folic acid (FA) in aqueous media has been developed based on 8-aminonaphthalene-1,3,6-trisulfonate (ANTS) anchored to the surface of Zn-Al-CO3-layered double hydroxides (LDH) particles. The nanosensor showed high fluorescence intensity and good photostability due to a strong coordination interaction between surface Zn2+ ions of Zn-Al-CO3-LDH and N atoms of ANTS, which were verified by result of X-ray photoelectron spectroscopy (XPS). ANTS-anchored on the surface of Zn-Al-CO3-LDH restricted the intra-molecular rotation leading to ANTS-anchored J-type aggregation emission enhancement. ANTS-anchored Zn-Al-CO3-LDH particles exhibited highly sensitive and selective response to FA over other common metal ions and saccharides present in biological fluids. The proposed mechanism was that oxygen atoms of -SO3 groups in ANTS-anchored on the surface of Zn-Al-CO3-LDH were easily collided by FA molecules to form potential hydrogen bonds between ANTS-anchored and FA molecules, which could effectively quench the ANTS-anchored fluorescence. Under the simulated physiological conditions (pH of 7.4), the fluorescence quenching was fitted to Stern-Volmer equation with a linear response in the concentration range of 1 μM to 200 μM with a limit of detection of 0.1 μM. The results indicate that ANTS-anchored Zn-Al-CO3-LDH particles can afford a very sensitive system for the sensing FA in aqueous solution.

  20. Lactate dehydrogenase activity of rat epididymis and spermatozoa: Effect of constant light

    Directory of Open Access Journals (Sweden)

    RH Ponce

    2009-12-01

    Full Text Available During its passage through the epididymis, the gamete undergoes a process of “maturation” leading to the acquisition of its fertilizing ability. The epididymis displays regional variations in the morphology and metabolic properties of its epithelium which are relevant for the progressive development of mature sperm characteristics. The epididymis has spontaneous peristaltic contractions and receives sympathetic innervation that is modulated by melatonin, a hormone synthesized and released by the pineal gland. Constant lighting disrupts melatonin synthesis and secretion. We have studied the effect of constant light on lactate dehydrogenase (LDH; EC 1.1.1.27 and its isozyme C4 activities and protein content in whole epididymis, epididymal tissue and in spermatozoa from caput and cauda segments. Animals were exposed from birth to an illumination schedule of 14 h light: 10 h dark (group L:D. At 60 days of age one group of animals was submitted to constant light over 50 days (group L:L. In order to test the fertilizing ability, the rats of each group were mated with soliciting estrous females. The percentage of pregnancies in females mated with males maintained in L:L was remarkably lower than those in females mated with males maintained in the L:D photoperiod (44% and 88% respectively. Constant light increased protein concentration and LDH activity in caput as well as in cauda of total epididymis. On the contrary, in epididymal tissue, the protein content decreased in both epididymal sections compared with controls. When enzymatic activity was expressed in Units per spermatozoa, constant light induced a significant reduction of total LDH and LDHC4 in caput and cauda spermatozoa while LDH activity of epididymal tissue was not affected. In spite of the decrease in LDH per sperm cell when rats were exposed to constant light, in total epididymis (epididymis tissue plus sperm cells content and in spermatozoa, values of enzyme activities expressed per

  1. Highly stereoselective biosynthesis of (R)-α-hydroxy carboxylic acids through rationally re-designed mutation of D-lactate dehydrogenase.

    Science.gov (United States)

    Zheng, Zhaojuan; Sheng, Binbin; Gao, Chao; Zhang, Haiwei; Qin, Tong; Ma, Cuiqing; Xu, Ping

    2013-12-02

    An NAD-dependent D-lactate dehydrogenase (D-nLDH) of Lactobacillus bulgaricus ATCC 11842 was rationally re-designed for asymmetric reduction of a homologous series of α-keto carboxylic acids such as phenylpyruvic acid (PPA), α-ketobutyric acid, α-ketovaleric acid, β-hydroxypyruvate. Compared with wild-type D-nLDH, the Y52L mutant D-nLDH showed elevated activities toward unnatural substrates especially with large substitutes at C-3. By the biocatalysis combined with a formate dehydrogenase for in situ generation of NADH, the corresponding (R)-α-hydroxy carboxylic acids could be produced at high yields and highly optical purities. Taking the production of chiral (R)-phenyllactic acid (PLA) from PPA for example, 50 mM PPA was completely reduced to (R)-PLA in 90 min with a high yield of 99.0% and a highly optical purity (>99.9% e.e.) by the coupling system. The results presented in this work suggest a promising alternative for the production of chiral α-hydroxy carboxylic acids.

  2. Novel 11β-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV

    OpenAIRE

    Boudon, Stéphanie M.; Vuorinen, Anna; Geotti-Bianchini, Piero; Wandeler, Eliane; Kratschmar, Denise V.; Heidl, Marc; Campiche, Remo; Jackson, Eileen; Odermatt, Alex

    2017-01-01

    Activity and selectivity assessment of new bi-aryl amide 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11β-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11β-HSD1 over 11β-HSD2, 17β-HSD1 and 17β-HSD2. These inhibitors also potently inhibited 11β-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme a...

  3. Technical note: comparison of the PrestoBlue and LDH release assays with the MTT assay for skin viability assessment.

    Science.gov (United States)

    Gaucher, Sonia; Jarraya, Mohamed

    2015-09-01

    MTT assay is the gold standard for assessing skin sample viability but it is time-consuming. Here we compared the MTT test with two other assays for the assessment of skin viability. The MTT, PrestoBlue (colorimetric method) and LDH release assays were applied to fresh and cryopreserved skin. Skin viability was considered proportional to the optical density values of the relevant analytes. PrestoBlue did not reliably distinguish between fresh and cryopreserved skin. The LDH release assay did not allow us to establish a viability index. We recommend the MTT assay for assessing skin viability.

  4. Transcriptional Regulation of Pyruvate Dehydrogenase Kinase

    Directory of Open Access Journals (Sweden)

    Ji Yun Jeong

    2012-10-01

    Full Text Available The pyruvate dehydrogenase complex (PDC activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK isoenzymes. Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear. Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway. Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified. It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners. In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.

  5. Preparation and Morphology of Polyvinyl Chloride/LDH Nanocomposites%PVC/LDH纳米复合材料的制备及形貌

    Institute of Scientific and Technical Information of China (English)

    黄年华; 李治华; 王维; 刘肖

    2009-01-01

    Exfoliated polyvinyl chloride(PVC)/MgAl hyered double hydroxide(LDH) nanocomposites were synthesized by a solution delamination-restacking method through tetrahydrofuran(THF) as solvent. The structures of hurylether phosphate modified LDH and PVC/LDH nanocomposites were characterized by FTIR, XRD, TEM and TGA. The effects of preparation conditions including the content of LDH in PVC matix, the concentration and delamination time of LDH in THF on the struc-ture of nanocornposites were studied. The XRD and TEM results show completely exfoliated LDH layers can be achieved by de-creasing the content of LDH and the concentration of LDH in THF, elongating the delamination time of LDH in TFIF, and ex-foliated LDH hyers disorderedly disperse in the PVC matrix. The TGA results show that PVC/LDH nanocomposites have sig-nificandy enhanced thermal stability. When 30% weight loss is selected as a point of comparison, the thermal decomposition temperature of exfoliated PVC/LDH nanocomposite with 2% LDH is 16 ℃ higher than that of pristine PVC. The char residue of these nanocomposites at 650 ℃ is increased by the presence of LDH.%以四氢呋喃为溶剂,通过溶液层离/重组法制备了聚氯乙烯(PVC)/层状双氢氧化物(LDH)纳米复合材料.采用TEM、XRD、FTIR和TGA等手段研究了十二烷基单磷酸根离子(PK)改性的层状双氢氧化物(LDH-PK)及其纳米复合材料的结构与性能,并系统考察了各种制备条件对纳米复合材料结构的影响.XRD和TEM结果表明,剥离型纳米复合材料可通过减少LDH在聚合物中的含量及在四氢呋喃中的浓度和增加层离时间等条件获得;剥离的LDH片层无序的分散在PVC基材中.TGA结果表明,纳米复合材料相比于纯PVC具有更好的热稳定性;以30%失重为比较点,当LDH的质量百分含量为2%时,纳米复合材料的热降解温度比纯PVC高出近16℃,并能显著促进PVC成炭.

  6. NAD-independent L-lactate dehydrogenase is required for L-lactate utilization in Pseudomonas stutzeri SDM.

    Directory of Open Access Journals (Sweden)

    Chao Gao

    Full Text Available BACKGROUND: Various Pseudomonas strains can use L-lactate as their sole carbon source for growth. However, the L-lactate-utilizing enzymes in Pseudomonas have never been identified and further studied. METHODOLOGY/PRINCIPAL FINDINGS: An NAD-independent L-lactate dehydrogenase (L-iLDH was purified from the membrane fraction of Pseudomonas stutzeri SDM. The enzyme catalyzes the oxidation of L-lactate to pyruvate by using FMN as cofactor. After cloning its encoding gene (lldD, L-iLDH was successfully expressed, purified from a recombinant Escherichia coli strain, and characterized. An lldD mutant of P. stutzeri SDM was constructed by gene knockout technology. This mutant was unable to grow on L-lactate, but retained the ability to grow on pyruvate. CONCLUSIONS/SIGNIFICANCE: It is proposed that L-iLDH plays an indispensable function in Pseudomonas L-lactate utilization by catalyzing the conversion of L-lactate into pyruvate.

  7. Adsorption of lactate dehydrogenase enzyme on carbon nanotubes: how to get accurate results for the cytotoxicity of these nanomaterials.

    Science.gov (United States)

    Forest, Valérie; Figarol, Agathe; Boudard, Delphine; Cottier, Michèle; Grosseau, Philippe; Pourchez, Jérémie

    2015-03-31

    Carbon nanotube (CNT) cytotoxicity is frequently investigated using in vitro classical toxicology assays. However, these cellular tests, usually based on the use of colorimetric or fluorimetric dyes, were designed for chemicals and may not be suitable for nanosized materials. Indeed, because of their unique physicochemical properties CNT can interfere with the assays and bias the results. To get accurate data and draw reliable conclusions, these artifacts should be carefully taken into account. The aim of this study was to evaluate qualitatively and quantitatively the interferences occurring between CNT and the commonly used lactate dehydrogenase (LDH) assay. Experiments under cell-free conditions were performed, and it was clearly demonstrated that artifacts occurred. They were due to the intrinsic absorbance of CNT on one hand and the adsorption of LDH at the CNT surface on the other hand. The adsorption of LDH on CNT was modeled and was found to fit the Langmuir model. The K(ads) and n(eq) constants were defined, allowing the correction of results obtained from cellular experiments to get more accurate data and lead to proper conclusions on the cytotoxicity of CNT.

  8. The role of hydrophobic amino acids of K-segments in the cryoprotection of lactate dehydrogenase by dehydrins.

    Science.gov (United States)

    Hara, Masakazu; Endo, Takuya; Kamiya, Keita; Kameyama, Ayuko

    2017-03-01

    Dehydrins, which are group 2 late embryogenesis abundant (LEA) proteins, accumulate in plants during the development of the embryo and exposure to abiotic stresses including low temperature. Dehydrins exhibit cryoprotection of freezing-sensitive enzymes, e.g. lactate dehydrogenase (LDH). Although it has been reported that K-segments conserved in dehydrins are related to their cryoprotection activity, it has not been determined which sequence features of the K-segments contribute to the cryoprotection. A cryoprotection assay using LDH indicated that 13 K-segments including 12 K-segments found in Arabidopsis dehydrins and a typical K-segment (TypK, EKKGIMEKIKEKLPG) derived from the K-segments of many plants showed similar cryoprotective activities. Mutation of the TypK sequence demonstrated that hydrophobic amino acids were clearly involved in preventing the cryoinactivation, cryoaggregation, and cryodenaturation of LDH. We propose that the cryoprotective activities of dehydrins may be made possible by the hydrophobic residues of the K-segments. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. A new high phenyl lactic acid-yielding Lactobacillus plantarum IMAU10124 and a comparative analysis of lactate dehydrogenase gene.

    Science.gov (United States)

    Zhang, Xiqing; Zhang, Shuli; Shi, Yan; Shen, Fadi; Wang, Haikuan

    2014-07-01

    Phenyl lactic acid (PLA) has been widely reported as a new natural antimicrobial compound. In this study, 120 Lactobacillus plantarum strains were demonstrated to produce PLA using high-performance liquid chromatography. Lactobacillus plantarum IMAU10124 was screened with a PLA yield of 0.229 g L(-1) . Compared with all previous reports, this is the highest PLA-producing lactic acid bacteria (LAB) when grown in MRS broth without any optimizing conditions. When 3.0 g L(-1) phenyl pyruvic acid (PPA) was added to the medium as substrate, PLA production reached 2.90 g L(-1) , with the highest 96.05% conversion rate. A lowest PLA-yielding L. plantarum IMAU40105 (0.043 g L(-1) ) was also screened. It was shown that the conversion from PPA to PLA by lactic dehydrogenase (LDH) is the key factor in the improvement of PLA production by LAB. Comparing the LDH gene of two strains, four amino acid mutation sites were found in this study in the LDH of L. plantarum IMAU10124.

