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Sample records for acid loading increased

  1. Effect of increased protein intake on renal acid load and renal hemodynamic responses.

    PubMed

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; van Baak, Marleen A

    2016-03-01

    Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function. PMID:26997623

  2. Effect of increased protein intake on renal acid load and renal hemodynamic responses.

    PubMed

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; van Baak, Marleen A

    2016-03-01

    Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function.

  3. Improvement of pea biomass and seed productivity by simultaneous increase of phloem and embryo loading with amino acids.

    PubMed

    Zhang, Lizhi; Garneau, Matthew G; Majumdar, Rajtilak; Grant, Jan; Tegeder, Mechthild

    2015-01-01

    The development of sink organs such as fruits and seeds strongly depends on the amount of nitrogen that is moved within the phloem from photosynthetic-active source leaves to the reproductive sinks. In many plant species nitrogen is transported as amino acids. In pea (Pisum sativum L.), source to sink partitioning of amino acids requires at least two active transport events mediated by plasma membrane-localized proteins, and these are: (i) amino acid phloem loading; and (ii) import of amino acids into the seed cotyledons via epidermal transfer cells. As each of these transport steps might potentially be limiting to efficient nitrogen delivery to the pea embryo, we manipulated both simultaneously. Additional copies of the pea amino acid permease PsAAP1 were introduced into the pea genome and expression of the transporter was targeted to the sieve element-companion cell complexes of the leaf phloem and to the epidermis of the seed cotyledons. The transgenic pea plants showed increased phloem loading and embryo loading of amino acids resulting in improved long distance transport of nitrogen, sink development and seed protein accumulation. Analyses of root and leaf tissues further revealed that genetic manipulation positively affected root nitrogen uptake, as well as primary source and sink metabolism. Overall, the results suggest that amino acid phloem loading exerts regulatory control over pea biomass production and seed yield, and that import of amino acids into the cotyledons limits seed protein levels.

  4. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis.

    PubMed

    Svahn, Sara L; Ulleryd, Marcus A; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov; Johansson, Maria E

    2016-04-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.

  5. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis

    PubMed Central

    Ulleryd, Marcus A.; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov

    2016-01-01

    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics, S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus. Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival. PMID:26857576

  6. Increased mucociliary differentiation and aquaporins formation of respiratory epithelial cells on retinoic acid-loaded hyaluronan-derivative membranes.

    PubMed

    Huang, Tsung-Wei; Chan, Yen-Hui; Su, Huang-Wei; Chou, Ya-Shuan; Young, Tai-Horng

    2013-06-01

    While playing a major role in maintaining the mucociliary phenotype of respiratory epithelial cells (RECs), retinoids are critical determinants of their normal function. However, despite being a powerful biological agent, retinoic acid (RA) is generally not used in regenerative medicine due to its scarce bioavailability via conventional administration. Therefore, the ability to incorporate RA into biomaterials allows for a combination of the biological effects of RA and biomaterials in influencing cellular behavior. This study attempts to develop RA-loaded hyaluronan-derivative membrane (RA-HAm) and investigates how this membrane affects the mucociliary differentiation and aquaporins (AQP) formation of RECs. In a simulated in vitro culture condition, the RA release from membranes is maintained for 7days. On the seventh day, the cumulative release rate of RA from supportive biomaterials is ~87% under detect limitation. RECs cultured on RA-HAm reveal numerous mature ciliated cells and microvilli compared to aggregated cilia-like structures on hyaluronan-derivative membrane (HAm). Moreover, the expression levels of MUC5AC and AQP on RA-HAm are higher than those on HAm. The proposed model elucidates the release of hydrophobic RA from hyaluronan-derivative biomaterials. We believe that RA-loaded hyaluronan biomaterials are highly promising biomaterials for use in sinonasal surgery and tissue engineering of the respiratory system.

  7. Citraturic response to oral citric acid load

    NASA Technical Reports Server (NTRS)

    Sakhaee, K.; Alpern, R.; Poindexter, J.; Pak, C. Y.

    1992-01-01

    It is possible that some orally administered citrate may appear in urine by escaping oxidation in vivo. To determine whether this mechanism contributes to the citraturic response to potassium citrate, we measured serum and urinary citrate for 4 hours after a single oral load of citric acid (40 mEq.) in 6 normal subjects. Since citric acid does not alter acid-base balance, the effect of absorbed citrate could be isolated from that of alkali load. Serum citrate concentration increased significantly (p less than 0.05) 30 minutes after a single oral dose of citric acid and remained significantly elevated for 3 hours after citric acid load. Commensurate with this change, urinary citrate excretion peaked at 2 hours and gradually decreased during the next 2 hours after citric acid load. In contrast, serum and urinary citrate remained unaltered following the control load (no drug). Differences of the citratemic and citraturic effects between phases were significant (p less than 0.05) at 2 and 3 hours. Urinary pH, carbon dioxide pressure, bicarbonate, total carbon dioxide and ammonium did not change at any time after citric acid load, and did not differ between the 2 phases. No significant difference was noted in serum electrolytes, arterialized venous pH and carbon dioxide pressure at any time after citric acid load and between the 2 phases. Thus, the citraturic and citratemic effects of oral citric acid are largely accountable by provision of absorbed citrate, which has escaped in vivo degradation.

  8. Dietary Polyunsaturated Fatty Acids Increase Survival and Decrease Bacterial Load during Septic Staphylococcus aureus Infection and Improve Neutrophil Function in Mice

    PubMed Central

    Grahnemo, Louise; Pálsdóttir, Vilborg; Nookaew, Intawat; Wendt, Karl; Gabrielsson, Britt; Schéle, Erik; Benrick, Anna; Andersson, Niklas; Nilsson, Staffan; Jansson, John-Olov

    2014-01-01

    Severe infection, including sepsis, is an increasing clinical problem that causes prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of resistance to antibiotics is increasing; therefore, it is critical to find new therapies for sepsis. Staphylococcus aureus is a major cause of septic mortality. Neutrophils play an important role in the defense against bacterial infections. We have shown that a diet with high levels of dietary saturated fatty acids decreases survival in septic mice, but the mechanisms behind this remain elusive. The aim of the present study was to investigate how the differences in dietary fat composition affect survival and bacterial load after experimental septic infection and neutrophil function in uninfected mice. We found that, after S. aureus infection, mice fed a polyunsaturated high-fat diet (HFD-P) for 8 weeks had increased survival and decreased bacterial load during sepsis compared with mice fed a saturated high-fat diet (HFD-S), similar to mice fed a low-fat diet (LFD). Uninfected mice fed HFD-P had a higher frequency of neutrophils in bone marrow than mice fed HFD-S. In addition, mice fed HFD-P had a higher frequency of neutrophils recruited to the site of inflammation in response to peritoneal injection of thioglycolate than mice fed HFD-S. Differences between the proportion of dietary protein and carbohydrate did not affect septic survival at all. In conclusion, polyunsaturated dietary fat increased both survival and efficiency of bacterial clearance during septic S. aureus infection. Moreover, this diet increased the frequency and chemotaxis of neutrophils, key components of the immune response to S. aureus infections. PMID:25404025

  9. Acid loading test (pH)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003615.htm Acid loading test (pH) To use the sharing features on this page, please enable JavaScript. The acid loading test (pH) measures the ability of the ...

  10. Increased airway glucose increases airway bacterial load in hyperglycaemia.

    PubMed

    Gill, Simren K; Hui, Kailyn; Farne, Hugo; Garnett, James P; Baines, Deborah L; Moore, Luke S P; Holmes, Alison H; Filloux, Alain; Tregoning, John S

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  11. Increased airway glucose increases airway bacterial load in hyperglycaemia

    PubMed Central

    Gill, Simren K.; Hui, Kailyn; Farne, Hugo; Garnett, James P.; Baines, Deborah L.; Moore, Luke S.P.; Holmes, Alison H.; Filloux, Alain; Tregoning, John S.

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  12. Running with a load increases leg stiffness.

    PubMed

    Silder, Amy; Besier, Thor; Delp, Scott L

    2015-04-13

    Spring-mass models have been used to characterize running mechanics and leg stiffness in a variety of conditions, yet it remains unknown how running while carrying a load affects running mechanics and leg stiffness. The purpose of this study was to test the hypothesis that running with a load increases leg stiffness. Twenty-seven subjects ran at a constant speed on a force-measuring treadmill while carrying no load, and while wearing weight vests loaded with 10%, 20%, and 30% of body weight. We measured lower extremity motion and created a scaled musculoskeletal model of each subject, which we used to estimate lower extremity joint angles and leg length. We estimated dimensionless leg stiffness as the ratio of the peak vertical ground reaction force (normalized to body weight) and the change in stance phase leg length (normalized to leg length at initial foot contact). Leg length was calculated as the distance from the center of the pelvis to the center-of-pressure under the foot. We found that dimensionless leg stiffness increased when running with load (p=0.001); this resulted from an increase in the peak vertical ground reaction force (p<0.001) and a smaller change in stance phase leg length (p=0.025). When running with load, subjects had longer ground contact times (p<0.020), greater hip (p<0.001) and knee flexion (p=0.048) at the time of initial foot contact, and greater peak stance phase hip, knee, and ankle flexion (p<0.05). Our results reveal that subjects run in a more crouched posture and with higher leg stiffness to accommodate an added load.

  13. Running with a load increases leg stiffness.

    PubMed

    Silder, Amy; Besier, Thor; Delp, Scott L

    2015-04-13

    Spring-mass models have been used to characterize running mechanics and leg stiffness in a variety of conditions, yet it remains unknown how running while carrying a load affects running mechanics and leg stiffness. The purpose of this study was to test the hypothesis that running with a load increases leg stiffness. Twenty-seven subjects ran at a constant speed on a force-measuring treadmill while carrying no load, and while wearing weight vests loaded with 10%, 20%, and 30% of body weight. We measured lower extremity motion and created a scaled musculoskeletal model of each subject, which we used to estimate lower extremity joint angles and leg length. We estimated dimensionless leg stiffness as the ratio of the peak vertical ground reaction force (normalized to body weight) and the change in stance phase leg length (normalized to leg length at initial foot contact). Leg length was calculated as the distance from the center of the pelvis to the center-of-pressure under the foot. We found that dimensionless leg stiffness increased when running with load (p=0.001); this resulted from an increase in the peak vertical ground reaction force (p<0.001) and a smaller change in stance phase leg length (p=0.025). When running with load, subjects had longer ground contact times (p<0.020), greater hip (p<0.001) and knee flexion (p=0.048) at the time of initial foot contact, and greater peak stance phase hip, knee, and ankle flexion (p<0.05). Our results reveal that subjects run in a more crouched posture and with higher leg stiffness to accommodate an added load. PMID:25728581

  14. Friction does not increase anchorage loading.

    PubMed

    Southard, Thomas E; Marshall, Steve D; Grosland, Nicole M

    2007-03-01

    Conventional wisdom suggests that orthodontists must apply added force to overcome friction during canine retraction (sliding mechanics), the result of which can be increased anchorage loading and anchorage loss. However, for a frictional force to be exerted mesially by the archwire against a canine during retraction, the archwire must be compressed between the canine and the anchor molar, and an equal but opposite force must be applied distally against the molar by the archwire. In other words, the frictional force that reduces the force of retraction on the canine must also reduce the protraction force on the molar. Emphasis on employing reduced-friction (eg, self-ligating) brackets during sliding mechanics to prevent added posterior anchorage loading is unwarranted and based more on bracket salesmanship than on orthodontic biomechanics. PMID:17346599

  15. Enhanced Sucrose Loading Improves Rice Yield by Increasing Grain Size.

    PubMed

    Wang, Liang; Lu, Qingtao; Wen, Xiaogang; Lu, Congming

    2015-12-01

    Yield in cereals is a function of grain number and size. Sucrose (Suc), the main carbohydrate product of photosynthesis in higher plants, is transported long distances from source leaves to sink organs such as seeds and roots. Here, we report that transgenic rice plants (Oryza sativa) expressing the Arabidopsis (Arabidopsis thaliana) phloem-specific Suc transporter (AtSUC2), which loads Suc into the phloem under control of the phloem protein2 promoter (pPP2), showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. Compared with wild-type plants, pPP2::AtSUC2 plants had larger spikelet hulls and larger and heavier grains. Grain filling was accelerated in the transgenic plants, and more photoassimilate was transported from the leaves to the grain. In addition, microarray analyses revealed that carbohydrate, amino acid, and lipid metabolism was enhanced in the leaves and grain of pPP2::AtSUC2 plants. Thus, enhancing Suc loading represents a promising strategy to improve rice yield to feed the global population.

  16. Sagittal rotational stiffness and damping increase in a porcine lumbar spine with increased or prolonged loading.

    PubMed

    Zondervan, Robert L; Popovich, John M; Radcliffe, Clark J; Pathak, Pramod K; Reeves, N Peter

    2016-02-29

    While the impact of load magnitude on spine dynamic parameters (stiffness and damping) has been reported, it is unclear how load history (exposure to prolonged loading) affects spine dynamic parameters in sagittal rotation. Furthermore, it is unknown if both spine stiffness and damping are equally affected to prolonged loading. Using a pendulum testing apparatus, the effect of load magnitude and load history on spine sagittal rotational stiffness and damping was assessed. Nine porcine lumbar functional spine units (FSUs) were tested in an increasing compressive load phase (ICP: 44.85, 68.55, 91.75, 114.6kg) and then a decreasing compressive load phase (DCP: 91.75, 68.55, and 44.85kg). Each trial consisted of flexing the FSU 5° and allowing it to oscillate unconstrained. During the ICP, both stiffness and damping linearly increased with load. However, in the DCP, stiffness and damping values were significantly higher than the identical load collected during the ICP, suggesting load history affects sagittal rotational dynamic parameters. In addition, spine damping was more affected by load history than spine stiffness. These results highlight the importance of controlling load magnitude and history when assessing spine dynamic parameters. PMID:26892899

  17. Critical loads of acidity for surface waters in China.

    PubMed

    Duan, L; Hao, J; Xie, S; Du, K

    2000-01-31

    For further control of acid rain and sulphur dioxide pollution, the Chinese government has designated the Acid Rain Control Zone and the Sulphur Dioxide Pollution Control Zone for those areas that are, or could become, affected by acid deposition or ambient sulphur dioxide concentrations. One of the most important principles for designating the Acid Rain Control Zone is that the critical load is exceeded by the sulphur deposition. Through the steady-state water chemistry method (SSWC), critical loads of acidity for surface waters were mapped based on available data. Results show that surface waters sensitive to acid deposition, i.e. surface waters with low critical loads, are mainly found in north-east China, on the Tibetan Plateau, and in north-west China. Compared with the critical loads of soils, critical loads of surface waters are usually higher in almost all areas in China. The reason for very low critical loads of surface waters in some regions dominated by soils geologically not sensitive to acid deposition may be attributed to the low temperature, high altitude and low runoff. In contrast, surface waters in south China are not susceptible to acid deposition, and so far acidification of surface water has not been found in spite of the heavy acid rain. As can be seen from the critical load exceedance map, nearly 10% of the surface waters are subject to risk of acidification in 1995.

  18. Mechanics of arterial subfailure with increasing loading rate.

    PubMed

    Stemper, Brian D; Yoganandan, Narayan; Pintar, Frank A

    2007-01-01

    Arterial subfailure leads to delayed symptomatology and high morbidity and mortality rates, particularly for the thoracic aorta and carotid arteries. Although arterial injuries occur during high-velocity automotive collisions, previous studies of arterial subfailure focused on quasi-static loading. This investigation subjected aortic segments to increasing loading rates to quantify effects on elastic, subfailure, and ultimate vessel mechanics. Sixty-two specimens were axially distracted, and 92% demonstrated subfailure before ultimate failure. With increasing loading rate, stress at initial subfailure and ultimate failure significantly increased, and strain at initial subfailure and ultimate failure significantly decreased. Present results indicate increased susceptibility for arterial subfailure and/or dissection under higher-rate extension. According to the present results, automotive occupants are at greater risk of arterial injury under higher velocity impacts due to greater body segment motions in addition to decreased strain tolerance to subfailure and catastrophic failure.

  19. Theophylline increases oxygen consumption during inspiratory resistive loading.

    PubMed

    Janssens, S; Derom, E; Vanhaecke, J; Decramer, M

    1995-04-01

    The effect of theophylline on diaphragmatic blood flow (Qdi) and oxygen consumption (VO2di) was studied in eight lightly anesthetized dogs during quiet breathing and inspiratory resistive loading. Qdi was determined with the radioactive microsphere tracer technique, and VO2di was calculated as the product of Qdi and the diaphragmatic arterio-venous oxygen difference. During quiet breathing, theophylline increased minute ventilation (9.3 +/- 1.7 versus 5.1 +/- 0.4 L/min), mean inspiratory flow (547 +/- 60 versus 378 +/- 56 ml/s), and duty cycle (0.270 +/- 0.042 versus 0.192 +/- 0.024) but did not significantly alter Qdi or VO2di. Conversely, Qdi increased significantly during loaded breathing compared with quiet breathing (37 +/- 4 versus 27 +/- 3 ml/100 g/min) and was further increased by theophylline (45 +/- 7 ml/100 g/min). Theophylline did not alter the tension-time index of the diaphragm (TTdi) during inspiratory resistive loading (0.054 +/- 0.006 versus 0.056 +/- 0.004, p NS) but resulted in a disproportionate and significant increase in VO2di (2.66 +/- 0.53 versus 1.78 +/- 0.26 ml/100 g/min). Similarly, total-body oxygen consumption (VO2TB) during inspiratory loading increased significantly after theophylline (24%), but the tension-time index of the inspiratory muscles (TTi), a measure of the total respiratory load, was unchanged. We conclude that theophylline significantly increases VO2di and VO2TB at the same TTdi and TTi during resistive loading. This enhanced energy expenditure needs consideration in the clinical management of pulmonary disorders that increase the work of breathing. PMID:7697222

  20. Increased fibroblast functionality on CNN2-loaded titania nanotubes.

    PubMed

    Wei, Hongbo; Wu, Shuyi; Feng, Zhihong; Zhou, Wei; Dong, Yan; Wu, Guofeng; Bai, Shizhu; Zhao, Yimin

    2012-01-01

    Infection and epithelial downgrowth are major problems associated with maxillofacial percutaneous implants. These complications are mainly due to the improper closure of the implant-skin interface. Therefore, designing a percutaneous implant that better promotes the formation of a stable soft tissue biologic seal around percutaneous sites is highly desirable. Additionally, the fibroblast has been proven to play an important role in the formation of biologic seals. In this study, titania nanotubes were filled with 11.2 kDa C-terminal CCN2 (connective tissue growth factor) fragment, which could exert full CCN2 activity to increase the biological functionality of fibroblasts. This drug delivery system was fabricated on a titanium implant surface. CCN2 was loaded into anodized titania nanotubes using a simplified lyophilization method and the loading efficiency was approximately 80%. Then, the release kinetics of CCN2 from these nanotubes was investigated. Furthermore, the influence of CCN2-loaded titania nanotubes on fibroblast functionality was examined. The results revealed increased fibroblast adhesion at 0.25, 0.5, 1, 2, 4, and 24 hours, increased fibroblast viability over the course of 5 days, as well as enhanced actin cytoskeleton organization on CCN2-loaded titania nanotubes surfaces compared to uncoated, unmodified counterparts. Therefore, the results from this in vitro study demonstrate that CCN2-loaded titania nanotubes have the ability to increase fibroblast functionality and should be further studied as a method of promoting the formation of a stable soft tissue biologic seal around percutaneous sites.

  1. Climate Change Impacts on Forest Soils Critical Acid Loads and Exceedances at a National Scale

    NASA Astrophysics Data System (ADS)

    McNulty, S. G.; Cohen, E.; Moore Myers, J.; Sun, G.; Caldwell, P.

    2011-12-01

    The Federal agencies of the United States (US) are currently developing guidelines for forest soil critical acid loads across the US. A critical acid load is defined as the amount of acid deposition (usually expressed on a annual basis) that an ecosystem can absorb. Traditionally, an ecosystem is considered to be at risk for health impairment when the critical acid load exceeds a level known to impair forest health. The excess over the critical acid load is termed the exceedance, and the larger the exceedance, the greater the risk of ecosystem damage. This definition of critical acid load applies to a single, long-term pollutant exposure. These guidelines are often used to establish regulations designed to maintain acidic deposition (e.g., nitrogen and sulfur) inputs below the level shown to exceed an ecosystem's critical acid load. The traditional definition for a critical acid load generally assume that the ecosystem is in a steady state condition (i.e. no major changes in the factors that regulate the ecosystems ability to absorb acids. Unfortunately, climate change is altering weather patterns and, thus, impacting the factors that regulate critical acid load limits. This paper explores which factors associated with establishing forest soil critical acid load limits will most likely be influenced by climate change, and how these changes might impact forest soil critical acid load limits across the US. Base cation weathering could increase with global warming, along with nitrogen uptake as a function of increased forest growth across New England. A moderate 20% increase in base cation weathering and nitrogen uptake would result in at least a 25% decrease in the amount of forest soil area that exceeded the critical acid load limit and at least a 50% decrease in the amount of high exceedance area across the US. While these results are encouraging, they do not account for other negative potential forest health risks associated with climate change such as elevated

  2. Longitudinal relationships between diet-dependent renal acid load and blood pressure development in healthy children.

    PubMed

    Krupp, Danika; Shi, Lijie; Remer, Thomas

    2014-01-01

    Diets high in sulfur-rich protein and low in fruits and vegetables affect human acid-base balance adversely. Corresponding subclinical forms of metabolic acidosis have been linked to hypertension in adults. We longitudinally examined relations of dietary acid load with blood pressure in 257 healthy prepuberty children with 3 or more parallel 3-day weighed dietary records, 24-h urine, and blood pressure measurements. Urinary net acid excretion and the potential renal acid load (PRAL), determined as the difference of major urinary nonbicarbonate anions and mineral cations, were used to predict dietary acid load. PRAL was also calculated from dietary data. In repeated-measures regression analyses, adjusted for body size and dietary fiber, an intraindividual increase of 10 mEq above the 'usual' net acid excretion or urine PRAL were each significantly related to a 0.6-0.7 mm Hg increased systolic blood pressure. Differences in urine PRAL among the children also significantly predicted between-person differences in systolic blood pressure. A higher individual net acid excretion or urine PRAL and intraindividual increase in urine PRAL were significantly related to higher diastolic blood pressure. Blood pressure associations were nonsignificant for dietary PRAL and urinary sodium. Thus, in healthy children, renal biomarker analyses reveal an association of proton load with higher blood pressure. Especially for systolic blood pressure, a more alkalizing nutrition may be beneficial for blood pressure development within a given individual. Experimental confirmation of a causal acid load-blood pressure link is required.

  3. The role of dietary acid load and mild metabolic acidosis in insulin resistance in humans.

    PubMed

    Williams, Rebecca S; Kozan, Pinar; Samocha-Bonet, Dorit

    2016-05-01

    Type 2 diabetes is increasingly being recognised as a global health crisis (World Health Organisation). Insulin resistance is closely associated with obesity and precedes the development of type 2 diabetes. However, there is now increasing evidence to suggest that diet itself may independently be associated with type 2 diabetes risk. A diet with a high acid load (or high potential renal net acid load, PRAL) can result in a decrease in pH towards the lower end of the normal physiological range, which may in turn lead to the development of insulin resistance. Conversely, reducing dietary acid load (the so called 'alkaline diet') may be protective and prevent the onset of type 2 diabetes. Here, we explore the influence of dietary acid load on the development of mild metabolic acidosis and induction of insulin resistance. Whilst large prospective cohort studies link high dietary acid load or low serum bicarbonate with the development of type 2 diabetes, the effect of a diet with a low acid (or high alkaline) load remains unclear. Further interventional studies are required to investigate the influence of dietary composition on the body's acid/base balance, insulin resistance and incidence of type 2 diabetes. PMID:26363101

  4. Increased lactulose/rhamnose ratio during fluid load is caused by increased urinary lactulose excretion.

    PubMed

    Hallemeesch, M M; Lamers, W H; Soeters, P B; Deutz, N E

    2000-01-01

    Noninvasive assessment of intestinal permeability in vivo is based on the measurement of urinary excretion of orally administered sugar probes. It is expressed as a ratio, usually lactulose/rhamnose or 3-O-methyl-D-glucose (3-OMG)/rhamnose. In both endotoxemic and control rats that were receiving fluid, we observed an increase in the recovery of lactulose and 3-OMG but not rhamnose in both groups, suggesting an enhancement of intestinal permeability. In the measurement of intestinal permeability, all pre- and postmucosal factors are considered equal for all sugars. We hypothesized that postmucosal factors and not changes in intestinal permeability caused the increased urinary lactulose and 3-OMG recoveries observed during fluid loading. Therefore, the effects of fluid loading on urinary excretion of the sugar probes were studied in healthy rats receiving the sugars intravenously. After intravenous injection, fluid loading increased urinary lactulose recovery threefold but not that of 3-OMG and rhamnose. In conclusion, fluid loading increases the lactulose/rhamnose ratio independent of changes in intestinal permeability. The 3-OMG/rhamnose ratio is not influenced by fluid loading.

  5. Increase of sample load without peak deterioration by careful selection of electrolyte in capillary zone electrophoresis.

    PubMed

    Andersson, E K Margareta; Hägglund, I

    2002-04-12

    In this study it is demonstrated that much higher concentrations of bases dissolved in water can be injected in capillary zone electrophoresis without causing peak deterioration, e.g., peak splitting, if it is the co-ion that buffers instead of the counter-ion. Those findings can be utilised to control peak shapes and in this way an increase in the sample load and indirectly a decrease in the detection limits of impurities in the sample can be obtained. Good results were obtained with 4-aminobutyric and 6-aminocaproic acids as buffering co-ions. Another possibility evaluated successfully was that of using a dibasic acid, malic acid or succinic acid. With an electrolyte containing both succinic acid and 6-aminocaproic acid at pH 4.5, it was possible to load at least 10-20 times more of the test substances imidazole, creatinine or 2-aminopyrimidine dissolved in water than with an electrolyte at the same pH containing acetic acid and tris(hydroxymethyl)aminomethane. PMID:12058936

  6. High Dietary Acid Load Predicts ESRD among Adults with CKD.

    PubMed

    Banerjee, Tanushree; Crews, Deidra C; Wesson, Donald E; Tilea, Anca M; Saran, Rajiv; Ríos-Burrows, Nilka; Williams, Desmond E; Powe, Neil R

    2015-07-01

    Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine-Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population.

  7. High Dietary Acid Load Predicts ESRD among Adults with CKD

    PubMed Central

    Crews, Deidra C.; Wesson, Donald E.; Tilea, Anca M.; Saran, Rajiv; Ríos-Burrows, Nilka; Williams, Desmond E.; Powe, Neil R.

    2015-01-01

    Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine–Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population. PMID:25677388

  8. In Vivo Evaluation of Ibuprofen-Loaded Poly(lactic-co-glycolic) Acid Nanoparticles in Rats

    NASA Astrophysics Data System (ADS)

    Abidin, Suhaili Zainal; Sameni, Javad; Julianto, Tommy; Bukhari, Nadeem Irfan

    2009-06-01

    The aim of our studies was to formulate a nanoparticulate system that delivers the required dose of ibuprofen to the blood serum. The poly (lactic-co-glycolic acid, 50:50) nanoparticles were fabricated using emulsion solvent evaporation technique for the encapsulation of Ibuprofen. After oral administration of Ibuprofen-loaded nanoparticles in rats, drug concentration in blood serum was detected using HPLC. Drug loading and drug entrapment efficiency was detected with different drug loading. The results indicated that drug loading and drug entrapment were increased with increasing drug/PLGA ratio. The concentration profiles of ibuprofen released from nanoparticles indicated that the burst effect was reduced with a sustain drug release after administration. SEM images show the spherical shape and smooth surface of nanoparticles, with low PDI. In conclusion, our studies showed the significant increases in release time of optimum drug loading with a sustain drug release using ibuprofen/PLGA nanoparticles.

  9. Different Serum Free Fatty Acid Profiles in NAFLD Subjects and Healthy Controls after Oral Fat Load

    PubMed Central

    Gambino, Roberto; Bugianesi, Elisabetta; Rosso, Chiara; Mezzabotta, Lavinia; Pinach, Silvia; Alemanno, Natalina; Saba, Francesca; Cassader, Maurizio

    2016-01-01

    Background: Free fatty acid (FFA) metabolism can impact on metabolic conditions, such as obesity and nonalcoholic fatty liver disease (NAFLD). This work studied the increase in total FFA shown in NAFLD subjects to possibly characterize which fatty acids significantly accounted for the whole increase. Methods: 21 patients with NAFLD were selected according to specified criteria. The control group consisted of nine healthy subjects. All subjects underwent an oral standard fat load. Triglycerides; cholesterol; FFA; glucose and insulin were measured every 2 h with the determination of fatty acid composition of FFA. Results: higher serum FFA levels in NAFLD subjects are mainly due to levels of oleic, palmitic and linoleic acids at different times. Significant increases were shown for docosahexaenoic acid, linolenic acid, eicosatrienoic acid, and arachidonic acid, although this was just on one occasion. In the postprandial phase, homeostatic model assessment HOMA index positively correlated with the ω3/ω6 ratio in NAFLD patients. Conclusions: the higher serum levels of FFA in NAFLD subjects are mainly due to levels of oleic and palmitic acids which are the most abundant circulating free fatty acids. This is almost exactly corresponded with significant increases in linoleic acid. An imbalance in the n-3/n-6 fatty acids ratio could modulate postprandial responses with more pronounced effects in insulin-resistant subjects, such as NAFLD patients. PMID:27043543

  10. A review of the calculation procedure for critical acid loads for terrestrial ecosystems.

    PubMed

    van der Salm, C; de Vries, W

    2001-04-23

    Target loads for acid deposition in the Netherlands, as formulated in the Dutch environmental policy plan, are based on critical load calculations at the end of the 1980s. Since then knowledge on the effect of acid deposition on terrestrial ecosystems has substantially increased. In the early 1990s a simple mass balance model was developed to calculate critical loads. This model was evaluated and the methods were adapted to represent the current knowledge. The main changes in the model are the use of actual empirical relationships between Al and H concentrations in the soil solution, the addition of a constant base saturation as a second criterion for soil quality and the use of tree species-dependant critical Al/base cation (BC) ratios for Dutch circumstances. The changes in the model parameterisation and in the Al/BC criteria led to considerably (50%) higher critical loads for root damage. The addition of a second criterion in the critical load calculations for soil quality caused a decrease in the critical loads for soils with a median to high base saturation such as loess and clay soils. The adaptation hardly effected the median critical load for soil quality in the Netherlands, since only 15% of the Dutch forests occur on these soils. On a regional scale, however, critical loads were (much) lower in areas where those soils are located.

  11. Sibling competition and hunger increase allostatic load in spotted hyaenas.

    PubMed

    Benhaiem, Sarah; Hofer, Heribert; Dehnhard, Martin; Helms, Janine; East, Marion L

    2013-06-23

    Allostatis is the process of maintaining homeostatis through behavioural or physiological responses to challenges, and its cumulative energetic cost is termed allostatic load. The allostatic load hypothesis predicts that hunger and the mechanisms that establish and maintain social dominance should have a strong impact on allostatic load. In spotted hyaenas, dominance between twin siblings emerges during intense early competition for maternal milk and involves trained winner/loser effects. Conflict over access to teats declines with age as behavioural dominance conventions are established. In young litters, the allostatic load of subordinates measured in terms of faecal glucocorticoid metabolite concentrations (fGMCs) should be higher than that of dominants. When low milk provisioning threatens survival, hungry subordinates are more assertive, particularly when competing against a dominant sister. Dominants challenged by assertive subordinates should have allostatic loads and fGMCs above those of dominants with subordinates that adhere to dominance conventions. We show that in young litters, subordinates had significantly higher fGMCs than dominants, and dominant sisters had significantly higher fGMCs than dominant brothers. When hungry, both dominants and subordinates had significantly higher fGMCs than when fed. Our results provide evidence that hunger and sibling competition affect allostatic load in spotted hyaenas.

  12. Sibling competition and hunger increase allostatic load in spotted hyaenas.

    PubMed

    Benhaiem, Sarah; Hofer, Heribert; Dehnhard, Martin; Helms, Janine; East, Marion L

    2013-06-23

    Allostatis is the process of maintaining homeostatis through behavioural or physiological responses to challenges, and its cumulative energetic cost is termed allostatic load. The allostatic load hypothesis predicts that hunger and the mechanisms that establish and maintain social dominance should have a strong impact on allostatic load. In spotted hyaenas, dominance between twin siblings emerges during intense early competition for maternal milk and involves trained winner/loser effects. Conflict over access to teats declines with age as behavioural dominance conventions are established. In young litters, the allostatic load of subordinates measured in terms of faecal glucocorticoid metabolite concentrations (fGMCs) should be higher than that of dominants. When low milk provisioning threatens survival, hungry subordinates are more assertive, particularly when competing against a dominant sister. Dominants challenged by assertive subordinates should have allostatic loads and fGMCs above those of dominants with subordinates that adhere to dominance conventions. We show that in young litters, subordinates had significantly higher fGMCs than dominants, and dominant sisters had significantly higher fGMCs than dominant brothers. When hungry, both dominants and subordinates had significantly higher fGMCs than when fed. Our results provide evidence that hunger and sibling competition affect allostatic load in spotted hyaenas. PMID:23616643

  13. Generation of hydroxyl radicals from metal-loaded humic acids

    SciTech Connect

    Paciolla, M.D.; Jansen, S.A.; Davies, G.

    1999-06-01

    Humic acids (HAs) are naturally occurring biopolymers that are ubiquitous in the environment. They are most commonly found in the soil, drinking water, and a variety of plants. Pharmacological and therapeutic studies involving humic acids have been reported to some extent. However, when certain transition metals are bound to humic acids, e.g., iron and copper, they can be harmful to biological organisms. For this study, humic acids were extracted from German, Irish, and New Hampshire soils that were selectively chosen because of their reich abundance in humic material. Each sample was treated at room temperature with 0.1 M ferric and cupric solutions for 48 h. The amount of iron and copper adsorbed by humic acid was accurately quantitated using atomic absorption spectroscopy. The authors further demonstrate that these metal-loaded humic acids can produce deleterious oxidizing species such as the hydroxyl radical (HO*) through the metal-driven Fenton reaction. Electron paramagnetic resonance (EPR) employing spin trapping techniques with 5,5-dimethylpyrroline N-oxide (DMPO) is used to confirm the generation of hydroxyl radicals. The DMPO-OH adduct with hyperfine splitting constants A{sub N} = A{sub H} = 14.9 G is observed upon the addition of exogenous hydrogen peroxide. The concentration of hydroxyl radical was determined using 4-hydroxytempo (TEMPO-OH) as a spin standard. The presence of another oxidizing species, Fe{double_bond}O{sup 2+}, is also proposed in the absence of hydrogen peroxide.

  14. Loading of Gemcitabine on chitosan magnetic nanoparticles increases the anti-cancer efficacy of the drug.

    PubMed

    Parsian, Maryam; Unsoy, Gozde; Mutlu, Pelin; Yalcin, Serap; Tezcaner, Aysen; Gunduz, Ufuk

    2016-08-01

    Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine. CsMNPs were synthesized by in situ co-precipitation and Gemcitabine was loaded onto the nanoparticles. Nanoparticle characterization was performed by TEM, FTIR, XPS, and zeta potential. Gemcitabine release and stability was analyzed. The cellular uptake was shown. Cytotoxicity of free-Gemcitabine and Gem-CsMNPs were examined on SKBR and MCF-7 breast cancer cells by XTT assay. Gemcitabine loading was optimized as 30µM by spectrophotometric analyses. Drug release was highest (65%) at pH 4.2, while it was 8% at pH 7.2. This is a desired release characteristic since pH of tumor-tissue and endosomes are acidic, while the blood-stream and healthy-tissues are neutral. Peaks reflecting the presence of Gemcitabine were observed in FTIR and XPS. At neutral pH, zeta potential increased after Gemcitabine loading. TEM images displayed, Gem-CsMNPs were 4nm with uniform size-distribution and have spherical shape. The cellular uptake and targetability of CsMNPs was studied on MCF-7 breast cancer cell lines. IC50 value of Gem-CsMNPs was 1.4 fold and 2.6 fold lower than free-Gem on SKBR-3 and MCF-7 cell lines respectively, indicating the increased efficacy of Gemcitabine when loaded onto nanoparticles. Targetability by magnetic field, stability, size distribution, cellular uptake and toxicity characteristics of CsMNPs in this study provides a useful targeted delivery system for Gemcitabine in cancer therapy. PMID:27181067

  15. Polymer etching in the oxygen afterglow - Increased etch rates with increased reactor loading

    NASA Technical Reports Server (NTRS)

    Lerner, N. R.; Wydeven, T.

    1989-01-01

    Reactor loading has an effect on the etch rate (rate of decrease of film thickness) of films of polyvinylfluoride (Tedlar) and polyethylene exposed in the afterglow of an RF discharge in oxygen. The etch rate is found to increase with the total surface area of the polymer exposed in the reactor. The etch rates of polypyromellitimide (Kapton H) and polystyrene under these conditions are very low. However, the etch rate of these polymers is greatly enhanced by adding either Tedlar or polyethylene to the reactor. A kinetic model is proposed based on the premise that the oxygen atoms produced by the RF discharge react with Tedlar or polyethylene to produce a much more reactive species, which dominates the etching of the polymers studied.

  16. Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid

    PubMed Central

    Keum, Chang-Gu; Noh, Young-Wook; Baek, Jong-Suep; Lim, Ji-Ho; Hwang, Chan-Ju; Na, Young-Guk; Shin, Sang-Chul; Cho, Cheong-Weon

    2011-01-01

    Background Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. Methods Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2–5 minutes of sonication time, 70–130 W sonication power, and 5–25 mg drug loading. Results A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. Conclusion Our research shows that the choice of surfactant is important for controlled release of

  17. Inhibition of Long Chain Acyl Coenzyme A Synthetases during Fatty Acid Loading Induces Lipotoxicity in Macrophages

    PubMed Central

    Saraswathi, Viswanathan; Hasty, Alyssa H.

    2009-01-01

    OBJECTIVES Obesity is often associated with hypertriglyceridemia and elevated free fatty acids (FFAs) which are independent risk factors for cardiovascular disease and diabetes. While impairment of cholesterol homeostasis is known to induce toxicity in macrophages, the consequence of altered fatty acid homeostasis is not clear. METHODS AND RESULTS Long chain acyl CoA synthetases (ACSLs) play a critical role in fatty acid homeostasis by channeling fatty acids to diverse metabolic pools. We treated mouse peritoneal macrophages (MPMs) with VLDL or FFAs in the presence of triacsin C, an inhibitor of the three ACSL isoforms present in macrophages. Treatment of macrophages with VLDL and triacsin C resulted in reduced TG accumulation but increased intracellular FFA levels which induced lipotoxicity characterized by induction of apoptosis. Treatment of MPMs with the saturated fatty acid stearic acid in the presence of triacsin C increased intracellular stearic acid and induced apoptosis. Stromal vascular cells collected from high fat diet-fed mice displayed foam cell morphology and exhibited increased mRNA levels of macrophage markers and ACSL1. Importantly, all of these changes were associated with increased FFA level in AT. CONCLUSIONS Inhibition of ACSLs during fatty acid loading results in apoptosis via accumulation of FFAs. Our data have implications in understanding the consequences of dysregulated fatty acid metabolism in macrophages. PMID:19679826

  18. Reduction of Dietary Acid Load as a Potential Countermeasure for Bone Loss Associated with Spaceflight

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Watts, S. M.; Sams, C. F.; Whitson, P. A.; Smith, S. M.

    2006-01-01

    In several studies we tested the concepts that diet can alter acid-base balance and that reducing the dietary acid load has a positive effect on maintenance of bone. In study 1, (n = 11, 60-90 d bed rest), the renal acid load of the diet was estimated from its chemical composition, and was positively correlated with urinary markers of bone resorption (P less than 0.05); that is, the greater the acid load, the greater the excretion of bone resorption markers. In study 2, in males (n = 8, 30 d bed rest), an estimate of the ratio of nonvolatile acid precursors to base precursors in the diet was positively correlated (P less than 0.05) with markers of bone resorption. In study 3, for 28 d subjects received either a placebo (n = 6) or an essential amino acid supplement (n = 7) that included methionine, a known acid precursor. During bed rest (28 d), urinary calcium was greater than baseline levels in the supplemented group but not the control group (P less than 0.05), and in the supplemented group, urinary pH decreased (P less than 0.05). In study 4, less bone resorption occurred in space crew members who received potassium citrate (n = 6) during spaceflight of 4-6 months than in crew members who received placebo or were not in the study (n = 8) (P less than 0.05). Reducing acid load has the potential to mitigate increased bone resorption during spaceflight, and may serve as a bone loss countermeasure.

  19. 29 CFR 1919.77 - Safe working load increase.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... or original design limitations unless such increase meets with the manufacturer's approval. Where the manufacturer's services are not available, or where the equipment is of foreign manufacture, engineering...

  20. Load-bearing increase in alumina evoked by introduction of a functional glass gradient

    PubMed Central

    Dorthé, Erik; Zhang, Yu

    2011-01-01

    Alumina is the most commonly used ceramic in orthopedics due mainly to its wear resistance and chemical inertness. However, alumina has relatively low load-bearing capacity compared to other advanced ceramics, such as zirconia. We hypothesized that grading the elastic modulus at the surfaces may substantially increase the load-bearing capacity of alumina. In this study, graded structures were fabricated by infiltrating glass into dense alumina plates, resulting in a diminished modulus at the surface layers. The plates were then bonded to polycarbonate substrates and subjected to flexural loading with various loading rates spanning five orders of magnitude (dynamic fatigue) in water. Infiltrated specimens showed an increase in flexural load over homogenous controls for all loading rates, despite the graded alumina exhibiting greater load rate dependence than their homogenous counterparts. Our results indicate that controlled elastic gradients at the surface could be highly beneficial in improving the load-bearing capacity of alumina ceramics. PMID:22639492

  1. Increased musculoskeletal stiffness during load carriage at increasing walking speeds maintains constant vertical excursion of the body center of mass.

    PubMed

    Holt, Kenneth G; Wagenaar, Robert C; LaFiandra, Michael E; Kubo, Masayoshi; Obusek, John P

    2003-04-01

    The primary objective of this research was to determine changes in body and joint stiffness parameters and kinematics of the knee and body center of mass (COM), that result from wearing a backpack (BP) with a 40% body weight load at increasing speeds of walking. It was hypothesized that there would be speed and load-related increases in stiffness that would prevent significant deviations in the COM trajectory and in lower-extremity joint angles. Three independent biomechanical models employing kinematic data were used to estimate global lower-extremity stiffness, vertical stiffness and knee joint rotational stiffness in the sagittal plane during walking on a treadmill at speeds of 0.6-1.6 ms(-1) in 0.2 ms(-1) increments in BP and no backpack conditions. Kinematic data were collected using an Optotrak, three-dimensional motion analysis system. Knee angles and vertical excursion of the COM during the compression (loading phase) increased as a function of speed but not load. All three estimates of stiffness showed significant increases as a function of both speed and load. Significant interaction effects indicated a convergence of load-related stiffness values at lower speeds. Results suggested that increases in muscle-mediated stiffness are used to maintain a constant vertical excursion of the COM under load across the speeds tested, and thereby limit increases in metabolic cost that would occur if the COM would travel through greater vertical range of motion. PMID:12600336

  2. Transdermal iontophoresis of flufenamic acid loaded PLGA nanoparticles.

    PubMed

    Malinovskaja-Gomez, K; Labouta, H I; Schneider, M; Hirvonen, J; Laaksonen, T

    2016-06-30

    The objective of this study was to test in vitro a drug delivery system that combines nanoencapsulation and iontophoresis for the transdermal delivery of lipophilic model drug using poly(lactic-co-glycolic acid) (PLGA) as the carrier polymer. Negatively charged fluorescent nanoparticles loaded with negatively charged flufenamic acid were prepared. The colloidal properties of the particles were stable under iontophoretic current (constant, pulsed and alternating) profiles and in contact with skin barrier. The release of the drug from the particles was not affected by iontophoresis and remained always limited (≈50%), leading to significantly lower transdermal fluxes across human epidermis and full thickness porcine skin compared to respective free drug formulation. From nanoparticles, pulsed current profile resulted in comparable or higher fluxes compared to constant current profile although fluorescence imaging was not able to confirm deeper distribution of nanoparticles in skin. Based on our results, there is no clear advantage with respect to drug permeation from nanoencapsulating flufenamic acid into PLGA nanoparticles compared to free drug formulation, either in passive or iontophoretic delivery regimens. However, pulsed current iontophoresis could be an effective alternative instead of traditional constant current iontophoresis to enhance transdermal permeation of drugs from nanoencapsulated formulations.

  3. Transdermal iontophoresis of flufenamic acid loaded PLGA nanoparticles.

    PubMed

    Malinovskaja-Gomez, K; Labouta, H I; Schneider, M; Hirvonen, J; Laaksonen, T

    2016-06-30

    The objective of this study was to test in vitro a drug delivery system that combines nanoencapsulation and iontophoresis for the transdermal delivery of lipophilic model drug using poly(lactic-co-glycolic acid) (PLGA) as the carrier polymer. Negatively charged fluorescent nanoparticles loaded with negatively charged flufenamic acid were prepared. The colloidal properties of the particles were stable under iontophoretic current (constant, pulsed and alternating) profiles and in contact with skin barrier. The release of the drug from the particles was not affected by iontophoresis and remained always limited (≈50%), leading to significantly lower transdermal fluxes across human epidermis and full thickness porcine skin compared to respective free drug formulation. From nanoparticles, pulsed current profile resulted in comparable or higher fluxes compared to constant current profile although fluorescence imaging was not able to confirm deeper distribution of nanoparticles in skin. Based on our results, there is no clear advantage with respect to drug permeation from nanoencapsulating flufenamic acid into PLGA nanoparticles compared to free drug formulation, either in passive or iontophoretic delivery regimens. However, pulsed current iontophoresis could be an effective alternative instead of traditional constant current iontophoresis to enhance transdermal permeation of drugs from nanoencapsulated formulations. PMID:27131608

  4. Evaluation of an Automated Nucleic Acid Extractor for Hepatitis C Virus Load Quantification▿

    PubMed Central

    Martró, Elisa; García-Sierra, Nerea; González, Victoria; Saludes, Verónica; Matas, Lurdes; Ausina, Vicenç

    2009-01-01

    The increasing use of molecular methods strongly motivates clinical laboratories to introduce automated nucleic acid extractors. We compared the easyMAG (bioMérieux) with a manual extraction method for hepatitis C virus (HCV) load quantification (RealTime HCV; Abbott). Both methods were comparable, and, therefore, the easyMAG is suitable to be implemented in our laboratory for the management of HCV-infected patients. PMID:19129408

  5. A Comparison of Increases in Volume Load Over 8 Weeks of Low-Versus High-Load Resistance Training

    PubMed Central

    Schoenfeld, Brad J.; Ogborn, Dan; Contreras, Bret; Cappaert, Tom; Silva Ribeiro, Alex; Alvar, Brent A.; Vigotsky, Andrew D.

    2016-01-01

    Background It has been hypothesized that the ability to increase volume load (VL) via a progressive increase in the magnitude of load for a given exercise within a given repetition range could enhance the adaptive response to resistance training. Objectives The purpose of this study was to compare changes in volume load (VL) over eight weeks of resistance training (RT) in high-versus low-load protocols. Materials and Methods Eighteen well-trained men were matched according to baseline strength were randomly assigned to either a low-load RT (LOW, n = 9) where 25 - 35 repetitions were performed per exercise, or a high-load RT (HIGH, n = 9) where 8 - 12 repetitions were performed per exercise. Both groups performed three sets of seven exercises for all major muscles three times per week on non-consecutive days. Results After adjusting for the pre-test scores, there was a significant difference between the two intervention groups on post-intervention total VL with a very large effect size (F (1, 15) = 16.598, P = .001, ηp2 = .525). There was a significant relationship between pre-intervention and post-intervention total VL (F (1, 15) = 32.048, P < .0001, ηp2 = .681) in which the pre-test scores explained 68% of the variance in the post-test scores. Conclusions This study indicates that low-load RT results in greater accumulations in VL compared to high-load RT over the course of 8 weeks of training. PMID:27625750

  6. A Comparison of Increases in Volume Load Over 8 Weeks of Low-Versus High-Load Resistance Training

    PubMed Central

    Schoenfeld, Brad J.; Ogborn, Dan; Contreras, Bret; Cappaert, Tom; Silva Ribeiro, Alex; Alvar, Brent A.; Vigotsky, Andrew D.

    2016-01-01

    Background It has been hypothesized that the ability to increase volume load (VL) via a progressive increase in the magnitude of load for a given exercise within a given repetition range could enhance the adaptive response to resistance training. Objectives The purpose of this study was to compare changes in volume load (VL) over eight weeks of resistance training (RT) in high-versus low-load protocols. Materials and Methods Eighteen well-trained men were matched according to baseline strength were randomly assigned to either a low-load RT (LOW, n = 9) where 25 - 35 repetitions were performed per exercise, or a high-load RT (HIGH, n = 9) where 8 - 12 repetitions were performed per exercise. Both groups performed three sets of seven exercises for all major muscles three times per week on non-consecutive days. Results After adjusting for the pre-test scores, there was a significant difference between the two intervention groups on post-intervention total VL with a very large effect size (F (1, 15) = 16.598, P = .001, ηp2 = .525). There was a significant relationship between pre-intervention and post-intervention total VL (F (1, 15) = 32.048, P < .0001, ηp2 = .681) in which the pre-test scores explained 68% of the variance in the post-test scores. Conclusions This study indicates that low-load RT results in greater accumulations in VL compared to high-load RT over the course of 8 weeks of training.

  7. A trend towards increasing viral load in newly diagnosed HIV-infected inpatients in southeast China.

    PubMed

    Chen, Y; Wang, Z; Huang, A; Yuan, J; Wei, D; Ye, H

    2016-06-01

    Peripheral blood viral load is an important indicator of viral production and clearance. Previous studies have suggested that viral load might predict the rate of decrease in CD4+ cell count and progression to AIDS and death. Here, we conducted a retrospective analysis of the trends in HIV-1 viral load in southeast China. Among inpatients newly diagnosed with HIV infection, we found that viral load has increased over the past decade from 4·20 log10 copies/ml in 2002 to 6·61 log10 copies/ml in 2014, with a mean increase of 0·19 log10 copies/ml each year. However, the CD4+ cell count was stable and insensitive to changes in viral load. Thus, increasing viral load appears to be an emerging trend in newly diagnosed HIV-infected inpatients.

  8. Acetic Acid Increases Stability of Silage under Aerobic Conditions

    PubMed Central

    Danner, H.; Holzer, M.; Mayrhuber, E.; Braun, R.

    2003-01-01

    The effects of various compounds on the aerobic stability of silages were evaluated. It has been observed that inoculation of whole-crop maize with homofermentative lactic acid bacteria leads to silages which have low stability against aerobic deterioration, while inoculation with heterofermentative lactic acid bacteria, such as Lactobacillus brevis or Lactobacillus buchneri, increases stability. Acetic acid has been proven to be the sole substance responsible for the increased aerobic stability, and this acid acts as an inhibitor of spoilage organisms. Therefore, stability increases exponentially with acetic acid concentration. Only butyric acid has a similar effect. Other compounds, like lactic acid, 1,2-propanediol, and 1-propanol, have been shown to have no effect, while fructose and mannitol reduce stability. PMID:12514042

  9. Method of increasing conversion of a fatty acid to its corresponding dicarboxylic acid

    DOEpatents

    Craft, David L.; Wilson, C. Ron; Eirich, Dudley; Zhang, Yeyan

    2004-09-14

    A nucleic acid sequence including a CYP promoter operably linked to nucleic acid encoding a heterologous protein is provided to increase transcription of the nucleic acid. Expression vectors and host cells containing the nucleic acid sequence are also provided. The methods and compositions described herein are especially useful in the production of polycarboxylic acids by yeast cells.

  10. Effects of a gradually increased load of fish waste silage in co-digestion with cow manure on methane production.

    PubMed

    Solli, Linn; Bergersen, Ove; Sørheim, Roald; Briseid, Tormod

    2014-08-01

    This study examined the effects of an increased load of nitrogen-rich organic material on anaerobic digestion and methane production. Co-digestion of fish waste silage (FWS) and cow manure (CM) was studied in two parallel laboratory-scale (8L effective volume) semi-continuous stirred tank reactors (designated R1 and R2). A reactor fed with CM only (R0) was used as control. The reactors were operated in the mesophilic range (37°C) with a hydraulic retention time of 30 days, and the entire experiment lasted for 450 days. The rate of organic loading was raised by increasing the content of FWS in the feed stock. During the experiment, the amount (volume%) of FWS was increased stepwise in the following order: 3% - 6% - 13% - 16%, and 19%. Measurements of methane production, and analysis of volatile fatty acids, ammonium and pH in the effluents were carried out. The highest methane production from co-digestion of FWS and CM was 0.400 L CH4 gVS(-1), obtained during the period with loading of 16% FWS in R2. Compared to anaerobic digestion of CM only, the methane production was increased by 100% at most, when FWS was added to the feed stock. The biogas processes failed in R1 and R2 during the periods, with loadings of 16% and 19% FWS, respectively. In both reactors, the biogas processes failed due to overloading and accumulation of ammonia and volatile fatty acids.

  11. Enhanced Sucrose Loading Improves Rice Yield by Increasing Grain Size1[OPEN

    PubMed Central

    Wang, Liang; Lu, Qingtao

    2015-01-01

    Yield in cereals is a function of grain number and size. Sucrose (Suc), the main carbohydrate product of photosynthesis in higher plants, is transported long distances from source leaves to sink organs such as seeds and roots. Here, we report that transgenic rice plants (Oryza sativa) expressing the Arabidopsis (Arabidopsis thaliana) phloem-specific Suc transporter (AtSUC2), which loads Suc into the phloem under control of the phloem protein2 promoter (pPP2), showed an increase in grain yield of up to 16% relative to wild-type plants in field trials. Compared with wild-type plants, pPP2::AtSUC2 plants had larger spikelet hulls and larger and heavier grains. Grain filling was accelerated in the transgenic plants, and more photoassimilate was transported from the leaves to the grain. In addition, microarray analyses revealed that carbohydrate, amino acid, and lipid metabolism was enhanced in the leaves and grain of pPP2::AtSUC2 plants. Thus, enhancing Suc loading represents a promising strategy to improve rice yield to feed the global population. PMID:26504138

  12. Estimates of critical acid loads and exceedances for forest soils across the conterminous United States.

    PubMed

    McNulty, Steven G; Cohen, Erika C; Moore Myers, Jennifer A; Sullivan, Timothy J; Li, Harbin

    2007-10-01

    Concern regarding the impacts of continued nitrogen and sulfur deposition on ecosystem health has prompted the development of critical acid load assessments for forest soils. A critical acid load is a quantitative estimate of exposure to one or more pollutants at or above which harmful acidification-related effects on sensitive elements of the environment occur. A pollutant load in excess of a critical acid load is termed exceedance. This study combined a simple mass balance equation with national-scale databases to estimate critical acid load and exceedance for forest soils at a 1-km(2) spatial resolution across the conterminous US. This study estimated that about 15% of US forest soils are in exceedance of their critical acid load by more than 250eqha(-1)yr(-1), including much of New England and West Virginia. Very few areas of exceedance were predicted in the western US.

  13. Estimates of critical acid loads and exceedances for forest soils across the conterminous United States.

    PubMed

    McNulty, Steven G; Cohen, Erika C; Moore Myers, Jennifer A; Sullivan, Timothy J; Li, Harbin

    2007-10-01

    Concern regarding the impacts of continued nitrogen and sulfur deposition on ecosystem health has prompted the development of critical acid load assessments for forest soils. A critical acid load is a quantitative estimate of exposure to one or more pollutants at or above which harmful acidification-related effects on sensitive elements of the environment occur. A pollutant load in excess of a critical acid load is termed exceedance. This study combined a simple mass balance equation with national-scale databases to estimate critical acid load and exceedance for forest soils at a 1-km(2) spatial resolution across the conterminous US. This study estimated that about 15% of US forest soils are in exceedance of their critical acid load by more than 250eqha(-1)yr(-1), including much of New England and West Virginia. Very few areas of exceedance were predicted in the western US. PMID:17629382

  14. Breeding Vegetables with Increased Content in Bioactive Phenolic Acids.

    PubMed

    Kaushik, Prashant; Andújar, Isabel; Vilanova, Santiago; Plazas, Mariola; Gramazio, Pietro; Herraiz, Francisco Javier; Brar, Navjot Singh; Prohens, Jaime

    2015-01-01

    Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. Major phenolic acids present in vegetables are derivatives of cinnamic acid and to a lesser extent of benzoic acid. A large diversity in phenolic acids content has been found among cultivars and wild relatives of many vegetable crops. Identification of sources of variation for phenolic acids content can be accomplished by screening germplasm collections, but also through morphological characteristics and origin, as well as by evaluating mutations in key genes. Gene action estimates together with relatively high values for heritability indicate that selection for enhanced phenolic acids content will be efficient. Modern genomics and biotechnological strategies, such as QTL detection, candidate genes approaches and genetic transformation, are powerful tools for identification of genomic regions and genes with a key role in accumulation of phenolic acids in vegetables. However, genetically increasing the content in phenolic acids may also affect other traits important for the success of a variety. We anticipate that the combination of conventional and modern strategies will facilitate the development of a new generation of vegetable varieties with enhanced content in phenolic acids.

  15. Biomethanation from enzymatically hydrolyzed brewer's spent grain: Impact of rapid increase in loadings.

    PubMed

    Wang, Haoyu; Tao, Yu; Temudo, Margarida; Bijl, Henk; Kloek, Joris; Ren, Nanqi; van Lier, Jules B; de Kreuk, Merle

    2015-08-01

    Enzymatically hydrolyzed brewer's spent grain (BSG) was digested in two expanded granular sludge beds (EGSBs, named BSG1 and BSG2, respectively). Both reactors were operated with the same organic loading rate (OLR) from 1 to 10kgCODm(-3)d(-1) during the first 45days. Hereafter a rapid OLR increase was applied to BSG2 from 10 to 16kgCODm(-3)d(-1) within three weeks, while the OLR of BSG1 was increased by less than 2kgCODm(-3)d(-1) in the same period. Results showed that a 30% decrease in COD removal and 70% decrease in methane yield appeared in BSG2 after the rapid OLR increase, and volatile fatty acid (VFA) accumulated more than thirty times compared to BSG1. The biomass structure deteriorated and 15% of the biomass was lost from the BSG2 reactor. 454-PyroTag and qPCR analysis revealed a rapid growth of acidifiers (i.e., Bacteroides) and a unique microbial community in BSG2 following the rapid increase in OLR. PMID:25941758

  16. Novel fenofibric acid-loaded controlled release pellet bioequivalent to choline fenofibrate-loaded commercial product in beagle dogs.

    PubMed

    Kim, Kyung Soo; Jin, Sung Giu; Mustapha, Omer; Yousaf, Abid Mehmood; Kim, Dong Wuk; Kim, Young Hun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2015-07-25

    The objective of this study was to develop a novel fenofibric acid-loaded controlled release pellet showing enhanced, or equivalent to, bioavailability compared with two commercially available products containing fenofibrate or choline fenofibrate. The effect of solubilizing agents on drug solubility and the impact of fillers on core properties were investigated. Among them, magnesium carbonate most improved drug solubility, and κ-carrageenan provided the best spherical cores. The fenofibric acid-loaded pellet was prepared with magnesium carbonate and κ-carrageenan employing the extrusion/spheronizing technique followed by coating with ethylcellulose. Furthermore, dissolution and pharmacokinetic study in beagle dogs were performed compared to the fenofibrate-loaded commercial tablet (FCT) and choline fenofibrate-loaded commercial mini-tablet (CFCM). This fenofibric acid-loaded pellet showed controlled release of the drug in phosphate buffer (pH 6.8) and 0.025 M sodium laurylsulfate within 4h. Furthermore, this pellet and CFCM exhibited similar dissolution profiles. Plasma concentrations greater than 1,000 ng/ml were maintained from 30 min to 8h, suggesting a sustained release pattern. Also, the fenofibric acid-loaded pellet gave significantly higher AUC and Cmax values than FCT, indicating that it improved the bioavailability of fenofibrate due to enhanced solubility and sustained release. In addition, this pellet and CFCM were not significantly different in terms of pharmacokinetic parameters including AUC, Cmax and Tmax. Thus, this pellet was bioequivalent to CFCM in beagle dogs. In conclusion, this fenofibric acid-loaded controlled release pellet would be a potential alternative to the choline fenofibrate-loaded commercial product.

  17. Solid Lipid Nanoparticles Loaded with Retinoic Acid and Lauric Acid as an Alternative for Topical Treatment of Acne Vulgaris.

    PubMed

    Silva, Elton Luiz; Carneiro, Guilherme; De Araújo, Lidiane Advíncula; Trindade, Mariana de Jesus Vaz; Yoshida, Maria Irene; Oréfice, Rodrigo Lambert; Farias, Luis de Macêdo; De Carvalho, Maria Auxiliadora Roque; Dos Santos, Simone Gonçalves; Goulart, Gisele Assis Castro; Alves, Ricardo José; Ferreira, Lucas Antônio Miranda

    2015-01-01

    Topical therapy is the first choice for the treatment of mild to moderate acne and all-trans retinoic acid is one of the most used drugs. The combination of retinoids and antimicrobials is an innovative approach for acne therapy. Recently, lauric acid, a saturated fatty acid, has shown strong antimicrobial activity against Propionibacterium acnes. However, topical application of retinoic acid is followed by high incidence of side-effects, including erythema and irritation. Solid lipid nanoparticles represent an alternative to overcome these side-effects. This work aims to develop solid lipid nanoparticles loaded with retinoic acid and lauric acid and evaluate their antibacterial activity. The influence of lipophilic stearylamine on the characteristics of solid lipid nanoparticles was investigated. Solid lipid nanoparticles were characterized for size, zeta potential, encapsulation efficiency, differential scanning calorimetry and X-ray diffraction. The in vitro inhibitory activity of retinoic acid-lauric acid-loaded solid lipid nanoparticles was evaluated against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. High encapsulation efficiency was obtained at initial time (94 ± 7% and 100 ± 4% for retinoic acid and lauric acid, respectively) and it was demonstrated that lauric acid-loaded-solid lipid nanoparticles provided the incorporation of retinoic acid. However, the presence of stearylamine is necessary to ensure stability of encapsulation. Moreover, retinoic acid-lauric acid-loaded solid lipid nanoparticles showed growth inhibitory activity against Staphylococcus epidermidis, Propionibacterium acnes and Staphylococcus aureus, representing an interesting alternative for the topical therapy of acne vulgaris. PMID:26328443

  18. Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

    PubMed

    Kiwull-Schöne, Heidrun; Kiwull, Peter; Manz, Friedrich; Kalhoff, Hermann

    2008-02-01

    Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

  19. Dietary potential renal Acid load in venezuelan children.

    PubMed

    López-Sayers, Mayerling; Bernal, Jennifer; López, Michelle

    2015-05-01

    Objetivo: Determinar y analizar la carga acida potencial renal de la dieta (Potential Renal Acid Load PRAL) y el patron de alimentacion de ninos entre 1 a 6 anos aparentemente sanos. Métodos: Se seleccionaron segun conveniencia a padres de 52 ninos asistentes a una consulta de ninos sanos. La calidad de la dieta y el patron de alimentacion se evaluo mediante un recordatorio de 24 horas y un cuestionario de frecuencia de alimentos. Se calculo la ingesta de macronutrientes y grupos de alimentos, como carnes, lacteos, frutas y verduras. La ingesta de nutrientes se comparo con las recomendaciones de energia y nutrientes. El PRAL se determino segun el metodo de Remer y Manz, para determinar la carga acida de la dieta. Se aplico estadistica descriptiva y correlaciones entre el PRAL, nutrientes y grupos de alimentos. Resultados: La ingesta de proteinas, de leche y de carnes fue elevada, mientras que la ingesta de rutas y hortalizas fue baja. El PRAL fue positivo en 92% de los ninos, se asocio con mayor ingesta de energia, proteinas, grasas, carne y lacteos. La ingesta de proteinas fue > 2,5 g/kg/ dia en 46,2% de los ninos. Los grupos de alimentos con mayor desequilibrio debido a exceso fueron la carne y los productos lacteos, mientras que por deficit fue el grupo de frutas y hortalizas. Conclusión: La dieta se caracteriza por una elevada carga de acido o PRAL, lo que aumenta el riesgo de acidosis sistemica y sus consecuencias metabolicas.

  20. Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

    PubMed

    Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-08-01

    In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

  1. Exacerbation of Alcohol-Induced Oxidative Stress in Rats by Polyunsaturated Fatty Acids and Iron Load

    PubMed Central

    Patere, S. N.; Majumdar, A. S.; Saraf, M. N.

    2011-01-01

    The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron. PMID:22303057

  2. STRUCTURAL RESPONSE OF THE DIII-D TOROIDAL FIELD COIL TO INCREASED LATERAL LOADS

    SciTech Connect

    REIS,E.E; CHIN,E

    2003-10-01

    OAK-B135 Recent calibration shots in which full toroidal field (TF) coil current interacted with the maximum poloidal field coils have produced increased lateral loads on the outer sections of the TF-coil. The increased lateral loads have resulted in deflections that have been sufficient to cause the TF-coil to contact adjacent equipment and produce a transient short to ground within the coil. The six outer turns of each TF-coil bundle are clamped together by insulated preloaded studs to provide increased bending stiffness. These sections of the outer bundles depend on friction to react the lateral loads as a bundle rather than six individual turns. A major concern is that the increased loads will produce slip between turns resulting in excessive lateral deflections and possible damage to the insulating sleeve on the preloaded studs. A finite element structural model of the TF-coil was developed for the calculation of deflections and the shear load distribution throughout the coil for the applied lateral loads from a full current calibration shot. The purpose of the updated structural model is to correlate the applied lateral loads to the total shear force between the unbonded sections of the outer turns. An allowable integrated lateral load applied to the outer turns is established based on the maximum shear force that can be reacted by friction. A program that calculates the magnetic fields and integrated lateral load along the outer turns can be incorporated into the plasma control system. The integrated load can then be compared to the calculated allowable value prior to execution of calibration shots. Calibration shots with a calculated total lateral load greater than the allowable value will be prevented.

  3. Association between Dietary Acid Load and Insulin Resistance: Tehran Lipid and Glucose Study

    PubMed Central

    Moghadam, Sajjad Khalili; Bahadoran, Zahra; Mirmiran, Parvin; Tohidi, Maryam; Azizi, Fereidoun

    2016-01-01

    In the current study, we investigated the longitudinal association between dietary acid load and the risk of insulin resistance (IR) in the Tehranian adult population. This longitudinal study was conducted on 925 participants, aged 22~80 years old, in the framework of the third (2006~2008) and fourth (2009~2011) phases of the Tehran Lipid and Glucose Study. At baseline, the dietary intake of subjects was assessed using a validated semi-quantitative food frequency questionnaire, and the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were calculated at baseline. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up; IR was defined according to optimal cut-off values. Multiple logistic regression models were used to estimate the risk of IR according to the PRAL and NEAP quartile categories. Mean age and body mass index of the participants were 40.3 years old of 26.4 kg/m2, respectively. Mean PRAL and NEAP scores were −11.2 and 35.6 mEq/d, respectively. After adjustment for potential confounders, compared to the lowest quartile of PRAL and NEAP, the highest quartile was accompanied with increased risk of IR [odds ratio (OR)=2.81, 95% confidence interval (CI)=1.32~5.97 and OR=2.18, 95% CI=1.03 ~4.61, respectively]. Our findings suggest that higher acidic dietary acid-base load, defined by higher PRAL and NEAP scores, may be a risk factor for the development of IR and related metabolic disorders. PMID:27390726

  4. Association between Dietary Acid Load and Insulin Resistance: Tehran Lipid and Glucose Study.

    PubMed

    Moghadam, Sajjad Khalili; Bahadoran, Zahra; Mirmiran, Parvin; Tohidi, Maryam; Azizi, Fereidoun

    2016-06-01

    In the current study, we investigated the longitudinal association between dietary acid load and the risk of insulin resistance (IR) in the Tehranian adult population. This longitudinal study was conducted on 925 participants, aged 22~80 years old, in the framework of the third (2006~2008) and fourth (2009~2011) phases of the Tehran Lipid and Glucose Study. At baseline, the dietary intake of subjects was assessed using a validated semi-quantitative food frequency questionnaire, and the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were calculated at baseline. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up; IR was defined according to optimal cut-off values. Multiple logistic regression models were used to estimate the risk of IR according to the PRAL and NEAP quartile categories. Mean age and body mass index of the participants were 40.3 years old of 26.4 kg/m(2), respectively. Mean PRAL and NEAP scores were -11.2 and 35.6 mEq/d, respectively. After adjustment for potential confounders, compared to the lowest quartile of PRAL and NEAP, the highest quartile was accompanied with increased risk of IR [odds ratio (OR)=2.81, 95% confidence interval (CI)=1.32~5.97 and OR=2.18, 95% CI=1.03 ~4.61, respectively]. Our findings suggest that higher acidic dietary acid-base load, defined by higher PRAL and NEAP scores, may be a risk factor for the development of IR and related metabolic disorders. PMID:27390726

  5. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

    PubMed Central

    Simopoulos, Artemis P.