  10. Preparation and electrochemical performances of in-situ Ni/Al-LDH/MCNTs composites%Ni/Al-LDH/MCNTs原位复合材料的制备与电化学性能

    Institute of Scientific and Technical Information of China (English)

    李延伟; 梁晓丽; 姚金环; 姜吉琼

    2014-01-01

    Ni/Al-LDH/MCNTs composites with MCNTs contents of 1%, 3%, and 5%were prepared by the in-situ homogeneous precipitation method with Ni(NO3)3·6H2O, Al(NO3)3·9H2O, urea, and MCNTs as raw materials. The microstructure and morphology of the Ni/Al-LDH/MCNTs composites were analyzed with X-ray diffraction (XRD), Fourier transform infrared (FTIR) and field emission scanning electron microscopy (FESEM). The electrochemical performance of the Ni/Al-LDH/MCNTs composites used as cathode materials for nickel-hydrogen battery were characterized with cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and charge-discharge tests. The results demonstrated that the introduction of MCNTs could enhance electrochemical activity, decrease electrochemical reaction resistance, and significantly improve high rate performance of Ni/Al-LDH. In particular, the Ni/Al-LDH/MCNTs composite with MCNTs content of 3% had the best electrochemical performance. For example, the specific discharge capacities of the Ni/Al-LDH/MCNTs composite with MCNTs content of 3%under current densities of 200, 500, 1000, and 2000 mA·g-1 were 330, 321, 307, and 288 mA·h·g-1, respectively. While for the Ni/Al-LDH without MCNTs, the specific discharge capacity was only 205 mA·h·g-1 under the current density of 2000 mA·g-1.%以Ni(NO3)2·6H2O、Al(NO3)3·9H2O、尿素和MCNTs为原料,采用原位均相沉淀法制备了MCNTs含量(质量分数)分别为1%、3%和5%的Ni/Al-LDH/MCNTs复合电极活性材料。采用X射线衍射(XRD)、傅里叶变换红外光谱(FTIR)和场发射扫描电子显微镜(FESEM)表征了材料的微观结构和形貌;采用循环伏安(CV)、电化学交流阻抗(EIS)和充放电测试研究了该复合材料作为镍氢电池正极材料的电化学性能。结果表明,在Ni/Al-LDH 中复合 MCNTs 能够提高材料的电化学活性,降低电化学反应电阻,显著改善材料的大电流充放电性能。其中MCNTs含量为3

  11. Ni adsorption and Ni-Al LDH precipitation in a sandy aquifer: An experimental and mechanistic modeling study

    NARCIS (Netherlands)

    Regelink, I.C.; Temminghoff, E.J.M.

    2011-01-01

    Mining activities and industries have created nickel (Ni) contaminations in many parts of the world. The objective of this study is to increase our understanding of Ni adsorption and Nickel-Aluminium Layered Double Hydroxide (Ni-Al LDH) precipitation to reduce Ni mobility in a sandy soil aquifer. At

  12. Electrostatic self-assembly of sandwich-like CoAl-LDH/polypyrrole/graphene nanocomposites with enhanced capacitive performance.

    Science.gov (United States)

    Zhang, Yu; Du, Dongfeng; Li, Xuejin; Sun, Hongman; Li, Li; Bai, Peng; Xing, Wei; Xue, Qingzhong; Yan, Zifeng

    2017-09-01

    A novel sandwich-like composite with ultrathin CoAl-LDH nanoplates electrostatically assembled on both sides of 2D polypyrrole/graphene (PG) substrate has been successfully fabricated using facile hydrothermal techniques. The PG not only serves as an excellent conductive and structural scaffold to enhance the transmission of electrons and prevents aggregation of CoAl-LDH nanoplates, but also contributes to the enhancement of the specific capacitance. Owing to the homogeneous dispersion of CoAl-LDH nanoplates and its intimate interaction with PG substrate, the resulting CoAl-LDH/PG nanocomposite material exhibits excellent capacitive performance, e.g. enhanced gravimetric specific capacitance (864 F g-1 at 1 A g-1 ), high rate performance (75% retention at 20 A g-1) and excellent cyclic life (almost no degradation in supercapacitor performance after 5000 cycles) in aqueous KOH solution. Furthermore, the assembled asymmetric capacitor is able to deliver superhigh energy density of 46.8 Wh kg-1 at 1.2 kW kg-1 and maintain 90.1% of its initial capacitance after 10000 cycles. These results indicate a rational assembly strategy towards a high-performance pseudocapacitive electrode material with excellent rate performance, high specific capacitance and outstanding cycle stability.

  13. Co intake mediated formation of ultrathin nanosheets of transition metal LDH-an advanced electrocatalyst for oxygen evolution reaction.

    Science.gov (United States)

    Long, Xia; Xiao, Shuang; Wang, Zilong; Zheng, Xiaoli; Yang, Shihe

    2015-01-21

    By controlling the ratio of tri- and bi-valent ions, multi-transition metal based layered double hydroxide (LDH) ultrathin nanosheets are synthesized. They show advanced OER performance with low overpotentials (∼0.2 V) and decreased Tafel slopes with increasing Co incorporation due to the modulated electronic structures of catalytic centers and the increased surface area and electronic conductivity.

  14. Efficient production of (R-2-hydroxy-4-phenylbutyric acid by using a coupled reconstructed D-lactate dehydrogenase and formate dehydrogenase system.

    Directory of Open Access Journals (Sweden)

    Binbin Sheng

    Full Text Available (R-2-hydroxy-4-phenylbutyric acid [(R-HPBA] is a key precursor for the production of angiotensin-converting enzyme inhibitors. However, the product yield and concentration of reported (R-HPBA synthetic processes remain unsatisfactory.The Y52L/F299Y mutant of NAD-dependent D-lactate dehydrogenase (D-nLDH in Lactobacillus bulgaricus ATCC 11842 was found to have high bio-reduction activity toward 2-oxo-4-phenylbutyric acid (OPBA. The mutant D-nLDHY52L/F299Y was then coexpressed with formate dehydrogenase in Escherichia coli BL21 (DE3 to construct a novel biocatalyst E. coli DF. Thus, a novel bio-reduction process utilizing whole cells of E. coli DF as the biocatalyst and formate as the co-substrate for cofactor regeneration was developed for the production of (R-HPBA from OPBA. The biocatalysis conditions were then optimized.Under the optimum conditions, 73.4 mM OPBA was reduced to 71.8 mM (R-HPBA in 90 min. Given its high product enantiomeric excess (>99% and productivity (47.9 mM h(-1, the constructed coupling biocatalysis system is a promising alternative for (R-HPBA production.

  15. Direct Enzymatic Assay for Alcohol Oxidase, Alcohol Dehydrogenase, and Formaldehyde Dehydrogenase in Colonies of Hansenula polymorpha

    OpenAIRE

    Eggeling, L; Sahm, H

    1980-01-01

    A procedure is described for the qualitative direct identification of alcohol oxidase, alcohol dehydrogenase, and formaldehyde dehydrogenase in yeast colonies. The method has been applied successfully to isolate mutants of Hansenula polymorpha with altered glucose repression of alcohol oxidase.

  16. Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.

    Directory of Open Access Journals (Sweden)

    Delphine Mirebeau-Prunier

    Full Text Available Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα, a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis.

  17. The enzymatic reaction catalyzed by lactate dehydrogenase exhibits one dominant reaction path

    Science.gov (United States)

    Masterson, Jean E.; Schwartz, Steven D.

    2014-10-01

    Enzymes are the most efficient chemical catalysts known, but the exact nature of chemical barrier crossing in enzymes is not fully understood. Application of transition state theory to enzymatic reactions indicates that the rates of all possible reaction paths, weighted by their relative probabilities, must be considered in order to achieve an accurate calculation of the overall rate. Previous studies in our group have shown a single mechanism for enzymatic barrier passage in human heart lactate dehydrogenase (LDH). To ensure that this result was not due to our methodology insufficiently sampling reactive phase space, we implement high-perturbation transition path sampling in both microcanonical and canonical regimes for the reaction catalyzed by human heart LDH. We find that, although multiple, distinct paths through reactive phase space are possible for this enzymatic reaction, one specific reaction path is dominant. Since the frequency of these paths in a canonical ensemble is inversely proportional to the free energy barriers separating them from other regions of phase space, we conclude that the rarer reaction paths are likely to have a negligible contribution. Furthermore, the non-dominate reaction paths correspond to altered reactive conformations and only occur after multiple steps of high perturbation, suggesting that these paths may be the result of non-biologically significant changes to the structure of the enzymatic active site.

  18. Comparison of Activity of Four Dehydrogenases in Ginseng from Different Origins%不同产地人参中4种脱氢酶活力比较

    Institute of Scientific and Technical Information of China (English)

    杨菲; 赵雨; 王思明; 刘美辰; 李晓华

    2012-01-01

    The aim was to provide theoretical basis for the cultivation and optimization of ginseng.Adopt neutral buffer solution to extract the enzyme solution of Radix Ginseng.The activities of malate dehydrogenase (MDH), lactate dehydrogenase (LDH), alcohol dehydrogenase (ADH) and glucose-6-phosphate dehydrogenase (G6PDH) were detected by spectrophotometry, and compared.The clustering analysis was performed using the software SPSS 13.0 to system for 15 batch sample.There were obvious differences of the activities dehydrogenase of ginseng from different origin.The activities of four dehydrogenases from the same origin were basically same.In Antu County Wanbao Town, MDH, LDH and G6PDH had the highest activities, 124.58 LV(g·FW), 129.88 U/(g·FW) and 109.84 U/(g·FW) respectively.The four kinds of enzymes activity of two origins in Heilongjiang Province were generally low.The sample was divided into four categories.The activities of MDH, LDH, ADH and G6PDH could provide theoretical basis for the cultivation and optimization of ginseng.%为了给人参的培育和优选提供理论依据,采用中性缓冲液提取粗酶液,应用分光光度法对15个不同产地的人参中苹果酸脱氢酶(malate dehydrogenase,MDH)、乳酸脱氢酶(lactate dehydrogenase,LDH)、乙醇脱氢酶(alcohol dehydrogenase,ADH)、葡萄糖-6-磷酸脱氢酶(glucose-6-phosphate dehydrogenase,G6PDH)4种脱氢酶活力进行比较.运用SPSS 13.0软件对15批样品进行系统聚类分析.结果表明不同产地人参脱氢酶活力差别明显,同一产地4种脱氢酶活力趋势基本相同.其中安图县万宝镇的人参样品的MDH、LDH、G6PDH 3种酶活力均是最高值,分别为124.58 U/(g· FW)、129.88 U/(g·FW)、109.84U/(g·FW);黑龙江2个产地的4种酶活力普遍比较低.聚类分析的结果将样品分为4类.MDH、LDH、ADH、G6PDH的活力可以作为人参培育和优选提供理论依据.

  19. Butachlor impact on protein, free amino acid and glutamine contents, and on activity levels of aminotransferases, glutamate dehydrogenase and glutamine synthetase in the fresh water snail, Pila globosa (Swainson).

    Science.gov (United States)

    Rajyalakshmi, T; Srinivas, T; Swamy, K V; Mohan, P M

    1996-08-01

    Biochemical changes followed in the freshwater snail Pila globosa (Swainson) during exposure to sublethal concentrations of the herbicide butachlor (26.6 ppm) in the ambient medium, at 3,6,12,24 and 48 h intervals, were marked by a significant decrease in total and soluble proteins, and an increase in free amino acids in foot and hepatopancreas up to 12 h before gradually recovering. Aminotransferase activities and glutamine content decreased during the early periods of exposure, while glutamate dehydrogenase activity increased. After an initial elevation, glutamate synthetase activity decreased at later intervals. Maximum effect of butachlor on the enzymes was seen after 12 h exposure. The extent of increase or decrease in different parameters examined varied between the two tissues studied. These changes are discussed in relation to the toxic stress of butachlor.

  20. Effect of osmolytes on protein dynamics in the lactate dehydrogenase-catalyzed reaction.

    Science.gov (United States)

    Zhadin, Nickolay; Callender, Robert

    2011-03-15

    Laser-induced temperature jump relaxation spectroscopy was used to probe the effect of osmolytes on the microscopic rate constants of the lactate dehydrogenase-catalyzed reaction. NADH fluorescence and absorption relaxation kinetics were measured for the lactate dehydrogenase (LDH) reaction system in the presence of varying amounts of trimethylamine N-oxide (TMAO), a protein-stabilizing osmolyte, or urea, a protein-destabilizing osmolyte. Trimethylamine N-oxide (TMAO) at a concentration of 1 M strongly increases the rate of hydride transfer, nearly nullifies its activation energy, and also slightly increases the enthalpy of hydride transfer. In 1 M urea, the hydride transfer enthalpy is almost nullified, but the activation energy of the step is not affected significantly. TMAO increases the preference of the closed conformation of the active site loop in the LDH·NAD(+)·lactate complex; urea decreases it. The loop opening rate in the LDH·NADH·pyruvate complex changes its temperature dependence to inverse Arrhenius with TMAO. In this complex, urea accelerates the loop motion, without changing the loop opening enthalpy. A strong, non-Arrhenius decrease in the pyruvate binding rate in the presence of TMAO offers a decrease in the fraction of the open loop, pyruvate binding competent form at higher temperatures. The pyruvate off rate is not affected by urea but decreases with TMAO. Thus, the osmolytes strongly affect the rates and thermodynamics of specific events along the LDH-catalyzed reaction: binding of substrates, loop closure, and the chemical event. Qualitatively, these results can be understood as an osmolyte-induced change in the energy landscape of the protein complexes, shifting the conformational nature of functional substates within the protein ensemble.