    2016-01-01

    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

  6. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity.

    PubMed

    Simopoulos, Artemis P

    2016-03-02

    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

  7. Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

    PubMed Central

    Woo, J. O.; Misran, M.; Lee, P. F.; Tan, L. P.

    2014-01-01

    Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release. PMID:24578624

  8. Development of a controlled release of salicylic acid loaded stearic acid-oleic acid nanoparticles in cream for topical delivery.

    PubMed

    Woo, J O; Misran, M; Lee, P F; Tan, L P

    2014-01-01

    Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release.

  9. Cyclic loading increases friction and changes cartilage surface integrity in lubricin-mutant mouse knees

    PubMed Central

    Drewniak, Elizabeth I; Jay, Gregory D; Fleming, Braden C; Zhang, Ling; Warman, Matthew L; Crisco, Joseph J

    2012-01-01

    Objective To investigate the effects of lubricin gene dosage and cyclic loading on whole joint coefficient of friction and articular cartilage surface integrity in mouse knee joints. Methods Joints from mice with 2 (Prg4+/+), 1 (Prg4+/−), or no (Prg4−/−) functioning lubricin alleles were subjected to 26 hours of cyclic loading using a custom-built pendulum. Coefficient of friction values were measured at multiple time points. Contralateral control joints were left unloaded. Following testing, joints were examined for histologic evidence of damage and cell viability. Results At baseline, the coefficient of friction values in Prg4−/− mice were significantly higher than those in Prg4+/+ and Prg4+/− mice (P < 0.001). Cyclic loading continuously increased the coefficient of friction in Prg4−/− mouse joints. In contrast, Prg4+/− and Prg4+/+ mouse joints had no coefficient of friction increases during the first 4 hours of loading. After 26 hours of loading, joints from all genotypes had increased coefficient of friction values compared to baseline and unloaded controls. Significantly greater increases occurred in Prg4−/− and Prg4+/− mouse joints compared to Prg4+/+ mouse joints. The coefficient of friction values were not significantly associated with histologic evidence of damage or loss of cell viability. Conclusion Our findings indicate that mice lacking lubricin have increased baseline coefficient of friction values and are not protected against further increases caused by loading. Prg4+/− mice are indistinguishable from Prg4+/+ mice at baseline, but have significantly greater coefficient of friction values following 26 hours of loading. Lubricin dosage affects joint properties during loading, and may have clinical implications in patients for whom injury or illness alters lubricin abundance. PMID:21905020

  10. Acid mine drainage and subsidence: effects of increased coal utilization.

    PubMed Central

    Hill, R D; Bates, E R

    1979-01-01

    The increases above 1975 levels for acid mine drainage and subsidence for the years 1985 and 2000 based on projections of current mining trends and the National Energy Plan are presented. No increases are projected for acid mine drainage from surface mines or waste since enforcement under present laws should control this problem. The increase in acid mine drainage from underground mines is projected to be 16 percent by 1985 and 10 percent by 2000. The smaller increase in 2000 over 1985 reflects the impact of the PL 95-87 abandoned mine program. Mine subsidence is projected to increase by 34 and 115 percent respectively for 1985 and 2000. This estimate assumes that subsidence will parallel the rate of underground coal production and that no new subsidence control measures are adopted to mitigate subsidence occurrence. PMID:540617

  11. Increased Brain Fatty Acid Uptake in Metabolic Syndrome

    PubMed Central

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti; Hirvonen, Jussi; Fielding, Barbara A.; Virtanen, Kirsi; Oikonen, Vesa; Kemppainen, Jukka; Viljanen, Tapio; Guiducci, Letizia; Haaparanta-Solin, Merja; Någren, Kjell; Solin, Olof; Nuutila, Pirjo

    2010-01-01

    OBJECTIVE To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS At baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction. PMID:20566663

  12. Acidification sensitivity and critical loads of acid deposition for surface waters in China.

    PubMed

    Ye, Xuemei; Hao, Jiming; Duan, Lei; Zhou, Zhongping

    2002-04-22

    Although decades of severe acid deposition have not resulted in serious surface water acidification in China, at present, the risk of some freshwaters becoming acidified cannot be neglected. To know more clearly about the possible impact acid deposition would have on Chinese surface waters, it is necessary to study the sensitivity of those surface waters to acidification and their critical loads of acid deposition on a national scale. Here we assess the acidification sensitivity of Chinese surface waters using an approach based on geology, soils, land use and hydrological conditions. Critical loads of S, N and acidity were also evaluated by a first-order acidity balance (FAB) model. Results show that most surface waters in China have very high critical loads of S and acidity and are not susceptible to acidification. Surface waters can be divided into three groups according to both sensitivity classes and critical loads. The few most sensitive surface waters are located in the northern part of Daxinganling region, with critical loads of S deposition and acidity lower than 2 keq ha(-1) year(-1). Surface waters in the northeastern region draining dark brown forest soils and in southern China belong to the second class of acidification sensitivity and their critical loads of S and acidity are generally between 2 and 15 keq ha(-1) year(-1), indicating they are not likely to be acidified under any flow conditions. Surface waters in other parts of China will not be acidified to any degree, with critical loads much higher than 15 keq ha(-1) year(-1). The magnitude and spatial distribution pattern of acidification sensitivity have significant similarity to the critical loads of S and acidity for Chinese surface waters. Although most surface waters are not likely to be acidified, attention should still be paid to the possible adverse impact acid deposition would have, especially in northeastern China, where the surface waters are the most sensitive, and the southern region

  13. Cinnamic acid increases lignin production and inhibits soybean root growth.

    PubMed

    Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth.

  14. Cinnamic acid increases lignin production and inhibits soybean root growth.

    PubMed

    Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth. PMID:23922685

  15. Effects of a gradually increased load of fish waste silage in co-digestion with cow manure on methane production

    SciTech Connect

    Solli, Linn Bergersen, Ove; Sørheim, Roald; Briseid, Tormod

    2014-08-15

    Highlights: • New results from continuous anaerobic co-digestion of fish waste silage (FWS) and cow manure (CM). • Co-digestion of FWS and CM has a high biogas potential. • Optimal mixing ratio of FWS/CM is 13–16/87–84 volume%. • High input of FWS leads to accumulation of NH4+ and VFAs and process failure. - Abstract: This study examined the effects of an increased load of nitrogen-rich organic material on anaerobic digestion and methane production. Co-digestion of fish waste silage (FWS) and cow manure (CM) was studied in two parallel laboratory-scale (8 L effective volume) semi-continuous stirred tank reactors (designated R1 and R2). A reactor fed with CM only (R0) was used as control. The reactors were operated in the mesophilic range (37 °C) with a hydraulic retention time of 30 days, and the entire experiment lasted for 450 days. The rate of organic loading was raised by increasing the content of FWS in the feed stock. During the experiment, the amount (volume%) of FWS was increased stepwise in the following order: 3% – 6% – 13% – 16%, and 19%. Measurements of methane production, and analysis of volatile fatty acids, ammonium and pH in the effluents were carried out. The highest methane production from co-digestion of FWS and CM was 0.400 L CH4 gVS{sup −1}, obtained during the period with loading of 16% FWS in R2. Compared to anaerobic digestion of CM only, the methane production was increased by 100% at most, when FWS was added to the feed stock. The biogas processes failed in R1 and R2 during the periods, with loadings of 16% and 19% FWS, respectively. In both reactors, the biogas processes failed due to overloading and accumulation of ammonia and volatile fatty acids.

  16. Reduced Burst Release and Enhanced Oral Bioavailability in Shikimic Acid-Loaded Polylactic Acid Submicron Particles by Coaxial Electrospray.

    PubMed

    Wang, Miaomiao; Wang, Yuanwen; Omari-Siaw, Emmanuel; Wang, Shengli; Zhu, Yuan; Xu, Ximing

    2016-08-01

    In this study, using the coaxial electrospray method, we prepared submicron particles of the water-soluble drug shikimic acid (SA) with polylactic acid (PLA) as a polymer, to reduce the burst release and enhance the oral bioavailability. In vitro release study performed in HCl solution (pH 1.2) showed that the coaxial electrospray submicron particles could reduce burst release effect and presented a sustained release profile, compared with free SA and the particles prepared by electrospray method. The absorption of SA in the intestinal tract, studied using an in situ perfusion method in rats, also revealed jejunum as the main absorptive segment followed by duodenum and ileum. Moreover, the SA-loaded particles greatly enhanced the absorption of SA in the tested intestinal segments. The intestinal absorption rate was not enhanced with increasing drug concentration (5-15 μg/mL) which suggested that active transport or facilitated diffusion could play vital role in SA absorption. In addition, the SA-loaded PLA coaxial electrospray particle exhibited a prolonged plasma circulation with enhanced bioavailability after oral administration. In all, the coaxial electrospray technique could provide notable advantages for the oral delivery of SA, thereby enhancing its clinical application.

  17. Higher diet-dependent renal acid load associates with higher glucocorticoid secretion and potentially bioactive free glucocorticoids in healthy children.

    PubMed

    Esche, Jonas; Shi, Lijie; Sánchez-Guijo, Alberto; Hartmann, Michaela F; Wudy, Stefan A; Remer, Thomas

    2016-08-01

    Metabolic acidosis induces elevated glucocorticoid (GC) levels. However, the influence of less strong daily acid loads on GCs is largely unexplored. To investigate this, we studied whether higher acid loads in children, fully within the normal range of habitual diets, associate with endogenous GCs. In a specific quasi-experimental design, we examined 200 6- to 10-year-old healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study equally divided to either high or low 24-hour renal net acid excretion. Major urinary GC metabolites were analyzed by gas chromatography-mass spectrometry to assess daily adrenal GC secretion and metabolites of tissue cortisol catabolism (6β-hydroxycortisol and 20α-dihydrocortisol). Liquid chromatography-mass spectrometry was used to quantify urinary free cortisol and cortisone. After confounder adjustment, significant positive associations were unmasked for urinary potential renal acid load and net acid excretion with adrenal GC secretion, free cortisone, free cortisone plus cortisol, 6β-hydroxycortisol, and 20α-dihydrocortisol. An inverse association emerged for an enzymatic marker (5β-reductase) of irreversible GC inactivation. Our data suggest that existing moderate elevations in diet-dependent acid loads suffice to raise GCs and affect cortisol metabolism. Thus, potential detrimental effects of high acid loading appear to be mediated, in part, by increased GC activity via increased GC secretion and/or reduced GC inactivation. Higher cortisone levels, directly available for intracrine activation to cortisol may play a special role. PMID:27165611

  18. Vulnerability of boreal zone for increased nitrogen loading due to climate change

    NASA Astrophysics Data System (ADS)

    Rankinen, Katri; Holmberg, Maria

    2016-04-01

    The observed rapid warming of the boreal zone that has been observed in Finland (0.14 °C by decade) is expected to continue (http://www.ipcc.ch/report/ar5/wg1/). Also precipitation is assumed to increase in future. These changes may increase nitrogen (N) loading from terrestrial environments to water bodies by accelerating soil organic matter decay and by increasing runoff. Nitrogen is limiting nutrient in the Baltic Sea but also in some lakes, so increased loading may increase eutrophication. Further, high nitrate levels in drinking water may cause methaemoglobin anemia for humans, and nitrate is also connected to increased risk of diabetes and cancer. Thus EU has set upper limits to nitrate concentration in drinking water. MONIMET (LIFE12 ENV/FI/000409) is a project about Climate Change Indicators and Vulnerability of Boreal Zone. We simulated N loading from two boreal catchments to the receiving waters by the dynamic, catchment scale model INCA in different climate change and land use change scenarios. We calculated land use specific N loading values for these two well monitored catchments that belong to the LTER (The Long Term Ecological Research) monitoring network. We upscaled the results to the larger river basin, combining them with the information on drinking water supply to assess the vulnerability. Specific emphasis was paid on nitrate concentrations in soil water and groundwater. In general, land use change has higher influence on N loading than increase in precipitation and temperature alone. Peak runoff will sift from snow melting peak in April to late autumn and winter. Growing season will become longer allowing more efficient vegetation uptake of nutrients. Small groundwater aquifers and private wells in the middle of agricultural fields will be in the risk of increased N concentrations, if agricultural N loading increases due to changes in agricultural patterns and land use change.

  19. Musculoskeletal stiffness changes linearly in response to increasing load during walking gait.

    PubMed

    Caron, Robert R; Lewis, Cara L; Saltzman, Elliot; Wagenaar, Robert C; Holt, Kenneth G

    2015-04-13

    Development of biologically inspired exoskeletons to assist soldiers in carrying load is a rapidly expanding field. Understanding how the body modulates stiffness in response to changing loads may inform the development of these exoskeletons and is the purpose of the present study. Seventeen subjects walked on a treadmill at a constant preferred walking velocity while nine different backpack loading conditions ranging from 12.5% to 40% bodyweight (BW) were introduced in an ascending and then descending order. Kinematic data were collected using Optotrak, a 3D motion analysis system, and used to estimate the position of the center of mass (COM). Two different estimates of stiffness were computed for the stance phase of gait. Both measures of stiffness were positively and linearly related to load magnitudes, with the slopes of the relationships being larger for the descending than the ascending conditions. These results indicate that changes in mechanical stiffness brought about in the musculoskeletal system vary systematically during increases in load to ensure that critical kinematic variables measured in a previous publication remain invariant (Caron et al., 2013). Changes in stiffness and other kinematics measured at the 40% BW condition suggest a boundary in which gait stiffness control limit is reached and a new gait pattern is required. Since soldiers are now carrying up to 96% of body weight, the need for research with even heavier loads is warranted. These findings have implications on the development of exoskeletons to assist in carrying loads. PMID:25678200

  20. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  1. [Calculating critical loads of acid deposition with different percentiles in China].

    PubMed

    Duan, Lei; Hao, Jiming; Zhou, Zhongping; Xie, Shaodong

    2002-09-01

    While mapping critical loads of acid deposition in China, the 1 degree (latitude) x 1 degree (longitude) resolution was always adopted in critical load calculation. However, the results of mapping can not show the difference of sensitivity of ecosystems to acid deposition within a 1 degree x 1 degree grid. For the convenience of policy-makers to formulate acid deposition control strategies based on critical loads, and to improve the representation and practicability of 1 degree x 1 degree results, a series of critical load maps with different percentiles were compiled, which may be accordance with a given economic or technological level, and allows some degree of damage. Based on the cumulative distribution function, the critical load exceedance maps with different percentiles and the maximum allowable deposition of each province was also derived.

  2. Increased energy harvesting and reduced accelerative load for backpacks via frequency tuning

    NASA Astrophysics Data System (ADS)

    Xie, Longhan; Cai, Mingjing

    2015-06-01

    In this research, a backpack-based frequency-tuneable harvesting device was developed to harvest part of the human kinetic energy during walking and to relieve part of the accelerative load of the backpack from the bearer. The harvester employed a tuning mechanism to adjust the stretch ratio of the springs to adjust the system's stiffness so that the harvesting device can work in an appropriate status to generate more power and relieve a greater load from the bearer. The analysis indicates that adjusting the stiffness harvesting system to fit well with various external excitation conditions, can not only achieve more power output but also relieve part of the accelerative load from the bearer; and the experimental results agreed with the simulation. Compared with previous work, the harvester in this work had a higher efficiency in energy harvesting and could relieve an increased accelerative load from the bearer.

  3. Assessment of increasing loading rate on two-stage digestion of food waste.

    PubMed

    Voelklein, M A; Jacob, A; O' Shea, R; Murphy, J D

    2016-02-01

    A two-stage food waste digestion system involved a first stage hydrolysis reactor followed by a second stage methanogenic reactor. Organic loading rates (OLR) were increased from 6 to 15 g VS L(-1) d(-1) in the hydrolysis reactor and from 2 to 5 g VS L(-1) d(-1) in the methanogenic reactor. The retention time was fixed at 4 days (hydrolysis reactor) and 12 days (methane reactor). A single-stage digester was subjected to similar loading rates as the methanogenic reactor at 16 days retention. Increased OLR resulted in higher quantities of liquid fermentation products from the first stage hydrolysis reactor. Solubilisation of chemical oxygen demand peaked at 47% at the maximum loading. However, enhanced hydrolysis yields had no significant impact on the specific methane yields. The two-stage system increased methane yields up to 23% and enriched methane content by an average of 14% to levels of 71%. PMID:26708485

  4. Neomycin-loaded poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials.

    PubMed

    Nitanan, Todsapon; Akkaramongkolporn, Prasert; Rojanarata, Theerasak; Ngawhirunpat, Tanasait; Opanasopit, Praneet

    2013-05-01

    In this study, poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA) blended with polyvinyl alcohol (PVA) was electrospun and then subjected to thermal crosslinking to produce PSSA-MA/PVA ion exchange nanofiber mats. The cationic drug neomycin (0.001, 0.01, and 0.1%, w/v) was loaded onto the cationic exchange fibers. The amount of neomycin loaded and released and the cytotoxicity of the fiber mats were analyzed. In vivo wound healing tests were also performed in Wistar rats. The results indicated that the diameters of the fibers were on the nanoscale (250 ± 21 nm). The ion exchange capacity (IEC) value and the percentage of water uptake were 2.19 ± 0.1 mequiv./g-dry fibers and 268 ± 15%, respectively. The loading capacity was increased upon increasing the neomycin concentration. An initial concentration of 0.1% (w/v) neomycin (F3) showed the highest loading capacity (65.7 mg/g-dry fibers). The neomycin-loaded nanofiber mats demonstrated satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria, and an in vivo wound healing test revealed that these mats performed better than gauze and blank nanofiber mats in decreasing acute wound size during the first week after tissue damage. In conclusion, the antibacterial neomycin-loaded PSSA-MA/PVA cationic exchange nanofiber mats have the potential for use as wound dressing materials.

  5. Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

    PubMed

    García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

    2015-03-30

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes.

  6. Increased loading rates and specific methane yields facilitated by digesting grass silage at thermophilic rather than mesophilic temperatures.

    PubMed

    Voelklein, M A; Rusmanis, D; Murphy, J D

    2016-09-01

    This study was conducted to advance the understanding of thermophilic grass digestion. Late harvested grass silage was fermented at thermophilic conditions at increasing organic loading rates (OLR). Stable digestion took place at an OLR between 3 and 4gVSL(-1)d(-1). This enabled specific methane yields (SMY) as high as 405LCH4kgVS(-1). An accumulation of volatile fatty acids (VFA), accompanied by a gradual deterioration of pH, FOS/TAC (ratio of VFA to alkalinity) arose at an OLR between 5 and 7gVSL(-1)d(-1), yet inhibition did not occur. SMY decreased with reduced retention time ranging between 336 and 358LCH4kgVS(-1) at OLR 7 and 5gVSL(-1)d(-1) respectively. The biomethane efficiencies remained high (92-103%) at corresponding retention times. Comparative results indicated a superior performance with respect to higher loading and SMY as compared with mesophilic conditions.

  7. Towards increased waste loading in high level waste glasses: Developing a better understanding of crystallization behavior

    DOE PAGES

    Marra, James C.; Kim, Dong -Sang

    2014-12-18

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JCHM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these ''troublesome'' waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Thus, recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized.more » Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating. The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe2O3 (with higher Al2O3). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group.« less

  8. Towards increased waste loading in high level waste glasses: Developing a better understanding of crystallization behavior

    SciTech Connect

    Marra, James C.; Kim, Dong -Sang

    2014-12-18

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JCHM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these ''troublesome'' waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Thus, recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized. Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating. The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe2O3 (with higher Al2O3). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group.

  9. Rapid increase in training load affects markers of skeletal muscle damage and mechanical performance.

    PubMed

    Kamandulis, Sigitas; Snieckus, Audrius; Venckunas, Tomas; Aagaard, Per; Masiulis, Nerijus; Skurvydas, Albertas

    2012-11-01

    The aim of this study was to monitor the changes in indirect markers of muscle damage during 3 weeks (9 training sessions) of stretch-shortening (drop jump) exercise with constant load alternated with steep increases in load. Physically active men (n = 9, mean age 19.1 years) performed a program involving a rapid stepwise increase in the number of jumps, drop height, and squat depth, and the addition of weight. Concentric, isometric maximal voluntary contraction (MVC), and stimulated knee extension torque were measured before and 10 minutes after each session. Muscle soreness and plasma creatine kinase activity were assessed after each session. Steep increments in stretch-shortening exercise load in sessions 4 and 7 amplified the postexercise decrease in stimulated muscle torque and slightly increased muscle soreness but had a minimal effect on the recovery of MVC and stimulated torque. Maximal jump height increased by 7.8 ± 6.3% (p < 0.05), 11.4 ± 3.3% (p < 0.05), and 12.8 ± 3.6% (p < 0.05) at 3, 10, and 17 days after the final training session, respectively. Gains in isometric knee extension MVC (7.9 ± 8.2%) and 100-Hz-evoked torque (9.9 ± 9.6%) (both p < 0.05) were observed within 17 days after the end of the training. The magnitude of improvement was greater after this protocol than that induced by a continuous constant progression loading pattern with small gradual load increments in each training session. These findings suggest that plyometric training using infrequent but steep increases in loading intensity and volume may be beneficial to athletic performance. PMID:22158097

  10. Corn starch granules with enhanced load-carrying capacity via citric acid treatment.

    PubMed

    Kim, Jong-Yea; Huber, Kerry C

    2013-01-01

    This research investigated conditions by which maize starch granule porosity and load-carrying capacity (LCC) might be enhanced via treatment with varying citric acid concentrations (0.5-1.5 M), temperatures (40-60 °C), and lengths of treatment (1-8 h). At the lowest temperatures (40 and 50 °C), citric acid treatment induced minimal physicochemical changes to granules. In contrast, both aqueous and oil LCCs of starches treated at 60 °C (0.5 M citric acid, 2 h) were almost doubled (15.69 and 14.48 mL/10 g starch, respectively), recovering 92% of the granular starch after treatment. Such treatment increased starch hydration capacity (0.97-1.91) and reduced gelatinization enthalpy (10.6-7.4 J/g). More severe treatment conditions adversely impacted aqueous LCC (due to excessive granule swelling), but improved oil absorption. The basis for LCC enhancement by citric acid treatment was ascribed to leaching of starch material from granules and partial disruption of the granule crystalline structure, as opposed to starch hydrolysis or chemical substitution.

  11. Accumulation of Phosphatidic Acid Increases Vancomycin Resistance in Escherichia coli

    PubMed Central

    Sutterlin, Holly A.; Zhang, Sisi

    2014-01-01

    In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in lptD, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of lptD mutations. We find that all seven suppressors analyzed mapped to the essential gene cdsA, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These cdsA mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these cdsA mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than cdsA mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall. PMID:24957626

  12. Release behavior of tetracycline hydrochloride loaded chitosan/poly(lactic acid) antimicrobial nanofibrous membranes.

    PubMed

    Jiang, Suwei; Lv, Jian; Ding, Man; Li, Yanan; Wang, Hualin; Jiang, Shaotong

    2016-02-01

    The present work aimed to evaluate the release behavior of tetracycline hydrochloride loaded chitosan/poly(lactic acid) (Tet-CS/PLA) antimicrobial nanofibrous membranes fabricated via electrospinning technique. The electrospinning solution was a blend of Tet, CS formic acid solution and PLA chloroform/ethanol solution. The interaction between CS and PLA in CS/PLA nanofibers was confirmed to be hydrogen bond. The incorporation of Tet caused a slight decrease in the diameter of nanofibers with Tet content below 30%. Tet-CS/PLA nanofibrous membrane showed a slight initial burst within the first 4h before a gradual increase in cumulative release, and the release percentage increased with increasing Tet contents. Tet release (Mt/M∞<0.6) from the medicated nanofibers could be described by Fickian diffusion model and the release profiles showed two sequential stages. Tet-CS/PLA nanofibrous membranes exhibited an effective and sustainable inhabitance on the growth of Staphylococcus aureus, and the antimicrobial activity increased rapidly with increasing Tet contents below 20%. Furthermore, the incorporation of Tet promoted the degradation of nanofibrous membranes.

  13. Release behavior of tetracycline hydrochloride loaded chitosan/poly(lactic acid) antimicrobial nanofibrous membranes.

    PubMed

    Jiang, Suwei; Lv, Jian; Ding, Man; Li, Yanan; Wang, Hualin; Jiang, Shaotong

    2016-02-01

    The present work aimed to evaluate the release behavior of tetracycline hydrochloride loaded chitosan/poly(lactic acid) (Tet-CS/PLA) antimicrobial nanofibrous membranes fabricated via electrospinning technique. The electrospinning solution was a blend of Tet, CS formic acid solution and PLA chloroform/ethanol solution. The interaction between CS and PLA in CS/PLA nanofibers was confirmed to be hydrogen bond. The incorporation of Tet caused a slight decrease in the diameter of nanofibers with Tet content below 30%. Tet-CS/PLA nanofibrous membrane showed a slight initial burst within the first 4h before a gradual increase in cumulative release, and the release percentage increased with increasing Tet contents. Tet release (Mt/M∞<0.6) from the medicated nanofibers could be described by Fickian diffusion model and the release profiles showed two sequential stages. Tet-CS/PLA nanofibrous membranes exhibited an effective and sustainable inhabitance on the growth of Staphylococcus aureus, and the antimicrobial activity increased rapidly with increasing Tet contents below 20%. Furthermore, the incorporation of Tet promoted the degradation of nanofibrous membranes. PMID:26652352

  14. Increased cloud activation potential of secondary organic aerosol for atmospheric mass loadings

    NASA Astrophysics Data System (ADS)

    King, S. M.; Rosenoern, T.; Shilling, J. E.; Chen, Q.; Martin, S. T.

    2009-05-01

    The effect of organic particle mass loading from 1 to ≥100 μg m-3 on the cloud condensation nuclei (CCN) properties of mixed organic-sulfate particles was investigated in the Harvard Environmental Chamber. Mixed particles were produced by the condensation of organic molecules onto ammonium sulfate particles during the dark ozonolysis of α-pinene. A continuous-flow mode of the chamber provided stable conditions over long time periods, allowing for signal integration and hence increased measurement precision at low organic mass loadings representative of atmospheric conditions. CCN activity was measured at eight mass loadings for 80- and 100-nm particles grown on 50-nm sulfate seeds. A two-component (organic/sulfate) Köhler model, which included the particle heterogeneity arising from DMA size selection and from organic volume fraction for the selected 80- and 100-nm particles, was used to predict CCN activity. For organic mass loadings of 2.9 μg m-3 and greater, the observed activation curves were well predicted using a single set of physicochemical parameters for the organic component. For mass loadings of 1.74 μg m-3 and less, the observed CCN activity increased beyond predicted values using the same parameters, implying changed physicochemical properties of the organic component. A sensitivity analysis suggests that a drop in surface tension must be invoked to explain quantitatively the CCN observations at low SOA particle mass loadings. Other factors, such as decreased molecular weight, increased density, or increased van't Hoff factor, can contribute to the explanation but are quantitatively insufficient as the full explanation.

  15. Improved In Vitro Antileukemic Activity of All-Trans Retinoic Acid Loaded in Cholesteryl Butyrate Solid Lipid Nanoparticles.

    PubMed

    Silva, Elton Luiz; Lima, Flávia Alves; Carneiro, Guilherme; Ramos Jonas Periera; Gomes, Dawidson Assis; de Souza-Fagundes, Elaine Maria; Ferreira, Lucas Antônio Miranda

    2016-02-01

    All-trans retinoic acid, a hydrophobic drug, has become one of the most successful examples of differentiation agents used for treatment of acute promyelocytic leukemia. On the other hand, histone deacetylase inhibitors, such as cholesteryl butyrate, present differentiating activity and.can potentiate action of drugs such as all-trans retinoic acid. Solid lipid nanoparticles represent a promising alternative for administration of hydrophobic drugs such as ATRA. This study aimed to develop, characterize, and evaluate the cytotoxicity of all-trans retinoic acid-loaded solid lipid nanoparticles for leukemia treatment. The influence of in situ formation of an ion pairing between all-trans retinoic acid and lipophilic amines on the characteristics of the particles (size, zeta potential, encapsulation efficiency) was evaluated. Cholesteryl butyrate, a butyric acid donor, was used as a component of the lipid matrix. In vitro activity on cell viability and distribution of cell cycle phases were evaluated for HL-60, Jurkat, and THP-1 cell lines. The encapsulation efficiency of all-trans retinoic acid in cholesteryl butyrate-solid lipid nanoparticles was significantly increased by the presence of the amine. Inhibition of cell viability by all-trans retinoic acid-loaded solid lipid nanoparticles was more pronounced than the free drug. Analysis of the distribution of cell cycle phases also showed increased activity for all-trans retinoic acid-loaded cholesteryl butyrate-solid lipid nanoparticles, with a clear increase in subdiploid DNA content. The ion pair formation in SLN containing cholesteryl butyrate can be explored as a simple and inexpensive strategy to improve the efficacy and bioavail-ability of ATRA in the treatment of the cancer and metabolic diseases in which this retinoid plays an important role. PMID:27433579

  16. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, M.; Millard, C.S.; Stols, L.

    1998-06-23

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria. 2 figs.

  17. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2002-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  18. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  19. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    1998-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  20. Elastic Attention: Enhanced, then Sharpened Response to Auditory Input as Attentional Load Increases

    PubMed Central

    Neelon, Michael F.; Williams, Justin; Garell, P. Charles

    2011-01-01

    A long debate in selective attention research is whether attention enhances sensory response or sharpens neural tuning by suppressing response to non-target input. In fact, both processes may occur as a function of load: an uncertain listener might use a broad attentional filter to enhance responses to all inputs (i.e., vigilance), yet employ sharpened tuning to focus on hard to discriminate targets. The present work used the greater signal gain, anatomical precision, and laterality separation of intracranial electrophysiological recordings (electrocorticograms) to investigate these competing effects. Data were recorded from acoustically-responsive cortex in the perisylvian region of a single hemisphere in five neurosurgery patients. Patients performed a dichotic listening task in which they alternately attended toward, away from, or completely ignored (silent reading) tones presented to designated ears at varying presentation rates. Comparisons between the grand-averaged event-related potential (ERP) waveforms show a striking change in the effect of selective auditory attention with attentional load. At slower presentation rates (low-load), ERPs were overall enhanced in response to both input channels and regardless of attended ear, including a significant enhancement of ipsilateral input. This result supports a broadly enhancing model of attention under low perceptual load conditions. At the fastest rate, however, only responses to attended inputs contralateral to grid location remained enhanced. This result supports an increasing suppression, or “sharpening,” of neural responses to non-targets with increasing attentional load. These data provide support for an elastic model of attention in which attentional scope narrows with increasing load. PMID:21559348

  1. Increased Cloud Activation Potential of Secondary Organic Aerosol for Atmospheric Mass Loadings

    SciTech Connect

    King, Stephanie M.; Rosenoern, Thomas; Shilling, John E.; Chen, Qi; Martin, Scot T.

    2009-05-01

    The effect of organic particle mass loading from 1 to ≥100 μg m-3 on the cloud condensation nuclei (CCN) properties of mixed organic-sulfate particles was investigated in the Harvard Environmental Chamber. Mixed particles were produced by the condensation of organic molecules onto ammonium sulfate particles during the dark ozonolysis of α-pinene. A continuous-flow mode of the chamber provided stable conditions over long time periods, allowing for signal integration and hence increased measurement precision at low organic mass loadings representative of atmospheric conditions. CCN activity was measured at eight mass loadings for 80- and 100-nm particles grown on 50-nm sulfate seeds. A two-component (organic/sulfate) Köhler model, which included the particle heterogeneity arising from DMA size selection and from organic volume fraction for the selected 80- and 100-nm particles, was used to predict CCN activity. For organic mass loadings of 2.9 μg m-3 and greater, the observed activation curves were well predicted using a single set of physicochemical parameters for the organic component. For mass loadings of 1.74 μg m-3 and less, the observed CCN activity increased beyond predicted values using the same parameters, implying changed physicochemical properties of the organic component. Of possible changes in surface tension, effective molecular weight, and effective density, a sensitivity analysis implicated a decrease of up to 10% in surface tension at low mass loadings as the plausible dominant mechanism for the observed increase in CCN activity.

  2. Antiretroviral Treatment is Associated with Increased Attentional Load-Dependent Brain Activation in HIV Patients

    PubMed Central

    Chang, L.; Yakupov, R.; Nakama, H.; Stokes, B.; Ernst, T.

    2009-01-01

    Objective The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Methods Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n=18), HIV subjects treated with antiretroviral medications (HIV+ ARV, n=12), or not treated with antiretroviral medications (HIV+NARV, n=12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. Results HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected=0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected=0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. Interpretation These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention. PMID:18247124

  3. Covalent and non-covalent curcumin loading in acid-responsive polymeric micellar nanocarriers

    NASA Astrophysics Data System (ADS)

    Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Zhao, Yanjun

    2015-07-01

    Poor aqueous solubility, potential degradation, rapid metabolism and elimination lead to low bioavailability of pleiotropic impotent curcumin. Herein, we report two types of acid-responsive polymeric micelles where curcumin was encapsulated via both covalent and non-covalent modes for enhanced loading capacity and on-demand release. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a hydrazone linker, generating two conjugates differing in architecture (single-tail versus double-tail) and free curcumin was encapsulated therein. The two micelles exhibited similar hydrodynamic size at 95 ± 3 nm (single-tail) and 96 ± 3 nm (double-tail), but their loading capacities differed significantly at 15.0 ± 0.5% (w/w) (single-tail) and 4.8 ± 0.5% (w/w) (double-tail). Under acidic sink conditions (pH 5.0 and 6.0), curcumin displayed a faster release from the single-tail nanocarrier, which was correlated to a low IC50 of 14.7 ± 1.6 (μg mL-1) compared to the value of double-tail micelle (24.9 ± 1.3 μg mL-1) in HeLa cells. The confocal imaging and flow cytometry analysis demonstrated a superior capability of single-tail micelle for intracellular curcumin delivery, which was a consequence of the higher loading capacity and lower degree of mPEG surface coverage. In conclusion, the dual loading mode is an effective means to increase the drug content in the micellar nanocarriers whose delivery efficiency is highly dependent on its polymer-drug conjugate architecture. This strategy offers an alternative nanoplatform for intracellularly delivering impotent hydrophobic agents (i.e. curcumin) in an efficient stimuli-triggered way, which is valuable for the enhancement of curcumin’s efficacy in managing a diverse range of disorders.

  4. Acidic beverages increase the risk of in vitro tooth erosion.

    PubMed

    Ehlen, Leslie A; Marshall, Teresa A; Qian, Fang; Wefel, James S; Warren, John J

    2008-05-01

    Acidic beverages are thought to increase the potential for dental erosion. We report pH and titratable acidities (ie, quantity of base required to bring a solution to neutral pH) of beverages popular in the United States and lesion depths in enamel and root surfaces after beverage exposure, and we describe associations among pH, titratable acidity, and both enamel and root erosive lesion depths. The pH of 100% juices, regular sodas, diet sodas, and sports drinks upon opening and the titratable acidity both upon opening and after 60 minutes of stirring were measured. Enamel and root surfaces of healthy permanent molars and premolars were exposed to individual beverages (4 enamel and 4 root surfaces per beverage) for 25 hours, and erosion was measured. Statistical analyses included 2-sample t tests, analyses of variance with post hoc Tukey studentized range test; and Spearman rank correlation coefficients. All beverages were acidic; the titratable acidity of energy drinks was greater than that of regular and diet sodas that were greater than that of 100% juices and sports drinks (P < .05). Enamel lesion depths after beverage exposures were greatest for Gatorade, followed by those for Red Bull and Coke that were greater than those for Diet Coke and 100% apple juice (P < .05). Root lesion depths were greatest for Gatorade, followed by Red Bull, Coke, 100% apple juice, and Diet Coke (P < .05). Lesion depths were not associated with pH or titratable acidity. Beverages popular in the United States can produce dental erosion.

  5. Changes in global and regional modularity associated with increasing working memory load

    PubMed Central

    Stanley, Matthew L.; Dagenbach, Dale; Lyday, Robert G.; Burdette, Jonathan H.; Laurienti, Paul J.

    2014-01-01

    Using graph theory measures common to complex network analyses of neuroimaging data, the objective of this study was to explore the effects of increasing working memory processing load on functional brain network topology in a cohort of young adults. Measures of modularity in complex brain networks quantify how well a network is organized into densely interconnected communities. We investigated changes in both the large-scale modular organization of the functional brain network as a whole and regional changes in modular organization as demands on working memory increased from n = 1 to n = 2 on the standard n-back task. We further investigated the relationship between modular properties across working memory load conditions and behavioral performance. Our results showed that regional modular organization within the default mode and working memory circuits significantly changed from 1-back to 2-back task conditions. However, the regional modular organization was not associated with behavioral performance. Global measures of modular organization did not change with working memory load but were associated with individual variability in behavioral performance. These findings indicate that regional and global network properties are modulated by different aspects of working memory under increasing load conditions. These findings highlight the importance of assessing multiple features of functional brain network topology at both global and regional scales rather than focusing on a single network property. PMID:25520639

  6. Fatty acids increase neuronal hypertrophy of Pten knockdown neurons

    PubMed Central

    Fricano, Catherine J.; DeSpenza, Tyrone; Frazel, Paul W.; Li, Meijie; O'Malley, A. James; Westbrook, Gary L.; Luikart, Bryan W.

    2014-01-01

    Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy could influence the severity of the Pten knockdown-induced hypertrophy. Implantation of mini-osmotic pumps delivering fatty acids results in increased neuronal hypertrophy and p-S6/p-mTOR staining. These hypertrophic effects were reversed in response to rapamycin treatment. However, we did not observe a similar increase in hypertrophy in response to dietary manipulations of fatty acids. Thus, we conclude that by driving growth signaling with fatty acids and knocking down a critical regulator of growth, Pten, we are able to observe an additive morphological phenotype of increased soma size mediated by the mTOR pathway. PMID:24795563

  7. Sex-based differences in lifting technique under increasing load conditions: A principal component analysis.

    PubMed

    Sheppard, P S; Stevenson, J M; Graham, R B

    2016-05-01

    The objective of the present study was to determine if there is a sex-based difference in lifting technique across increasing-load conditions. Eleven male and 14 female participants (n = 25) with no previous history of low back disorder participated in the study. Participants completed freestyle, symmetric lifts of a box with handles from the floor to a table positioned at 50% of their height for five trials under three load conditions (10%, 20%, and 30% of their individual maximum isometric back strength). Joint kinematic data for the ankle, knee, hip, and lumbar and thoracic spine were collected using a two-camera Optotrak motion capture system. Joint angles were calculated using a three-dimensional Euler rotation sequence. Principal component analysis (PCA) and single component reconstruction were applied to assess differences in lifting technique across the entire waveforms. Thirty-two PCs were retained from the five joints and three axes in accordance with the 90% trace criterion. Repeated-measures ANOVA with a mixed design revealed no significant effect of sex for any of the PCs. This is contrary to previous research that used discrete points on the lifting curve to analyze sex-based differences, but agrees with more recent research using more complex analysis techniques. There was a significant effect of load on lifting technique for five PCs of the lower limb (PC1 of ankle flexion, knee flexion, and knee adduction, as well as PC2 and PC3 of hip flexion) (p < 0.005). However, there was no significant effect of load on the thoracic and lumbar spine. It was concluded that when load is standardized to individual back strength characteristics, males and females adopted a similar lifting technique. In addition, as load increased male and female participants changed their lifting technique in a similar manner. PMID:26851478

  8. Polymorphonuclear leukocytes increase glomerular albumin permeability via hypohalous acid.

    PubMed

    Li, J Z; Sharma, R; Dileepan, K N; Savin, V J

    1994-10-01

    Acute glomerulonephritis is characterized by the presence of neutrophils within glomeruli and the generation of reactive oxygen species (ROS) by activated polymorphonuclear leukocytes (PMNs). Hydrogen peroxide (H2O2) and other ROS including hypothalous acids have been implicated in PMN mediated injury. To determine the role of specific ROS in PMN mediated glomerular injury, isolated rat glomeruli were incubated for 30 minutes at 37 degrees C with H2O2, with H2O2 and myeloperoxidase, or with activated PMNs. Scavengers of ROS were included in some experiments. PMNs were harvested from rat peritoneal cavity and activated with phorbol myristate acetate (PMA). Glomerular albumin permeability (Palbumin) was calculated from the volume response to an oncotic gradient. Palbumin of glomeruli incubated with H2O2 (10(-3) or 10(-1) M) was not increased, while Palbumin after incubation with H2O2 and MPO was markedly increased (0.94 +/- 0.004). Palbumin after incubation with PMA, or with non-activated PMNs was not different from that of control glomeruli, Palbumin of the glomeruli incubated with activated PMNs increased (0.85 +/- 0.01, P < 0.001). This increase in Palbumin was inhibited by superoxide dismutase, catalase, or taurine (Palbumin = 0.035 +/- 0.06, -0.39 +/- 0.10, 0.028 +/- 0.06, respectively) and ameliorated by sodium azide (Palbumin = 0.21 +/- 0.03). In contrast, dimethyl sulfoxide did not prevent the increase in Palbumin (Palbumin = 0.92 +/- 0.01). Our results show that the hypohalous acid derived from that of H2O2-MPO-halide system is capable of increasing Palbumin. We conclude that hypohalous acid may be the primary mediator of the immediate increase in glomerular protein permeability induced by PMNs. PMID:7861697

  9. Effects of dietary Acid load on exercise metabolism and anaerobic exercise performance.

    PubMed

    Caciano, Susan L; Inman, Cynthia L; Gockel-Blessing, Elizabeth E; Weiss, Edward P

    2015-06-01

    Dietary acid load, quantified as the potential renal acid load (PRAL) of the diet, affects systemic pH and acid-base regulation. In a previous cross-sectional study, we reported that a low dietary PRAL (i.e. alkaline promoting diet) is associated with higher respiratory exchange ratio (RER) values during maximal exercise. The purpose of the present study was to confirm the previous findings with a short-term dietary intervention study. Additionally, we sought to determine if changes in PRAL affects submaximal exercise RER (as a reflection of substrate utilization) and anaerobic exercise performance. Subjects underwent a graded treadmill exercise test (GXT) to exhaustion and an anaerobic exercise performance test on two occasions, once after following a low-PRAL diet and on a separate occasion, after a high-PRAL diet. The diets were continued as long as needed to achieve an alkaline or acid fasted morning urine pH, respectively, with all being 4-9 days in duration. RER was measured during the GXT with indirect calorimetry. The anaerobic performance test was a running time-to-exhaustion test lasting 1-4 min. Maximal exercise RER was lower in the low-PRAL trial compared to the high-PRAL trial (1.10 ± 0.02 vs. 1.20 ± 0.05, p = 0.037). The low-PRAL diet also resulted in a 21% greater time to exhaustion during anaerobic exercise (2.56 ± 0.36 vs. 2.11 ± 0.31 sec, p = 0.044) and a strong tendency for lower RER values during submaximal exercise at 70% VO2max (0.88 ± 0.02 vs. 0.96 ± 0.04, p = 0.060). Contrary to our expectations, a short-term low-PRAL (alkaline promoting) diet resulted in lower RER values during maximal-intensity exercise. However, the low-PRAL diet also increased anaerobic exercise time to exhaustion and appears to have shifted submaximal exercise substrate utilization to favor lipid oxidation and spare carbohydrate, both of which would be considered favorable effects in the context of exercise performance. Key pointsShort-term (4-9 days) changes in

  10. Effects of Dietary Acid Load on Exercise Metabolism and Anaerobic Exercise Performance

    PubMed Central

    Caciano, Susan L.; Inman, Cynthia L.; Gockel-Blessing, Elizabeth E.; Weiss, Edward P.

    2015-01-01

    Dietary acid load, quantified as the potential renal acid load (PRAL) of the diet, affects systemic pH and acid-base regulation. In a previous cross-sectional study, we reported that a low dietary PRAL (i.e. alkaline promoting diet) is associated with higher respiratory exchange ratio (RER) values during maximal exercise. The purpose of the present study was to confirm the previous findings with a short-term dietary intervention study. Additionally, we sought to determine if changes in PRAL affects submaximal exercise RER (as a reflection of substrate utilization) and anaerobic exercise performance. Subjects underwent a graded treadmill exercise test (GXT) to exhaustion and an anaerobic exercise performance test on two occasions, once after following a low-PRAL diet and on a separate occasion, after a high-PRAL diet. The diets were continued as long as needed to achieve an alkaline or acid fasted morning urine pH, respectively, with all being 4-9 days in duration. RER was measured during the GXT with indirect calorimetry. The anaerobic performance test was a running time-to-exhaustion test lasting 1-4 min. Maximal exercise RER was lower in the low-PRAL trial compared to the high-PRAL trial (1.10 ± 0.02 vs. 1.20 ± 0.05, p = 0.037). The low-PRAL diet also resulted in a 21% greater time to exhaustion during anaerobic exercise (2.56 ± 0.36 vs. 2.11 ± 0.31 sec, p = 0.044) and a strong tendency for lower RER values during submaximal exercise at 70% VO2max (0.88 ± 0.02 vs. 0.96 ± 0.04, p = 0.060). Contrary to our expectations, a short-term low-PRAL (alkaline promoting) diet resulted in lower RER values during maximal-intensity exercise. However, the low-PRAL diet also increased anaerobic exercise time to exhaustion and appears to have shifted submaximal exercise substrate utilization to favor lipid oxidation and spare carbohydrate, both of which would be considered favorable effects in the context of exercise performance. Key points Short-term (4-9 days) changes in

  11. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations

    PubMed Central

    Makita-Chingombe, Faithful; Kutscher, Hilliard L.; DiTursi, Sara L.; Morse, Gene D.; Maponga, Charles C.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and −20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  12. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations.

    PubMed

    Makita-Chingombe, Faithful; Kutscher, Hilliard L; DiTursi, Sara L; Morse, Gene D; Maponga, Charles C

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and -20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1.

  13. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations.

    PubMed

    Makita-Chingombe, Faithful; Kutscher, Hilliard L; DiTursi, Sara L; Morse, Gene D; Maponga, Charles C

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and -20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  14. Increased Instream Wood Loading Attributed to Mountain Pine Beetle Outbreak in Subalpine Watersheds

    NASA Astrophysics Data System (ADS)

    Ryan, S. E.; Dwire, K. A.; Young, M. K.; Daniels, J. M.; Bishop, E. L.

    2006-12-01

    Many lodgepole pine (Pinus contorta) forests in North-Central Colorado have undergone recent widespread infestation by mountain pine beetle (Dendroctous ponderosae), causing high levels of mortality over substantial areas. The reach of this epidemic, thought to be related to increased temperatures and sustained drought conditions, continues into previously unaffected watersheds, including areas of the Fraser Experimental Forest (FEF), CO. Widespread forest loss from beetle outbreak may potentially increase water yield and rates of sedimentation from steep hillslopes. Several watersheds within FEF have extensive records of water and sediment yield, providing an opportunity to evaluate changes in flow and sedimentation following the outbreak. However, perhaps the most immediate impact to streams will be increased instream wood loading as beetle-killed trees begin to fall from steep hillslopes. Many of the small streams on FEF are directly adjacent to steep hillslopes and up to one third of current load of instream wood can be traced to hillslope origins. Baseline information on volumes, sources, and geomorphic influences of large wood in these systems indicate that much of the wood is relatively immobile and often becomes incorporated into the channel form (e.g., steps, banks, and small falls) rather than being transported. Typical numbers of pieces of large wood vary from 0.5 to 0.8 pieces per meter channel length, with most reaches falling in the 0.7 to 0.8 range. Large wood in streams can both increase and decrease local channel stability so the net effect of increases in wood loading are uncertain. Conceptual models of potential changes in wood loading and its impacts on channel form are addressed in this presentation.

  15. Increased muscle fatty acid oxidation in dairy cows with intensive body fat mobilization during early lactation.

    PubMed

    Schäff, C; Börner, S; Hacke, S; Kautzsch, U; Sauerwein, H; Spachmann, S K; Schweigel-Röntgen, M; Hammon, H M; Kuhla, B

    2013-10-01

    The beginning of lactation requires huge metabolic adaptations to meet increased energy demands for milk production of dairy cows. One of the adaptations is the mobilization of body reserves mainly from adipose tissue as reflected by increased plasma nonesterified fatty acid (NEFA) concentrations. The capacity of the liver for complete oxidation of NEFA is limited, leading to an increased formation of ketone bodies, reesterification, and accumulation of triglycerides in the liver. As the skeletal muscle also may oxidize fatty acids, it may help to decrease the fatty acid load on the liver. To test this hypothesis, 19 German Holstein cows were weekly blood sampled from 7 wk before until 5 wk after parturition to analyze plasma NEFA concentrations. Liver biopsies were obtained at d 3, 18, and 30 after parturition and, based on the mean liver fat content, cows were grouped to the 10 highest (HI) and 9 lowest (LO). In addition, muscle biopsies were obtained at d -17, 3, and 30 relative to parturition and used to quantify mRNA abundance of genes involved in fatty acid degradation. Plasma NEFA concentrations peaked after parturition and were 1.5-fold higher in HI than LO cows. Muscle carnitine palmitoyltransferase 1α and β mRNA was upregulated in early lactation. The mRNA abundance of muscle peroxisome proliferator-activated receptor γ (PPARG) increased in early lactation and was higher in HI than in LO cows, whereas the abundance of PPARA continuously decreased after parturition. The mRNA abundance of muscle PPARD, uncoupling protein 3, and the β-oxidative enzymes 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, very long-chain acyl-CoA dehydrogenase, and 3-ketoacyl-CoA was greatest at d 3 after parturition, whereas the abundance of PPARγ coactivator 1α decreased after parturition. Our results indicate that around parturition, oxidation of fatty acids in skeletal muscle is highly activated, which may contribute to diminish the fatty acid load on the liver. The

  16. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

    PubMed

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

  17. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

    PubMed Central

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

  18. Increased joint loads during walking--a consequence of pain relief in knee osteoarthritis.

    PubMed

    Henriksen, Marius; Simonsen, Erik B; Alkjaer, Tine; Lund, Hans; Graven-Nielsen, Thomas; Danneskiold-Samsøe, Bente; Bliddal, Henning

    2006-12-01

    Joint pain is a primary symptom in knee osteoarthritis (OA), but the effect of pain and pain relief on the knee joint mechanics of walking is not clear. In this study, the effects of local knee joint analgesia on knee joint loads during walking were studied in a group of knee osteoarthritis patients. A group of healthy subjects was included as a reference group. The joint loads were calculated from standard gait analysis data obtained with standardised walking speed (4 km/h). The gait analyses were performed before and after pain relief by intra-articular injections of 10 mL lidocaine (1%). Pre-injection measurements revealed lower joint loads in the OA group compared to the reference group. Following injections pain during walking decreased significantly and the joint loads increased in the OA group during the late single support phase to a level comparable to the reference group. Although the patients walked with less compressive knee joint forces compared to the reference group, the effects of pain relief may accelerate the degenerative changes. PMID:17011194

  19. A conceptual framework: redefining forest soil's critical acid loads under a changing climate.

    PubMed

    McNulty, Steven G; Boggs, Johnny L

    2010-06-01

    Federal agencies of several nations have or are currently developing guidelines for critical forest soil acid loads. These guidelines are used to establish regulations designed to maintain atmospheric acid inputs below levels shown to damage forests and streams. Traditionally, when the critical soil acid load exceeds the amount of acid that the ecosystem can absorb, it is believed to potentially impair forest health. The excess over the critical soil acid load is termed the exceedance, and the larger the exceedance, the greater the risk of ecosystem damage. This definition of critical soil acid load applies to exposure of the soil to a single, long-term pollutant (i.e., acidic deposition). However, ecosystems can be simultaneously under multiple ecosystem stresses and a single critical soil acid load level may not accurately reflect ecosystem health risk when subjected to multiple, episodic environmental stress. For example, the Appalachian Mountains of western North Carolina receive some of the highest rates of acidic deposition in the eastern United States, but these levels are considered to be below the critical acid load (CAL) that would cause forest damage. However, the area experienced a moderate three-year drought from 1999 to 2002, and in 2001 red spruce (Picea rubens Sarg.) trees in the area began to die in large numbers. The initial survey indicated that the affected trees were killed by the southern pine beetle (Dendroctonus frontalis Zimm.). This insect is not normally successful at colonizing these tree species because the trees produce large amounts of oleoresin that exclude the boring beetles. Subsequent investigations revealed that long-term acid deposition may have altered red spruce forest structure and function. There is some evidence that elevated acid deposition (particularly nitrogen) reduced tree water uptake potential, oleoresin production, and caused the trees to become more susceptible to insect colonization during the drought period

  20. A conceptual framework: redefining forest soil's critical acid loads under a changing climate.

    PubMed

    McNulty, Steven G; Boggs, Johnny L

    2010-06-01

    Federal agencies of several nations have or are currently developing guidelines for critical forest soil acid loads. These guidelines are used to establish regulations designed to maintain atmospheric acid inputs below levels shown to damage forests and streams. Traditionally, when the critical soil acid load exceeds the amount of acid that the ecosystem can absorb, it is believed to potentially impair forest health. The excess over the critical soil acid load is termed the exceedance, and the larger the exceedance, the greater the risk of ecosystem damage. This definition of critical soil acid load applies to exposure of the soil to a single, long-term pollutant (i.e., acidic deposition). However, ecosystems can be simultaneously under multiple ecosystem stresses and a single critical soil acid load level may not accurately reflect ecosystem health risk when subjected to multiple, episodic environmental stress. For example, the Appalachian Mountains of western North Carolina receive some of the highest rates of acidic deposition in the eastern United States, but these levels are considered to be below the critical acid load (CAL) that would cause forest damage. However, the area experienced a moderate three-year drought from 1999 to 2002, and in 2001 red spruce (Picea rubens Sarg.) trees in the area began to die in large numbers. The initial survey indicated that the affected trees were killed by the southern pine beetle (Dendroctonus frontalis Zimm.). This insect is not normally successful at colonizing these tree species because the trees produce large amounts of oleoresin that exclude the boring beetles. Subsequent investigations revealed that long-term acid deposition may have altered red spruce forest structure and function. There is some evidence that elevated acid deposition (particularly nitrogen) reduced tree water uptake potential, oleoresin production, and caused the trees to become more susceptible to insect colonization during the drought period

  1. Monitoring HCV RNA viral load by locked nucleic acid molecular beacons real time PCR.

    PubMed

    Morandi, Luca; Ferrari, Daniela; Lombardo, Claudia; Pession, Annalisa; Tallini, Giovanni

    2007-03-01

    Locked nucleic acids (LNA) based real time PCR was used in particular situations where there are difficulties in primer design due to sequence complexity. In this study a new real time RT-PCR assay was developed using LNA modified primers and LNA molecular beacon probes to monitor hepatitis C virus (HCV) viral load in plasma and serum samples. The technique did not suffer from an heterogeneity of the HCV genome and, in addition, an internal RNA control was amplified in the same reaction tube with different short primers and beacon probe. Due to the short consensus LNA primers length, the PCR efficiency was close to 100% with no formation of hairpin loop structures. In summary a new LNA molecular beacon based real time RT-PCR assay was used successfully to measure quantitatively the total level of HCV RNA in both experimental and clinical specimens. The high sensitivity (50 IU/ml), the wide range of genotype detection, increased specificity and robustness obtained with this test are particularly useful for screening large number of specimens and measuring viral loads to monitor the progress of the disease.

  2. Dietary n-6 polyunsaturated fatty acid deprivation increases docosahexaenoic acid metabolism in rat brain.

    PubMed

    Igarashi, Miki; Kim, Hyung-Wook; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

    2012-03-01

    Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A(2) (cPLA(2) -IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective calcium-independent phospholipase A(2) (iPLA(2) )-VIA expression. We hypothesized that these changes are accompanied by up-regulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA 'adequate' (31.4 wt% linoleic acid) or 'deficient' (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-(14) C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid n-3 (DPAn-3, 22:5n-3), and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid (EtnGpl). Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promotes neuroprotection and alters neurotransmission.

  3. Economic impact of total solids loading on enzymatic hydrolysis of dilute acid pretreated corn stover.

    PubMed

    Humbird, David; Mohagheghi, Ali; Dowe, Nancy; Schell, Daniel J

    2010-01-01

    In process integration studies of the biomass-to-ethanol conversion process, it is necessary to understand how cellulose conversion yields vary as a function of solids and enzyme loading and other key operating variables. The impact of solids loading on enzymatic cellulose hydrolysis of dilute acid pretreated corn stover slurry was determined using an experimental response surface design methodology. From the experimental work, an empirical correlation was obtained that expresses monomeric glucose yield from enzymatic cellulose hydrolysis as a function of solids loading, enzyme loading, and temperature. This correlation was used in a technoeconomic model to study the impact of solids loading on ethanol production economics. The empirical correlation was used to provide a more realistic assessment of process cost by accounting for changes in cellulose conversion yields at different solids and enzyme loadings as well as enzyme cost. As long as enzymatic cellulose conversion drops off at higher total solids loading (due to end-product inhibition or other factors), there is an optimum value for the total solids loading that minimizes the ethanol production cost. The optimum total solids loading shifts to higher values as enzyme cost decreases.

  4. Evaluation of Hemostatic Effects of Carbonized Hair-Loaded Poly(L-Lactic) Acid Nanofabrics.

    PubMed

    Zhu, Yuanyuan; Qiu, Yan; Liao, Lianming

    2015-06-01

    Carbonized human hair is used to stop bleeding in traditional Chinese medicine. The present study was aimed to prepare a novel nanofiber containing carbonized human hair and evaluate its hemostatic effect. Carbonized human hair-loaded poly(L-lactic) acid nanofiber was prepared by electrospinning. The hemostatic efficacies of dressings composed of either carbonized human hair, carbonized human hair-loaded poly(L-lactic) acid nanofiber, Yunnan White Drug power or poly(L-lactic) acid nanofiber were investigated in several swine arterial and venous bleeding models. Blood loss and bleeding time were measured. In vitro, carbonized human hair, carbonized human hair-loaded nanofiber and Yunnan White Drug Powder significantly shortened the clotting time in comparison with the nanofiber control group. The hemostatic effects of the carbonized human hair-load nanofiber on liver and spleen traumatic wounds were better than those of carbonized human hair and Yunnan White Drug Powder in terms of blood loss and bleeding time. Similar effects were observed in swine femoral artery wound model. In the swine femoral vein wound model, bleeding could not be stopped in the control animals. In the carbonized human hair group, Yunnan White Drug Powder group and carbonized human hair-load nanofiber group, bleeding was stopped in 83.3%, 83.3% and 100% of the animals, respectively. In conclusion, dressing using carbonized human hair-load nanofibers is effective in controlling severe, uncontrolled bleeding. This dressing may offer a cheap alternative to dressings composed of coagulation proteins.

  5. Increased interstitial loading reduces the effect of microstructural variations in cardiac tissue.

    PubMed

    Hubbard, Marjorie Letitia; Henriquez, Craig S

    2010-04-01

    Electrical propagation in diseased and aging hearts is strongly influenced by structural changes that occur in both the intracellular and interstitial spaces of cardiac tissue; however, very few studies have investigated how interactions between the two spaces affect propagation at the microscale. In this study, we used one-dimensional microstructural computer models of interconnected ventricular myocytes to systematically investigate how increasing the effective interstitial resistivity (rho(oeff)) influences action potential propagation in fibers with variations in intracellular properties such as cell coupling and cell length. Changes in rho(oeff) were incorporated into a monodomain model using a correction to the intracellular properties that was based on bidomain simulations. The results showed that increasing rho(oeff) in poorly coupled one-dimensional fibers alters the distribution of electrical load at the microscale and causes propagation to become more continuous. In the poorly coupled fiber, this continuous state is characterized by decreased gap junction delay, sustained conduction velocity, increased sodium current, reduced maximum upstroke velocity, and increased safety factor. Long, poorly coupled cells experience greater loading effects than short cells and show the greatest initial response to changes in rho(oeff). In inhomogeneous fibers with adjacent well-coupled and poorly coupled regions, increasing rho(oeff) in the poorly coupled region also reduces source-load mismatch, which delays the onset of conduction block and reduces the dispersion of repolarization at the transition between the two regions. Increasing the rho(oeff) minimizes the effect of cell-to-cell variations and may influence the pattern of activation in critical regimes characterized by low intercellular coupling, microstructural heterogeneity, and reduced or abnormal membrane excitability. PMID:20097772

  6. Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences

    PubMed Central

    Derr, Julien; Manapat, Michael L.; Rajamani, Sudha; Leu, Kevin; Xulvi-Brunet, Ramon; Joseph, Isaac; Nowak, Martin A.; Chen, Irene A.

    2012-01-01

    During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life. PMID:22319215

  7. Nanostructured lipid carriers loaded with tributyrin as an alternative to improve anticancer activity of all-trans retinoic acid

    PubMed Central

    Silva, Elton Luiz; Carneiro, Guilherme; Caetano, Priscila Albuquerque; Costa, Daniel Ferreira; de Souza-Fagundes, Elaine Maria; Gomes, Dawidson Assis; Ferreira, Lucas Antônio Miranda

    2015-01-01

    Objectives All-trans retinoic acid (ATRA) is one of the most successful examples of differentiation agents and histone deacetylase inhibitors, such as tributyrin (TB), are known for their antitumor activity and potentiating action of drugs such as ATRA. Nanostructured lipid carriers (NLC) represent a promising alternative to the encapsulation of lipophilic drugs such as ATRA. This study aimed to develop, characterize, and evaluate the cytotoxicity of ATRA-TB-loaded nanostructured lipid carriers (NLC) for cancer treatment. Methods The influence of in situ formation of an ion pairing between ATRA and a lipophilic amine (benethamine; BNT) on the characteristics of NLC (size, zeta potential, encapsulation efficiency) was evaluated. Tributyrin (TB), a butyric acid donor, was used as a component of the lipid matrix. In vitro activity on cell viability and distribution of cell cycle phases were evaluated for MCF-7, MDA-MB-231, HL-60, and Jurkat cell lines. Results The presence of the amine significantly increased the encapsulation efficiency of ATRA in NLC. Inhibition of cell viability by TB-ATRA-loaded NLC was more pronounced than the free drug. Analysis of the distribution of cell cycle phases also showed increased activity for TB-ATRA-loaded NLC, with the clear effect of cell cycle arrest in G0/G1 phase transition. The presence of TB played an important role in the activity of the formulation. Conclusion Taken together, these findings suggest that TB-ATRA-loaded NLC represent a promising alternative to intravenous administration of ATRA in cancer treatment. PMID:25611812

  8. The role of low acid load in vegetarian diet on bone health: a narrative review.

    PubMed

    Burckhardt, Peter

    2016-01-01

    Vegetarian and vegan diets contain low amounts of protein and calcium. For this reason they are supposed to cause low bone mineral density (BMD) and osteoporosis. But this is not the case, except for vegans with a particularly low calcium intake. The absence of osteoporosis or low BMD can be explained by the low acid load of these diets. Nutritional acid load is negatively correlated with bone mineral density (BMD) and positively with fracture risk. Low acid load is correlated with lower bone resorption and higher BMD. It is linked to high intake of potassium-rich nutrients, such as fruits and vegetables, as found in vegetarian diets. The total nutritional acid load, which not only depends on the potassium content of the nutrition, was recently assessed in several studies on vegetarian and vegan diets and was found to be very low or absent, while the diet of Western-style omnivores produces daily 50 to 70 mEq of acid. This might be an important factor for the protection of vegetarians from osteoporosis.

  9. The role of low acid load in vegetarian diet on bone health: a narrative review.

    PubMed

    Burckhardt, Peter

    2016-01-01

    Vegetarian and vegan diets contain low amounts of protein and calcium. For this reason they are supposed to cause low bone mineral density (BMD) and osteoporosis. But this is not the case, except for vegans with a particularly low calcium intake. The absence of osteoporosis or low BMD can be explained by the low acid load of these diets. Nutritional acid load is negatively correlated with bone mineral density (BMD) and positively with fracture risk. Low acid load is correlated with lower bone resorption and higher BMD. It is linked to high intake of potassium-rich nutrients, such as fruits and vegetables, as found in vegetarian diets. The total nutritional acid load, which not only depends on the potassium content of the nutrition, was recently assessed in several studies on vegetarian and vegan diets and was found to be very low or absent, while the diet of Western-style omnivores produces daily 50 to 70 mEq of acid. This might be an important factor for the protection of vegetarians from osteoporosis. PMID:26900949

  10. Effect of aspartame and aspartate loading upon plasma and erythrocyte free amino acid levels in normal adult volunteers.

    PubMed

    Stegink, L D; Filer, L J; Baker, G L

    1977-10-01

    Aspartame is a dipeptide (L-aspartyl-L-phenylalanyl-methyl ester) with a sweeting potential 180 to 200 times that of sucrose. Questions have been raised about potential toxic effects of its constituent amino acids, aspartate and phenylalanine when the compound is ingested in large amounts. Plasma and erythrocyte amino acid levels were measured in 12 normal subjects after administration of either Aspartame (34 mg/kg) or equimolar quantities of aspartate (13 mg/kg) in a crossover design. No changes in either plasma or erythrocyte aspartate levels were noted at any time after either Aspartame or aspartate ingestion. Plasma phenylalanine levels decrease slightly after aspartate loading, and increased from fasting levels (4.9 +/- 1 mumoles/100 ml) to 10.7 +/- 1.9 mumoles/100 ml about 45 to 60 minutes after Aspartame loading. Phenylalanine levels returned to baseline by 4 hours. Erythrocyte phenylalanine levels showed similar changes.

  11. Comparative response of lead-acid and nickel-iron batteries to pulsed and constant-current loads

    NASA Astrophysics Data System (ADS)

    Deluca, W. H.; Tummillo, A. F.; Biwer, T. L.; Christianson, C. C.; Hornstra, F.; Yao, N. P.

    1983-06-01

    Improved lead acid and nickel iron batteries were developed for use in electric vehicles. The response of these batteries to given discharge conditions differs according to characteristics of each system. The discharge capacity of the lead acid system is reduced at increased discharge rates and its internal resistance is a function of both depth of discharge (DOD) and discharge rate. Open circuit stand times at DOD levels 50% reduce the internal resistance of the lead acid system and provide a corresponding increase in its availability capacity. The discharge capacity and internal resistance of the nickel/iron system are virtually independent of both discharge rate and open circuit stand times during discharge. With pulsed current loads, the available energy and power output of both battery systems are always less than those obtained with equivalent constant current loads due to increased internal power losses. The nickel-iron system exhibits an internal inductance that is significantly greater than that for the lead acid system thereby causing potentially damaging voltage transients. The test procedures and system employed, test data, and methods for predicting battery response are described.

  12. Spontaneous arrangement of a tumor targeting hyaluronic acid shell on irinotecan loaded PLGA nanoparticles.

    PubMed

    Giarra, Simona; Serri, Carla; Russo, Luisa; Zeppetelli, Stefania; De Rosa, Giuseppe; Borzacchiello, Assunta; Biondi, Marco; Ambrosio, Luigi; Mayol, Laura

    2016-04-20

    The arrangement of tumor targeting hyaluronic acid (HA) moieties on irinotecan (IRIN)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) has been directed by means of a gradient of lipophilicity between the oil and water phases of the emulsion used to produce the NPs. PLGA constitutes the NP bulk while HA is superficially exposed, with amphiphilic poloxamers acting as a bridge between PLGA and HA. Differential scanning calorimetry, zeta potential analyses and ELISA tests were employed to support the hypothesis of polymer assembly in NP formulations. The presence of flexible HA chains on NP surface enhances NP size stability over time due to an increased electrostatic repulsion between NPs and a higher degree of hydration of the device surface. IRIN in vitro release kinetics can be sustained up to 7-13 days. In vitro biologic studies indicated that HA-containing NPs were more toxic than bare PLGA NPs against CD44-overexpressing breast carcinoma cells (HS578T), therefore indicating their ability to target CD44 receptor. PMID:26876867

  13. Spontaneous arrangement of a tumor targeting hyaluronic acid shell on irinotecan loaded PLGA nanoparticles.

    PubMed

    Giarra, Simona; Serri, Carla; Russo, Luisa; Zeppetelli, Stefania; De Rosa, Giuseppe; Borzacchiello, Assunta; Biondi, Marco; Ambrosio, Luigi; Mayol, Laura

    2016-04-20

    The arrangement of tumor targeting hyaluronic acid (HA) moieties on irinotecan (IRIN)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) has been directed by means of a gradient of lipophilicity between the oil and water phases of the emulsion used to produce the NPs. PLGA constitutes the NP bulk while HA is superficially exposed, with amphiphilic poloxamers acting as a bridge between PLGA and HA. Differential scanning calorimetry, zeta potential analyses and ELISA tests were employed to support the hypothesis of polymer assembly in NP formulations. The presence of flexible HA chains on NP surface enhances NP size stability over time due to an increased electrostatic repulsion between NPs and a higher degree of hydration of the device surface. IRIN in vitro release kinetics can be sustained up to 7-13 days. In vitro biologic studies indicated that HA-containing NPs were more toxic than bare PLGA NPs against CD44-overexpressing breast carcinoma cells (HS578T), therefore indicating their ability to target CD44 receptor.