  1. Synthesis of Co-Al-Cl LDH by cathodic material reprocessing from cellular phone batteries

    Energy Technology Data Exchange (ETDEWEB)

    Amaral, Fabio Augusto do; Machado, Erica Oliveira; Freitas, Leonardo Luis de; Santana, Laiane Kalita; Canobre, Sheila Cristina, E-mail: fabioamaral@yahoo.com.br, E-mail: fabioamaral@iqufu.ufu.br [Universidade Federal de Uberlandia (UFU/LAETE), (Brazil). Inst. de Quimica. Lab. de Armazenamento de Energia e Tratamento de Efluente

    2014-08-15

    The aim of this paper was the recovering of the cathodic material from discarded lithium ion batteries for obtainment of the lamellar double hydroxides (LDHs) by the co-precipitation method at variable pH in HCl and H{sub 2}O{sub 2} 1:1 (v/v) acid solution containing Co and Al (extracted from cathodic material composed of LiCoO{sub 2} and aluminum foil). These metals were precipitated in LiOH at pH 9 or 11, or NH{sub 4}OH at pH 9 and submitted to the hydrothermal treatment (HT) to improve the structural organization of the LDHs lamellae. After precipitation, the resulting solids were structurally characterized by XRD for phase identification and calculation of the unit cell parameter, thermally by TGA for the identification of the mass loss and morphologically by SEM. The sample obtained by precipitation with LiOH at pH 11 / hydrothermal treatment showed diffraction peaks similar to hydrotalcite, morphological and thermal characteristics similar to the pattern Co-Al-Cl LDH obtained by co-precipitation at constant pH 8. (author)

  2. Direct Synthesis of Unilamellar MgAl-LDH Nanosheets and Stacking in Aqueous Solution.

    Science.gov (United States)

    Liang, Dujuan; Yue, Wenbo; Sun, Genban; Zheng, Dong; Ooi, Kenta; Yang, Xiaojing

    2015-11-17

    Two-dimensional (2D) materials, such as graphene, inorganic oxides, and hydroxides, are one of the most extensively studied classes of materials due to their unilamellar crystallites or nanosheet structures. In this study, instead of using the universal exfoliation method of the bulky crystal precursor, 2D crystals/nanosheets of MgAl-layered double hydroxides (LDHs) were synthesized in formamide. We propose that the obtained crystals are unilamellar according to the XRD, TEM, and AFM observations. The HRTEM and fast Fourier transform images confirm that the crystal structures are the same as those of the exfoliated MgAl-LDH nanosheets. The directly synthesized sheets can stack into a 3D crystal structure, which is the same as that of typical LDHs except for the disordered orientation of the a-/b- crystal axis of each sheet. This result provides not only a novel approach to the preparation of 2D crystals but also insight into the formation mechanism of LDHs.

  3. Role of the synthesis route on the properties of hybrid LDH-graphene as basic catalysts

    Science.gov (United States)

    Álvarez, Mayra G.; Tichit, Didier; Medina, Francesc; Llorca, Jordi

    2017-02-01

    Layered double hydroxides (LDH or HT) or their derived mixed oxides present marked acid-base properties useful in catalysis, but they lead to agglomerate inducing a weak accessibility to the active sites. In this study we report the preparation and characterization of HT/Graphene (HT/rGO) nanocomposites as active and selective basic catalysts for the acetone condensation reaction. The graphene high specific surface area and structural compatibility with the HT allowed increasing the number and accessibility of the active sites and activity of this later. Two series of HT/rGO nanocomposites with 0.5 ≤ HT/rGO ≤ 10 mass ratio were prepared by: i) direct HT coprecipitation in the presence of GO; ii) self-assembly of preformed HT with GO. The prepared HT/rGO nanocomposites were dried either in air at 80 °C or freeze-dried. A series of characterizations showed the great influence of the preparation method and HT/rGO mass ratio on both the nanocomposite structure and catalytic activity. An optimum activity was observed for a HT/rGO = 10 catalyst. Particularly, the highest catalytic activity was found in those nanocomposites obtained by coprecipitation and freeze dried (3 times more active than bulk HT) which can be connected to their structure with a better accessibility to the basic sites.

  4. Potassium but not lactate dehydrogenase elevation due to in vitro hemolysis is higher in capillary than in venous blood samples.

    Science.gov (United States)

    Oostendorp, Marlies; van Solinge, Wouter W; Kemperman, Hans

    2012-10-01

    Elevated potassium concentrations due to in vitro hemolysis can lead to errors in diagnoses and treatment. Recently, we observed that potassium elevation in capillary samples appeared higher than expected, based on hemolytic index (H-index). To investigate the relation between potassium increase and H-index for capillary samples. As a control, the same analysis was performed for lactate dehydrogenase (LDH). Potassium results of 332 760 venous and 2620 capillary samples were selected. For LDH, 135 974 venous and 999 capillary samples were included. Venous and capillary samples were differentiated by using patient age, as we perform mostly capillary blood sampling in children and venous sampling in adults. Results were obtained with Beckman-Coulter DxC800 analyzers. The increase in potassium with increasing H-index was considerably higher for capillary samples than venous samples. Linear regression revealed a potassium increase of 0.38 mEq/L per increment in H-index for capillary samples, whereas a 0.17 mEq/L increase was found for venous samples. For LDH, no differences were found between venous and capillary samples. At identical H-index, capillary samples showed higher potassium elevations than venous samples. A possible explanation is that capillary sampling causes increased leakage of ions, such as potassium, from erythrocytes, compared with proteins such as hemoglobin and LDH. These results are especially important considering the increasing use of whole blood point-of-care analyzers, where the H-index is often not determined. Potassium results should therefore be interpreted with caution to avoid severe misdiagnosis of hypokalemia and hyperkalemia.

  5. Prognostic value of neglected biomarker in sepsis patients with the old and new criteria: predictive role of lactate dehydrogenase.

    Science.gov (United States)

    Duman, Ali; Akoz, Ayhan; Kapci, Mucahit; Ture, Mevlut; Orun, Serhat; Karaman, Kıvanc; Turkdogan, Kenan Ahmet

    2016-11-01

    This study examined the pH, lactate dehydrogenase (LDH), and heart rate values on the first day of hospitalization in patients with a prediagnosis of sepsis and biomarkers that may predict mortality. Patients hospitalized in an emergency intensive care unit with a diagnosis of systemic inflammatory response syndrome were classified as having sepsis (n = 28), septic shock (n = 8), or severe sepsis (n = 8) according to International Sepsis Guidelines (old criteria). Forty-four patients were classified as having sepsis (n = 4), septic shock (n = 30), or infection (n = 10) according to The Third International Consensus Definitions for Sepsis and Septic Shock (new criteria). The effects of these patients' laboratory values on survival between groups were compared. Significant values were evaluated by χ(2) automatic interaction detection analysis. When the patients were categorized according to the new classification criteria, there was an increase in the number of septic shock patients and a decrease in the number of sepsis patients. In addition, 10 patients were removed from the sepsis category. There was a significant difference between ex and discharged patients in terms of heart rate, pH, sodium bicarbonate, lactate, and LDH (P= .007, P= .002, P= .034, P= .009, and P= .002, respectively). Based on a χ(2) automatic interaction detection analysis of the significant values, pH, LDH, and heart rate were prominent predictors of prognosis. Systemic pH, LDH, and heart rate values may be used to determine the best time to discharge patients from intensive care to other, more affordable hospital units. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Anti-Metastatic and Anti-Angiogenic Activities of Core-Shell SiO2@LDH Loaded with Etoposide in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Zhu, Yanjing; Zhu, Rongrong; Wang, Mei; Wu, Bin; He, Xiaolie; Qian, Yechang; Wang, Shilong

    2016-11-01

    Currently, nanoparticles have gained a great attention in the anti-tumor research area. However, to date, studies on the anti-metastasis action of core-shell SiO2@LDH (LDH: layered double hydroxide) nanoparticles remain untouched. Two emerging aspects considered are establishing research on the controlling delivery effect of SiO2@LDH combined with anti-cancer medicine from a new perspective. The fine properties synthetic SiO2@LDH-VP16 (VP16: etoposide) are practiced to exhibit the nanoparticle's suppression on migration and invasion of non-small cell lung cancer (NSCLC). Both in vitro and in vivo inspection shows that SiO2@LDH can help VP16 better function as an anti-metastasis agent. On the other hand, anti-angiogenic efficiency, co-localization, as well as western blot are investigated to explain the possible mechanism. A clear mergence of SiO2@LDH-VP16 and cytomembrane/microtubule may be observed from co-location images. Results offer evidence that SiO2@LDH-VP16 plays positions on cytomembrane and microtubules. It efficiently inhibits metastasis on NSCLC by reducing vascularization, and eliciting depression of the PI3K-AKT and FAK-Paxillin signaling pathways. SiO2@LDH-VP16, the overall particle morphology, and function on anti-metastasis and anti-angiogenic may be tuned to give new opportunities for novel strategies for cancer therapy.

  7. C-REACTIVE PROTEIN AND LACTATE DEHYDROGENASE IN SERUM AND CEREBROSPINAL FLUID IN RAPID AND EARLY DIAGNOSIS OF CHILDHOOD MENINGITIS

    Directory of Open Access Journals (Sweden)

    F. Jadali MD,

    2007-08-01

    Full Text Available ObjectiveBacterial meningitis is still a life threatening epidemiological problem especiallyin many developing countries; considering its dire consequences, its promptand accurate diagnosis has become a priority for clinicians. Because of thevarious limitations of conventionally used laboratory techniques, we evaluatedand compared the diagnostic utility of C-reactive protein(CRP and lactatedehydrogenase (LDHin serum and cerebrospinal fluid (CSFin the diagnosisof bacterial meningitis and its effectivity in distinguishing it from asepticmeningitis (AP.Material and MethodsA total of 125 pediatric cases, aged between 1 month and 12 years, includingpatients with bacterial meningitis (n=45, aseptic meningitis (n=42 and acontrol group (n=38, were retrospectively analyzed on the basis of datafrom the initial clinical examinations. Cultures, smears and other commonserum and CSF indices were compared with serum and CSF CRP levels andLDH activity.ResultsCompared with each of the other variables, there were significant differencesin the mean values of serum-CRP, CSF-glucose, CSF-LDH and CSF/serumLDH ratio between the bacterial and aseptic meningitis groups (p<0.001.Of all the tests applied, the highest sensitivity (95% and negative predictivevalue (95% belonged to CSF-LDH activity and the most specific (100% testwith the highest positive predictive value (100% was CSF-CRP titration aswell as smear and culture. Combination of CSF-CRP serum-CRP, and CSFLDHyielded the highest sensitivity (100% and negative predictive value butthe combined application of CSF-LDH and CSF-CRP proved to be the mostspecific and efficient.ConclusionIn the presence of a normal CRP titration and low glucose level in CSF,bacterial meningitis is excluded, whereas elevated level of CSF-LDH activityis a valid confirmatory predictor of BM. In addition, combination of thesethree tests with serum CRP is far more effective than the separate determinationof any of these parameters.

  8. 猪带绦虫乳酸脱氢酶A和B的生物信息学比较分析%Bioinformatics Analysis and Comparision of the Genes Encoding Lactate Dehydrogenase A and B from Taenia solium

    Institute of Scientific and Technical Information of China (English)

    杜武英; 戴佳琳; 黄艳; 胡旭初; 余新炳; 徐劲; 廖兴江; 黄江

    2010-01-01

    目的 预测及比较分析猪带绦虫乳酸脱氢酶A(Taenia solium lactate dehydrogenase A,TsLDH-A)和乳酸脱氢酶B(Taenia solium lactate dehydrogenase B,TsLDH-B),用于指导其生物学功能的研究.方法 利用生物信息网站如美国国家生物技术信息中心(NCBI,http://www.ncbi.nlm.nih.gov/)和瑞士生物信息学研究所的蛋白分析专家系统(ExPASY,http://ca.expasy.org/)中有关基因和蛋白的序列和结构信息分析的各种工具,结合其它生物信息学分析软件包,从猪带绦虫成虫全长cDNA质粒文库中识别LDH-A和LDH-B的全长编码基因并对其结构与功能进行生物信息学预测分析.结果 两序列都是包含完整开放阅读框的全长基因,推导出的氨基酸序列与其它物种LDH-A或LDH-B同源基因的氨基酸序列的一致性均大于50%.两者编码的蛋白在编码的氨基酸数目(331)、蛋白的理化性质、L-乳酸脱氢酶结构域、构成LDH酶催化中心的关键氨基酸、包含LDH活性位点的线性表位、无亚细胞定位等方面是一致的,但两者在翻译后的修饰位点、3个跨膜区和其他线性表位方面既相似也有区别.结论 应用生物信息方法从猪带绦虫成虫cDNA文库中筛选出了TsLDH-A和TsLDH-B的cDNA全长序列,并预测和比较了两者结构与功能方面的信息,为进一步研究所编码蛋白的功能奠定了基础.

  9. Elevated serum level of YKL-40 is an independent prognostic factor for poor survival in patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Johansen, Julia Sidenius; Gehl, Julie

    2006-01-01

    BACKGROUND: YKL-40 is a growth factor for connective tissue cells and       stimulates migration of endothelial cells. Cancer cells, macrophages, and       neutrophils secrete YKL-40. Its function in cancer is unknown. High serum       YKL-40 levels have been associated with a poor prognosis...... that serum YKL-40 (hazard ratio       [HR] = 1.9; 95% confidence interval [CI], 1.2-2.8; P = 0.004) and serum       lactate dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2-2.9; P = 0.004) were       independent prognostic factors for survival. A combination variable of       elevated serum YKL-40 and LDH...... quadrupled the risk of early death (HR =       4.4; 95% CI, 2.5-7.7; P Cancer (AJCC) Stage IV       classification. Furthermore, serum...