  14. Increasing dietary crude protein does not increase the essential amino acid requirements of kittens.

    PubMed

    Strieker, M J; Morris, J G; Rogers, Q R

    2006-08-01

    Essential amino acid (EAA) requirements of omnivores and herbivores (e.g. chicks, lambs, pigs and rats) are directly related to the concentration of dietary crude protein (CP). When an EAA is limiting in the diet, addition of a mixture of EAA lacking the limiting one (which increases dietary CP) results in a decrease in food intake and weight gain. This interaction has been referred to as an AA imbalance and has not been studied in depth in strict carnivores. The objectives of these experiments were to examine the effects on growing kittens (2-week periods) of the addition to diets of a mixture of AA lacking the limiting one. The control diets were at the requirement of the respective limiting EAA (or about 85% of the 1986 National Research Council requirement). In experiment 1, with the dietary EAAs at the minimally determined requirements, the concentration of the essential or dispensable amino acids was increased to determine if CP or an EAA was limiting. Results of growth rates (n = 12) and plasma AA concentrations indicated that tryptophan was limiting, but increased body weight gain also occurred when the concentration of CP was increased as dispensable amino acids without additional tryptophan. Experiment 1 was repeated in experiment 2 using a crossover design. Again, when tryptophan was limiting additional concentrations of dispensable AAs increased body weight gain. This response is the opposite of that in herbivores and omnivores. Experiment 3 consisted of 10 separate crossover trials, one for each of the 10 EAA and examined the effect of two concentrations of dietary CP (200 and 300 g CP/kg diet) on body weight gain of kittens (n = 8) offered diets limiting in each respective EAA. Body weight gain was numerically greater when diets contained 300 g CP/kg than 200 g CP/kg for eight of 10 EAAs (p < 0.05 for only isoleucine and threonine) when each amino acid was limiting. This response is the reverse of that which occurs in chicks, lambs, pigs and rats when

  15. Internal waves as a proposed mechanism for increasing ambient noise in an increasingly acidic ocean.

    PubMed

    Rouseff, Daniel; Tang, Dajun

    2010-06-01

    The effect on the ambient noise level in shallow water of the ocean growing more acidic is modeled. Because most noise sources are near the surface, high-order acoustic modes are preferentially excited. Linear internal waves, however, can scatter the noise into the low-order, low-loss modes most affected by the changes in acidity. The model uses transport theory to couple the modes and assumes an isotropic distribution for the noise sources. For a scenario typical of the East China Sea, the noise at 3 kHz is predicted to increase by 30%, about one decibel, as the pH decreases from 8.0 to 7.4.

  16. Expiratory muscle loading increases intercostal muscle blood flow during leg exercise in healthy humans.

    PubMed

    Athanasopoulos, Dimitris; Louvaris, Zafeiris; Cherouveim, Evgenia; Andrianopoulos, Vasilis; Roussos, Charis; Zakynthinos, Spyros; Vogiatzis, Ioannis

    2010-08-01

    We investigated whether expiratory muscle loading induced by the application of expiratory flow limitation (EFL) during exercise in healthy subjects causes a reduction in quadriceps muscle blood flow in favor of the blood flow to the intercostal muscles. We hypothesized that, during exercise with EFL quadriceps muscle blood flow would be reduced, whereas intercostal muscle blood flow would be increased compared with exercise without EFL. We initially performed an incremental exercise test on eight healthy male subjects with a Starling resistor in the expiratory line limiting expiratory flow to approximately 1 l/s to determine peak EFL exercise workload. On a different day, two constant-load exercise trials were performed in a balanced ordering sequence, during which subjects exercised with or without EFL at peak EFL exercise workload for 6 min. Intercostal (probe over the 7th intercostal space) and vastus lateralis muscle blood flow index (BFI) was calculated by near-infrared spectroscopy using indocyanine green, whereas cardiac output (CO) was measured by an impedance cardiography technique. At exercise termination, CO and stroke volume were not significantly different during exercise, with or without EFL (CO: 16.5 vs. 15.2 l/min, stroke volume: 104 vs. 107 ml/beat). Quadriceps muscle BFI during exercise with EFL (5.4 nM/s) was significantly (P = 0.043) lower compared with exercise without EFL (7.6 nM/s), whereas intercostal muscle BFI during exercise with EFL (3.5 nM/s) was significantly (P = 0.021) greater compared with that recorded during control exercise (0.4 nM/s). In conclusion, increased respiratory muscle loading during exercise in healthy humans causes an increase in blood flow to the intercostal muscles and a concomitant decrease in quadriceps muscle blood flow.

  17. Standardization of formulations for the acute amino acid depletion and loading tests.

    PubMed

    Badawy, Abdulla A-B; Dougherty, Donald M

    2015-04-01

    The acute tryptophan depletion and loading and the acute tyrosine plus phenylalanine depletion tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAAs) by the latter. The high content of BCAA (30-60%) is responsible for the poor specificity in humans and we recommend, in a 50g dose, a control formulation with a lowered BCAA content (18%) as a common control for the above tests. With protein-based formulations, α-lactalbumin is specific for acute tryptophan loading, whereas gelatine is only partially effective for acute tryptophan depletion. We recommend the use of the whey protein fraction glycomacropeptide as an alternative protein. Its BCAA content is ideal for specificity and the absence of tryptophan, tyrosine and phenylalanine render it suitable as a template for seven formulations (separate and combined depletion or loading and a truly balanced control). We invite the research community to participate in standardization of the depletion and loading methodologies by using our recommended amino acid formulation and developing those based on glycomacropeptide.

  18. Stress of different types increases the proinflammatory load in rheumatoid arthritis.

    PubMed

    Straub, Rainer H; Kalden, Joachim R

    2009-01-01

    Stress in patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) stimulates proinflammatory mechanisms due to the defect of stress response systems (for example, the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis). Among other mechanisms, the loss of sympathetic nerve fibers in inflamed tissue and inadequate cortisol secretion in relation to inflammation lead to an enhanced proinflammatory load in RA. Stress and the subsequent stimulation of inflammation (systemic and local) lead to increased sensitization of pain and further defects of stress response systems (vicious cycle of stress, pain, and inflammation).

  19. When Interference Helps: Increasing Executive Load to Facilitate Deception Detection in the Concealed Information Test

    PubMed Central

    Visu-Petra, George; Varga, Mihai; Miclea, Mircea; Visu-Petra, Laura

    2013-01-01

    The possibility to enhance the detection efficiency of the Concealed Information Test (CIT) by increasing executive load was investigated, using an interference design. After learning and executing a mock crime scenario, subjects underwent three deception detection tests: an RT-based CIT, an RT-based CIT plus a concurrent memory task (CITMem), and an RT-based CIT plus a concurrent set-shifting task (CITShift). The concealed information effect, consisting in increased RT and lower response accuracy for probe items compared to irrelevant items, was evidenced across all three conditions. The group analyses indicated a larger difference between RTs to probe and irrelevant items in the dual-task conditions, but this difference was not translated in a significantly increased detection efficiency at an individual level. Signal detection parameters based on the comparison with a simulated innocent group showed accurate discrimination for all conditions. Overall response accuracy on the CITMem was highest and the difference between response accuracy to probes and irrelevants was smallest in this condition. Accuracy on the concurrent tasks (Mem and Shift) was high, and responses on these tasks were significantly influenced by CIT stimulus type (probes vs. irrelevants). The findings are interpreted in relation to the cognitive load/dual-task interference literature, generating important insights for research on the involvement of executive functions in deceptive behavior. PMID:23543918

  20. An evaluation of critical loads of soil acidity in areas of high sea salt deposition.

    PubMed

    Reynolds, B

    2000-05-15

    The empirical and mass balance approaches to setting critical loads of acidity for mineral soils have been evaluated using field data from forest sites in Wales. Using the Simple Mass Balance Equation (SMBE) with Sitka spruce as the biological target, critical loads ranged between 2.3 and 9.8 keq H+ ha(-1) year(-1) compared to mapped empirical critical loads which ranged between 0.2 and 0.5 keq H+ ha(-1) year(-1). At all sites the empirical critical load was exceeded with respect to deposited sulfur acidity. There were no exceeded sites for the SMBE critical loads. The big differences between the two methods arise from the large ANC leaching term in the SMBE model which is determined by the relatively low (Ca + Mg + K)/Al(crit) ratio for Sitka spruce, compared to other conifers, and the influence of the large deposition of sea salt base cations. The low value of the (Ca + Mg + K)/Al(crit) ratio for Sitka spruce implies that it is tolerant of very acidic soil conditions, however, the ratio is based on the results of only one solution culture study and may thus be uncertain under field conditions. Large sea salt base cation deposition directly influences SMBE critical loads because the predicted soil water base cation concentrations permit large concentrations of hydrogen ions and aluminium (low ANC values) before the critical chemical limit is transgressed. Where weathering rates are low, critical ANC leaching (ANC(lecrit)) becomes the dominant term in the SMBE, with the counter intuitive result that the critical load becomes a linear function of sea salt base cation deposition. Thus the current formulation of the SMBE may not be appropriate for low weathering rate areas receiving large amounts of sea salt base cation deposition.

  1. Preparation of ultrafine poly(methyl methacrylate-co-methacrylic acid) biodegradable nanoparticles loaded with ibuprofen.

    PubMed

    Saade, Hened; Diaz de León-Gómez, Ramón; Enríquez-Medrano, Francisco Javier; López, Raúl Guillermo

    2016-08-01

    Ibuprofen-loaded polymeric particles with around 9.2 nm in mean diameter, as determined by electron microscopy, dispersed in an aqueous media containing up to 12.8% solids were prepared by semicontinuous heterophase polymerization. The polymeric material is a (2/1 mol/mol) methyl methacrylate-co-methacrylic acid copolymer similar to Eudragit S100, deemed safe for human consumption and used in the manufacturing of drug-loaded pills as well as micro- and nanoparticles. The loading efficiency was 100%, attaining around 10-12% in drug content. Release studies showed that the drug is released from the nanoparticles at a slower rate than that in the case of free IB. Given their size as well as the pH values required for their dissolution, it is believed that this type of particles could be used as a basis for preparing nanosystems loaded with a variety of drugs.

  2. Preparation of ultrafine poly(methyl methacrylate-co-methacrylic acid) biodegradable nanoparticles loaded with ibuprofen.

    PubMed

    Saade, Hened; Diaz de León-Gómez, Ramón; Enríquez-Medrano, Francisco Javier; López, Raúl Guillermo

    2016-08-01

    Ibuprofen-loaded polymeric particles with around 9.2 nm in mean diameter, as determined by electron microscopy, dispersed in an aqueous media containing up to 12.8% solids were prepared by semicontinuous heterophase polymerization. The polymeric material is a (2/1 mol/mol) methyl methacrylate-co-methacrylic acid copolymer similar to Eudragit S100, deemed safe for human consumption and used in the manufacturing of drug-loaded pills as well as micro- and nanoparticles. The loading efficiency was 100%, attaining around 10-12% in drug content. Release studies showed that the drug is released from the nanoparticles at a slower rate than that in the case of free IB. Given their size as well as the pH values required for their dissolution, it is believed that this type of particles could be used as a basis for preparing nanosystems loaded with a variety of drugs. PMID:27126476

  3. In vivo pharmacokinetics, biodistribution and antitumor effect of amphiphilic poly(L-amino acids) micelles loaded with a novel all-trans retinoic acid derivative.

    PubMed

    Tang, Jihui; Wang, Xinqun; Wang, Ting; Chen, Feihu; Zhou, Jianping

    2014-01-23

    Poly(amino acid)s are well-known as biodegradable and environmentally acceptable materials. In this study, a series of poly(L-aspartic acid)-b-poly(L-phenylalanine) (PAA-PPA) compounds with different degrees of polymerization were used to prepare copolymer micelles for a poorly water-soluble drug 4-amino-2-trifluoromethyl-phenyl retinate (ATPR, a novel all-trans retinoic acid derivative) and in vivo pharmacokinetics, biodistribution and antitumor efficacy of ATPR delivered by PAA-PPA micelles were evaluated. The area under the plasma concentration time curve AUC0→∞ of ATPR-loaded PAA20PPA20 micelles was 2.23 and 1.97 times higher than that of ATPR solution and ATPR CrmEL solution, respectively; In addition, the mean residence time (MRT) was increased 1.67 and 1.97-fold, respectively and the total body clearance (CL) was reduced 2.25 and 1.98-fold, respectively. The biodistribution study indicated that most of the ATPR in the ATPR-M group was distributed in the liver and there was delayed liver aggregation compared with the ATPR solution and ATPR CrmEL solution groups. Furthermore, the antitumor efficacy of ATPR-loaded PAA20PPA20 micelles was demonstrated in in vivo antitumor models involving mice inoculated with the human gastric cancer cell line SGC-7901. At the same dose of 7mg/kg, the ATPR-loaded micelles group demonstrated a better tumor growth inhibition and induced differentiation than the groups given ATPR solution and ATPR CrmEL solution. Therefore, the ATPR-loaded PAA-PPA micelles appear to be a potentially useful drug delivery system for ATPR and suitable for the chemotherapy of gastric cancer.

  4. Antimicrobial activity of curcumin-loaded myristic acid microemulsions against Staphylococcus epidermidis.

    PubMed

    Liu, Chi-Hsien; Huang, Hsin-Ying

    2012-01-01

    The bactericidal properties of myristic acid and curcumin were revealed in a number of studies. However, whether curcumin-loaded myristic acid microemulsions can be used to inhibit Staphylococcus epidermidis, which causes nosocomial infections, has not been reported. Our aim was to develop curcumin-loaded myristic acid microemulsions to inhibit S. epidermidis on the skin. The interfacial tension, size distribution, and viscosity data of the microemulsions were characterized to elucidate the physicochemical properties of the curcumin microemulsions. Curcumin distribution in neonate pig skin was visualized using confocal laser scanning microscopy. Dermal curcumin accumulation (326 µg/g skin) and transdermal curcumin penetration (87 µg/cm(2)/d) were obtained with the microemulsions developed herein. Curcumin at the concentration of 0.86 µg/mL in the myristic acid microemulsion could inhibit 50% of the bacterial growth, which was 12 times more effective than curcumin dissolved in dimethyl sulfoxide (DMSO). The cocktail combination of myristic acid and curcumin in the microemulsion carrier synergistically inhibited the growth of S. epidermidis. The results we obtained highlight the potential of using curcumin-loaded microemulsions as an alternative treatment for S. epidermidis-associated diseases and acne vulgaris. PMID:22976319

  5. Increased loading rates and specific methane yields facilitated by digesting grass silage at thermophilic rather than mesophilic temperatures.

    PubMed

    Voelklein, M A; Rusmanis, D; Murphy, J D

    2016-09-01

    This study was conducted to advance the understanding of thermophilic grass digestion. Late harvested grass silage was fermented at thermophilic conditions at increasing organic loading rates (OLR). Stable digestion took place at an OLR between 3 and 4gVSL(-1)d(-1). This enabled specific methane yields (SMY) as high as 405LCH4kgVS(-1). An accumulation of volatile fatty acids (VFA), accompanied by a gradual deterioration of pH, FOS/TAC (ratio of VFA to alkalinity) arose at an OLR between 5 and 7gVSL(-1)d(-1), yet inhibition did not occur. SMY decreased with reduced retention time ranging between 336 and 358LCH4kgVS(-1) at OLR 7 and 5gVSL(-1)d(-1) respectively. The biomethane efficiencies remained high (92-103%) at corresponding retention times. Comparative results indicated a superior performance with respect to higher loading and SMY as compared with mesophilic conditions. PMID:27268433

  6. Periostin deficiency increases bone damage and impairs injury response to fatigue loading in adult mice.

    PubMed

    Bonnet, Nicolas; Gineyts, Evelyne; Ammann, Patrick; Conway, Simon J; Garnero, Patrick; Ferrari, Serge

    2013-01-01

    Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn) is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn(-/-) and Postn(+/+) mice after fatigue stimulus by axial compression of their tibia. In Postn(+/+) mice, cracks number and surface (CsNb, CsS) increased 1h after fatigue, with a decrease in strength compared to non-fatigued tibia. At 15 days, CsNb had started to decline, while CtTV and CtBV increased in fatigued vs non-fatigued tibia, reflecting a woven bone response that was present in 75% of the fatigued bones. Cortical porosity and remodelling also prominently increased in the fatigued tibia of Postn(+/+) mice. At 30 days, paralleling a continuous removal of cortical damage, strength of the fatigued tibia was similar to the non-fatigue tibia. In Postn(-/-) mice, cracks were detectable even in the absence of fatigue, while the amount of collagen crosslinks and tissue hardness was decreased compared to Postn(+/+). Fatigue significantly increased CsNb and CsS in Postn(-/-), but was not associated with changes in CtTV and CtBV, as only 16% of the fatigued bones formed some woven bone. Cortical porosity and remodelling did not increase either after fatigue in Postn(-/-), and the level of damage remained high even after 30 days. As a result, strength remained compromised in Postn(-/-) mice. Contrary to Postn(+/+), which osteocytic lacunae showed a change in the degree of anisotropy (DA) after fatigue, Postn(-/-) showed no DA change. Hence periostin appears to influence bone materials properties, damage accumulation and repair, including local modeling/remodeling processes in response to fatigue. These observations suggest that the level of periostin expression could influence the propensity to fatigue fractures. PMID

  7. Taking the easy way out? Increasing implementation effort reduces probability maximizing under cognitive load.

    PubMed

    Schulze, Christin; Newell, Ben R

    2016-07-01

    Cognitive load has previously been found to have a positive effect on strategy selection in repeated risky choice. Specifically, whereas inferior probability matching often prevails under single-task conditions, optimal probability maximizing sometimes dominates when a concurrent task competes for cognitive resources. We examined the extent to which this seemingly beneficial effect of increased task demands hinges on the effort required to implement each of the choice strategies. Probability maximizing typically involves a simple repeated response to a single option, whereas probability matching requires choice proportions to be tracked carefully throughout a sequential choice task. Here, we flipped this pattern by introducing a manipulation that made the implementation of maximizing more taxing and, at the same time, allowed decision makers to probability match via a simple repeated response to a single option. The results from two experiments showed that increasing the implementation effort of probability maximizing resulted in decreased adoption rates of this strategy. This was the case both when decision makers simultaneously learned about the outcome probabilities and responded to a dual task (Exp. 1) and when these two aspects were procedurally separated in two distinct stages (Exp. 2). We conclude that the effort involved in implementing a choice strategy is a key factor in shaping repeated choice under uncertainty. Moreover, highlighting the importance of implementation effort casts new light on the sometimes surprising and inconsistent effects of cognitive load that have previously been reported in the literature.

  8. Taking the easy way out? Increasing implementation effort reduces probability maximizing under cognitive load.

    PubMed

    Schulze, Christin; Newell, Ben R

    2016-07-01

    Cognitive load has previously been found to have a positive effect on strategy selection in repeated risky choice. Specifically, whereas inferior probability matching often prevails under single-task conditions, optimal probability maximizing sometimes dominates when a concurrent task competes for cognitive resources. We examined the extent to which this seemingly beneficial effect of increased task demands hinges on the effort required to implement each of the choice strategies. Probability maximizing typically involves a simple repeated response to a single option, whereas probability matching requires choice proportions to be tracked carefully throughout a sequential choice task. Here, we flipped this pattern by introducing a manipulation that made the implementation of maximizing more taxing and, at the same time, allowed decision makers to probability match via a simple repeated response to a single option. The results from two experiments showed that increasing the implementation effort of probability maximizing resulted in decreased adoption rates of this strategy. This was the case both when decision makers simultaneously learned about the outcome probabilities and responded to a dual task (Exp. 1) and when these two aspects were procedurally separated in two distinct stages (Exp. 2). We conclude that the effort involved in implementing a choice strategy is a key factor in shaping repeated choice under uncertainty. Moreover, highlighting the importance of implementation effort casts new light on the sometimes surprising and inconsistent effects of cognitive load that have previously been reported in the literature. PMID:26884088

  9. Toxic effects of increased sediment nutrient and organic matter loading on the seagrass Zostera noltii.

    PubMed

    Govers, Laura L; de Brouwer, Jan H F; Suykerbuyk, Wouter; Bouma, Tjeerd J; Lamers, Leon P M; Smolders, Alfons J P; van Katwijk, Marieke M

    2014-10-01

    As a result of anthropogenic disturbances and natural stressors, seagrass beds are often patchy and heterogeneous. The effects of high loads of nutrients and organic matter in patch development and expansion in heterogeneous seagrass beds have, however, poorly been studied. We experimentally assessed the in situ effects of sediment quality on seagrass (Zostera noltii) patch dynamics by studying patch (0.35 m diameter) development and expansion for 4 sediment treatments: control, nutrient addition (NPK), organic matter addition (OM) and a combination (NPK+OM). OM addition strongly increased porewater sulfide concentrations whereas NPK increased porewater ammonium, nitrate and phosphate concentrations. As high nitrate concentrations suppressed sulfide production in NPK+OM, this treatment was biogeochemically comparable to NPK. Sulfide and ammonium concentrations differed within treatments, but over a 77 days period, seagrass patch survival and expansion were impaired by all additions compared to the control treatment. Expansion decreased at porewater ammonium concentrations >2,000 μmol L(-1). Mother patch biomass was not affected by high porewater ammonium concentrations as a result of its detoxification by higher seagrass densities. Sulfide concentrations >1,000 μmol L(-1) were toxic to both patch expansion and mother patch. We conclude that patch survival and expansion are constrained at high loads of nutrients or organic matter as a result of porewater ammonium or sulfide toxicity. PMID:25064458

  10. Curcumin loaded poly (lactic-co-glycolic) acid nanofiber for the treatment of carcinoma.

    PubMed

    Sampath, Malathi; Lakra, Rachita; Korrapati, Purnasai; Sengottuvelan, Balasubramanian

    2014-05-01

    Poly (DL-lactic-co-glycolic) acid [PLGA] copolymers with different ratios (78/22, 68/32 and 61/39) and molecular weight (15,400, 11,000 and 10,000 Da) were synthesized and characterized by (1)H NMR, FTIR, GPC and TGA-DTA studies. Curcumin loaded PLGA with the size of 100-300 nm were obtained by electrospinning in which no visible aggregation observed on the surface. The diameter of CPNF (61/39) nanofiber obtained from the topographical imaging by AFM is 160±10 nm. The water contact angle measurements indicate that an increase in GA content results in increase in the hydrophilicity of the PLGA copolymer. The in vitro release profile and release kinetics from the CPNF demonstrated a sustained release of curcumin from CPNF. The release profile follows Korsmeyer-Peppas model suggesting a combination of surface drug dissolution and non-Fickian diffusion as a major drug release mechanism. The effect of CPNF on cell viability was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay to examine the cytotoxic effect of released curcumin on A431 cells in vitro. PMID:24646452

  11. Curcumin loaded poly (lactic-co-glycolic) acid nanofiber for the treatment of carcinoma.

    PubMed

    Sampath, Malathi; Lakra, Rachita; Korrapati, Purnasai; Sengottuvelan, Balasubramanian

    2014-05-01

    Poly (DL-lactic-co-glycolic) acid [PLGA] copolymers with different ratios (78/22, 68/32 and 61/39) and molecular weight (15,400, 11,000 and 10,000 Da) were synthesized and characterized by (1)H NMR, FTIR, GPC and TGA-DTA studies. Curcumin loaded PLGA with the size of 100-300 nm were obtained by electrospinning in which no visible aggregation observed on the surface. The diameter of CPNF (61/39) nanofiber obtained from the topographical imaging by AFM is 160±10 nm. The water contact angle measurements indicate that an increase in GA content results in increase in the hydrophilicity of the PLGA copolymer. The in vitro release profile and release kinetics from the CPNF demonstrated a sustained release of curcumin from CPNF. The release profile follows Korsmeyer-Peppas model suggesting a combination of surface drug dissolution and non-Fickian diffusion as a major drug release mechanism. The effect of CPNF on cell viability was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay to examine the cytotoxic effect of released curcumin on A431 cells in vitro.

  12. Connecting Source with Sink: The Role of Arabidopsis AAP8 in Phloem Loading of Amino Acids.

    PubMed

    Santiago, James P; Tegeder, Mechthild

    2016-05-01

    Allocation of large amounts of nitrogen to developing organs occurs in the phloem and is essential for plant growth and seed development. In Arabidopsis (Arabidopsis thaliana) and many other plant species, amino acids represent the dominant nitrogen transport forms in the phloem, and they are mainly synthesized in photosynthetically active source leaves. Following their synthesis, a broad spectrum of the amino nitrogen is actively loaded into the phloem of leaf minor veins and transported within the phloem sap to sinks such as developing leaves, fruits, or seeds. Controlled regulation of the source-to-sink transport of amino acids has long been postulated; however, the molecular mechanism of amino acid phloem loading was still unknown. In this study, Arabidopsis AMINO ACID PERMEASE8 (AAP8) was shown to be expressed in the source leaf phloem and localized to the plasma membrane, suggesting its function in phloem loading. This was further supported by transport studies with aap8 mutants fed with radiolabeled amino acids and by leaf exudate analyses. In addition, biochemical and molecular analyses revealed alterations in leaf nitrogen pools and metabolism dependent on the developmental stage of the mutants. Decreased amino acid phloem loading and partitioning to sinks led to decreased silique and seed numbers, but seed protein levels were unchanged, demonstrating the importance of AAP8 function for sink development rather than seed quality. Overall, these results show that AAP8 plays an important role in source-to-sink partitioning of nitrogen and that its function affects source leaf physiology and seed yield. PMID:27016446

  13. Incremental training intensities increases loads on the lower back of elite female rowers.

    PubMed

    Buckeridge, Erica M; Bull, Anthony M J; McGregor, Alison H

    2016-01-01

    Lumbar-pelvic kinematics change in response to increasing rowing stroke rates, but little is known about the effect of incremental stroke rates on changes in joint kinetics and their implications for injury. The purpose of this study was to quantify the effects of incremental rowing intensities on lower limb and lumbar-pelvic kinetics. Twelve female rowers performed an incremental test on a rowing ergometer. Kinematic data of rowers' ankle, knee, hip and lumbar-pelvic joints, as well as external forces at the handle, seat and foot-stretchers of the rowing machine were recorded. Inter-segmental moments and forces were calculated using inverse dynamics and were compared across stroke rates using repeated measures ANOVA. Rowers exhibited increases in peak ankle and L5/S1 extensor moments, reductions in peak knee moments and no change in peak hip moments, with respect to stroke rate. Large shear and compressive forces were seen at L5/S1 and increased with stroke rate (P < 0.05). This coincided with increased levels of lumbar-pelvic flexion. High levels of lumbar-pelvic loading at higher stroke rates have implications with respect to injury and indicated that technique was declining, leading to increased lumbar-pelvic flexion. Such changes are not advantageous to performance and can potentially increase the risk of developing injuries.

  14. Incremental training intensities increases loads on the lower back of elite female rowers.

    PubMed

    Buckeridge, Erica M; Bull, Anthony M J; McGregor, Alison H

    2016-01-01

    Lumbar-pelvic kinematics change in response to increasing rowing stroke rates, but little is known about the effect of incremental stroke rates on changes in joint kinetics and their implications for injury. The purpose of this study was to quantify the effects of incremental rowing intensities on lower limb and lumbar-pelvic kinetics. Twelve female rowers performed an incremental test on a rowing ergometer. Kinematic data of rowers' ankle, knee, hip and lumbar-pelvic joints, as well as external forces at the handle, seat and foot-stretchers of the rowing machine were recorded. Inter-segmental moments and forces were calculated using inverse dynamics and were compared across stroke rates using repeated measures ANOVA. Rowers exhibited increases in peak ankle and L5/S1 extensor moments, reductions in peak knee moments and no change in peak hip moments, with respect to stroke rate. Large shear and compressive forces were seen at L5/S1 and increased with stroke rate (P < 0.05). This coincided with increased levels of lumbar-pelvic flexion. High levels of lumbar-pelvic loading at higher stroke rates have implications with respect to injury and indicated that technique was declining, leading to increased lumbar-pelvic flexion. Such changes are not advantageous to performance and can potentially increase the risk of developing injuries. PMID:26090702

  15. Fabrication and Characterization of Gd-DTPA-Loaded Chitosan-Poly(Acrylic Acid) Nanoparticles for Magnetic Resonance Imaging.

    PubMed

    Ahmed, Arsalan; Zhang, Chao; Guo, Jian; Hu, Yong; Jiang, Xiqun

    2015-08-01

    Gd-DTPA-loaded chitosan-poly(acrylic acid) nanoparticles (Gd-DTPA@CS-PAA NPs) were formulated based on the reaction system of water-soluble polymer-monomer pairs of acrylic acid in chitosan solution followed by sorption of Gd-DTPA. Morphological investigations revealed the spherical shape of these NPs with about 220 nm particle size. These NPs showed charge reversal characteristic in acidic solution. In vitro and in vivo magnetic characteristics of these NPs were explored to estimate their utilization in targeted enhanced magnetic resonance imaging. Relaxation studies showed that these NPs possessed pH susceptible relaxation properties, which could introduce in vivo-specific distribution of contrast agent. MRI experiment showed that these nanoparticles had better results in contrast enhancement, and the concentration of contrast agent increased in liver and brain with increment in time. Thus, these NPs could maintain in vivo long circulation and high relaxation rate and were suitable agents for magnetic resonance imaging.

  16. Estimation of critical loads of acidity for lakes in northeastern United States and eastern Canada.

    PubMed

    Dupont, J; Clair, T A; Gagnon, C; Jeffries, D S; Kahl, J S; Nelson, S J; Peckenham, J M

    2005-10-01

    The New England Governors and Eastern Canadian Premiers (NEG/ECP) adopted the Acid Rain Action Plan in June 1998, and issued a series of action items to support its work toward a reduction of sulfur dioxide (SO(2)) and nitrogen oxide (NO(x)) emissions in northeastern North America. One of these action items was the preparation of an updated critical load map using data from lakes in the NEG/ECP area. Critical load maps provide a more complete index of the surface water sensitivity to acidification. Combined sulfur and nitrogen critical loads and deposition exceedances were computed using Henriksen's Steady-State Water Chemistry (SSWC) model. Results show that 28% of all 2053 lakes studied have a critical load of 20 kg/ha/year or less, making them vulnerable to acid deposition. Emission reductions, and more specifically SO(2) emission reductions have proven beneficial because critical loads were exceeded in 2002 for 12.3% of all studied lakes. Those lakes are located in the more sensitive areas where geology is carbonate-poor. Of these lakes, 2.9% will never recover even with a complete removal of SO(4) deposition. Recovery from acidification for the remaining 9.4% of the lakes will require additional emission SO(2) reductions.

  17. Optimization of the production of solid Witepsol nanoparticles loaded with rosmarinic acid.

    PubMed

    Campos, Débora A; Madureira, Ana Raquel; Gomes, Ana Maria; Sarmento, Bruno; Pintado, Maria Manuela

    2014-03-01

    During the last decade there has been a growing interest in the formulation of new food and nutraceutical products containing compounds with antioxidant activity. Unfortunately, due to their structure, certain compounds such as polyphenols, in particular rosmarinic acid (RA) are not stable and may interact easily with matrices in which they are incorporated. To overcome such limitations, the formulation of loaded polyphenols nanoparticles can offer an efficient solution to protect such compounds. Based on this rationale, the aim of this study was to prepare solid lipid nanoparticles (SLNs) loaded with RA using a hot melt ultrasonication method, where Witepsol H15 was used as lipid and Polysorbate 80 (Tween 80) as surfactant, following a 3(2) fractional factorial design, resulting in the use of 3 different percentages of surfactant (viz. 1, 2 and 3%, v/v) and lipid (0.5, 1.0 and 1.5%, w/v). The stability of the nanoparticles systems were tested during 28 d in aqueous solution stored at refrigeration temperature (ca. 5 °C), tracking the mean particle size of different formulations by photon correlation spectroscopy. To confirm RA entrapment, thermal analyses of the nanoparticles by DSC and FTIR were performed. The association efficiencies percentages (AE%) were determined using HPLC to quantitatively assess the RA in supernatants. Results showed that Witepsol H15 produced nanoparticles with initial mean diameters between 270 and 1000 nm, yet over time, a slight increase occurred, but without occurrence of aggregation. The AE% showed a high percentage of encapsulation (ca. 99%), which reveals low polyphenol releases from SLNs throughout storage time. In general, results showed a successful production of SLNs with properties that can be used to food applications. PMID:24413308

  18. Acid-activated biochar increased sulfamethazine retention in soils.

    PubMed

    Vithanage, Meththika; Rajapaksha, Anushka Upamali; Zhang, Ming; Thiele-Bruhn, Sören; Lee, Sang Soo; Ok, Yong Sik

    2015-02-01

    Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils.

  19. Increased mutagenicity of chromium compounds by nitrilotriacetic acid

    SciTech Connect

    Loprieno, N.; Boncristiani, G.; Venier, P.; Montaldi, A.; Majone, F.; Bianchi, V.; Paglialunga, S.; Levis, A.G.

    1985-01-01

    Nitrilotriacetic acid trisodium salt (NTA), which is a substitute for polyphosphates in household laundry detergents, and N-nitrosoiminodiacetic acid (NIDA), a derivative of NTA produced by metabolism of soil microorganisms, were tested for in vitro mutagenicity in bacteria and yeasts. No gene reversions in five strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, and TA100), no forward gene mutations in Schizosaccharomyces pombe P1, and no mitotic gene conversions at two loci in Saccharomyces cerevisiae D4 were induced by NTA and NIDA independently of the presence of rat liver metabolic activation. The influence of NTA on the mutagenic and clastogenic activity of several chromium compounds was examined in the Salmonella/microsome assay and in the sister chromatid exchange (SCE) assay in mammalian cell cultures (Chinese hamster ovary (CHO) line). NTA does not affect the genetic inactivity of water-soluble Cr(III) (Cr/sub 2/(SO/sub 4/)/sub 3/) and the direct mutagenicity of soluble Cr(VI) (Na/sub 2/CrO/sub 4/, K/sub 2/Cr/sub 2/O/sub 7/) compounds. The very insoluble Cr(VI) compounds PbCrO/sub 4/ and PbCrO/sub 4/ x PbO are instead clearly mutagenic in the Salmonella/microsome assay (TA100 strain) only in the presence of NTA or NaOH. The chromosome-damaging activity of PbCrO/sub 4/ is significantly increased by NTA but not by NaOH.