  10. ANTS-anchored Zn-Al-CO{sub 3}-LDH particles as fluorescent probe for sensing of folic acid

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Pengfei; Liu, Dan; Liu, Yanhuan [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Beijing Key Laboratory of Environmentally Harmful Chemical Analysis, Beijing University of Chemical Technology, Beijing 100029 (China); Li, Lei, E-mail: lilei@mail.buct.edu.cn [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029 (China); Beijing Key Laboratory of Environmentally Harmful Chemical Analysis, Beijing University of Chemical Technology, Beijing 100029 (China)

    2016-09-15

    A novel fluorescent nanosensor for detecting folic acid (FA) in aqueous media has been developed based on 8-aminonaphthalene-1,3,6-trisulfonate (ANTS) anchored to the surface of Zn-Al-CO{sub 3}-layered double hydroxides (LDH) particles. The nanosensor showed high fluorescence intensity and good photostability due to a strong coordination interaction between surface Zn{sup 2+} ions of Zn-Al-CO{sub 3}-LDH and N atoms of ANTS, which were verified by result of X-ray photoelectron spectroscopy (XPS). ANTS-anchored on the surface of Zn-Al-CO{sub 3}-LDH restricted the intra-molecular rotation leading to ANTS-anchored J-type aggregation emission enhancement. ANTS-anchored Zn-Al-CO{sub 3}-LDH particles exhibited highly sensitive and selective response to FA over other common metal ions and saccharides present in biological fluids. The proposed mechanism was that oxygen atoms of -SO{sub 3} groups in ANTS-anchored on the surface of Zn-Al-CO{sub 3}-LDH were easily collided by FA molecules to form potential hydrogen bonds between ANTS-anchored and FA molecules, which could effectively quench the ANTS-anchored fluorescence. Under the simulated physiological conditions (pH of 7.4), the fluorescence quenching was fitted to Stern-Volmer equation with a linear response in the concentration range of 1 μM to 200 μM with a limit of detection of 0.1 μM. The results indicate that ANTS-anchored Zn-Al-CO{sub 3}-LDH particles can afford a very sensitive system for the sensing FA in aqueous solution. - Highlights: • A novel fluorescent nanosensor has been developed. • The sensor exhibited highly sensitive and selective response to FA. • The fluorescence quenching was fitted to Stern–Volmer equation. • The linear response range was 1–200 μM with a limit of detection of 0.1 μM.

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

    Science.gov (United States)

    Fernández, Silvina; Córdoba, Mariana

    2017-04-01

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

  12. The separate roles of PQQ and apo-enzyme syntheses in the regulation of glucose dehydrogenase activity in Klebsiella pneumoniae NCTC 418.

    Science.gov (United States)

    Hommes, R W; Herman, P T; Postma, P W; Tempest, D W; Neijssel, O M

    1989-01-01

    No holoenzyme pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase and only very low apoenzyme levels could be detected in cells of Klebsiella pneumoniae, growing anaerobically, or carrying out a fumarate or nitrate respiration. Low glucose dehydrogenase activity in some aerobic glucose-excess cultures of K. pneumoniae (ammonia or sulphate limitation) was increased significantly by addition of PQQ, whereas in cells already possessing a high glucose dehydrogenase activity (phosphate or potassium limitation) extra PQQ had almost no effect. These observations indicate that the glucose dehydrogenase activity in K. pneumoniae is modulated by both PQQ synthesis and synthesis of the glucose dehydrogenase apo-enzyme.

  13. A new dawn for plant mitochondrial NAD(P)H dehydrogenases

    DEFF Research Database (Denmark)

    Møller, I.M.

    2002-01-01

    The expression of complex I and two homologues of bacterial and yeast NADH dehydrogenases, NDA and NDB, have been studied in potato leaf mitochondria. The mRNA level of NDA is completely light dependent and shows a diurnal rhythm with a sharp maximum just after dawn. NDA protein quantity and inte...... and internal rotenone-insensitive NADH dehydrogenase activity are also light dependent. These findings suggest that NDA has a role in photorespiration and might be identical to the previously unidentified internal rotenone-insensitive NADH dehydrogenase....

  14. 复合水滑石热稳定剂对PVC热稳定性能的影响%Effect of MgAl-CO_3-LDH/ZnAl-CO_3-LDH composites on thermal stability of PVC

    Institute of Scientific and Technical Information of China (English)

    刘庆艳; 杨占红; 易师

    2010-01-01

    采用共沉淀法制备镁铝水滑石和锌铝水滑石,采用XRD、FT-IR对其进行表征,同时将其按不同比例进行复配应用到聚氯乙烯(PVC)中.利用静态热老化法研究复合水滑石稳定剂在聚氯乙烯中的热稳定性能.结果表明:合成的镁铝水滑石和锌铝水滑石结晶度高,结构规整;镁铝水滑石和锌铝水滑石复配物的热稳定性能优于单一镁铝水滑石、锌铝水滑石,其最佳复配摩尔比为x(MgAl-CO_3-LDH)-x(ZnAl-CO_3-LDH)=1-0.7.当该复配物与同样金属含量的ZnMgAl-CO_3-LDH(x(Zn)-x(Mg)-x(Al)=0.7-1-1.7)相比时,前者热稳定性能更好.另外,制备该复配物的工艺较制备ZnMgAl-CO_3-LDH的工艺更简单.

  15. Novel 11β-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV.

    Science.gov (United States)

    Boudon, Stéphanie M; Vuorinen, Anna; Geotti-Bianchini, Piero; Wandeler, Eliane; Kratschmar, Denise V; Heidl, Marc; Campiche, Remo; Jackson, Eileen; Odermatt, Alex

    2017-01-01

    Activity and selectivity assessment of new bi-aryl amide 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11β-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11β-HSD1 over 11β-HSD2, 17β-HSD1 and 17β-HSD2. These inhibitors also potently inhibited 11β-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme and in intact primary human keratinocytes expressing endogenous 11β-HSD1. Moreover, compounds 2b, 3e and 12e were tested for their activity in human skin biopsies. They were able to prevent, at least in part, both the cortisone- and the UV-mediated decreases in collagen content. Thus, inhibition of 11β-HSD1 by these compounds can be further investigated to delay or prevent UV-mediated skin damage and skin aging.

  16. Probing the interaction between di- and tri-functionalized carboxy-phosphonic acid and LDH layer structure

    Science.gov (United States)

    Sabbar, El Mouloudi; de Roy, Marie Elisabeth; Leroux, Fabrice

    2006-11-01

    A series of carboxyphosphonate-derivatives of (Zn, Al) layered double hydroxide (LDH) was prepared and characterized by a combination of techniques including powder X-ray diffraction, FTIR spectroscopy and solid-state 13C CP-MAS and 31P MAS NMR spectroscopies. The number of carbon atoms, n=1 or 2 in HO2C(CH2)nPO3H2, was found to have an influence on the accommodation of the interleaved molecule, the carboxylate function lying perpendicular or parallel to the inorganic sheets of the LDH host material. These observations are in agreement with NMR results which evidence an interaction of the interlayered molecules through either the carbonyl or the phosphonate group or both in the case of the larger molecule, N-(phosphonomethyl)iminodiacetic acid. The variation of the basal spacing of the hybrid materials as a function of the temperature indicates a rearrangement of the molecule within the host material gap.

  17. Adsorption of charged protein residues on an inorganic nanosheet: Computer simulation of LDH interaction with ion channel

    Science.gov (United States)

    Tsukanov, Alexey A.; Psakhie, Sergey G.

    2016-08-01

    Quasi-two-dimensional and hybrid nanomaterials based on layered double hydroxides (LDH), cationic clays, layered oxyhydroxides and hydroxides of metals possess large specific surface area and strong electrostatic properties with permanent or pH-dependent electric charge. Such nanomaterials may impact cellular electrostatics, changing the ion balance, pH and membrane potential. Selective ion adsorption/exchange may alter the transmembrane electrochemical gradient, disrupting potential-dependent cellular processes. Cellular proteins as a rule have charged residues which can be effectively adsorbed on the surface of layered hydroxide based nanomaterials. The aim of this study is to attempt to shed some light on the possibility and mechanisms of protein "adhesion" an LDH nanosheet and to propose a new direction in anticancer medicine, based on physical impact and strong electrostatics. An unbiased molecular dynamics simulation was performed and the combined process free energy estimation (COPFEE) approach was used.

  18. Selective Oxidation of Glycerol with 3% H2O2 Catalyzed by LDH-Hosted Cr(III Complex

    Directory of Open Access Journals (Sweden)

    Gongde Wu

    2015-11-01

    Full Text Available A series of layered double hydroxides (LDHs –hosted sulphonato-salen Cr(III complexes were prepared and characterized by various physico-chemical measurements, such as Fourier transform infrared spectroscopy (FTIR, ultraviolet-visible spectroscopy (UV-Vis, powder X-ray diffraction (XRD, transmission electron microscope (TEM, scanning electron microscope (SEM and elemental analysis. Additionally, their catalytic performances were investigated in the selective oxidation of glycerol (GLY using 3% H2O2 as an oxidant. It was found that all the LDH-hosted Cr(III complexes exhibited significantly enhanced catalytic performance compared to the homogeneous Cr(III complex. Additionally, it was worth mentioning that the metal composition of LDH plates played an important role in the catalytic performances of LDH-hosted Cr(III complex catalysts. Under the optimal reaction conditions, the highest GLY conversion reached 85.5% with 59.3% of the selectivity to 1,3-dihydroxyacetone (DHA. In addition, the catalytic activity remained after being recycled five times.

  19. A mitochondria targeting Mn nanoassembly of BODIPY for LDH-A, mitochondria modulated therapy and bimodal imaging of cancer.

    Science.gov (United States)

    Boison, Daniel; Lu, Wen-Long; Xu, Qin-Mei; Yang, Huang; Huang, Tao; Chen, Qiu-Yun; Gao, Jing; Zhao, Yao

    2016-11-01

    HIF-1α and LDH-A are important targets for hypoxia-driven drug resistance. Mitochondria targeted fluorescent manganese(II)-complexes can be used as potential fluorescence imaging agents, MRI contrast agents and HIF-1α and LDH-A involved anticancer complexes. In this study, a fluorescent manganese(II) nanoparticle, labeled as (PEG-Mn-BDA), was synthesized and used as both fluorescent and MRI imaging agents in cancer cells. In vitro bioassay results indicate that PEG-Mn-BDA was able to inhibit LDH-A activity and depolarize mitochondrial membrane potential with the generation of intracellular ROS, which contributed to the induction of apoptosis. Moreover, the pro-apoptotic protein, caspase 3 was highly expressed. In vivo, PEG-Mn-BDA could also exert inhibition on a mouse hepatocellular carcinoma xenograft. These results suggest that mitochondria targeted PEG-Mn-BDA was able to simultaneously induce selective inhibition on cancer cells and a mouse carcinoma xenograft, label cancer cells with fluorescence and enhance MRI contrast. Therefore, PEG-Mn-BDA is a good candidate for cancer treatment and imaging.

  20. The functional investigation of the ldh-luc reporter strain of Streptococcus mutans%变异链球菌ldh-luc荧光报告株的生物学活性检测

    Institute of Scientific and Technical Information of China (English)

    霍丽珺; 凌均棨

    2014-01-01

    Objective To investigate the efficacy of ldh-luc reporter strain of Streptococcus mutans (S.mutans), which was constructed in our previous study, and to probe the metabolic status of the reporter strain of S.mutans growing as either in a planktonic culture or a in biofilm community . Methods Growth curve, scanning electron microscope (SEM) and colony-forming units (CFU) counts were used to investigate the metabolic status of the reporter strain and the wide type of S.mutans growing as either in a planktonic culture or in a biofilm community . The fluorescence activity of this reporter strain was also measured. Results Growth curves and CFU counts of the reporter strain and the wide type of S.mutans were similar. There was no significant difference between the 4, 12 and 24 h biofilm of the reporter strain and the wide type of S.mutans by SEM. The fluorescence expression of the report strain was steady from exponential phase to stationary phases . The RLU reflected the amount of live S.mutans. Conclusions The growth abilities of the reporter strain were similar with the wide type of S.mutans. And the fluorescence activity of this reporter strain was stable . All of these results suggested that the reporter strain could be used to probe the metabolic status of S.mutans and response of S.mutans to antimicrobial agents instead of the wild type .%目的:探讨本课题组前期所构建的变异链球菌(S.mutans)ldh-luc荧光报告株在浮游态及生物膜状态下的活性及代谢状态的有效性,为探讨抗菌剂对多菌种生物膜中S.mutans的作用提供研究基础。方法采用生长曲线、扫描电子显微镜、活菌菌落计数等方法研究浮游态及生物膜状态下S.mutans ldh-luc荧光报告株的生长活性及代谢状态,并测定荧光报告株的荧光活性。结果 S.mutans ldh-luc荧光报告株和野生株生长趋势一致,生物膜内可培养活菌数无差别(4h:F=2.13,P>0.05;12 h:F=1.45,P >0.05;24

  1. A novel platform designed by Au core/inorganic shell structure conjugated onto MTX/LDH for chemo-photothermal therapy.