  20. Macroporous chitosan hydrogels: Effects of sulfur on the loading and release behaviour of amino acid-based compounds.

    PubMed

    Elviri, Lisa; Asadzadeh, Maliheh; Cucinelli, Roberta; Bianchera, Annalisa; Bettini, Ruggero

    2015-11-01

    Chitosan is a biodegradable, biocompatible polymer of natural origin widely applied to the preparation of functional hydrogels suitable for controlled release of drugs, peptides and proteins. Non-covalent interactions, expecially ionic interactions, are the main driver of the loading and release behaviour of amino acids or peptides from chitosan hydrogels. With the aim to improve the understanding of the mechanisms governing the behaviour of chitosan hydrogels on peptide uptake and delivery, in this paper the attention was focused on the role played by sulfur on the interactions of chitosan hydrogels with sulfur-containing amino acids (AA) and peptides. Hence, loading and release experiments on cysteine, cystine and glutathione (SH containing amino acid, dipeptide and tripeptide, respectively) as well as on glycine and valine as apolar amino acids were carried out. For these puroses, chitosan hydrogels were prepared in an easy and reproducible manner by a freeze-gelation process on a poly-L-lysine coated support. The hydrogel surface pore size, uniformity and distribution were tested. Optimal results (D50 = 26 ± 4 μm) were obtained by using the poly-L-lysine positively-charged surface. The loading results gathered evidenced that the sulfur-containing molecules presented an increased absorption both in terms of rate and extent by chitosan hydrogels with respect to nonpolar amino acids, mainly due to ionic and hydrogen bond interactions. ATR-FTIR analysis carried out on chitosan hydrogels, with and without the AA related compounds to study putative interactions, supported these apparent sulfur-dependent results. Finally, chitosan hydrogels displayed excellent retention capabilities (AA release <5%) for all AA, strongly supporting the use of chitosan hydrogels as matrix for controlled drug release.

  1. Topiramate increases the risk of valproic acid-induced encephalopathy.

    PubMed

    Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

    2013-01-01

    Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment.

  2. Development of the Zebra load region for increased capability plasma diagnostics and improved Leopard laser access

    NASA Astrophysics Data System (ADS)

    Astanovitskiy, Alexey; Presura, R.; Ivanov, V. V.; Haboub, A.; Plachaty, C.; Kindel, J. M.

    2008-11-01

    A new geometry for the load area in the Zebra (1MA pulse generator) is developed. It will form the basis for future experiments requiring Leopard (1057nm, 50TW laser) to Zebra coupling and give extended capability to z-pinch diagnostics. This required the development of a new current return, which allows laser access and installation of the OD 4'' parabolic mirror for the x-ray radiography, isochoric heating and magnetized plasma experiments, and accommodates wire-array z-pinch loads, to which the laser may then be coupled. In addition, this configuration allows diagnostics access close to the plasma, leading to a significant increase of the spatial resolution for imaging of z-pinches, as well as the photon flux in imaging and spectroscopy of laser produced plasmas. These diagnostics will allow coupling of the Leopard beam for x-ray laser probing of the pinch plasma and we will test point-projection x-ray backlighting of the pinch plasma.

  3. Uric acid excretion predicts increased aggression in urban adolescents.

    PubMed

    Mrug, Sylvie; Mrug, Michal

    2016-09-01

    Elevated levels of uric acid have been linked with impulsive and disinhibited behavior in clinical and community populations of adults, but no studies have examined uric acid in relation to adolescent aggression. This study examined the prospective role of uric acid in aggressive behavior among urban, low income adolescents, and whether this relationship varies by gender. A total of 84 adolescents (M age 13.36years; 50% male; 95% African American) self-reported on their physical aggression at baseline and 1.5years later. At baseline, the youth also completed a 12-h (overnight) urine collection at home which was used to measure uric acid excretion. After adjusting for baseline aggression and age, greater uric acid excretion predicted more frequent aggressive behavior at follow up, with no significant gender differences. The results suggest that lowering uric acid levels may help reduce youth aggression. PMID:27180134

  4. Sucrose Loading in Isolated Veins of Pisum sativum: Regulation by Abscisic Acid, Gibberellic Acid, and Cell Turgor.

    PubMed

    Estruch, J J; Peretó, J G; Vercher, Y; Beltrán, J P

    1989-09-01

    Enzymatically isolated vein networks from mature pea (Pisum sativum L. cv Alaska) leaves were employed to investigate the properties of sucrose loading and the effect of phytohormones and cell turgor on this process. The sucrose uptake showed two components: a saturable and a first-order kinetics system. The high affinity system (K(m), 3.3 millimolar) was located at the plasmalemma (p-chloromercuriphenylsulfonic acid and orthovanadate sensitivity). Further characterization of this system, including pH dependence and effects of energy metabolism inhibitors, supported the H(+)-sugar symport concept for sucrose loading. Within a physiological range (0.1-100 micromolar) and after 90 min, abscisic acid (ABA) inhibited and gibberellic acid (GA(3)) promoted 1 millimolar sucrose uptake. These responses were partially (ABA) or totally (GA(3)) turgor-dependent. In experiments of combined hormonal treatments, ABA counteracted the GA(3) positive effects on sucrose uptake. The abolishment of these responses by p-chloromercuriphenylsulfonic acid and experiments on proton flux suggest that both factors (cell turgor and hormones) are modulating the H(+) ATPase plasmalemma activity. The results are discussed in terms of their physiological relevance. PMID:16667007

  5. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian; Kleff, Susanne; Guettler, Michael V

    2013-04-30

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  6. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian; Kleff, Susanne; Guettler, Michael V.

    2012-02-21

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  7. Development of lovastatin-loaded poly(lactic acid) microspheres for sustained oral delivery: in vitro and ex vivo evaluation

    PubMed Central

    Guan, Qigang; Chen, Wei; Hu, Xianming

    2015-01-01

    Background A novel lovastatin (LVT)-loaded poly(lactic acid) microsphere suitable for oral administration was developed in this study, and in vitro and in vivo characteristics were evaluated. Methods The designed microspheres were obtained by an improved emulsion-solvent evaporation method. The morphological examination, particle size, encapsulation ratio, drug loading, and in vitro release were characterized. Pharmacokinetics studies were used to show that microspheres possess more advantages than the conventional formulations. Results By using the emulsion-solvent evaporation method, it was simple to prepare microspheres and easy to scale up production. The morphology of formed microspheres showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the microspheres was 2.65±0.69 μm; the encapsulation efficiency was 92.5%±3.6%, and drug loading was 16.7%±2.1%. In vitro release indicated that the LVT microspheres had a well-sustained release efficacy, and ex vivo studies showed that after LVT was loaded to microspheres, the area under the plasma concentration-time curve from zero to the last measurable plasma concentration point and the extrapolation to time infinity increased significantly, which represented 2.63-fold and 2.49-fold increases, respectively, compared to suspensions. The rate of ex vivo clearance was significantly reduced. Conclusion This research proved that poly(lactic acid) microspheres can significantly prolong the drug circulation time in vivo and can also significantly increase the relative bioavailability of the drug. PMID:25709403

  8. Increased load computerized dynamic posturography in prefrail and nonfrail community-dwelling older adults.

    PubMed

    Biggan, John R; Melton, Forest; Horvat, Michael A; Ricard, Mark; Keller, David; Ray, Christopher T

    2014-01-01

    The understanding of prefrail and nonfrail older adults' postural control with and without increased environmental and cognitive stress is imperative to the development of targeted interventions to decrease fall risk within these populations. Thirty-eight individuals participated in this study. Postural control testing included the Sensory Organization Test (SOT) on a NeuroCom EquiTest. Cognitive and environmental load testing was performed during Condition 6 of the SOT. Though there were no group differences on composite equilibrium score (p = .06), the cognitive task (Stroop task) impaired equilibrium scores more than the auditory or visual distracter tasks (p < .05 and p < .01) for both groups. These results suggest that both prefrail and nonfrail older adults' postural control is reduced in demanding environments. Given these findings, the need for multimodal exercise interventions to target both physical and cognitive factors is apparent. PMID:23416307

  9. How Sorbitan Monostearate Can Increase Drug-Loading Capacity of Lipid-Core Polymeric Nanocapsules.

    PubMed

    Poletto, Fernanda S; De Oliveira, Catiúscia P; Wender, Heberton; Regent, Dorothée; Donida, Bruna; Teixeira, Sérgio R; Guterres, Sílvia S; Rossi-Bergmann, Bartira; Pohlmann, Adriana R

    2015-01-01

    Lipid-core polymeric nanocapsules are innovative devices that present distinguished characteristics due to the presence of sorbitan monostearate into the oily-core. This component acted as low-molecular-mass organic gelator for the oil (medium chain triglycerides). The organogel-structured core influenced the polymeric wall characteristics disfavoring the formation of more stable polymer crystallites. This probably occurred due to interpenetration of these pseudo-phases. Sorbitan monostearate dispersed in the oily-core was also able to interact by non-covalent bonding with the drugs increasing the drug loading capacity more than 40 times compared to conventional nanocapsules. We demonstrated that the drug-models quercetin and quercetin pentaacetate stabilized the organogel network probably due to interactions of the drug molecules with the sorbitan monostearate headgroups by hydrogen bonding. PMID:26328447

  10. Effects of Increased Loading on In Vivo Tendon Properties: A Systematic Review

    PubMed Central

    WIESINGER, HANS-PETER; KÖSTERS, ALEXANDER; MÜLLER, ERICH; SEYNNES, OLIVIER R.

    2015-01-01

    ABSTRACT Introduction In vivo measurements have been used in the past two decades to investigate the effects of increased loading on tendon properties, yet the current understanding of tendon macroscopic changes to training is rather fragmented, limited to reports of tendon stiffening, supported by changes in material properties and/or tendon hypertrophy. The main aim of this review was to analyze the existing literature to gain further insights into tendon adaptations by extracting patterns of dose-response and time-course. Methods PubMed/Medline, SPORTDiscus, and Google Scholar databases were searched for studies examining the effect of training on material, mechanical, and morphological properties via longitudinal or cross-sectional designs. Results Thirty-five of 6440 peer-reviewed articles met the inclusion criteria. The key findings were i) the confirmation of a nearly systematic adaptation of tendon tissue to training, ii) the important variability in the observed changes in tendon properties between and within studies, and iii) the absence of a consistent incremental pattern regarding the dose-response or the time-course relation of tendon adaptation within the first months of training. However, long-term (years) training was associated with a larger tendon cross-sectional area, without any evidence of differences in material properties. Our analysis also highlighted several gaps in the existing literature, which may be addressed in future research. Conclusions In line with some cross-species observations about tendon design, tendon cross-sectional area allegedly constitutes the ultimate adjusting parameter to increased loading. We propose here a theoretical model placing tendon hypertrophy and adjustments in material properties as parts of the same adaptive continuum. PMID:25563908

  11. Fatty acid composition of an oral load affects chylomicron size in human subjects.

    PubMed

    Sakr, S W; Attia, N; Haourigui, M; Paul, J L; Soni, T; Vacher, D; Girard-Globa, A

    1997-01-01

    HDL-phospholipids are determinants in reverse cholesterol transport. They are mostly derived from triacylglycerol (TG)-rich lipoproteins. Chylomicron size is important, therefore, because it is related to the ratio surface phospholipids: core TG and, thus, determines the availability of postprandial phospholipids for transfer to HDL. Eleven healthy young women each ingested four different fat loads supplemented with retinyl palmitate and containing 60 g sunflower oil (SO), oleic-sunflower oil (OSO), mixed oil (MO; (g/kg) linoleic acid 480, oleic acid 380, linolenic acid 13) or beef tallow (BT). At the peak of TG absorption for all loads (4 h) chylomicron diameters, determined by agarose-gel filtration, were larger after SO compared with OSO (P < 0.05) and BT (P = 0.06) and after MO compared with BT (P < 0.05). At 6 h chylomicron size was larger after the vegetable oils compared with BT (P < 0.05 in each case). After each fat load chylomicron size decreased at 6 and 8 h compared with that at 4 h (P < 0.05) except for OSO. Retinyl ester and TG concentrations were lower in chylomicrons after BT than after the other fats but not in the chylomicron-free serum (containing chylomicron remnants), suggesting absorption in the form of very small particles. Compared with the fasting value, the concentration of the Svedberg unit of flotation 20-400 fraction, which contains VLDL and chylomicron remnants, was lower 8 h after MO, the only fat to contain significant amounts of linolenic acid. We conclude that chylomicron size is dependent on the fatty acid composition of ingested fats and the time-course of digestion, being larger for polyunsaturated fatty acid-rich fats and in the early phase of digestion. On the basis of retinyl ester concentration there were no differences between fats in chylomicron-remnant clearance.

  12. A novel nanofiber Cur-loaded polylactic acid constructed by electrospinning

    NASA Astrophysics Data System (ADS)

    Thu Trang Mai, Thi; Thu Thuy Nguyen, Thi; Duong Le, Quang; Ngoan Nguyen, Thi; Cham Ba, Thi; Binh Nguyen, Hai; Bich Hoa Phan, Thi; Tran, Dai Lam; Phuc Nguyen, Xuan; Park, Jun Seo

    2012-06-01

    Curcumin (Cur), extracted from the Curcuma longa L. plant, is well known for its anti-tumor, anti-oxidant, anti-inflammatory and anti-bacterial properties. Nanofiber mats of polylactic acid (PLA) loading Cur (5 wt%) were fabricated by electrospinning (e-spinning). Morphology and structure of the fibers were characterized by field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared (FTIR) spectroscopy, respectively. The diameters of the obtained fibers varied from 200 to 300 nm. The release capacity of curcumin from curcumin-loaded PLA fibers was investigated in phosphate buffer saline (PBS) containing ethanol. After 24 h, 50% of the curcumin was released from curcumin-loaded PLA fibers. These results of electrospun (e-spun) fibers exhibit the potential for biomedical application.

  13. Thiol peroxidase deficiency leads to increased mutational load and decreased fitness in Saccharomyces cerevisiae.

    PubMed

    Kaya, Alaattin; Lobanov, Alexei V; Gerashchenko, Maxim V; Koren, Amnon; Fomenko, Dmitri E; Koc, Ahmet; Gladyshev, Vadim N

    2014-11-01

    Thiol peroxidases are critical enzymes in the redox control of cellular processes that function by reducing low levels of hydroperoxides and regulating redox signaling. These proteins were also shown to regulate genome stability, but how their dysfunction affects the actual mutations in the genome is not known. Saccharomyces cerevisiae has eight thiol peroxidases of glutathione peroxidase and peroxiredoxin families, and the mutant lacking all these genes (∆8) is viable. In this study, we employed two independent ∆8 isolates to analyze the genome-wide mutation spectrum that results from deficiency in these enzymes. Deletion of these genes was accompanied by a dramatic increase in point mutations, many of which clustered in close proximity and scattered throughout the genome, suggesting strong mutational bias. We further subjected multiple lines of wild-type and ∆8 cells to long-term mutation accumulation, followed by genome sequencing and phenotypic characterization. ∆8 lines showed a significant increase in nonrecurrent point mutations and indels. The original ∆8 cells exhibited reduced growth rate and decreased life span, which were further reduced in all ∆8 mutation accumulation lines. Although the mutation spectrum of the two independent isolates was different, similar patterns of gene expression were observed, suggesting the direct contribution of thiol peroxidases to the observed phenotypes. Expression of a single thiol peroxidase could partially restore the growth phenotype of ∆8 cells. This study shows how deficiency in nonessential, yet critical and conserved oxidoreductase function, leads to increased mutational load and decreased fitness.

  14. Thiol Peroxidase Deficiency Leads to Increased Mutational Load and Decreased Fitness in Saccharomyces cerevisiae

    PubMed Central

    Kaya, Alaattin; Lobanov, Alexei V.; Gerashchenko, Maxim V.; Koren, Amnon; Fomenko, Dmitri E.; Koc, Ahmet; Gladyshev, Vadim N.

    2014-01-01

    Thiol peroxidases are critical enzymes in the redox control of cellular processes that function by reducing low levels of hydroperoxides and regulating redox signaling. These proteins were also shown to regulate genome stability, but how their dysfunction affects the actual mutations in the genome is not known. Saccharomyces cerevisiae has eight thiol peroxidases of glutathione peroxidase and peroxiredoxin families, and the mutant lacking all these genes (∆8) is viable. In this study, we employed two independent ∆8 isolates to analyze the genome-wide mutation spectrum that results from deficiency in these enzymes. Deletion of these genes was accompanied by a dramatic increase in point mutations, many of which clustered in close proximity and scattered throughout the genome, suggesting strong mutational bias. We further subjected multiple lines of wild-type and ∆8 cells to long-term mutation accumulation, followed by genome sequencing and phenotypic characterization. ∆8 lines showed a significant increase in nonrecurrent point mutations and indels. The original ∆8 cells exhibited reduced growth rate and decreased life span, which were further reduced in all ∆8 mutation accumulation lines. Although the mutation spectrum of the two independent isolates was different, similar patterns of gene expression were observed, suggesting the direct contribution of thiol peroxidases to the observed phenotypes. Expression of a single thiol peroxidase could partially restore the growth phenotype of ∆8 cells. This study shows how deficiency in nonessential, yet critical and conserved oxidoreductase function, leads to increased mutational load and decreased fitness. PMID:25173844

  15. Benefits of omega-3 fatty acid against bone changes in salt-loaded rats: possible role of kidney.

    PubMed

    Ahmed, Mona A; Abd El Samad, Abeer A

    2013-10-01

    There is evidence that dietary fats are important components contributing in bone health and that bone mineral density is inversely related to sodium intake. Salt loading is also known to impose negative effects on renal function. The present study aimed to determine the effect of the polyunsaturated fatty acid omega-3 on bone changes imposed by salt loading, highlighting the role of kidney as a potential mechanism involved in this effect. Male Wistar rats were divided into three groups: control group, salt-loaded group consuming 2% NaCl solution as drinking water for 8 weeks, and omega-3-treated salt-loaded group receiving 1 g/kg/day omega-3 by gavage with consumption of 2% NaCl solution for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Plasma levels of sodium, potassium, calcium, inorganic phosphorus (Pi), alkaline phosphatase (ALP), creatinine, urea, 1,25-dihydroxyvitamin D [1,25(OH)2D3], and transforming growth factor-beta1 (TGF-β1) were measured. The right tibia and kidney were removed for histologic examination and renal immunohistochemical analysis for endothelial nitric oxide synthase (eNOS) was performed. The results revealed that omega-3 reduced SBP, DBP, and MAP and plasma levels of sodium, potassium, Pi, creatinine, urea, and TGF-β1, but increased plasma levels of calcium, ALP, and 1,25(OH)2D3 as well as renal eNOS. Omega-3 increased cortical and trabecular bone thickness, decreased osteoclast number, and increased newly formed osteoid bone. Renal morphology was found preserved. In conclusion, omega-3 prevents the disturbed bone status imposed by salt loading. This osteoprotective effect is possibly mediated by attenuation of alterations in Ca(2+), Pi, and ALP, and improvement of renal function and arterial blood pressure. PMID:24303178

  16. Benefits of omega-3 fatty acid against bone changes in salt-loaded rats: possible role of kidney.

    PubMed

    Ahmed, Mona A; Abd El Samad, Abeer A

    2013-10-01

    There is evidence that dietary fats are important components contributing in bone health and that bone mineral density is inversely related to sodium intake. Salt loading is also known to impose negative effects on renal function. The present study aimed to determine the effect of the polyunsaturated fatty acid omega-3 on bone changes imposed by salt loading, highlighting the role of kidney as a potential mechanism involved in this effect. Male Wistar rats were divided into three groups: control group, salt-loaded group consuming 2% NaCl solution as drinking water for 8 weeks, and omega-3-treated salt-loaded group receiving 1 g/kg/day omega-3 by gavage with consumption of 2% NaCl solution for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Plasma levels of sodium, potassium, calcium, inorganic phosphorus (Pi), alkaline phosphatase (ALP), creatinine, urea, 1,25-dihydroxyvitamin D [1,25(OH)2D3], and transforming growth factor-beta1 (TGF-β1) were measured. The right tibia and kidney were removed for histologic examination and renal immunohistochemical analysis for endothelial nitric oxide synthase (eNOS) was performed. The results revealed that omega-3 reduced SBP, DBP, and MAP and plasma levels of sodium, potassium, Pi, creatinine, urea, and TGF-β1, but increased plasma levels of calcium, ALP, and 1,25(OH)2D3 as well as renal eNOS. Omega-3 increased cortical and trabecular bone thickness, decreased osteoclast number, and increased newly formed osteoid bone. Renal morphology was found preserved. In conclusion, omega-3 prevents the disturbed bone status imposed by salt loading. This osteoprotective effect is possibly mediated by attenuation of alterations in Ca(2+), Pi, and ALP, and improvement of renal function and arterial blood pressure.

  17. Benefits of omega-3 fatty acid against bone changes in salt-loaded rats: possible role of kidney

    PubMed Central

    Ahmed, Mona A; Abd EL Samad, Abeer A

    2013-01-01

    There is evidence that dietary fats are important components contributing in bone health and that bone mineral density is inversely related to sodium intake. Salt loading is also known to impose negative effects on renal function. The present study aimed to determine the effect of the polyunsaturated fatty acid omega-3 on bone changes imposed by salt loading, highlighting the role of kidney as a potential mechanism involved in this effect. Male Wistar rats were divided into three groups: control group, salt-loaded group consuming 2% NaCl solution as drinking water for 8 weeks, and omega-3-treated salt-loaded group receiving 1 g/kg/day omega-3 by gavage with consumption of 2% NaCl solution for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Plasma levels of sodium, potassium, calcium, inorganic phosphorus (Pi), alkaline phosphatase (ALP), creatinine, urea, 1,25-dihydroxyvitamin D [1,25(OH)2D3], and transforming growth factor-beta1 (TGF-β1) were measured. The right tibia and kidney were removed for histologic examination and renal immunohistochemical analysis for endothelial nitric oxide synthase (eNOS) was performed. The results revealed that omega-3 reduced SBP, DBP, and MAP and plasma levels of sodium, potassium, Pi, creatinine, urea, and TGF-β1, but increased plasma levels of calcium, ALP, and 1,25(OH)2D3 as well as renal eNOS. Omega-3 increased cortical and trabecular bone thickness, decreased osteoclast number, and increased newly formed osteoid bone. Renal morphology was found preserved. In conclusion, omega-3 prevents the disturbed bone status imposed by salt loading. This osteoprotective effect is possibly mediated by attenuation of alterations in Ca2+, Pi, and ALP, and improvement of renal function and arterial blood pressure. PMID:24303178

  18. [Degradation of Acid Orange 7 with Persulfate Activated by Silver Loaded Granular Activated Carbon].

    PubMed

    Wang, Zhong-ming; Huang, Tian-yin; Chen, Jia-bin; Li, Wen-wei; Zhang, Li-ming

    2015-11-01

    Granular activated carbon with silver loaded as activator (Ag/GAC) was prepared using impregnation method. N2 adsorption, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were adopted to characterize the Ag/GAC, showing that silver was successfully loaded on granular activated carbon. The oxidation degradation of acid orange 7 (AO7) by the Ag/GAC activated by persulfate (PS) was investigated at ambient temperature. The influences of factors such as Ag loading, PS or Ag/GAC dosages and initial pH on the degradation of AO7 were evaluated. The results demonstrated that the degradation rate of AO7 could reach more than 95.0% after 180 min when the Ag loading content, PS/AO7 molar ratio, the Ag/GAC dosage were 12.7 mg x g(-1), 120: 1, 1.0 g x L(-1), respectively. The initial pH had significant effect on the AO7 degradation, with pH 5.0 as the optimal pH for the degradation of AO7. The possible degradation pathway was proposed for the AO7 degradation by using UV-visible spectroscopy and gas chromatography-mass spectrometry (GG/MS). The azo bond and naphthalene ring in the AO7 were destroyed during the degradation, with phthalic acid and acetophenone as the main degradation products. PMID:26910999

  19. Laboratory evaluation and analysis of advanced lead-acid load-leveling batteries

    NASA Astrophysics Data System (ADS)

    Miller, J. F.; Mulcahey, T. P.; Christianson, C. C.; Marr, J. J.; Smaga, J. A.

    Argonne National Laboratory has conducted an extensive evaluation of advanced lead-acid batteries developed by the Exide Corporation for load-leveling applications. This paper presents the results of performance and accelerated life tests conducted on these batteries over a five-year period. This paper describes the operational reliability and maintenance requirements for this technology, and also includes analyses of the batteries' thermal characteristics, arsine/stibine emission rates, and cell degradation modes as determined from post-test examinations.

  20. A national discharge load of perfluoroalkyl acids derived from industrial wastewater treatment plants in Korea.

    PubMed

    Kim, Hee-Young; Seok, Hyun-Woo; Kwon, Hye-Ok; Choi, Sung-Deuk; Seok, Kwang-Seol; Oh, Jeong Eun

    2016-09-01

    Levels of 11 perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were measured in wastewater (influent and effluent) and sludge samples collected from 25 industrial wastewater treatment plants (I-WWTPs) in five industrial sectors (chemicals, electronics, metals, paper, and textiles) in South Korea. The highest ∑11PFAAs concentrations were detected in the influent and effluent from the paper (median: 411ng/L) and textile (median: 106ng/L) industries, and PFOA and PFOS were the predominant PFAAs (49-66%) in wastewater. Exceptionally high levels of PFAAs were detected in the sludge associated with the electronics (median: 91.0ng/g) and chemical (median: 81.5ng/g) industries with PFOS being the predominant PFAA. The discharge loads of 11 PFAAs from I-WWTP were calculated that total discharge loads for the five industries were 0.146ton/yr. The textile industry had the highest discharge load with 0.055ton/yr (PFOA: 0.039ton/yr, PFOS: 0.010ton/yr). Municipal wastewater contributed more to the overall discharge of PFAAs (0.489ton/yr) due to the very small industrial wastewater discharge compared to municipal wastewater discharge, but the contribution of PFAAs from I-WWTPs cannot be ignored.

  1. A national discharge load of perfluoroalkyl acids derived from industrial wastewater treatment plants in Korea.

    PubMed

    Kim, Hee-Young; Seok, Hyun-Woo; Kwon, Hye-Ok; Choi, Sung-Deuk; Seok, Kwang-Seol; Oh, Jeong Eun

    2016-09-01

    Levels of 11 perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were measured in wastewater (influent and effluent) and sludge samples collected from 25 industrial wastewater treatment plants (I-WWTPs) in five industrial sectors (chemicals, electronics, metals, paper, and textiles) in South Korea. The highest ∑11PFAAs concentrations were detected in the influent and effluent from the paper (median: 411ng/L) and textile (median: 106ng/L) industries, and PFOA and PFOS were the predominant PFAAs (49-66%) in wastewater. Exceptionally high levels of PFAAs were detected in the sludge associated with the electronics (median: 91.0ng/g) and chemical (median: 81.5ng/g) industries with PFOS being the predominant PFAA. The discharge loads of 11 PFAAs from I-WWTP were calculated that total discharge loads for the five industries were 0.146ton/yr. The textile industry had the highest discharge load with 0.055ton/yr (PFOA: 0.039ton/yr, PFOS: 0.010ton/yr). Municipal wastewater contributed more to the overall discharge of PFAAs (0.489ton/yr) due to the very small industrial wastewater discharge compared to municipal wastewater discharge, but the contribution of PFAAs from I-WWTPs cannot be ignored. PMID:27152994

  2. Generalized Joint Laxity Associated With Increased Medial Foot Loading in Female Athletes

    PubMed Central

    Barber Foss, Kim D; Ford, Kevin R; Myer, Gregory D; Hewett, Timothy E

    2009-01-01

    Context: The relationship between generalized joint laxity and plantar pressure distribution of the foot and the potential implications for lower extremity injury have not been studied. Objective: To determine the relationship between generalized joint laxity and dynamic plantar pressure distribution. We hypothesized that individuals with greater generalized joint laxity, or hypermobility, would have greater dynamic medial midfoot pressure and loading during walking than nonhypermobile individuals. Design: Case control. Setting: Institutional biomechanics laboratory. Patients or Other Participants: Participants included 112 female soccer players between 11 and 21 years of age. Main Outcome Measure(s): Each participant was tested for generalized joint laxity using the Beighton and Horan Joint Mobility Index (BHJMI; range, 0–9) and was categorized as having either high (BHJMI score ≥4) or low (BHJMI score <4) generalized joint laxity. Peak pressure and maximum force were calculated from a dynamic, barefoot plantar pressure distribution system. Results: Peak pressure and maximum force were greater in the 27 participants categorized as having high generalized joint laxity than in the 85 participants categorized as having low generalized joint laxity. The midfoot region exhibited greater loading in participants with high generalized joint laxity than in the other participants. We found an effect of BHJMI classification in the medial midfoot; peak pressure in the dominant (F1,109  =  11.262, P  =  .001) and nondominant (F1,109  =  14.32, P < .001) sides and maximum force in the dominant (F1,109  =  7.88, P  =  .006) and nondominant (F1,109  =  9.18, P  =  .003) sides were greater in the high generalized joint laxity group than in the low generalized joint laxity group. Conclusions: Athletes classified as having high generalized joint laxity demonstrated increased midfoot loading. Delineation of risk factors for medial collapse of the foot

  3. An Increase Incidence in Uric Acid Nephrolithiasis: Changing Patterns

    PubMed Central

    Kumari, Asha; Mittal, Pawan; Kumar, Rajender; Goel, Richa; Bansal, Piyush; Kumar, Himanshu Devender; Bhutani, Jaikrit

    2016-01-01

    Introduction Nephrolithiasis is a complex disease affecting all age groups globally. As the causative factors for nephrolithiasis rises significantly, its incidence, prevalence and recurrence continues to baffle clinicians and patients. Aim To study the prevalence of different types of renal stones extracted by Percutaneous Nephrolithotomy (PCNL) and open surgical procedures. Materials and Methods Renal stones from 50 patients were retrieved by Percutaneous Nephrolithotomy (PCNL), Ureterorenoscopy (URS) and open surgical techniques for qualitative tests for detection of calcium, oxalate, uric acid, phosphate, ammonium ion, carbonate, cystine and xanthine. Results Three patients had stone removed by open surgery and rest had undergone PCNL. Nine of the stones were pure of calcium oxalate, 9 were of pure uric acid and 32 were mixed stones. Forty one stones had calcium. Among the mixed stones, oxalate was present in 25 samples (39 of total), uric acid was seen in 17 (25 of total stones), phosphate was present in 23 (23 of total) and carbonate was present in 4 stones (4 of total). Only 1 patient had triple phosphate stone. 12 were of staghorn appearance of which 6 were of struvite type, 6 were pure uric acid and remaining were mixed oxalate-phosphate stones. Conclusion Our study, though in a small number of hospital based patients, found much higher prevalence of uric acid stones and mixed stones than reported by previous hospital based studies in north India (oxalate stones~90%, uric acid~1% and mixed stones~3%). Biochemical analysis of renal stones is warranted in all cases. PMID:27630833

  4. An Increase Incidence in Uric Acid Nephrolithiasis: Changing Patterns

    PubMed Central

    Kumari, Asha; Mittal, Pawan; Kumar, Rajender; Goel, Richa; Bansal, Piyush; Kumar, Himanshu Devender; Bhutani, Jaikrit

    2016-01-01

    Introduction Nephrolithiasis is a complex disease affecting all age groups globally. As the causative factors for nephrolithiasis rises significantly, its incidence, prevalence and recurrence continues to baffle clinicians and patients. Aim To study the prevalence of different types of renal stones extracted by Percutaneous Nephrolithotomy (PCNL) and open surgical procedures. Materials and Methods Renal stones from 50 patients were retrieved by Percutaneous Nephrolithotomy (PCNL), Ureterorenoscopy (URS) and open surgical techniques for qualitative tests for detection of calcium, oxalate, uric acid, phosphate, ammonium ion, carbonate, cystine and xanthine. Results Three patients had stone removed by open surgery and rest had undergone PCNL. Nine of the stones were pure of calcium oxalate, 9 were of pure uric acid and 32 were mixed stones. Forty one stones had calcium. Among the mixed stones, oxalate was present in 25 samples (39 of total), uric acid was seen in 17 (25 of total stones), phosphate was present in 23 (23 of total) and carbonate was present in 4 stones (4 of total). Only 1 patient had triple phosphate stone. 12 were of staghorn appearance of which 6 were of struvite type, 6 were pure uric acid and remaining were mixed oxalate-phosphate stones. Conclusion Our study, though in a small number of hospital based patients, found much higher prevalence of uric acid stones and mixed stones than reported by previous hospital based studies in north India (oxalate stones~90%, uric acid~1% and mixed stones~3%). Biochemical analysis of renal stones is warranted in all cases.

  5. Cytotoxicity of food preservatives in cultured rat hepatocytes loaded with linolenic acid.

    PubMed

    Sugihara, N; Shimomichi, K; Furuno, K

    1997-06-01

    We investigated the ability of eight food preservatives to induce lipid peroxidation in normal and alpha-linolenic acid (LNA)-loaded cultured rat hepatocytes. On the addition of sodium dehydroacetate (DHA-Na), potassium sorbate (SA-K) or thiabendazole (TBZ) to the cell culture, lipid peroxidation, assessed in terms of the production of malondialdehyde (MDA), was induced in LNA-loaded cells, but not in normal cells. At the low concentrations, induction of lipid peroxidation in LNA-loaded cells was highest with TBZ, whereas at high concentrations DHA-Na greatly induced lipid peroxidation. The occurrence of lipid peroxidation in LNA-loaded cells was accompanied by a decrease in cellular GSH levels with the three preservatives and by a decrease in cellular protein-SH levels with DHA-Na and TBZ. Furthermore, cell injury, measured by the release of LDH, was produced in LNA-loaded cells exposed to DHA-Na and SA-K. The addition of TBZ caused substantial cell injury in normal cells, and even greater injury in LNA-loaded cells. The prevention of lipid peroxidation in LNA-loaded hepatocytes by addition of an antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD) almost completely prevented DHA-Na- and SA-K-induced cell injury, and reduced TBZ-induced cell injury. The addition of diphenyl (DP), o-phenylphenol (OPP) or butyl p-hydroxybenzoate (BHB) caused severe cell injury, in association with a marked decrease in cellular levels of both of GSH and protein-SH in both groups of cells. However, lipid peroxidation was not detectable in either group of cells exposed to these preservatives. Sodium propionate (PA-Na) and sodium benzoate (BA-Na) had little effect on any cytotoxic parameter in either group of cells.