    Science.gov (United States)

    Tian, De-Ying; Wang, Wei-Yuan; Li, Shu-Ping; Li, Xiao-Dong; Sha, Zhao-Lin

    2016-05-30

    A novel platform making up of methotrexate intercalated layered double hydroxide (MTX/LDH) hybrid doped with gold nanoparticles (NPs) may have great potential both in chemo-photothermal therapy and the simultaneous drug delivery. In this paper, a promising platform of Au@PDDA-MTX/LDH was developed for anti-tumor drug delivery and synergistic therapy. Firstly, Au NPs were coated using Layer-by-Layer (LbL) technology by alternate deposition of poly (diallyldimethylammonium chloride) (PDDA) and MTX molecules, and then the resulting core-shell structures (named as Au@PDDA-MTX) were directly conjugated onto the surface of MTX/LDH hybrid by electrostatic attraction to afford Au@PDDA-MTX/LDH NPs. Here MTX was used as both the agent for surface modification and the anti-tumor drug for chemotherapy. The platform of Au@PDDA-MTX/LDH NPs not only had a high drug-loading capacity, but also showed excellent colloidal stability and interesting pH-responsive release profile. In vitro drug release studies demonstrated that MTX released from Au@PDDA-MTX/LDH was relatively slow under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. Furthermore, the combined treatment of cancer cells by using Au@PDDA-MTX/LDH for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy.

  2. [Effect of overexpression of malate dehydrogenase on succinic acid production in Escherichia coli NZN111].

    Science.gov (United States)

    Liang, Liya; Ma, Jiangfeng; Liu, Rongming; Wang, Guangming; Xu, Bing; Zhang, Min; Jiang, Min

    2011-07-01

    Escherichia coli NZN111 is a double mutant with lactate dehydrogenase (ldhA) and pyruvate formate-lyase (pflB) inactivated. Under anaerobic conditions, disequilibrium of coenzyme NADH and NAD+ causes Escherichia coli NZN111 losing the glucose utilizing capability. In this study, we constructed a recombinant strain E. coli NZN111/pTrc99a-mdh and overexpressed the mdh gene with 0.3 mmol/L of IPTG under anaerobic fermentation condition in sealed bottles. The specific malate dehydrogenase (MDH) activity in the recombinant strain was 14.8-fold higher than that in E. coli NZN111. The NADH/ NAD+ ratio decreased from 0.64 to 0.26 and the concentration of NAD+ and NADH increased 1.5-fold and 0.2-fold respectively. Under anaerobic conditions, the recombinant strain possessed the capability of growth and glucose absorption. We took dual-phase fermentation for succinate production. After the dry cell weight (DCW) reached 6.4 g/L under aerobic conditions, the cell culture was changed to anaerobic conditions. After 15 h, 14.75 g/L glucose was consumed and succinic acid reached 15.18 g/L. The yield of succinic acid was 1.03 g/g Glu and the productivity of succinic acid was 1.012 g/(L x h).

  3. [Activity of liver mitochondrial NAD+-dependent dehydrogenases of the krebs cycle in rats with acetaminophen-induced hepatitis developed under conditions of alimentary protein deficiency].

    Science.gov (United States)

    Voloshchuk, O N; Kopylchuk, G P

    2016-01-01

    Activity of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and the NAD(+)/NADН ratio were studied in the liver mitochondrial fraction of rats with toxic hepatitis induced by acetaminophen under conditions of alimentary protein deprivation. Acetaminophen-induced hepatitis was characterized by a decrease of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and malate dehydrogenase activities, while the mitochondrial NAD(+)/NADН ratio remained at the control level. Modeling of acetaminophen-induced hepatitis in rats with alimentary protein caused a more pronounced decrease in the activity of NAD(+)-dependent dehydrogenases studied and a 2.2-fold increase of the mitochondrial NAD(+)/NADН ratio. This suggests that alimentary protein deprivation potentiated drug-induced liver damage.

  4. Intercalation chemistry in a LDH system: anion exchange process and staging phenomenon investigated by means of time-resolved, in situ X-ray diffraction.

    Science.gov (United States)

    Taviot-Guého, Christine; Feng, Yongjun; Faour, Azzam; Leroux, Fabrice

    2010-07-14

    Using time-resolved, in situ energy-dispersive X-ray diffraction (EDXRD), the formation of interstratified LDH structures, with alternate interlayer spaces occupied by different anions, have been demonstrated during anion exchange reactions. Novel hybrid LDH nanostructures can thus be prepared, combining the physicochemical properties of two intercalated anions plus those of the LDH host. A general trend is that inorganic-inorganic anion exchange reactions occur in a one-step process while inorganic-organic exchanges may proceed via a second-stage intermediate, suggesting that staging occurs partly as a result of organic-inorganic separation. Yet, other influencing parameters must be considered such as LDH host composition, LDH affinity for different anions and LDH particle size as well as extrinsic parameters like the reaction temperature. Hence, a correlation between the occurrence of staging phenomenon and the difficulty of the exchange of the initial anion is observed, suggesting that staging is needed to overcome the energy barrier in the case of the exchange by organic anions. Notwithstanding the LiAl(2) system, staging has mainly been observed with Zn(2)Cr LDH host so far, a peculiar LDH composition with a unique Zn/Cr ratio of two and a local order of the cations within the hydroxide layers. The formation of a higher order-staged intermediate than stage two, observed during the exchange reaction of CO(3)(2-) or SO(4)(2-) anions with Zn(2)Cr-tartrate, is in favour of a Daumas-Herold model although this model implies a bending of LDH layers. The analysis of the X-ray powder diffraction pattern of Zn(2)Cr-Cl/tartrate second-stage intermediate, isolated almost as a pure phase during the exchange of Cl(-) with tartrate anions in Zn(2)Cr LDH, indicates a disorder in the stacking sequence and a relative proportion of the two kinds of interlayers slightly different from 50/50. Besides, the microstructural analysis of the XRD pattern reveals a great reduction of the

  5. Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species.

    Science.gov (United States)

    Starkov, Anatoly A; Fiskum, Gary; Chinopoulos, Christos; Lorenzo, Beverly J; Browne, Susan E; Patel, Mulchand S; Beal, M Flint

    2004-09-08

    Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H(2)O(2) production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p-trifluoromethoxyphenylhydrazone,alpha-ketoglutarate supported the highest rate of H(2)O(2) production. In the absence of ADP or in the presence of rotenone, H(2)O(2) production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of alpha-ketoglutarate. Isolated mitochondrial alpha-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H(2)O(2). NAD(+) inhibited ROS production by the isolated enzymes and by permeabilized mitochondria. We also measured H(2)O(2) production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H(2)O(2) than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria.

  6. Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria

    Directory of Open Access Journals (Sweden)

    Leimanis Mara

    2009-10-01

    Full Text Available Abstract Background In areas where non-falciparum malaria is common rapid diagnostic tests (RDTs capable of distinguishing malaria species reliably are needed. Such tests are often based on the detection of parasite lactate dehydrogenase (pLDH. Methods In Dawei, southern Myanmar, three pLDH based RDTs (CareStart™ Malaria pLDH (Pan, CareStart™ Malaria pLDH (Pan, Pf and OptiMAL-IT®were evaluated in patients presenting with clinically suspected malaria. Each RDT was read independently by two readers. A subset of patients with microscopically confirmed malaria had their RDTs repeated on days 2, 7 and then weekly until negative. At the end of the study, samples of study batches were sent for heat stability testing. Results Between August and November 2007, 1004 patients aged between 1 and 93 years were enrolled in the study. Slide microscopy (the reference standard diagnosed 213 Plasmodium vivax (Pv monoinfections, 98 Plasmodium falciparum (Pf mono-infections and no malaria in 650 cases. The sensitivities (sens and specificities (spec, of the RDTs for the detection of malaria were- CareStart Malaria™ pLDH (Pan test: sens 89.1% [CI95 84.2-92.6], spec 97.6% [CI95 96.5-98.4] OptiMal-IT®: Pf+/- other species detection: sens 95.2% [CI95 87.5-98.2], spec 94.7% [CI95 93.3-95.8]; non-Pf detection alone: sens 89.6% [CI95 83.6-93.6], spec 96.5% [CI95 94.8-97.7] CareStart Malaria™ pLDH (Pan, Pf: Pf+/- other species: sens 93.5% [CI9585.4-97.3], spec 97.4% [95.9-98.3]; non-Pf: sens 78.5% [CI9571.1-84.4], spec 97.8% [CI95 96.3-98.7] Inter-observer agreement was excellent for all tests (kappa > 0.9. The median time for the RDTs to become negative was two days for the CareStart™ Malaria tests and seven days for OptiMAL-IT®. Tests were heat stable up to 90 days except for OptiMAL-IT® (Pf specific pLDH stable to day 20 at 35°C. Conclusion None of the pLDH-based RDTs evaluated was able to detect non-falciparum malaria with high sensitivity, particularly

  7. Production of L-lactic acid by the yeast Candida sonorensis expressing heterologous bacterial and fungal lactate dehydrogenases.

    Science.gov (United States)

    Ilmén, Marja; Koivuranta, Kari; Ruohonen, Laura; Rajgarhia, Vineet; Suominen, Pirkko; Penttilä, Merja

    2013-05-25

    Polylactic acid is a renewable raw material that is increasingly used in the manufacture of bioplastics, which offers a more sustainable alternative to materials derived from fossil resources. Both lactic acid bacteria and genetically engineered yeast have been implemented in commercial scale in biotechnological production of lactic acid. In the present work, genes encoding L-lactate dehydrogenase (LDH) of Lactobacillus helveticus, Bacillus megaterium and Rhizopus oryzae were expressed in a new host organism, the non-conventional yeast Candida sonorensis, with or without the competing ethanol fermentation pathway. Each LDH strain produced substantial amounts of lactate, but the properties of the heterologous LDH affected the distribution of carbon between lactate and by-products significantly, which was reflected in extra-and intracellular metabolite concentrations. Under neutralizing conditions C. sonorensis expressing L. helveticus LDH accumulated lactate up to 92 g/l at a yield of 0.94 g/g glucose, free of ethanol, in minimal medium containing 5 g/l dry cell weight. In rich medium with a final pH of 3.8, 49 g/l lactate was produced. The fermentation pathway was modified in some of the strains studied by deleting either one or both of the pyruvate decarboxylase encoding genes, PDC1 and PDC2. The deletion of both PDC genes together abolished ethanol production and did not result in significantly reduced growth characteristic to Saccharomyces cerevisiae deleted of PDC1 and PDC5. We developed an organism without previous record of genetic engineering to produce L-lactic acid to a high concentration, introducing a novel host for the production of an industrially important metabolite, and opening the way for exploiting C. sonorensis in additional biotechnological applications. Comparison of metabolite production, growth, and enzyme activities in a representative set of transformed strains expressing different LDH genes in the presence and absence of a functional

  8. 21 CFR 862.1670 - Sorbitol dehydrogenase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Sorbitol dehydrogenase test system. 862.1670... Systems § 862.1670 Sorbitol dehydrogenase test system. (a) Identification. A sorbitol dehydrogenase test system is a device intended to measure the activity of the enzyme sorbitol dehydrogenase in...

  9. 21 CFR 862.1445 - Lactate dehydrogenase isoenzymes test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactate dehydrogenase isoenzymes test system. 862... Test Systems § 862.1445 Lactate dehydrogenase isoenzymes test system. (a) Identification. A lactate dehydrogenase isoenzymes test system is a device intended to measure the activity of lactate dehydrogenase...

  10. Microbial alcohol dehydrogenases: identification, characterization and engineering

    NARCIS (Netherlands)

    Machielsen, M.P.

    2007-01-01

    Keywords: alcohol dehydrogenase, laboratory evolution, rational protein engineering, Pyrococcus furiosus, biocatalysis, characterization, computational design, thermostability.   Alcohol dehydrogeases (ADHs) catalyze the interconversion of alcohols, aldehydes and ketones. They display a wide variety

  11. Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

    Science.gov (United States)

    ... of the skin on the palms and soles (hand-foot syndrome); shortness of breath; and hair loss may also ... dehydrogenase deficiency , with its early-onset neurological symptoms, is a rare disorder. Its prevalence is ...

  12. Isocitrate dehydrogenase mutations in gliomas.

    Science.gov (United States)

    Waitkus, Matthew S; Diplas, Bill H; Yan, Hai

    2016-01-01

    Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg(132) of IDH1 and Arg(172) of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy.

  13. Effect of surfactant alkyl chain length on the dispersion, and thermal and dynamic mechanical properties of LDPE/organo-LDH composites

    National Research Council Canada - National Science Library

    Muksing, N; Magaraphan, R; Coiai, S; Passaglia, E

    2011-01-01

    Low density polyethylene/layered double hydroxide (LDH) composites were prepared via melt compounding using different kinds of organo-LDHs and polyethylene-grafted maleic anhydride as the compatibilizer...

  14. Decrease in nicotinamide adenine dinucleotide dehydrogenase is related to skin pigmentation.

    Science.gov (United States)

    Nakama, Mitsuo; Murakami, Yuhko; Tanaka, Hiroshi; Nakata, Satoru

    2012-03-01

    Skin pigmentation is caused by various physical and chemical factors. It might also be influenced by changes in the physiological function of skin with aging. Nicotinamide adenine dinucleotide (NADH) dehydrogenase is an enzyme related to the mitochondrial electron transport system and plays a key role in cellular energy production. It has been reported that the functional decrease in this system causes Parkinson's disease. Another study reports that the amount of NADH dehydrogenase in heart and skeletal muscle decreases with aging. A similar decrease in the skin would probably affect its physiological function. However, no reports have examined the age-related change in levels of NADH dehydrogenase in human skin. In this study, we investigated this change and its effect on skin pigmentation using cultured human epidermal keratinocytes. The mRNA expression of NDUFA1, NDUFB7, and NDUFS2, subunits of NADH dehydrogenase, and its activity were significantly decreased in late passage keratinocytes compared to early passage cells. Conversely, the mRNA expression of melanocyte-stimulating cytokines, interleukin-1 alpha and endothelin 1, was increased in late passage cells. On the other hand, the inhibition of NADH dehydrogenase upregulated the mRNA expression of melanocyte-stimulating cytokines. Moreover, the level of NDUFB7 mRNA was lower in pigmented than in nonpigmented regions of skin in vivo. These results suggest the decrease in NADH dehydrogenase with aging to be involved in skin pigmentation.

  15. Identification of a novel operon in Lactococcus lactis encoding three enzymes for lactic acid synthesis: phosphofructokinase, pyruvate kinase, and lactate dehydrogenase.

    Science.gov (United States)

    Llanos, R M; Harris, C J; Hillier, A J; Davidson, B E

    1993-01-01

    The discovery of a novel multicistronic operon that encodes phosphofructokinase, pyruvate kinase, and lactate dehydrogenase in the lactic acid bacterium Lactococcus lactis is reported. The three genes in the operon, designated pfk, pyk, and ldh, contain 340, 502, and 325 codons, respectively. The intergenic distances are 87 bp between pfk and pyk and 117 bp between pyk and ldh. Plasmids containing pfk and pyk conferred phosphofructokinase and pyruvate kinase activity, respectively, on their host. The identity of ldh was established previously by the same approach (R. M. Llanos, A. J. Hillier, and B. E. Davidson, J. Bacteriol. 174:6956-6964, 1992). Each of the genes is preceded by a potential ribosome binding site. The operon is expressed in a 4.1-kb transcript. The 5' end of the transcript was determined to be a G nucleotide positioned 81 bp upstream from the pfk start codon. The pattern of codon usage within the operon is highly biased, with 11 unused amino acid codons. This degree of bias suggests that the operon is highly expressed. The three proteins encoded on the operon are key enzymes in the Embden-Meyerhoff pathway, the central pathway of energy production and lactic acid synthesis in L. lactis. For this reason, we have called the operon the las (lactic acid synthesis) operon. Images PMID:8478320

  16. Highly efficient and selective adsorption of In3+ on pristine Zn/Al layered double hydroxide (Zn/Al-LDH) from aqueous solutions

    Science.gov (United States)

    Barnabas, Mary Jenisha; Parambadath, Surendran; Mathew, Aneesh; Park, Sung Soo; Vinu, Ajayan; Ha, Chang-Sik

    2016-01-01

    A pristine Zn/Al-layered double hydroxide (Zn/Al-LDH) showed excellent adsorption ability and selectivity towards In3+ ions from aqueous solutions. The adsorption behaviour as a function of the contact time, solution pH, ionic strength, and amount of adsorbent under ambient conditions revealed a strong dependency on the pH and ionic strength over In3+ intake. The structure and properties of Zn/Al-LDH and In3+ adsorbed Zn/Al-LDH (In-Zn/Al-LDH) were examined carefully by X-ray diffraction, Fourier transform infrared spectroscopy, N2-sorption/desorption, UV-vis spectroscopy, and X-ray photoelectron spectroscopy. The adsorbent had a sufficient number of active sites that were responsible for the In3+ adsorption and quite stable even after the adsorption process. The selective adsorption of In3+ on Zn/Al-LDH was also observed even from a mixture containing competing ions, such as Mn2+, Co2+, Ni2+, Cd2+, Pb2+, and Cu2+. The adsorption experiments showed that Zn/Al-LDH is a promising material for the pre-concentration and selective removal of In3+ from large volumes of aqueous solutions.

  17. Effect of Hypertension on Hearing Function, LDH and ChE of the Cochlea in Older Rats

    Institute of Scientific and Technical Information of China (English)

    李穗; 龚树生; 杨燕珍; 余青松

    2003-01-01

    The relationship between the hypertension and the aging process of hearing organ was in-vestigated. Twenty Wistar 3-month old rats and 20 Wistar 12-month old rats, 20 spontaneously hy-pertensive rat stroke-prone (SHRSP) 3-month old rats and 20 SHRSP 12-month old rats free ofmiddle ear infections as observed under otomicroscopy, with normal tympanic membrane and auriclereflex, were selected to be divided into two experimental groups and two control groups respective-ly. The tail artery blood pressure was measured non-invasively. The threshold of auditory brain-stem response (ABR) was measured by SpiritTM evoked potential meter. The LDH and ChE stai-ning in the inner ear was performed and the optical density was analyzed by the HPIAS analysis sys-tem. The results showed that there was no difference in the ABR thresholds, the activities of LDHand ChE between Wistar 3-month old group and SHRSP 3-month old group (P>0. 05). The meanvalue of ABR threshold and the activities of LDH and ChE in the Wistar 12-month old group at rel-evant sections were significantly greater than those in the two 3-month old groups (P<0.05),whereas the mean value of ABR threshold and the activities of LDH and ChE in the SHRSP 12-month old group at relevant sections were significantly higher than those in the 3-month old controlgroup (P<0. 01). It was concluded that presbycusis existed in the Wistar 12-month old group rats.The glycogenosis and the abnormal secretion of neural transmitter were discerned after hyperten-sion. All the above factors may worsen the aging of the hearing system.

  18. Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways.

    Science.gov (United States)

    Farabegoli, F; Vettraino, M; Manerba, M; Fiume, L; Roberti, M; Di Stefano, G

    2012-11-20

    Galloflavin (GF), a recently identified lactate dehydrogenase inhibitor, hinders the proliferation of cancer cells by blocking glycolysis and ATP production. The aim of the present experiments was to study the effect of this compound on breast cancer cell lines reproducing different pathological subtypes of this tumor: MCF-7 (the well differentiated form), MDA-MB-231 (the aggressive triple negative tumor) and MCF-Tam (a sub-line of MCF-7 with acquired tamoxifen resistance). We observed marked differences in the energetic metabolism of these cell lines. Compared to MCF-7 cells, both MDA-MB-231 and MCF-Tam cells exhibited higher LDH levels and glucose uptake and showed lower capacity of oxygen consumption. In spite of these differences, GF exerted similar growth inhibitory effects. This result was explained by the finding of a constitutively activated stress response in MDA-MB-231 and MCF-Tam cells, which reproduce the poor prognosis tumor forms. As a further proof, different signaling pathways were found to be involved in the antiproliferative action of GF. In MCF-7 cells we observed a down regulation of the ERα-mediated signaling needed for cell survival. On the contrary, in MCF-Tam and MDA-MB-231 cells growth inhibition appeared to be contributed by an oxidative stress condition. The prevalent mechanism of cell death was found to be apoptosis induction. Because of the clinical relevance of breast cancer forms having the triple negative and/or chemoresistant phenotype, our results showing comparable effects of GF even on aggressively growing cells encourage further studies to verify the potential of this compound in improving the chemotherapy of breast cancer.

  19. Research Progress and Industrial Application of Leucine Dehydrogenase%亮氨酸脱氢酶研究进展及其工业应用

    Institute of Scientific and Technical Information of China (English)

    黄春辉; 林陈水

    2012-01-01

    Microbial dehydrogenase, such as leucine dehydrogenase (LDH) , has great advantages in the synthesis of optical amino acid and its derivatives by asymmetrical reductions of carbonyl compounds. This review covers the latest development of LDH from various sources, studies of its biochemical property, substrate specificity, kinetics of enzyme-catalyzed reactions as well as construction of engineering bacteria. Furthermore, its industrial application is discussed from the aspects of cofactor regeneration strategy and enzyme-membrane reactor and future development is also illustrated.%微生物脱氢酶催化羰基不对称还原制备光学纯氨基酸及其衍生物具有非常大的优势.亮氨酸脱氢酶能选择性地催化α-酮酸,氨化还原得到α-氨基酸及其衍生物.本文综述了亮氨酸脱氢酶的来源,理化性质,底物特异性,酶基因工程菌构建等方面的内容及研究进展.从辅酶再生策略,酶膜反应器两方面讨论了其工业化应用,并展望了今后的发展前景.

  20. Effect of Water Pollution onActivitiy of CAT and LDH of Carassius auratus in Yongcheng Coal Collapse Area%永煤塌陷区水污染对鲫鱼过氧化氢酶和乳酸脱氢酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    闫永峰; 郑娜; 李壹

    2011-01-01

    To investigate the influence of low concentration mixed heavy metal pollution in Yongcheng coal collapse area towards the activitiy of blood catalase (CAT) and serum lactate dehydrogenase(LDH), Carassius auratus of Yongcheng coal collapse area was selected as the research object and that from a relatively pollution-free Tianmu lake of Shangqiu was used as the control. The results showed that compared to Tianmu lake,the activity of blood CAT and LDH of Yongcheng coal collapse area decreased significantly (P<0.01). The result suggested that the normal physiological process was inhibited by low concentration mixed heavy metal pollution.%2010年5月,选择永城煤矿塌陷区天然鱼塘的野生鲫鱼(Carassius auratus)为对象,以相对无煤矿污染的商丘市天沐湖为对照,研究了永城煤矿塌陷区低浓度混合重金属污染对鲫鱼血液过氧化氢酶(CAT)和血清乳酸脱氢酶(LDH)活性的影响.结果表明,永城煤矿塌陷区鲫鱼CAT的OD值(0.600)极显著高于天沐湖鲫鱼CAT的OD值(0.411)(P<0.01),塌陷区鲤鱼血清中LDH的OD值(0.310)极显著低于天沐湖鲫鱼CAT的OD值(0.421)(P<0.01),说明煤矿塌陷区低浓度混合重金属污染对鲫鱼的正常生理过程有明显的抑制.

  1. THE EFFECT OF USING VITAMIN E ON MUSCLE DAMAGE, OXIDANT AND ANTIOXIDANT LEVELS OF RUNNERS PERFORMING ENDURANCE TRAINING

    Directory of Open Access Journals (Sweden)

    Serdar BÜYÜKİPEKÇİ

    2012-12-01

    Full Text Available This study was made to research the effect of vitamin E on muscle damage, oxidant and antioxidant levels of runners. 28 students participated in the study as the experiment group at the age of 20,75±1,84 (n=16 and the control group (n=12 at the age of 20,42±1,78 who are physically active, have the similar physical features and education at Erciyes University. In this study, the same exercises were performed on both groups three times a week for thirty days. 400 IU (268 mg vitamin E was given to the athletes in experiment group in every day for 30 days. Nothing was given to the control group. The body weights and the percentage of body fat were measured at the pre and post one month exercise. Total antioxidant capacity, malondialdehyde, creatine kinase and lactate dehydrogenase were measured by making biochemical analyses. While any significant difference on pre-exercise CK and LDH levels, pre and post exercise TAC and MDA levels of experiment and control groups was not found, there was a significant difference on post exercise CK and LDH levels as a result of the intergroup comparison. As for the intragroup comparison, there was a significant increase on post exercise MDA level of both experiment and control group. This result was thought that the antioxidant capacity remains incapable; despite usage of vitamin E counter to oxidative stress increasing connectedly exercise. The reason of this inability in the antioxidant defense system is thought that this is because of the amount of daily vitamin E.

  2. Cell Damage, Antioxidant Status, and Cortisol Levels Related to Nutrition in Ski Mountaineering During a Two-Day Race

    Science.gov (United States)

    Diaz, Elena; Ruiz, Fatima; Hoyos, Itziar; Zubero, Jaime; Gravina, Leyre; Gil, Javier; Irazusta, Jon; Gil, Susana Maria

    2010-01-01

    The aim of this study was to measure the effect of nutrition on cell damage, antioxidant enzymes, and cortisol during a two-day ski mountaineering competition. Twenty-one male skiers participated in the study. Creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), cortisol and C-reactive protein (CRP), glutathione peroxidase (GPx) and reductase activities (GR) and C-reactive protein (CRP) levels, total antioxidant status, and cortisol levels were measured in serum the day before and immediately after the race. Their diet was also analysed during the competition. Enzymes and cortisol levels significantly increased after the competition. CK and LDH and cortisol levels were negatively correlated to total energy, protein, and fat intake. Intake of vitamin A, B1, B2, B6 and niacin was negatively correlated to LDH and AP. A negative correlation was also found between CK activity and Na, Fe, and Zn intake. Cortisol levels were negatively correlated to the intake of vitamins C, B1 and B2, and niacin. A positive correlation was found between serum GPx and intake of energy, carbohydrates, proteins, A and B vitamins, and folic acid. Skiers with the lowest nutrient intake during the competition were the ones who showed greater cell damage and lower antioxidant enzyme activity and cortisol levels, which may impair performance and also cause injuries and accidents. Particularly, skiers should have high intakes of total energy, macronutrients, vitamins A and B, Na, Zn, and Fe in order to decrease the deleterious effect of strenuous exercise. Key points A two-day ski mountaineering race produced muscle cell damage and oxidative stress and an increase in cortisol levels. There was a marked insufficient intake of carbohydrates which has been shown to affect performance Those skiers with lowest nutrient intake showed greater cell damage, lower antioxidant

  3. Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase.