  6. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming Western-type diets: a systematic review

    PubMed Central

    2011-01-01

    Background Linoleic acid, with a DRI of 12-17 g/d, is the most highly consumed polyunsaturated fatty acid in the Western diet and is found in virtually all commonly consumed foods. The concern with dietary linoleic acid, being the metabolic precursor of arachidonic acid, is its consumption may enrich tissues with arachidonic acid and contribute to chronic and overproduction of bioactive eicosanoids. However, no systematic review of human trials regarding linoleic acid consumption and subsequent changes in tissue levels of arachidonic acid has been undertaken. Objective In this study, we reviewed the human literature that reported changes in dietary linoleic acid and its subsequent impact on changing tissue arachidonic acid in erythrocytes and plasma/serum phospholipids. Design We identified, reviewed, and evaluated all peer-reviewed published literature presenting data outlining changes in dietary linoleic acid in adult human clinical trials that reported changes in phospholipid fatty acid composition (specifically arachidonic acid) in plasma/serum and erythrocytes within the parameters of our inclusion/exclusion criteria. Results Decreasing dietary linoleic acid by up to 90% was not significantly correlated with changes in arachidonic acid levels in the phospholipid pool of plasma/serum (p = 0.39). Similarly, when dietary linoleic acid levels were increased up to six fold, no significant correlations with arachidonic acid levels were observed (p = 0.72). However, there was a positive relationship between dietary gamma-linolenic acid and dietary arachidonic acid on changes in arachidonic levels in plasma/serum phospholipids. Conclusions Our results do not support the concept that modifying current intakes of dietary linoleic acid has an effect on changing levels of arachidonic acid in plasma/serum or erythrocytes in adults consuming Western-type diets. PMID:21663641

  7. Streamwater acid-base chemistry and critical loads of atmospheric sulfur deposition in Shenandoah National Park, Virginia.

    PubMed

    Sullivan, T J; Cosby, B J; Webb, J R; Dennis, R L; Bulger, A J; Deviney, F A

    2008-02-01

    A modeling study was conducted to evaluate the acid-base chemistry of streams within Shenandoah National Park, Virginia and to project future responses to sulfur (S) and nitrogen (N) atmospheric emissions controls. Many of the major stream systems in the park have acid neutralizing capacity (ANC) less than 20 microeq/L, levels at which chronic and/or episodic adverse impacts on native brook trout are possible. Model hindcasts suggested that none of these streams had ANC less than 50 microeq/L in 1900. Model projections, based on atmospheric emissions controls representative of laws already enacted as of 2003, suggested that the ANC of those streams simulated to have experienced the largest historical decreases in ANC will increase in the future. The levels of S deposition that were simulated to cause streamwater ANC to increase or decrease to three specified critical levels (0, 20, and 50 microeq/L) ranged from less than zero (ANC level not attainable) to several hundred kg/ha/year, depending on the selected site and its inherent acid-sensitivity, selected ANC endpoint criterion, and evaluation year for which the critical load was calculated. Several of the modeled streams situated on siliciclastic geology exhibited critical loads <0 kg/ha/year to achieve ANC >50 microeq/L in the year 2040, probably due at least in part to base cation losses from watershed soil. The median modeled siliciclastic stream had a calculated critical load to achieve ANC >50 microeq/L in 2100 that was about 3 kg/ha/year, or 77% lower than deposition in 1990, representing the time of model calibration.

  8. Streamwater acid-base chemistry and critical loads of atmospheric sulfur deposition in Shenandoah National Park, Virginia.

    PubMed

    Sullivan, T J; Cosby, B J; Webb, J R; Dennis, R L; Bulger, A J; Deviney, F A

    2008-02-01

    A modeling study was conducted to evaluate the acid-base chemistry of streams within Shenandoah National Park, Virginia and to project future responses to sulfur (S) and nitrogen (N) atmospheric emissions controls. Many of the major stream systems in the park have acid neutralizing capacity (ANC) less than 20 microeq/L, levels at which chronic and/or episodic adverse impacts on native brook trout are possible. Model hindcasts suggested that none of these streams had ANC less than 50 microeq/L in 1900. Model projections, based on atmospheric emissions controls representative of laws already enacted as of 2003, suggested that the ANC of those streams simulated to have experienced the largest historical decreases in ANC will increase in the future. The levels of S deposition that were simulated to cause streamwater ANC to increase or decrease to three specified critical levels (0, 20, and 50 microeq/L) ranged from less than zero (ANC level not attainable) to several hundred kg/ha/year, depending on the selected site and its inherent acid-sensitivity, selected ANC endpoint criterion, and evaluation year for which the critical load was calculated. Several of the modeled streams situated on siliciclastic geology exhibited critical loads <0 kg/ha/year to achieve ANC >50 microeq/L in the year 2040, probably due at least in part to base cation losses from watershed soil. The median modeled siliciclastic stream had a calculated critical load to achieve ANC >50 microeq/L in 2100 that was about 3 kg/ha/year, or 77% lower than deposition in 1990, representing the time of model calibration. PMID:17492359

  9. Cellular and molecular responses to increased skeletal muscle loading after irradiation

    NASA Technical Reports Server (NTRS)

    Adams, Gregory R.; Caiozzo, Vincent J.; Haddad, Fadia; Baldwin, Kenneth M.

    2002-01-01

    Irradiation of rat skeletal muscles before increased loading has been shown to prevent compensatory hypertrophy for periods of up to 4 wk, possibly by preventing satellite cells from proliferating and providing new myonuclei. Recent work suggested that stem cell populations exist that might allow irradiated muscles to eventually hypertrophy over time. We report that irradiation essentially prevented hypertrophy in rat muscles subjected to 3 mo of functional overload (OL-Ir). The time course and magnitude of changes in cellular and molecular markers of anabolic and myogenic responses were similar in the OL-Ir and the contralateral nonirradiated, overloaded (OL) muscles for the first 3-7 days. These markers then returned to control levels in OL-Ir muscles while remaining elevated in OL muscles. The number of myonuclei and amount of DNA were increased markedly in OL but not OL-Ir muscles. Thus it appears that stem cells were not added to the irradiated muscles in this time period. These data are consistent with the theory that the addition of new myonuclei may be required for compensatory hypertrophy in the rat.

  10. Increase in Levels of Stratospheric Chlorine and Fluorine Loading between 1985 and 1992

    NASA Technical Reports Server (NTRS)

    Gunson, M. R.; Abrams, M. C.; Lowes, L. L.; Mahieu, E.; Zander, R.; Rinsland, C. P.; Ko, M. K. W.; Sze, N. D.; Weisenstein, D. K.

    1994-01-01

    Mixing ratios of 3.44 ppbv (parts per billion by volume) and 1.23 ppbv for HCl and HF above 50 km, surrogates for total chlorine and fluorine, have been measured by the Atmospheric Trace Molecule Spectroscopy (ATMOS) experiment on a March 1992 flight of the Space Shuttle. Compared to the measured values obtained on a 1985 flight, these correspond to a 37% and 62% increase for HCl and HF, respectively. The derived trend in HCl (approx. 0.13 ppbv per year) is in good agreement with the model-predicted increase in chlorine loading of 0.13 ppbv per year, and with the measured trends in HCl total column abundance from reported ground-based observations. The main source of this change can be attributed to the release of man-made chlorofluorocarbons (CFC's) and hydro-chloro-fluoro-carbons (HCFC's). This new value for HCl represents an upper limit to the inorganic chlorine concentration in the stratosphere available for participation in photochemical processes which destroy ozone.

  11. Enhancement of skin wound healing with decellularized scaffolds loaded with hyaluronic acid and epidermal growth factor.

    PubMed

    Su, Zhongchun; Ma, Huan; Wu, Zhengzheng; Zeng, Huilan; Li, Zhizhong; Wang, Yuechun; Liu, Gexiu; Xu, Bin; Lin, Yongliang; Zhang, Peng; Wei, Xing

    2014-11-01

    Current therapy for skin wound healing still relies on skin transplantation. Many studies were done to try to find out ways to replace skin transplantation, but there is still no effective alternative therapy. In this study, decellularized scaffolds were prepared from pig peritoneum by a series of physical and chemical treatments, and scaffolds loaded with hyaluronic acid (HA) and epidermal growth factor (EGF) were tested for their effect on wound healing. MTT assay showed that EGF increased NIH3T3 cell viability and confirmed that EGF used in this study was biologically active in vitro. Scanning electron microscope (SEM) showed that HA stably attached to scaffolds even after soaking in PBS for 48 h. ELISA assay showed that HA increased the adsorption of EGF to scaffolds and sustained the release of EGF from scaffolds. Animal study showed that the wounds covered with scaffolds containing HA and EGF recovered best among all 4 groups and had wound healing rates of 49.86%, 70.94% and 87.41% respectively for days 10, 15 and 20 post-surgery compared to scaffolds alone with wound healing rates of 29.26%, 42.80% and 70.14%. In addition, the wounds covered with scaffolds containing EGF alone were smaller than no EGF scaffolds on days 10, 15 and 20 post-surgery. Hematoxylin-Eosin (HE) staining confirmed these results by showing that on days 10, 15 and 20 post-surgery, the thicker epidermis and dermis layers were observed in the wounds covered with scaffolds containing HA and EGF than scaffolds alone. In addition, the thicker epidermis and dermis layers were also observed in the wounds covered with scaffolds containing EGF than scaffolds alone. Skin appendages were observed on day 20 only in the wound covered with scaffolds containing HA and EGF. These results demonstrate that the scaffolds containing HA and EGF can enhance wound healing.

  12. An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.

    PubMed

    Baier, L J; Sacchettini, J C; Knowler, W C; Eads, J; Paolisso, G; Tataranni, P A; Mochizuki, H; Bennett, P H; Bogardus, C; Prochazka, M

    1995-03-01

    The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine-containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action. PMID:7883976

  13. Ostα depletion protects liver from oral bile acid load

    PubMed Central

    Velazquez, Heino; Mennone, Albert; Ballatori, Nazzareno; Boyer, James L.

    2011-01-01

    Bile acid homeostasis is tightly maintained through interactions between the liver, intestine, and kidney. During cholestasis, the liver is incapable of properly clearing bile acids from the circulation, and alternative excretory pathways are utilized. In obstructive cholestasis, urinary elimination is often increased, and this pathway is further enhanced after bile duct ligation in mice that are genetically deficient in the heteromeric, basolateral organic solute transporter alpha-beta (Ostα-Ostβ). In this study, we examined renal and intestinal function in Ostα-deficient and wild-type mice in a model of bile acid overload. After 1% cholic acid feeding, Ostα-deficient mice had significantly lower serum ALT levels compared with wild-type controls, indicating partial protection from liver injury. Urinary clearance of bile acids, but not clearance of [3H]inulin, was significantly higher in cholic acid-fed Ostα-deficient mice compared with wild-type mice but was not sufficient to account for the protection. Fecal excretion of bile acids over the 5 days of cholic acid feeding was responsible for almost all of the bile acid loss in Ostα-deficient mice, suggesting that intestinal losses of bile acids accounted for the protection from liver injury. Thus fecal loss of bile acids after bile acid overload reduced the need for the kidney to filter and excrete the excess bile acids. In conclusion, Ostα-deficient mice efficiently eliminate excess bile acids via the feces. Inhibition of intestinal bile acid absorption might be an effective therapeutic target in early stages of cholestasis when bile acids are still excreted into bile. PMID:21719738

  14. Hyaluronic acid/poly(lactic-co-glycolic acid) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate as skin tissue engineering scaffolds.

    PubMed

    Lee, Eun Ji; Lee, Jong Ho; Jin, Linhua; Jin, Oh Seong; Shin, Yong Cheol; Sang, Jin Oh; Lee, Jaebeom; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-11-01

    In this study, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) for application to tissue engineering scaffolds for skin regeneration were prepared via coaxial electrospinning. Physicochemical properties of HA/PLGA-E core/shell fiber meshes were characterized by SEM, Raman spectroscopy, contact angle, EGCG release profiling and in vitro degradation. Biomechanical properties of HA/PLGA-E meshes were also investigated by a tensile strength test. SEM images showed that HA/PLGA-E fiber meshes had a three-dimensional interconnected pore structure with an average fiber diameter of about 1270 nm. Raman spectra revealed that EGCG was uniformly dispersed in the PLGA shell of meshes. HA/PLGA-E meshes showed sustained EGCG release patterns by controlled diffusion and PLGA degradation over 4 weeks. EGCG loading did not adversely affect the tensile strength and elastic modulus of HA/PLGA meshes, while increased their hydrophilicity and surface energy. Attachment of human dermal fibroblasts on HA/PLGA-E meshes was appreciably increased and their proliferation was steadily retained during the culture period. These results suggest that HA/PLGA-E core/shell fiber meshes can be potentially used as scaffolds supporting skin regeneration. PMID:25958546

  15. The response of epiphytic bacteria on Vallisneria natans (Lour.) Hara (Hydrocharitaceae) to increasing nutrient loadings.

    PubMed

    Cai, Xianlei; Yao, Ling; Gao, Guang; Xie, Yinfeng; Zhang, Yingying; Tang, Xiangming

    2016-06-01

    To investigate the effects of water column nutrient loading on epiphytic bacteria, we determined the abundance and community composition of epiphytic bacteria on the submerged macrophyte Vallisneria natans (Lour.) Hara during the growth season (June-October) under four different nutrient concentrations (nitrogen (N)-phosphorus (P) in mg L(-1) : 0.5-0.05, 1.0-0.1, 5.0-0.5, 10.0-1.0; hereafter NP-1, NP-2, NP-3, NP-4, respectively), using epifluorescence microscopy method and terminal restriction fragment length polymorphism (T-RFLP) analysis, respectively. Relative to low nutrient conditions (NP-1), there was no significant effect on the epiphytic bacterial community, and even a decrease in the number of epiphytic bacteria, which linked to the well growth status of host macrophytes at moderate nutrient conditions (NP-2). However, further nutrient enrichment induced significant increase in the abundance of epiphytic bacteria, and marked changes in the community structures of epiphytic bacteria. Furthermore, at high nutrient conditions, epiphytic bacterial communities varied widely temporally, and were not stable compared with those at the lower nutrient conditions. These results indicated that the effects of nutrient enrichment on epiphytic bacteria were nonlinear and dependent on the nutrient concentrations in the water. PMID:27143295

  16. An unexpected truth: increasing nitrate loading can decrease nitrate export from watersheds

    NASA Astrophysics Data System (ADS)

    Askarizadeh Bardsiri, A.; Grant, S. B.; Rippy, M.

    2015-12-01

    The discharge of anthropogenic nitrate (e.g., from partially treated sewage, return flows from agricultural irrigation, and runoff from animal feeding operations) to streams can negatively impact both human and ecosystem health. Managing these many point and non-point sources to achieve some specific end-point—for example, reducing the annual mass of nitrate exported from a watershed—can be a challenge, particularly in rapidly growing urban areas. Adding to this complexity is the fact that streams are not inert: they too can add or remove nitrate through assimilation (e.g., by stream-associated plants and animals) and microbially-mediated biogeochemical reactions that occur in streambed sediments (e.g., respiration, ammonification, nitrification, denitrification). By coupling a previously published correlation for in-stream processing of nitrate [Mulholland et al., Nature, 2008, 452, 202-205] with a stream network model of the Jacksons Creek watershed (Victoria, Australia) I demonstrate that managing anthropogenic sources of stream nitrate without consideration of in-stream processing can result in a number of non-intuitive "surprises"; for example, wastewater effluent discharges that increase nitrate loading but decrease in-stream nitrate concentrations can reduce the mass of nitrate exported from a watershed.

  17. Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming.

    PubMed

    Nüsken, Eva; Gellhaus, Alexandra; Kühnel, Elisabeth; Swoboda, Isabelle; Wohlfarth, Maria; Vohlen, Christina; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

    2016-07-01

    Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc.

  18. Hygienic quality of artificial greywater subjected to aerobic treatment: a comparison of three filter media at increasing organic loading rates

    PubMed Central

    Lalander, Cecilia; Dalahmeh, Sahar; Jönsson, Håkan; Vinnerås, Björn

    2013-01-01

    With a growing world population, the lack of reliable water sources is becoming an increasing problem. Reusing greywater could alleviate this problem. When reusing greywater for crop irrigation it is paramount to ensure the removal of pathogenic organisms. This study compared the pathogen removal efficiency of pine bark and activated charcoal filters with that of conventional sand filters at three organic loading rates. The removal efficiency of Escherichia coli O157:H7 decreased drastically when the organic loading rate increased fivefold in the charcoal and sand filters, but increased by 2 log10 in the bark filters. The reduction in the virus model organism coliphage ΦX174 remained unchanged with increasing organic loading in the charcoal and sand filters, but increased by 2 log10 in the bark filters. Thus, bark was demonstrated to be the most promising material for greywater treatment in terms of pathogen removal. PMID:24527627

  19. Hygienic quality of artificial greywater subjected to aerobic treatment: a comparison of three filter media at increasing organic loading rates.

    PubMed

    Lalander, Cecilia; Dalahmeh, Sahar; Jönsson, Håkan; Vinnerås, Björn

    2013-01-01

    With a growing world population, the lack of reliable water sources is becoming an increasing problem. Reusing greywater could alleviate this problem. When reusing greywater for crop irrigation it is paramount to ensure the removal of pathogenic organisms. This study compared the pathogen removal efficiency of pine bark and activated charcoal filters with that of conventional sand filters at three organic loading rates. The removal efficiency of Escherichia coli O157:H7 decreased drastically when the organic loading rate increased fivefold in the charcoal and sand filters, but increased by 2 log10 in the bark filters. The reduction in the virus model organism coliphage phiX174 remained unchanged with increasing organic loading in the charcoal and sand filters, but increased by 2 log10 in the bark filters. Thus, bark was demonstrated to be the most promising material for greywater treatment in terms of pathogen removal.

  20. Transcript and metabolite alterations increase ganoderic acid content in Ganoderma lucidum using acetic acid as an inducer.

    PubMed

    Ren, Ang; Li, Xiong-Biao; Miao, Zhi-Gang; Shi, Liang; Jaing, Ai-Liang; Zhao, Ming-Wen

    2014-12-01

    Acetic acid at 5-8 mM increased ganoderic acid (GA) accumulation in Ganoderma lucidum. After optimization by the response surface methodology, the GA content reached 5.5/100 mg dry weight, an increase of 105% compared with the control. The intermediate metabolites of GA biosynthesis, lanosterol and squalene also increased to 47 and 15.8 μg/g dry weight, respectively, in response to acetic acid. Acetic acid significantly induced transcription levels of sqs, lano, hmgs and cyp51 in the GA biosynthesis pathway. An acetic acid-unregulated acetyl coenzyme A synthase (acs) gene was selected from ten candidate homologous acs genes. The results indicate that acetic acid alters the expression of genes related to acetic acid assimilation and increases GA biosynthesis and the metabolic levels of lanosterol, squalene and GA-a, thereby resulting in GA accumulation.

  1. Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

    NASA Astrophysics Data System (ADS)

    Li, Fengxia; Li, Xiaoli; Li, Bin

    2011-11-01

    In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe 3O 4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.

  2. Docetaxel-loaded polyglutamic acid-PEG nanocapsules for the treatment of metastatic cancer.

    PubMed

    Borrajo, Erea; Abellan-Pose, Raquel; Soto, Atenea; Garcia-Fuentes, Marcos; Csaba, Noemi; Alonso, Maria J; Vidal, Anxo

    2016-09-28

    The design of nanomedicines with suitable physicochemical characteristics for the lymphatic targeting of drugs is critical in order to reach the lymph nodes, where metastatic cells often accumulate. Based on the known effect of particle size and surface hydrophilicity on the capacity of nanocarriers to reach the lymph nodes, here we report the formation and characterization of 100nm polyglutamic acid-polyethylene glycol (PGA-PEG) nanocapsules together with the assessment of their potential for the treatment of cancer with lymphatic metastatic spread. To this purpose, we first studied the biodistribution of fluorescently labeled PGA-PEG nanocapsules (100nm), following, either intravenous or subcutaneous administration. The results confirmed the accumulation of nanocapsules in the lymphatic system, especially upon subcutaneous administration. Next, we evaluated the efficacy and toxicity of the docetaxel-loaded nanocapsules in an orthotopic lung cancer model that metastasizes to the lymph nodes. As expected from the rational design, DCX-loaded PGA-PEG nanocapsules exhibited a greatly enhanced antitumoral efficacy and a reduced toxicity when compared with the commercial formulation Taxotere®. Furthermore, the administration of DCX-loaded PGA-PEG nanocapsules resulted in the practical elimination of the metastatic load in the mediastinal lymph nodes, whereas the treatment with the commercial formulation had a minor effect. Overall, these findings underscore the potential of PGA-PEG nanocapsules for the delivery of anticancer drugs to both, the tumor tissue and the metastatic lymph nodes. Therefore, they represent a promising therapy for the treatment of lung metastatic cancer.

  3. Assessment of thermal load on transported goats administered with ascorbic acid during the hot-dry conditions

    NASA Astrophysics Data System (ADS)

    Minka, N. S.; Ayo, J. O.

    2012-03-01

    The major factor in the induction of physiological stress during road transportation of livestock is the complex fluctuations of the thermal transport microenvironment, encountered when animals are transported across different ecological zones. Recommended guidelines on optimum "on-board" conditions in which goats should be transported are lacking, and there are no acceptable ranges and limits for the thermal loads to which goats may be subjected during long-distance road transportation in hot-dry conditions. Panting score (PS), rectal temperature (RT), heart rate (HR) and respiratory rate (RR) were employed as reliable stress indices to assess the effects of different thermal loads, measured as temperature humidity index (THI), encountered in the vehicle during 12 h of road transportation of 40 goats, and to suggest the administration of 100 mg/kg body weight of ascorbic acid (AA) as an ameliorating agent. The results obtained showed that the PS, RT, HR and RR rose above normal reference values with increase in the THI and journey duration. The rise in PS value, which is a visual indicator of the severity of thermal load, was the most pronounced. The results suggest that values of THI in the vehicle up to 94.6 constitute no risk, while at of 100 it presents a moderate risk and above 100 may result in severe stress. The relationships between the thermal load and the physiological variables were positive and significant ( P < 0.05). They reflect the degree of stress imposed by each THI value during the transportation, and may be used as recommended ranges and limit thermal load values in transported goats. The results demonstrated that administration of 100 mg/kg body weight of AA before road transportation mitigated the risk of adverse effects of high THI values and other stress factors due to road transportation in goats.

  4. Engineering Porous Organic Cage Crystals with Increased Acid Gas Resistance.

    PubMed

    Zhu, Guanghui; Hoffman, Christopher D; Liu, Yang; Bhattacharyya, Souryadeep; Tumuluri, Uma; Jue, Melinda L; Wu, Zili; Sholl, David S; Nair, Sankar; Jones, Christopher W; Lively, Ryan P

    2016-07-25

    Both known and new CC3-based porous organic cages are prepared and exposed to acidic SO2 in vapor and liquid conditions. Distinct differences in the stability of the CC3 cages exist depending on the chirality of the diamine linkers used. The acid catalyzed CC3 degradation mechanism is probed via in situ IR and a degradation pathway is proposed and supported with computational results. CC3 crystals synthesized with racemic mixtures of diaminocyclohexane exhibited enhanced stability compared to CC3-R and CC3-S. Confocal fluorescent microscope images reveal that the stability difference in CC3 species originates from an abundance of mesoporous grain boundaries in CC3-R and CC3-S, allowing facile access of aqueous SO2 throughout the crystal, promoting decomposition. These grain boundaries are absent from CC3 crystals made with racemic linkers. PMID:27253350

  5. NWTC Researchers Field-Test Advanced Control Turbine Systems to Increase Performance, Decrease Structural Loading of Wind Turbines and Plants

    SciTech Connect

    2015-08-01

    Researchers at the National Renewable Energy Laboratory's (NREL's) National Wind Technology Center (NWTC) are studying component controls, including new advanced actuators and sensors, for both conventional turbines as well as wind plants. This research will help develop innovative control strategies that reduce aerodynamic structural loads and improve performance. Structural loads can cause damage that increase maintenance costs and shorten the life of a turbine or wind plant.

  6. Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer.

    PubMed

    Jing, Lijia; Shao, Shangmin; Wang, Yang; Yang, Yongbo; Yue, Xiuli; Dai, Zhifei

    2016-01-01

    This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect.

  7. Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer

    PubMed Central

    Jing, Lijia; shao, shangmin; Wang, Yang; Yang, Yongbo; Yue, Xiuli; Dai, Zhifei

    2016-01-01

    This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect. PMID:26722372

  8. Electrospinning of curcumin loaded chitosan/poly (lactic acid) nanofilm and evaluation of its medicinal characteristics

    NASA Astrophysics Data System (ADS)

    Dhurai, Bhaarathi; Saraswathy, Nachimuthu; Maheswaran, Ramasamy; Sethupathi, Ponnusamy; Vanitha, Palanisamy; Vigneshwaran, Sukumar; Rameshbabu, Venugopal

    2013-12-01

    The curcumin loaded chitosan/poly (lactic acid) (PLA) nanofibers were produced using electrospinning. Box—Behnken experimental design was used for the optimization of variables (-1, 0, + 1 coded level) like chitosan/PLA strength (% w/v), curcumin strength (% w/v) and applied voltage (kV) to obtain uniform fiber diameter. The morphology of nanofibers was shown by SEM. Molecular interactions and the presence of each chemical compound of curcumin loaded chitosan/PLA fibers were characterized by FTIR and EDX analysis. Antioxidant, drug release and in vitro cytotoxicity tests were performed to evaluate the suitability of nanofibers that would be used for wound healing. In vivo wound healing studies on excision and incision wounds created on rat model showed significant reduction of wound area when compared to untreated. The better healing efficiency can be attributed to the presence of curcumin and chitosan.

  9. Preparation and investigation the release behaviour of wax microspheres loaded with salicylic acid.

    PubMed

    Gifani, Aida; Taghizadeh, Mojtaba; Seifkordi, Ali A; Ardjmand, Mehdi

    2009-09-01

    Salicylic acid-beeswax microspheres were prepared by melt dispersion technique. The effects of formulation parameters on the microscopic characteristic, drug loading and cumulative amount of released drug were investigated by experimental design. Results showed that all of the microparticles were spherical with porous surfaces. The average size of microspheres was 24-48 microm, the drug content was in the range of 22-45% and the encapsulation efficiency was 46-93%. Drug loading was influenced by emulsification speed as a main factor. All the microspheres had a burst release initially. The emulsifier concentration did not have a significant effect on drug release. The release behaviour of microspheres conformed best to Korsmeyer-Peppas semi-empirical model and the release of SA from beeswax microspheres was Fickian (n < 0.45).

  10. Bioaugmentation for treating transient 4-fluorocinnamic acid shock loads in a rotating biological contactor.

    PubMed

    Amorim, Catarina L; Duque, Anouk F; Afonso, Carlos M M; Castro, Paula M L

    2013-09-01

    A rotating biological contactor (RBC) was used to treat shock loadings of 4-fluorocinnamic acid (4-FCA). Intermittent 4-FCA shocks of 35 mg L(-1) were applied (ca. 3 months) with only limited mineralization occurring and accumulation of 4-fluorobenzoate (4-FBA) as an intermediate. After bioaugmentation with a degrading bacterium the RBC was able to deal with 4-FCA intermittent loading of 80 mg L(-1) however, a gradual decline in RBC performance occurred, leading to 4-FBA accumulation. The degrading strain was recovered from the biofilm during 2 months but intermittent feeding may have led to diminishing strain numbers. Distinct bacterial communities in the 1st and the 5th and 10th stages of the RBC were revealed by denaturating gradient gel electrophoresis. Several isolates retrieved from the RBC transformed 4-FCA into 4-FBA but only two strains mineralized the compound. Bioaugmentation allowed removal of the fluorinated compound however intermittent feeding may have compromised the bioreactor efficiency.

  11. Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

    NASA Astrophysics Data System (ADS)

    Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

    2016-08-01

    Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

  12. Pivot task increases knee frontal plane loading compared with sidestep and drop-jump

    PubMed Central

    CORTES, NELSON; ONATE, JAMES; LUNEN, BONNIE VAN

    2013-01-01

    The purpose of this study was to assess kinematic and kinetic differences between three tasks (drop-jump, sidestep cutting, and pivot tasks) commonly used to evaluate anterior cruciate ligament risk factors. Nineteen female collegiate soccer athletes from a Division I institution participated in this study. Participants performed a drop-jump task, and two unanticipated tasks, sidestep cutting and pivot. Repeated-measures analyses of variance were conducted to assess differences in the kinematic and kinetic parameters between tasks. The pivot task had lower knee flexion (−41.2 ± 8.8°) and a higher valgus angle (−7.6 ± 10.1°) than the sidestep (−53.9 ± 9.4° and −2.9 ± 10.0°, respectively) at maximum vertical ground reaction force. The pivot task (0.8 ± 0.3 multiples of body weight) had higher peak posterior ground reaction force than the drop-jump (0.3 ± 0.06 multiples of body weight) and sidestep cutting (0.3 ± 0.1 multiples of body weight), as well as higher internal varus moments (0.72 ± 0.3 N · m/kg · m) than the drop-jump (0.14 ± 0.07 N · m/kg · m) and sidestep (0.17 ± 0.5 N · m/kg · m) at peak stance. During the pivot task, the athletes presented a more erect posture and adopted strategies that may place higher loads on the knee joint and increase the strain on the anterior cruciate ligament. PMID:21086213

  13. Dynamics and control of phloem loading of indole-3-acetic acid in seedling cotyledons of Ricinus communis.

    PubMed

    Tamas, Imre A; Davies, Peter J

    2016-08-01

    During seed germination, sugars and auxin are produced from stored precursors or conjugates respectively, and transported to the seedling axis. To elucidate the mode of travel of indole-3-acetic acid (IAA) into the phloem, a solution of [(3)H]IAA, together with [(14)C]sucrose, was injected into the endosperm cavity harboring the cotyledons of germinating seedlings of Ricinus communis Phloem exudate from the cut hypocotyl was collected and the radioactivity recorded. Sucrose loading into the phloem was inhibited at higher IAA levels, and the rate of filling of the transient pool(s) was reduced by IAA. IAA was detected within 10min, with the concentration increasing over 30min and reaching a steady-state by 60min. The kinetics indicated that phloem loading of IAA involving both an active, carrier-based, and a passive, diffusion-based component, with IAA traveling along a pathway containing an intermediary pool, possibly the protoplasts of mesophyll cells. Phloem loading of IAA was altered by sucrose, K(+), and a range of non-specific and IAA-specific analogs and inhibitors in a manner that showed that IAA moves into the phloem from the extra cotyledonary solution by multiple pathways, with a carrier-mediated pathway playing a principal role.

  14. Dynamics and control of phloem loading of indole-3-acetic acid in seedling cotyledons of Ricinus communis.

    PubMed

    Tamas, Imre A; Davies, Peter J

    2016-08-01

    During seed germination, sugars and auxin are produced from stored precursors or conjugates respectively, and transported to the seedling axis. To elucidate the mode of travel of indole-3-acetic acid (IAA) into the phloem, a solution of [(3)H]IAA, together with [(14)C]sucrose, was injected into the endosperm cavity harboring the cotyledons of germinating seedlings of Ricinus communis Phloem exudate from the cut hypocotyl was collected and the radioactivity recorded. Sucrose loading into the phloem was inhibited at higher IAA levels, and the rate of filling of the transient pool(s) was reduced by IAA. IAA was detected within 10min, with the concentration increasing over 30min and reaching a steady-state by 60min. The kinetics indicated that phloem loading of IAA involving both an active, carrier-based, and a passive, diffusion-based component, with IAA traveling along a pathway containing an intermediary pool, possibly the protoplasts of mesophyll cells. Phloem loading of IAA was altered by sucrose, K(+), and a range of non-specific and IAA-specific analogs and inhibitors in a manner that showed that IAA moves into the phloem from the extra cotyledonary solution by multiple pathways, with a carrier-mediated pathway playing a principal role. PMID:27371947

  15. Stratification of Metal and Sulphate Loads in Acid Mine Drainage Receiving Water Dams - Variables Regionalization by Cluster Analysis.

    PubMed

    Grande, J A; de la Torre, M L; Valente, T; Fernández, J P; Borrego, J; Santisteban, M; Cerón, J C; Sánchez-Rodas, D

    2015-07-01

    The Sancho Reservoir (Iberian Pyrite Belt, SW Spain) is nourished by the waters of the river Meca, which is affected by acid mine drainage (AMD) processes from the abandoned Tharsis mine. The aim of the present work is to study the hydrochemical variations in this reservoir, in order to define potential stratification processes in metal load and sulphates. A stratified sampling from the surface, with one meter deep intervals to the bottom of the dam, was performed. The results show a clear stratification of temperature, pH, electric conductivity, dissolved oxygen, metal and sulphate loads associated with depth. There is an increase of metal loads at the bottom of the reservoir, though previous studies only detect iron. The proximity between pH and aluminium suggests that water chemistry is strongly influenced by aluminium precipitation processes. This indicates the buffer effect that aluminium exercises, which precipitates as amorphous or low crystalline phases, introducing hydrogen ions to the system, while alkalinity input tends to raise pH. PMID:26163498

  16. Dynamics and control of phloem loading of indole-3-acetic acid in seedling cotyledons of Ricinus communis

    PubMed Central

    Tamas, Imre A.; Davies, Peter J.

    2016-01-01

    During seed germination, sugars and auxin are produced from stored precursors or conjugates respectively, and transported to the seedling axis. To elucidate the mode of travel of indole-3-acetic acid (IAA) into the phloem, a solution of [3H]IAA, together with [14C]sucrose, was injected into the endosperm cavity harboring the cotyledons of germinating seedlings of Ricinus communis. Phloem exudate from the cut hypocotyl was collected and the radioactivity recorded. Sucrose loading into the phloem was inhibited at higher IAA levels, and the rate of filling of the transient pool(s) was reduced by IAA. IAA was detected within 10min, with the concentration increasing over 30min and reaching a steady-state by 60min. The kinetics indicated that phloem loading of IAA involving both an active, carrier-based, and a passive, diffusion-based component, with IAA traveling along a pathway containing an intermediary pool, possibly the protoplasts of mesophyll cells. Phloem loading of IAA was altered by sucrose, K+, and a range of non-specific and IAA-specific analogs and inhibitors in a manner that showed that IAA moves into the phloem from the extra cotyledonary solution by multiple pathways, with a carrier-mediated pathway playing a principal role. PMID:27371947

  17. Characterisation and evaluation of metal-loaded iminodiacetic acid-silica of different porosity for the selective enrichment of phosphopeptides.