    Science.gov (United States)

    Dragovich, Peter S; Fauber, Benjamin P; Corson, Laura B; Ding, Charles Z; Eigenbrot, Charles; Ge, HongXiu; Giannetti, Anthony M; Hunsaker, Thomas; Labadie, Sharada; Liu, Yichin; Malek, Shiva; Pan, Borlan; Peterson, David; Pitts, Keith; Purkey, Hans E; Sideris, Steve; Ultsch, Mark; VanderPorten, Erica; Wei, BinQing; Xu, Qing; Yen, Ivana; Yue, Qin; Zhang, Huihui; Zhang, Xuying

    2013-06-01

    A novel 2-thio-6-oxo-1,6-dihydropyrimidine-containing inhibitor of human lactate dehydrogenase (LDH) was identified by high-throughput screening (IC50=8.1 μM). Biochemical, surface plasmon resonance, and saturation transfer difference NMR experiments indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor. Structural variation of the screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50=0.48 μM). A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure-activity relationships. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. NAD(P-DEPENDENT DEHYDROGENASE ACTIVITY IN PERIPHERAL BLOOD LYMPHOCYTES OF INFANTS WITH ENLARGEMENT OF PHARYNGEAL TONSILS

    Directory of Open Access Journals (Sweden)

    L. M. Kurtasova

    2014-01-01

    Full Text Available We have observed and examined 57 children 1 to 3 years old diagnosed with enlargement of pharyngeal tonsils. A control group was presented by 35 healthy children. Bioluminescence technique was applied for studying NAD(P-dependent dehydrogenase activity in peripheral blood lymphocytes. Activation of aerobic respiration and increasing activity of pentose phosphate cycle-dependent plastic processes were registered in blood lymphocytes of children with hypertrophic pharyngeal tonsils; along with decreased function of malate-aspartate shunt in energy metabolism of the cells, diminished anaerobic reaction of NADHdependent LDH, lower interaction between Krebs cycle and reactions of amino acid metabolism, and reduced activity of glutathione reductase.

  5. High substrate specificity of ipsdienol dehydrogenase (IDOLDH), a short-chain dehydrogenase from Ips pini bark beetles.

    Science.gov (United States)

    Figueroa-Teran, Rubi; Pak, Heidi; Blomquist, Gary J; Tittiger, Claus

    2016-09-01

    Ips spp. bark beetles use ipsdienol, ipsenol, ipsdienone and ipsenone as aggregation pheromone components and pheromone precursors. For Ips pini, the short-chain oxidoreductase ipsdienol dehydrogenase (IDOLDH) converts (-)-ipsdienol to ipsdienone, and thus likely plays a role in determining pheromone composition. In order to further understand the role of IDOLDH in pheromone biosynthesis, we compared IDOLDH to its nearest functionally characterized ortholog with a solved structure: human L-3-hydroxyacyl-CoA dehydrogenase type II/ amyloid-β binding alcohol dehydrogenase (hHADH II/ABAD), and conducted functional assays of recombinant IDOLDH to determine substrate and product ranges and structural characteristics. Although IDOLDH and hHADH II/ABAD had only 35% sequence identity, their predicted tertiary structures had high identity. We found IDOLDH is a functional homo-tetramer. In addition to oxidizing (-)-ipsdienol, IDOLDH readily converted racemic ipsenol to ipsenone, and stereo-specifically reduced both ketones to their corresponding (-)-alcohols. The (+)-enantiomers were never observed as products. Assays with various substrate analogs showed IDOLDH had high substrate specificity for (-)-ipsdienol, ipsenol, ipsenone and ipsdienone, supporting that IDOLDH functions as a pheromone-biosynthetic enzyme. These results suggest that different IDOLDH orthologs and or activity levels contribute to differences in Ips spp. pheromone composition.

  6. The determination and arrangement of a combination of enzyme lactate dehydrogenase of bacteria Acinetobacter sp. as a device the identity important bacteria agent composts

    Science.gov (United States)

    Sukmawati, D.; Puspitaningrum, R.; Muzajjanah

    2017-07-01

    The number of garbage generated by the industry or society is a usual problem encountered by almost all urban centers, especially large cities such as Jakarta. Waste prevention strategy required quickly and accurately. One strategy for tackling the Junk was getting lactic acid-producing bacteria. It has been shown that lactic acid can increase the acceleration of organic matter such as an overhaul of lignin and cellulose as well as out causing toxic compounds arising from decay. This research will be conducted on the determination and characterization of the enzyme-producing compost bacteria LDH lactate dehydrogenase LDH - which in isolation from the garbage Landfill Rawasari. Methodology: Research carried out consists: isolation of lactic acid-producing bacteria; identification of microscopic, macroscopic and staining Gram; cellulose assay, and optimization of PCR conditions LDH enzymes producing bacteria. Isolation is performed by dilution method and the direct method. As many as 5-point sampling. Each stage is conducted from 10 grams of soil from the top surface of the compost. Isolation results obtained 100 isolate the bacteria. Base on the characteristic of macroscopic and microscopic observations retrieved 14 isolates of bacteria have shaped rods and brought forth a negative kind of Gram positive staining. Bacterial isolates with codes (BK1; BK3; BK4; BK5; BK6; BK7; BK8; BK9; BK10; BK11: BK12; BK 13). The potential bacteria with ability produce lactate dehydrogenase was BK1 and BK3. Base for analysis phylogenetic there was identification bacteria bak1 and bak3 where Acinetobacter sp.

  7. Combining parasite lactate dehydrogenase-based and histidine-rich protein 2-based rapid tests to improve specificity for diagnosis of malaria Due to Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia.

    Science.gov (United States)

    Grigg, Matthew J; William, Timothy; Barber, Bridget E; Parameswaran, Uma; Bird, Elspeth; Piera, Kim; Aziz, Ammar; Dhanaraj, Prabakaran; Yeo, Tsin W; Anstey, Nicholas M

    2014-06-01

    Plasmodium knowlesi causes severe and fatal malaria in Malaysia. Microscopic misdiagnosis is common and may delay appropriate treatment. P. knowlesi can cross-react with "species-specific" parasite lactate dehydrogenase (pLDH) monoclonal antibodies used in rapid diagnostic tests (RDTs) to detect P. falciparum and P. vivax. At one tertiary-care hospital and two district hospitals in Sabah, we prospectively evaluated two combination RDTs for malaria diagnosis by using both a pan-Plasmodium-pLDH (pan-pLDH)/P. falciparum-specific-pLDH (Pf-pLDH) RDT (OptiMAL-IT) and a non-P. falciparum VOM-pLDH/Pf-HRP2 RDT (CareStart). Differential cross-reactivity among these combinations was hypothesized to differentiate P. knowlesi from other Plasmodium monoinfections. Among 323 patients with PCR-confirmed P. knowlesi (n = 193), P. falciparum (n = 93), and P. vivax (n = 37) monoinfections, the VOM-pLDH individual component had the highest sensitivity for nonsevere (35%; 95% confidence interval [CI], 27 to 43%) and severe (92%; CI, 81 to 100%) P. knowlesi malaria. CareStart demonstrated a P. knowlesi sensitivity of 42% (CI, 34 to 49%) and specificity of 74% (CI, 65 to 82%), a P. vivax sensitivity of 83% (CI, 66 to 93%) and specificity of 71% (CI, 65 to 76%), and a P. falciparum sensitivity of 97% (CI, 90 to 99%) and specificity of 99% (CI, 97 to 100%). OptiMAL-IT demonstrated a P. knowlesi sensitivity of 32% (CI, 25 to 39%) and specificity of 21% (CI, 15 to 29%), a P. vivax sensitivity of 60% (CI, 42 to 75%) and specificity of 97% (CI, 94 to 99%), and a P. falciparum sensitivity of 82% (CI, 72 to 89%) and specificity of 39% (CI, 33 to 46%). The combination of CareStart plus OptiMAL-IT for P. knowlesi using predefined criteria gave a sensitivity of 25% (CI, 19 to 32%) and specificity of 97% (CI, 92 to 99%). Combining two RDT combinations was highly specific for P. knowlesi malaria diagnosis; however, sensitivity was poor. The specificity of pLDH RDTs was decreased for P. vivax and P

  8. Effect of varying rest intervals between sets of assistance exercises on creatine kinase and lactate dehydrogenase responses.

    Science.gov (United States)

    Machado, Marco; Koch, Alexander J; Willardson, Jeffrey M; Pereira, Luis S; Cardoso, M Isabel; Motta, Michela K S; Pereira, Rafael; Monteiro, André N

    2011-05-01

    To examine the effects of different rest intervals between sets on serum creatine kinase (CK) and lactate dehydrogenase (LDH) activity, 10 men (age = 25.6 ± 2.2 years, height = 173.1 ± 7.1 cm, and body mass = 75.9 ± 10.0 kg) participated in a randomized within-subject design that involved 4 resistance exercise sessions. Each session consisted of 4 sets of 10 repetitions with 10 repetition maximum loads for the chest press, pullover, biceps curl, triceps extension, leg extension, and prone leg curl. The sessions differed only in the length of the rest interval between sets and exercises, specifically: 60, 90, 120, 180 seconds. Serum CK and LDH were significantly (p resistance exercise sessions invoked similar damage to the muscle fibers independent of the rest interval between sets. These data indicate that the accumulated volume of work is the primary determinant of muscle damage in trained subjects who are accustomed to resistance exercise with short rest intervals.

  9. LDH, proliferation curves and cell cycle analysis are the most suitable assays to identify and characterize new phytotherapeutic compounds.

    Science.gov (United States)

    Specian, Ana Flávia L; Serpeloni, Juliana M; Tuttis, Katiuska; Ribeiro, Diego L; Cilião, Heloísa L; Varanda, Eliana A; Sannomiya, Miriam; Martinez-Lopez, Wilner; Vilegas, Wagner; Cólus, Ilce M S

    2016-12-01

    Brazilian flora biodiversity has been widely investigated to identify effective and safe phytotherapeutic compounds. Among the investigated plant species, the Byrsonima genus exhibits promising biological activities. This study aimed at evaluating the cytotoxicity of B. correifolia, B. verbascifolia, B. fagifolia and B. intermedia extracts using different assays in two cell lines (primary gastric and HepG2 cells). The different extract concentrations effects on cell viability were assayed using the MTT, aquabluer, neutral red and LDH assays. Non-cytotoxic concentrations were selected to generate cell proliferation curves and to assess cell cycle kinetics by flow cytometry. Byrsonima extracts differentially affected cell viability depending on the metabolic cellular state and the biological parameter evaluated. B. fagifolia and B. intermedia extracts exhibited lower cytotoxic effects than B. correifolia and B. verbascifolia in all assays. The results obtained with LDH and flow cytometry assays were more reliable, suggesting that they can be useful in the screening for herbal medicine and to further characterize these extracts as phytotherapeutic compounds.

  10. Towards novel adsorptive nanomaterials: Synthesis of Co2+Mo6+ LDH for sulfur and aromatic removal from crude petrolatum

    Directory of Open Access Journals (Sweden)

    Mohsen S. Mostafa

    2016-06-01

    Full Text Available In the present work Co/Mo(CO32−-LDH material of highly energetic surface was prepared by controlled titration of ammonium carbonate and ammonium hydroxide against Co and Mo cations at elevated temperatures, while different analytical techniques were applied to proof the chemical constitution and surface features of the material as XPS (X-ray Photoelectric Spectroscopy in addition to XRF metal analysis, FT-IR, SEM, XRD, DSC-TGA and N2 adsorption–desorption isotherm. The highly energetic surface due to formation of 4+ surface charge in the brucite layer between Co and Mo as confirmed by XPS was practically ensured when the freshly prepared Co2+Mo6+-LDH dried at 60 °C overnight without any activation has been applied as a novel adsorbent for the removal of the undesirable compounds (sulfur and aromatics compounds from crude waxes. Suez crude petrolatum has been used during this study. Depending on the experimental data, we were successful to prepare a new type of LDHs showed high ability for removing the undesirable compounds (sulfur and aromatics from Suez crude petrolatum. Also, in the same trend it removed low melting waxes. This leads to isolation of microcrystalline waxes from petroleum wastes which used as a lubricant, rust preventive, in the manufacture of cosmetics, and in medicine as a protective dressing, emollient, and in a lot of industrial applications.

  11. Serum S100B, lactate dehydrogenase and brain metastasis are prognostic factors in patients with distant melanoma metastasis and systemic therapy.

    Directory of Open Access Journals (Sweden)

    Benjamin Weide

    Full Text Available BACKGROUND: Prognostic factors of melanoma with distant metastasis and systemic treatment are only poorly established. This study aimed to analyse the impact of S100B, lactate dehydrogenase (LDH and the type of treatment on survival in advanced patients receiving systemic treatment. PATIENTS AND METHODS: We analysed overall survival of 499 patients from the university department of dermatology in Tuebingen, Germany, with unresectable melanoma at the time point of initiation of first-line systemic therapy. Only patients who started treatment between the years 2000 and 2010 were included. Disease-specific survival was calculated by bivariate Kaplan Meier survival probabilities and multivariate Cox hazard regression analysis. RESULTS: In univariate analysis LDH, S100B, the site of distant metastasis (soft tissue vs. lung vs. other visceral, the presence of brain metastases and the type of treatment (monochemotherapy, polychemotherapy, immunotherapy or biochemotherapy were associated with overall survival (all p<0.001. In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3-2.1]; p<0.001, S100B (HR 1.6 [1.2-2.1]; p<0.001 and the presence of brain metastases (HR 1.5 [1.1-1.9]; p = 0.009, but not the type of treatment had significant independent impact. Among those factors normal S100B was the best indicator of long-term survival, which was 12.3% after 5 years for this subgroup. CONCLUSION: Serum S100B is a prognostic marker predicting survival at the time of initiation of first-line treatment in unresectable melanoma patients. Compared to the other independent factors LDH and the presence of brain metastases it is most appropriate to predict long-term survival and requires further prospective investigation in patients treated with new and more potent drugs in metastatic melanoma.

  12. Water decontamination via the removal of Pb (II) using a new generation of highly energetic surface nano-material: Co(+2)Mo(+6) LDH.

    Science.gov (United States)

    Mostafa, Mohsen S; Bakr, Al-Sayed A; El Naggar, Ahmed M A; Sultan, El-Sayed A

    2016-01-01

    CoMo(CO3(2-)) layered double hydroxide of a highly energetic surface, as a new LDH consisting of divalent and hexavalent cations (M(+2)/M(+6)-LDH), was prepared by a homogeneous co-precipitation method. The structure and morphology of the prepared material was confirmed by several analytical techniques namely; X-ray diffraction analysis (XRD), X-ray fluorescence (XRF), Fourier transform infra-red (FT-IR) spectroscopy, differential scanning calorimetry and thermal gravimetric analysis (DSC-TGA), N2 adsorption-desorption isotherm and scanning electron microscope (SEM). The highly energetic surface of the prepared LDH was demonstrated via the X-ray photoelectron spectroscopy (XPS). The surface energy is due to the formation of +4 surface charges in the brucite layer between Co(+2) and Mo(+6). The prepared LDH was applied as a novel adsorbent for the removal of Pb (II) from its aqueous solution at different experimental conditions of time, temperature and initial Pb (II) concentrations. The change of the Pb (II) concentrations; due to adsorption, was monitored by atomic absorption spectrophotometer (AAS). The maximum uptake of Pb (II) by the Co Mo LDH was (73.4 mg/g) at 298 K. The Pb (II) adsorption was found to follow Langmuir isotherm and pseudo second order model. The adsorption process was spontaneous and endothermic. The interference of other cations on the removal of the Pb (II) was studied. Na(+) and K(+) were found to increase the adsorption capacity of the Co Mo LDH toward Pb (II) while it was slightly decreased by the presence of Mn(+2) and Cu(+2). The synthesized LDH showed a great degree of recoverability (7 times) while completely conserving its parental morphology and adsorption capacity. The mechanism of the lead ions removal had exhibited more reliability through a surface adsorption by the coordination between the Mo(+6) of the brucite layers and the oxygen atoms of the nitrates counter ions.

  13. Glusoce-6-phosphate dehydrogenase- History and diagnosis

    Directory of Open Access Journals (Sweden)

    K Gautam

    2016-09-01

    Full Text Available Glucose-6-phosphate dehydrogenase deficiency is the most common enzymatic defect of red blood cells, which increases the vulnerability of erythrocytes to oxidative stress leading to hemolytic anemia. Since its identification more than 60 years ago, much has been done with respect to its clinical diagnosis, laboratory diagnosis and treatment. Association of G6PD is not just limited to anti malarial drugs, but a vast number of other diseases. In this article, we aimed to review the history of Glucose-6-phosphate dehydrogenase, the diagnostic methods available along with its association with other noncommunicable diseases. 

  14. REGULATING FUNCTION OF COENZYMIZATION AND DECOENZYMIZATION OF THE LACTATE DEHYDROGENASE ISOZYMES IN THE MOUSE TISSUES DURING HYPOXIA

    Institute of Scientific and Technical Information of China (English)

    袁明秀; 蒋晖; 邓爱萍; 周晴中

    2003-01-01

    Objective. To study the characteristics of changes of LDH enzyme patterns of mice under slight hypoxia.Methods. Mice treated with artificial hypoxia, various tissues were made for the test of LDH enzy-matic activity by the specific staining technique. LDH (1-5) relative percentage enzymatic activity(RPEA) were measured with CS-910 dual-wavelength thin layer chromatography scanner.Results. The RPEA of LDH isozymes of various tissues after slight hypoxia shifted to the isozymesLDH1 and LDH2, whose principal subunits are H subunits, and the RPEA of LDH1(H4), LDH2(H3M)increased, while RPEA of LDH5(M4) in vahous tissues decreased prominently except the cardiac muscle,and that of LDH4(HM3) decreased as well. After polyacrylamide gel electrophoresis (PAGE) of the hypox-ia treated cardiac muscle specimen was made, activity subbands originated regularly in the isozyme pat-terns of LDH, with the regularity of LDH1 (0 subband), LDH2 (0-1 subbands), LDH3 (0-2 subbands),LDH4 (1-3 subbands), LDHs (2-4 subbands). After adding appropriate amount of NAD+ to the hypoxiatreated cardiac muscle specimen, PAGE showed the subbands of four isozymes (LDH2-LDH5) reduced oreven totally disappeared in the isozyme patterns.Conclusions. The negative feedback regulation of coenzymization and decoenzymization of LDHisozymes is one of the mouse stress responses to slight hypoxia.

  15. Efficient reduction of the formation of by-products and improvement of production yield of 2,3-butanediol by a combined deletion of alcohol dehydrogenase, acetate kinase-phosphotransacetylase, and lactate dehydrogenase genes in metabolically engineered Klebsiella oxytoca in mineral salts medium.

    Science.gov (United States)

    Jantama, Kaemwich; Polyiam, Pattharasedthi; Khunnonkwao, Panwana; Chan, Sitha; Sangproo, Maytawadee; Khor, Kirin; Jantama, Sirima Suvarnakuta; Kanchanatawee, Sunthorn

    2015-07-01

    Klebsiella oxytoca KMS005 (∆adhE∆ackA-pta∆ldhA) was metabolically engineered to improve 2,3-butanediol (BDO) yield. Elimination of alcohol dehydrogenase E (adhE), acetate kinase A-phosphotransacetylase (ackA-pta), and lactate dehydrogenase A (ldhA) enzymes allowed BDO production as a primary pathway for NADH re-oxidation, and significantly reduced by-products. KMS005 was screened for the efficient glucose utilization by metabolic evolution. KMS005-73T improved BDO production at a concentration of 23.5±0.5 g/L with yield of 0.46±0.02 g/g in mineral salts medium containing 50 g/L glucose in a shake flask. KMS005-73T also exhibited BDO yields of about 0.40-0.42 g/g from sugarcane molasses, cassava starch, and maltodextrin. During fed-batch fermentation, KMS005-73T produced BDO at a concentration, yield, and overall and specific productivities of 117.4±4.5 g/L, 0.49±0.02 g/g, 1.20±0.05 g/Lh, and 27.2±1.1 g/gCDW, respectively. No acetoin, lactate, and formate were detected, and only trace amounts of acetate and ethanol were formed. The strain also produced the least by-products and the highest BDO yield among other Klebsiella strains previously developed.

  16. Exposure of humans to ambient levels of ozone for 6. 6 hours causes cellular and biochemical changes in the lung

    Energy Technology Data Exchange (ETDEWEB)

    Devlin, R.B.; McDonnell, W.F.; Mann, R.; Becker, S.; House, D.E.; Schreinemachers, D.; Koren, H.S. (Environmental Protection Agency, Research Triangle Park, NC (USA))

    1991-01-01

    An acute (2 h) exposure of humans to 0.4 ppm ozone initiates biochemical changes in the lung that result in the production of components mediating inflammation and acute lung damage as well as components having the potential to lead to long-term effects such as fibrosis. However, many people are exposed to lower levels of ozone than this, but for periods of several hours. Therefore, it is important to determine if a prolonged exposure to low levels of ozone is also capable of causing cellular and biochemical changes in the lung. Nonsmoking males were randomly exposed to filtered air and either 0.10 ppm ozone or 0.08 ppm ozone for 6.6 h with moderate exercise (40 liters/min). Bronchoalveolar lavage (BAL) was performed 18 h after each exposure, and cells and fluid were analyzed. The BAL fluid of volunteers exposed to 0.10 ppm ozone had significant increases in neutrophils (PMNs), protein, prostaglandin E2 (PGE2), fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase (LDH) compared with BAL fluid from the same volunteers exposed to filtered air. In addition, there was a decrease in the ability of alveolar macrophages to phagocytize yeast via the complement receptor. Exposure to 0.08 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor. However, BAL fluid protein and fibronectin were no longer significantly elevated. We conclude that exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung.

  17. [Elevated pleural copeptin levels can distinguish to exudate from transudates].

    Science.gov (United States)

    Gümüş, Aziz; Çınarka, Halit; Karataş, Mevlüt; Kırbaş, Aynur; Kayhan, Servet; Şahin, Ünal

    2014-01-01

    Copeptin is released simultaneously along with arginine-vasopressine as a result of different stimuli from the neurohypophysis. Physiological function of copeptin is still unclear. Increased blood copeptin levels is associated with poor prognosis in many diseases. Pleural effusion is a common clinical condition. The most common causes of pleural effusions are heart failure, parapneumonic effusion, pulmonary embolism and malignacy.Tuberculosis is one of the other major causes of pleural effusion in developing countries. In this study, we aimed to assess whether pleural copeptin level may be a new discriminative biomarker for exudates and transudates pleural effusions. Research was done at Recep Tayyip Erdogan University School of Medicine in the Department of Chest Diseases. The concentrations of pleural copeptin and typical pleural and serum marker levels were measured in 76 subjects with pleural effusions including 22 transudates caused by congestive heart failure (CHF), and 54 exudates including 18 parapneumonic (PPE), 18 tuberculous pleural effusions (TBPEs), 18 malignant effusions (MPEs). Median pleural fluid copeptin levels were higher in exudates than in transudates (1936 ng/mL and 1313 pg/mL, p value exudates (n= 54). Pleural copeptin levels of exudates, with a cut off value of 1469 ng/mL, yielded a 79.6% sensitivity, 81.8% specificity, with an are a under the curve of 0.851. Pleural copeptin level is a new biomarker to separate exudates from transudates. Pleural effusion discriminative effect of copeptin is lower than plasma protein level and plasma lactat dehydrogenase (LDH). Pleural copeptin measurement is not recommended for routine clinical use. Pleural copeptin level is not contribute to different iate exudative pleural fluids from each other like PPE, TBPE and MPE.

  18. 15-hydroxyprostaglandin dehydrogenase activity in vitro in lung and kidney of essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Toft, B.S.

    1978-01-01

    Weanling rats were fed for 6 months on a diet deficient in essential fatty acids: either fat-free, or with 28% (w/w) partially hydrogenated fish oil. Control rats were fed a diet with 28% (w/w) arachis oil for 6 months. 15-Hydroxyprostaglandin dehydrogenase activity was determined as initial rates...... of the two groups on diets deficient in essential fatty acids as compared to the control group. No difference was observed in dehydrogenase activity in the kidneys. The dehydrogenase may be of importance for the regulation of the level of endogenous prostaglandins and, thus, a decrease in activity could...

  19. Yeast surface display of dehydrogenases in microbial fuel-cells.

    Science.gov (United States)

    Gal, Idan; Schlesinger, Orr; Amir, Liron; Alfonta, Lital

    2016-12-01

    Two dehydrogenases, cellobiose dehydrogenase from Corynascus thermophilus and pyranose dehydrogenase from Agaricus meleagris, were displayed for the first time on the surface of Saccharomyces cerevisiae using the yeast surface display system. Surface displayed dehydrogenases were used in a microbial fuel cell and generated high power outputs. Surface displayed cellobiose dehydrogenase has demonstrated a midpoint potential of -28mV (vs. Ag/AgCl) at pH=6.5 and was used in a mediator-less anode compartment of a microbial fuel cell producing a power output of 3.3μWcm(-2) using lactose as fuel. Surface-displayed pyranose dehydrogenase was used in a microbial fuel cell and generated high power outputs using different substrates, the highest power output that was achieved was 3.9μWcm(-2) using d-xylose. These results demonstrate that surface displayed cellobiose dehydrogenase and pyranose dehydrogenase may successfully be used in microbial bioelectrochemical systems.

  20. Regulation by retinoids of luteinizing hormone/chorionic gonadotropin receptor, cholesterol side-chain cleavage cytochrome P-450, 3 beta-hydroxysteroid dehydrogenase/delta (5-4)-isomerase and 17 alpha-hydroxylase/C17-20 lyase cytochrome P-450 messenger ribonucleic acid levels in the K9 mouse Leydig cell line.

    Science.gov (United States)

    Lefèvre, A; Rogier, E; Astraudo, C; Duquenne, C; Finaz, C

    1994-12-01

    Vitamin A is a potent regulator of testicular function. We have reported that retinol (R) and retinoic acid (RA) induced a down regulation of luteinizing hormone/human chorionic gonadotropin (LH/CG) binding sites in K9 Leydig cells. In the present study we evaluated the effect of R and RA on LH/CG receptors, cholesterol side-chain cleavage cytochrome P-450 (P-450 scc), 17 alpha-hydroxylase/C17-20 lyase (P-450 17 alpha) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) mRNA levels in K9 mouse Leydig cells. To validate K9 cells as a model for studying Leydig cell steroidogenesis at the molecular level, we first investigated the effect of hCG on mRNA levels of the steroidogenic enzymes. P-450 scc, 3 beta HSD and P-450 17 alpha were expressed constitutively. The addition of 10 ng/ml hCG enhanced mRNA levels for the three genes within 2 h. Maximal accumulation of P-450 scc, P-450 17 alpha and 3 beta HSD mRNA in treated cells represents a 2.5-, 8.5- and 4-fold increase over control values, respectively. P-450 17 alpha expression reached a maximum by 4 h and then declined rapidly to return to control value by 24 h. The pattern of LH/CG receptor mRNAs in K9 cells was very similar to that of MA10 Leydig cells and showed six transcripts of 1.1, 1.6, 1.9, 2.6, 4.2 and 7.0 kb. Treatment of cells with R or RA resulted in a time- and dose-dependent decrease in all six species.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

    DEFF Research Database (Denmark)

    Smelt, A H; Poorthuis, B J; Onkenhout, W;

    1998-01-01

    Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade......Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9......), tetradecadienoic acid, 14:2(n-6), and hexadecadienoic acid, 16:2(n-6). Palmitoyl-CoA and behenoyl-CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may...