    PubMed

    Trojer, L; Stecher, G; Feuerstein, I; Lubbad, S; Bonn, G K

    2005-06-24

    Silica particles of different porosity were functionalised with iminodiacetic acid (IDA) and loaded with Fe(III) to yield immobilised metal affinity chromatography stationary phases (Fe(III)-IDA-silica) for phosphopeptide enrichment. The elution step of bound phosphopeptides was optimised with a 32P radioactive labelled peptide by a comprehensive study. Several elution systems, including phosphate buffers of different pH and concentration and ethylenediaminetetraacetic acid solutions were employed. Furthermore the effect of support porosity on elution behaviour was investigated. Under best conditions recoveries higher than 90% were achieved. A solid-phase extraction (SPE) protocol was developed for fractionation of phosphorylated and non-phosphorylated peptides and desalting of the fractions which is essential for subsequent mass spectrometric analysis by the combination of Fe(III)-IDA-silica and C18-silica particles. The pH of the loading buffer was found to be a critical parameter for the efficiency of the SPE protocol. As tryptic digests of alpha-lactalbumin, lysozyme and ribonuclease A mixed with three synthetic phosphopeptides were fractionated, pH 2.5 provided minimal proportion of unspecific bound peptides when comparing the fractions after mu-LC-electrospray ionization MS separation. The effect of a sample derivatisation reaction (methylation) on the efficiency of phosphopeptide enrichment was further investigated. Blocking carboxylate groups by methyl ester formation totally prevented unspecific interaction with the immobilised Fe(III) ions, but generated partially methylated phosphopeptides that increased the complexity of the phosphorylated fraction. PMID:16038305

  18. Acetic acid enhances endurance capacity of exercise-trained mice by increasing skeletal muscle oxidative properties.

    PubMed

    Pan, Jeong Hoon; Kim, Jun Ho; Kim, Hyung Min; Lee, Eui Seop; Shin, Dong-Hoon; Kim, Seongpil; Shin, Minkyeong; Kim, Sang Ho; Lee, Jin Hyup; Kim, Young Jun

    2015-01-01

    Acetic acid has been shown to promote glycogen replenishment in skeletal muscle during exercise training. In this study, we investigated the effects of acetic acid on endurance capacity and muscle oxidative metabolism in the exercise training using in vivo mice model. In exercised mice, acetic acid induced a significant increase in endurance capacity accompanying a reduction in visceral adipose depots. Serum levels of non-esterified fatty acid and urea nitrogen were significantly lower in acetic acid-fed mice in the exercised mice. Importantly, in the mice, acetic acid significantly increased the muscle expression of key enzymes involved in fatty acid oxidation and glycolytic-to-oxidative fiber-type transformation. Taken together, these findings suggest that acetic acid improves endurance exercise capacity by promoting muscle oxidative properties, in part through the AMPK-mediated fatty acid oxidation and provide an important basis for the application of acetic acid as a major component of novel ergogenic aids.

  19. Systematic review of the association between dietary acid load, alkaline water and cancer

    PubMed Central

    Fenton, Tanis R; Huang, Tian

    2016-01-01

    Objectives To evaluate the evidence for a causal relationship between dietary acid/alkaline and alkaline water for the aetiology and treatment of cancer. Design A systematic review was conducted on published and grey literature separately for randomised intervention and observational studies with either varying acid–base dietary intakes and/or alkaline water with any cancer outcome or for cancer treatment. Outcome measures Incidence of cancer and outcomes of cancer treatment. Results 8278 citations were identified, and 252 abstracts were reviewed; 1 study met the inclusion criteria and was included in this systematic review. No randomised trials were located. No studies were located that examined dietary acid or alkaline or alkaline water for cancer treatment. The included study was a cohort study with a low risk of bias. This study revealed no association between the diet acid load with bladder cancer (OR=1.15: 95% CI 0.86 to 1.55, p=0.36). No association was found even among long-term smokers (OR=1.72: 95% CI 0.96 to 3.10, p=0.08). Conclusions Despite the promotion of the alkaline diet and alkaline water by the media and salespeople, there is almost no actual research to either support or disprove these ideas. This systematic review of the literature revealed a lack of evidence for or against diet acid load and/or alkaline water for the initiation or treatment of cancer. Promotion of alkaline diet and alkaline water to the public for cancer prevention or treatment is not justified. PMID:27297008

  20. Acid Loading of Soils by Magmatic CO2 at Mammoth Mountain, California

    NASA Astrophysics Data System (ADS)

    McGee, K. A.; Gerlach, T. M.; Doukas, M. P.

    2003-12-01

    Areas of tree kill appeared in the early 1990's after a shallow intrusion of magma under the south flank of Mammoth Mountain, California. Subsequent field measurements have revealed high concentrations of soil CO2 in these areas, the locations of which are controlled by faults and fractures that serve as conduits for magmatic CO2 streaming to the surface from depth. Detailed surveys at the largest of these tree-kill areas, Horseshoe Lake, about 14 ha in size, have consistently shown soil CO2 concentrations that range up to 90% or greater in the shallow soil layers. Continuous soil CO2 monitoring stations established in 1995 at Horseshoe Lake reveal a pattern of both short-term and seasonal variations in magmatic CO2. Because the pressure of CO2 is externally fixed by CO2 streaming to the surface, carbonic acid activity is constrained by open-system buffering of magmatic CO2. Eight years of intensive soil CO2 monitoring have documented a consistent pattern whereby pH values as low as 4 can be achieved in the soil solution during spring melting of the winter snow pack. Coupled with the seasonal drop in pH, aluminum, which can also be toxic to forest ecosystems, is released from soils in those areas with the highest CO2 concentrations. After more than a decade of exposure to elevated levels of CO2 and repeated cycles of acid loading, along with nearly complete tree and vegetation mortality and the release of Al3+, the soils at Horseshoe Lake and the other areas of tree kill may not recover their ability to sustain any significant level of forest production for several years, even if the CO2 degassing should stop immediately. The level of in-situ acid loading by magmatic CO2 in the tree kill areas around Mammoth Mountain rivals that of the better known process of rain-out of acid gases from volcanic plumes in the troposphere.

  1. Risk factors associated with increased bovine leukemia virus proviral load in infected cattle in Japan from 2012 to 2014.

    PubMed

    Ohno, Ayumu; Takeshima, Shin-nosuke; Matsumoto, Yuki; Aida, Yoko

    2015-12-01

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, a malignant B cell lymphoma. BLV has spread worldwide and causes serious problems. After infection, the BLV genome is integrated into the host DNA and can be amplified during periods of latency. We previously designed degenerate primers using the Coordination of Common Motifs (CoCoMo) algorithm to establish a new quantitative real-time PCR method (BLV-CoCoMo-qPCR-2) of measuring the proviral load of both known and novel BLV variants. Here, we aimed to examine the correlation between proviral load and risk factors for BLV infection, such as breeding systems, parousity, and colostrum feeding. Blood and serum samples were collected from 83 BLV-positive farms in 22 prefectures of Japan, and the BLV proviral load and anti-BLV antibody levels were measured. BLV was detected in 73.3% (1039/1,417) of cattle by BLV-CoCoMo-qPCR-2 and the provirus was detected in 93 of 1039 antibody-negative samples. The results showed that the proviral load increased with progression of lymphocytosis. Next, the risk factors associated with increasing BLV infection rate were examined along with any association with proviral load. The proviral load was higher in cattle with lymphocytosis than in healthy cattle, and higher in multiparous cows than in nulliparous cows. Finally, proviral loads were higher in contact breeding systems than in non-contact breeding systems. Taken together, these findings may help to formulate a plan for eliminating BLV from contaminated farms. This is the first nationwide study to estimate BLV proviral load in Japanese cattle.

  2. Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

    SciTech Connect

    Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.; Culley, David E.; Deng, Shuang; Collett, James R.; Umemura, Myco; Koike, Hideaki; Baker, Scott E.; Machida, Masa

    2013-01-01

    Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes we successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.

  3. Preparation and characterization of silver loaded montmorillonite modified with sulfur amino acid

    NASA Astrophysics Data System (ADS)

    Li, Tian; Lin, Oulian; Lu, Zhiyuan; He, Liuimei; Wang, Xiaosheng

    2014-06-01

    The Na+ montmorillonite (MMT) was modified with sulfur containing amino acid (L-cystine, L-cysteine or L-methionine) and characterized by energy dispersive spectrometer (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectrum (FT-IR). The results showed the modification was smooth and the surface condition of MMT was changed with sulfur containing groups. Then silver was loaded on the modified MMTs via ion-exchange reaction under microwave irradiation, the spectra of X-ray photoelectron spectroscopy (XPS), EDS and FT-IR confirmed the successful loading of massive silver and the strong interaction between sulfur and silver, the silver loaded L-cystine modified MMT (Ag@AA-MMT-3) with a silver content of 10.93 wt% was the highest of all. Further more, the Ag@AA-MMT-3 was under the irradiation of a UV lamp to turn silver ions to silver nano particles (Ag NPs). The XPS, specific surface area (SSA), transmission electron microscopy (TEM), XRD patterns and UV-vis spectra proved the existence of uniform nano scaled metallic Ag NPs. By contrast, the UV irradiated Ag@AA-MMT-3 (Ag@AA-MMT-UV) showed a much better slow release property than Ag@AA-MMT-3 or Ag@MMT. The Ag@AA-MMT-UV showing a large inhibition zone and high inhibition ratio presented very good antibacterial property.

  4. Tamoxifen loaded folic acid armed PEGylated magnetic nanoparticles for targeted imaging and therapy of cancer.

    PubMed

    Heidari Majd, Mostafa; Asgari, Davoud; Barar, Jaleh; Valizadeh, Hadi; Kafil, Vala; Abadpour, Alaleh; Moumivand, Efat; Mojarrad, Javid Shahbazi; Rashidi, Mohammad Reza; Coukos, George; Omidi, Yadollah

    2013-06-01

    Magnetic nanoparticles (MNPs) have been widely used as drug delivery nanosystems and contrast agent for imaging and detection. To engineer multifunctional nanomedicines for simultaneous imaging and therapy of cancer cells, in the current study, we synthesized tamoxifen (TMX) loaded folic acid (FA) armed MNPs to target the folate receptor (FR) positive cancer cells. To this end, Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3. Polyethylene glycol (PEG) was treated with excess bromoacetyl chloride (BrAc) and then with 3-aminopropyltriethoxysilane (APS) to synthesize bromoacetyl-terminal polyethylene glycol silane (APS-PEG-BrAc). The latter complex was treated with protected ethylene diamine to form a bifunctional PEG compound containing triethoxysilane at one end and amino group at the other end (APS-PEG-NH2). The Fe3O4-APS-PEG-NH2 NPs were prepared through self-assembly of APS-PEG-NH2 on MNPs, while the amino groups at the end of Fe3O4-APS-PEG-NH2 were conjugated with folic acid (FA), then loaded with TMX (Fe3O4-APS-PEG-FA-TMX). The average size of "Fe3O4-APS-PEG-FA-TMX" NPs was approximately 40 nm. The engineered MNPs were further characterized and examined in the human breast cancer MCF-7 cells that express FR. The TMX loaded MNPs (with loading efficiency of 49.1%) showed sustained liberation of TMX molecules (with 90% release in 72 h). Fluorescence microcopy and flow cytometry analyses revealed substantial interaction of Fe3O4-APS-PEG-FA-TMX NPs with the FR-positive MCF-7 cells. Cytotoxicity analysis resulted in significant growth inhibition in MCF-7 cells treated with Fe3O4-APS-PEG-FA-TMX NPs. Based on these findings, the TMX-loaded FA-armed PEGylated MNPs as a novel multifunctional nanomedicine/theranostic for concurrent targeting, imaging and therapy of the FR-positive cancer cells. PMID:23434700

  5. A novel cationic microbubble coated with stearic acid-modified polyethylenimine to enhance DNA loading and gene delivery by ultrasound.

    PubMed

    Jin, Qiaofeng; Wang, Zhiyong; Yan, Fei; Deng, Zhiting; Ni, Fei; Wu, Junru; Shandas, Robin; Liu, Xin; Zheng, Hairong

    2013-01-01

    A novel cationic microbubble (MB) for improvement of the DNA loading capacity and the ultrasound-mediated gene delivery efficiency has been developed; it has been prepared with commercial lipids and a stearic acid modified polyethylenimine 600 (Stearic-PEI600) polymer synthesized via acylation reaction of branched PEI600 and stearic acid mediated by N, N'-carbonyldiimidazole (CDI). The MBs' concentration, size distribution, stability and zeta potential (ζ-potential) were measured and the DNA loading capacity was examined as a function of the amount of Stearic-PEI600. The gene transfection efficiency and cytotoxicity were also examined using breast cancer MCF-7 cells via the reporter plasmid pCMV-Luc, encoding the firefly luciferase gene. The results showed that the Stearic-PEI600 polymer caused a significant increase in magnitude of ζ-potential of MBs. The addition of DNA into cationic MBs can shift ζ-potentials from positive to negative values. The DNA loading capacity of the MBs grew linearly from (5±0.2) ×10⁻³ pg/µm² to (20±1.8) ×10⁻³ pg/µm² when Stearic-PEI600 was increased from 5 mol% to 30 mol%. Transfection of MCF-7 cells using 5% PEI600 MBs plus ultrasound exposure yielded 5.76±2.58×10³ p/s/cm²/sr average radiance intensity, was 8.97- and 7.53-fold higher than those treated with plain MBs plus ultrasound (6.41±5.82) ×10² p/s/cm²/sr, (P<0.01) and PEI600 MBs without ultrasound (7.65±6.18) ×10² p/s/cm²/sr, (P<0.01), respectively. However, the PEI600 MBs showed slightly higher cytotoxicity than plain MBs. The cells treated with PEI600-MBs and plain MBs plus ultrasound showed 59.5±6.1% and 71.4±7.1% cell viability, respectively. In conclusion, our study demonstrated that the novel cationic MBs were able to increase DNA loading capacity and gene transfection efficiency and could be potentially applied in targeted gene delivery and therapy.

  6. A Novel Cationic Microbubble Coated with Stearic Acid-Modified Polyethylenimine to Enhance DNA Loading and Gene Delivery by Ultrasound

    PubMed Central

    Jin, Qiaofeng; Wang, Zhiyong; Yan, Fei; Deng, Zhiting; Ni, Fei; Wu, Junru; Shandas, Robin; Liu, Xin; Zheng, Hairong

    2013-01-01

    A novel cationic microbubble (MB) for improvement of the DNA loading capacity and the ultrasound-mediated gene delivery efficiency has been developed; it has been prepared with commercial lipids and a stearic acid modified polyethylenimine 600 (Stearic-PEI600) polymer synthesized via acylation reaction of branched PEI600 and stearic acid mediated by N, N'-carbonyldiimidazole (CDI). The MBs’ concentration, size distribution, stability and zeta potential (ζ-potential) were measured and the DNA loading capacity was examined as a function of the amount of Stearic-PEI600. The gene transfection efficiency and cytotoxicity were also examined using breast cancer MCF-7 cells via the reporter plasmid pCMV-Luc, encoding the firefly luciferase gene. The results showed that the Stearic-PEI600 polymer caused a significant increase in magnitude of ζ-potential of MBs. The addition of DNA into cationic MBs can shift ζ-potentials from positive to negative values. The DNA loading capacity of the MBs grew linearly from (5±0.2) ×10−3 pg/µm2 to (20±1.8) ×10−3 pg/µm2 when Stearic-PEI600 was increased from 5 mol% to 30 mol%. Transfection of MCF-7 cells using 5% PEI600 MBs plus ultrasound exposure yielded 5.76±2.58×103 p/s/cm2/sr average radiance intensity, was 8.97- and 7.53-fold higher than those treated with plain MBs plus ultrasound (6.41±5.82) ×102 p/s/cm2/sr, (P<0.01) and PEI600 MBs without ultrasound (7.65±6.18) ×102 p/s/cm2/sr, (P<0.01), respectively. However, the PEI600 MBs showed slightly higher cytotoxicity than plain MBs. The cells treated with PEI600-MBs and plain MBs plus ultrasound showed 59.5±6.1% and 71.4±7.1% cell viability, respectively. In conclusion, our study demonstrated that the novel cationic MBs were able to increase DNA loading capacity and gene transfection efficiency and could be potentially applied in targeted gene delivery and therapy. PMID:24086748

  7. Treadmill Exercise with Increased Body Loading Enhances Post Flight Functional Performance

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Batson, C. D.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Laurie, S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Peters, B. T.; Phillips, T.; Platts, S. H.; Ploutz-Snyder, L. L.; Reschke, M. F.; Ryder, J. W.; Stenger, M. B.; Taylor, L. C.; Wood, S. J.

    2014-01-01

    The goals of the Functional Task Test (FTT) study were to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We have previously shown that for Shuttle, ISS and bed rest subjects functional tasks requiring a greater demand for dynamic control of postural equilibrium (i.e. fall recovery, seat egress/obstacle avoidance during walking, object translation, jump down) showed the greatest decrement in performance. Functional tests with reduced requirements for postural stability (i.e. hatch opening, ladder climb, manual manipulation of objects and tool use) showed little reduction in performance. These changes in functional performance were paralleled by similar decrements in sensorimotor tests designed to specifically assess postural equilibrium and dynamic gait control. The bed rest analog allows us to investigate the impact of axial body unloading in isolation on both functional tasks and on the underlying physiological factors that lead to decrements in performance and then compare them with the results obtained in our space flight study. These results indicate that body support unloading experienced during space flight plays a central role in postflight alteration of functional task performance. Given the importance of body-support loading we set out to determine if there is a relationship between the load experienced during inflight treadmill exercise (produced by a harness and bungee system) and postflight functional performance. ISS crewmembers (n=13) were tested using the FTT protocol before and after 6 months in space. Crewmembers were tested three times before flight, and on 1, 6, and 30 days after landing. To determine how differences in body

  8. Increase in the permeability of tonoplast of garlic (Allium sativum) by monocarboxylic acids.

    PubMed

    Bai, Bing; Li, Lei; Hu, Xiaosong; Wang, Zhengfu; Zhao, Guanghua

    2006-10-18

    Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No color was formed upon treatment with other weak organic acids, such as citric and malic acids, and the inorganic hydrochloric acid under the same conditions. To understand the significance of monocarboxylic acids and their differing function from that of other acids, acetic acid was compared with organic acids citric and malic and the inorganic hydrochloric acid. The effects of these acids on the permeability of plasma and intracellular membrane of garlic cells were measured by conductivity, light microscopy, and transmission electron microscopy. Except for hydrochloric acid, treatment of garlic with all three organic acids greatly increased the relative conductivity of their respective pickling solutions, indicating that all tested organic acids increased the permeability of plasma membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold higher relative conductivity (approximately 90%) as compared to those (approximately 60%) of both citric and malic acids, implying that exposure of garlic cloves to acetic acid not only changed the permeability of the plasma membrane but also increased the permeability of intracellular membrane. Exposure of garlic to acetic acid led to the production of precipitate along the tonoplast, but no precipitate was formed by citric and malic acids. This indicates that the structure of the tonoplast was damaged by this treatment. Further support for this conclusion comes from results showing that the concentration of thiosulfinates [which are produced only by catalytic conversion of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no thiosulfinates were detected in the pickling solution of citric and malic acids. Thus, all present results suggest that damage of

  9. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  10. Ocean acidification increases fatty acids levels of larval fish

    PubMed Central

    Díaz-Gil, Carlos; Catalán, Ignacio A.; Palmer, Miquel; Faulk, Cynthia K.; Fuiman, Lee A.

    2015-01-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  11. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs.

  12. Preparation and Antibacterial Activity Evaluation of 18-β-glycyrrhetinic Acid Loaded PLGA Nanoparticles

    PubMed Central

    Darvishi, Behrad; Manoochehri, Saeed; Kamalinia, Golnaz; Samadi, Nasrin; Amini, Mohsen; Mostafavi, Seyyed Hossein; Maghazei, Shahab; Atyabi, Fatemeh; Dinarvand, Rassoul

    2015-01-01

    The aim of the present study was to formulate poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with 18-β-glycyrrhetinic acid (GLA) with appropriate physicochemical properties and antimicrobial activity. GLA loaded PLGA nanoparticles were prepared with different drug to polymer ratios, acetone contents and sonication times and the antibacterial activity of the developed nanoparticles was examined against different gram-negative and gram-positive bacteria. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration of nanoparticles. Results demonstrated that physicochemical properties of nanoparticles were affected by the above mentioned parameters where nanoscale size particles ranging from 175 to 212 nm were achieved. The highest encapsulation efficiency (53.2 ± 2.4%) was obtained when the ratio of drug to polymer was 1:4. Zeta potential of the developed nanoparticles was fairly negative (-11±1.5). In-vitro release profile of nanoparticles showed two phases: an initial phase of burst release for 10 h followed by a slow release pattern up to the end. The antimicrobial results revealed that the nanoparticles were more effective than pure GLA against P. aeuroginosa, S. aureus and S. epidermidis. This improvement in antibacterial activity of GLA loaded nanoparticles when compared to pure GLA may be related to higher nanoparticles penetration into infected cells and a higher amount of GLA delivery in its site of action. Herein, it was shown that GLA loaded PLGA nanoparticles displayed appropriate physicochemical properties as well as an improved antimicrobial effect. PMID:25901144

  13. Docetaxel-loaded polyglutamic acid-PEG nanocapsules for the treatment of metastatic cancer.

    PubMed

    Borrajo, Erea; Abellan-Pose, Raquel; Soto, Atenea; Garcia-Fuentes, Marcos; Csaba, Noemi; Alonso, Maria J; Vidal, Anxo

    2016-09-28

    The design of nanomedicines with suitable physicochemical characteristics for the lymphatic targeting of drugs is critical in order to reach the lymph nodes, where metastatic cells often accumulate. Based on the known effect of particle size and surface hydrophilicity on the capacity of nanocarriers to reach the lymph nodes, here we report the formation and characterization of 100nm polyglutamic acid-polyethylene glycol (PGA-PEG) nanocapsules together with the assessment of their potential for the treatment of cancer with lymphatic metastatic spread. To this purpose, we first studied the biodistribution of fluorescently labeled PGA-PEG nanocapsules (100nm), following, either intravenous or subcutaneous administration. The results confirmed the accumulation of nanocapsules in the lymphatic system, especially upon subcutaneous administration. Next, we evaluated the efficacy and toxicity of the docetaxel-loaded nanocapsules in an orthotopic lung cancer model that metastasizes to the lymph nodes. As expected from the rational design, DCX-loaded PGA-PEG nanocapsules exhibited a greatly enhanced antitumoral efficacy and a reduced toxicity when compared with the commercial formulation Taxotere®. Furthermore, the administration of DCX-loaded PGA-PEG nanocapsules resulted in the practical elimination of the metastatic load in the mediastinal lymph nodes, whereas the treatment with the commercial formulation had a minor effect. Overall, these findings underscore the potential of PGA-PEG nanocapsules for the delivery of anticancer drugs to both, the tumor tissue and the metastatic lymph nodes. Therefore, they represent a promising therapy for the treatment of lung metastatic cancer. PMID:27476608

  14. The Effect of Temperature and Acid Gas Loading on Corrosion Behavior of API 5L X52 Carbon Steel in Amine Unit

    NASA Astrophysics Data System (ADS)

    Javidi, M.; Lalehparvar, M. M.; Ghassemi, A.

    2016-05-01

    The effect of temperature and H2S concentration on amine corrosion of API 5L X52 carbon steel in a CO2-saturated 25 wt.% diethanolamine solution was investigated via electrochemical techniques. It was found that increase in temperature from 25 to 80 °C resulted in severe increase in corrosion rate from 0.88 to 16.24 mpy due to increase in degradation rate of amine. Also, it was concluded that increase in H2S concentration led to increase in corrosion rate because of formation of more heat stable amine salts. The effect of temperature on corrosion rate was more significant than acid gas loading.

  15. Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability.

    PubMed

    Tan, Suk Fei; Masoumi, Hamid Reza Fard; Karjiban, Roghayeh Abedi; Stanslas, Johnson; Kirby, Brian P; Basri, Mahiran; Basri, Hamidon Bin

    2016-03-01

    Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21±0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood-brain barrier in the treatment of epilepsy.

  16. Ultrasonic emulsification of parenteral valproic acid-loaded nanoemulsion with response surface methodology and evaluation of its stability.

    PubMed

    Tan, Suk Fei; Masoumi, Hamid Reza Fard; Karjiban, Roghayeh Abedi; Stanslas, Johnson; Kirby, Brian P; Basri, Mahiran; Basri, Hamidon Bin

    2016-03-01

    Response surface methodology (RSM) was used to optimize the formulation of a nanoemulsion for central delivery following parenteral administration. A mixture of medium-chain triglyceride (MCT) and safflower seed oil (SSO) was determined as a sole phase from the emulsification properties. Similarly, a natural surfactant (lecithin) and non-ionic surfactant (Tween 80) (ratio 1:2) were used in the formulation. A central composite design (CCD) with three-factor at five-levels was used to optimize the processing method of high energy ultrasonicator. Effects of pre-sonication ultrasonic intensity (A), sonication time (B), and temperature (C) were studied on the preparation of nanoemulsion loaded with valproic acid. Influence of the aforementioned specifically the effects of the ultrasonic processing parameters on droplet size and polydispersity index were investigated. From the analysis, it was found that the interaction between ultrasonic intensity and sonication time was the most influential factor on the droplet size of nanoemulsion formulated. Ultrasonic intensity (A) significantly affects the polydispersity index value. With this optimization method, a favorable droplet size of a nanoemulsion with reasonable polydispersity index was able to be formulated within a short sonication time. A valproic acid loaded nanoemulsion can be obtained with 60% power intensity for 15 min at 60 °C. Droplet size of 43.21±0.11 nm with polydispersity index of 0.211 were produced. The drug content was then increased to 1.5%. Stability study of nanoemulsion containing 1.5% of valproic acid had a good stability as there are no significant changes in physicochemical aspects such as droplet size and polydispersity index. With the characteristisation study of pH, viscosity, transmission electron microscope (TEM) and stability assessment study the formulated nanoemulsion has the potential to penetrate blood-brain barrier in the treatment of epilepsy. PMID:26585010

  17. Effect of increased load of high-strength food wastewater in thermophilic and mesophilic anaerobic co-digestion of waste activated sludge on bacterial community structure.

    PubMed

    Jang, Hyun Min; Ha, Jeong Hyub; Kim, Mi-Sun; Kim, Jong-Oh; Kim, Young Mo; Park, Jong Moon

    2016-08-01

    In recent years, anaerobic co-digestion (AcoD) has been widely used to improve reactor performance, especially methane production. In this study, we applied two different operating temperatures (thermophilic and mesophilic) and gradually increased the load of food wastewater (FWW) to investigate the bacterial communities during the AcoD of waste activated sludge (WAS) and FWW. As the load of FWW was increased, methane production rate (MPR; L CH4/L d) and methane content (%) in both Thermophilic AcoD (TAcoD) and Mesophilic AcoD (MAcoD) increased significantly; the highest MPR and methane content in TAcoD (1.423 L CH4/L d and 68.24%) and MAcoD (1.233 L CH4/L d and 65.21%) were observed when the FWW mixing ratio was 75%. However, MPR and methane yield in both reactors decreased markedly and methane production in TAcoD ceased completely when only FWW was fed into the reactor, resulting from acidification of the reactor caused by accumulation of organic acids. Pyrosequencing analysis revealed a decrease in bacterial diversity in TAcoD and a markedly different composition of bacterial communities between TAcoD and MAcoD with an increase in FWW load. For example, Bacterial members belonging to two genera Petrotoga (assigned to phylum Thermotogae) and Petrimonas (assigned to phylum Bacteroidetes) became dominant in TAcoD and MAcoD with an increase in FWW load, respectively. In addition, quantitative real-time PCR (qPCR) results showed higher bacterial and archaeal populations (expressed as 16S rRNA gene concentration) in TAcoD than MAcoD with an increase in FWW load and showed maximum population when the FWW mixing ratio was 75% in both reactors. Collectively, this study demonstrated the dynamics of key bacterial communities in TAcoD and MAcoD, which were highly affected by the load of FWW. PMID:27155112

  18. Evaluation of increased cesium loading on submerged demineralizer system (SDS) zeolite beds

    SciTech Connect

    Not Available

    1981-05-01

    A Submerged Demineralizer System (SDS) is being installed at the Three Mile Island Unit (TMI-2) Nuclear Power Station for decontamination of the Containment Building (CB) sump water and Reactor Coolant System (RCS) water. A Department of Energy (DOE) Task Force was assembled to evaluate the relative technical and financial benefits in storing, shipping, treating, and disposing of SDS zeolite liners, assuming that the liners will be loaded to a level higher than that (10,000 Ci/liner) originally planned by General Public Utilities (GPU). The DOE-SDS Task Force concludes that it is technically feasible to load the zeolite liners used in the SDS to levels up to 60,000 Ci of cesium per liner without additional preoperational testing. This would result in approximately ten such liners. The Task Force further concludes that these liners can be safely handled, stored, transported, and vitrified.

  19. Soil Respiration and Belowground Carbon Stores Among Salt Marshes Subjected to Increasing Watershed Nitrogen Loadings in Southern New England

    EPA Science Inventory

    Coastal salt marshes are ecosystems located between the uplands and sea, and because of their location are subject to increasing watershed nutrient loadings and rising sea levels. Residential development along the coast is intense, and there is a significant relationship between...

  20. Changes in Indirect Markers of Muscle Damage and Tendons After Daily Drop Jumping Exercise with Rapid Load Increase.

    PubMed

    Paleckis, Vidas; Mickevičius, Mantas; Snieckus, Audrius; Streckis, Vytautas; Pääsuke, Mati; Rutkauskas, Saulius; Steponavičiūtė, Rasa; Skurvydas, Albertas; Kamandulis, Sigitas

    2015-12-01

    The aim of this study was to assess changes in indirect markers of muscle damage and type I collagen degradation, as well as, patellar and Achilles tendon morphological differences during nine daily drop-jumps sessions with constant load alternated with rapid increases in load to test the hypothesis that frequent drop-jump training results in negative muscular and tendon adaptation. Young men (n = 9) performed daily drop jump workouts with progression every 3 days in terms of number of jumps, platform height and squat amplitude. Voluntary and electrically evoked knee extensor torque, muscle soreness, blood plasma creatine kinase (CK) activity and carboxyterminal cross-linked telopeptide (ICTP), patellar and Achilles tendon thickness and cross-sectional area (CSA) were assessed at different time points during the training period and again on days 1, 3, 10 and 17 after the training. The findings were as follows: (1) steady decline in maximal muscle strength with major recovery within 24 hours after the first six daily training sessions; (2) larger decline in electrically induced muscle torque and prolonged recovery during last three training sessions; (3) increase in patellar and Achilles tendons CSA without change in thickness towards the end of training period; (4) increase in jump height but not in muscle strength after whole training period. Our findings suggest that frequent drop-jump sessions with constant load alternated with rapid increases in load do not induce severe muscle damage or major changes in tendons, nonetheless, this type of loading is not advisable for muscle strength improvement. Key pointsFrequent drop jump training induces activation mode dependent muscle torque depression late in the training period.No significant changes in the thickness of patellar and Achilles tendons are observed during frequent training, while CSA increases towards the end of training period.Longitudinal effect for jump height but not for muscle strength is evident after

  1. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance

    PubMed Central

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H.; Patton-Vogt, Jana; Bakalinsky, Alan T.

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. PMID:25673654

  2. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance.

    PubMed

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H; Patton-Vogt, Jana; Bakalinsky, Alan T

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification.

  3. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance.

    PubMed

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H; Patton-Vogt, Jana; Bakalinsky, Alan T

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. PMID:25673654

  4. Influence of increased mechanical loading by hypergravity on the microtubule cytoskeleton and prostaglandin E2 release in primary osteoblasts

    NASA Technical Reports Server (NTRS)

    Searby, Nancy D.; Steele, Charles R.; Globus, Ruth K.

    2005-01-01

    Cells respond to a wide range of mechanical stimuli such as fluid shear and strain, although the contribution of gravity to cell structure and function is not understood. We hypothesized that bone-forming osteoblasts are sensitive to increased mechanical loading by hypergravity. A centrifuge suitable for cell culture was developed and validated, and then primary cultures of fetal rat calvarial osteoblasts at various stages of differentiation were mechanically loaded using hypergravity. We measured microtubule network morphology as well as release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts, a stimulus of 10x gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased microtubule network height 1.12-fold without affecting cell viability. Hypergravity (3 h) caused dose-dependent (5-50 g) increases in PGE2 (5.3-fold at 50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2 release depended on duration but not orientation of the hypergravity load. As osteoblasts differentiated, sensitivity to hypergravity declined. We conclude that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to gravitational loading, which appears to be blunted in mature osteoblasts.

  5. Lower vegetable protein intake and higher dietary acid load associated with lower carbohydrate intake are risk factors for metabolic syndrome in patients with type 2 diabetes: Post-hoc analysis of a cross-sectional study

    PubMed Central

    Iwase, Hiroya; Tanaka, Muhei; Kobayashi, Yukiko; Wada, Sayori; Kuwahata, Masashi; Kido, Yasuhiro; Hamaguchi, Masahide; Asano, Mai; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

    2015-01-01

    Aims/Introduction A low-carbohydrate diet based on animal sources is associated with higher all-cause mortality, whereas a vegetable-based low-carbohydrate diet is associated with lower cardiovascular disease mortality. It has been suggested that acid/base imbalance might play an important role in some cardiometabolic abnormalities. The aims of the present study were to evaluate whether carbohydrate intake is associated with quality of dietary protein and acid load, and whether these are related to metabolic syndrome in patients with type 2 diabetes. Materials and Methods The present cross-sectional study involved 149 patients with type 2 diabetes. Dietary intake was assessed using a validated self-administered diet history questionnaire. Dietary acid load was assessed by potential renal acid load and net endogenous acid production. Results Mean daily total energy intake, carbohydrate intake, animal protein intake and vegetable protein intake were 1821.5 kcal, 248.8 g, 36.1 g and 31.1 g, respectively. Carbohydrate energy/total energy was negatively correlated with animal protein energy/total energy, potential renal acid load or net endogenous acid production score, and was positively correlated with vegetable protein energy/total energy. Logistic regression analyses showed that the subgroup of patients with a lower vegetable protein energy/total energy or higher potential renal acid load or net endogenous acid production score was significantly associated with the prevalence of metabolic syndrome. Conclusions The present study showed that carbohydrate intake was associated with the quality of dietary protein and dietary acid load. Furthermore, decreased vegetable protein intake and increased dietary acid load were associated with the prevalence of metabolic syndrome. PMID:26221526

  6. Higher estimated net endogenous Acid production may be associated with increased prevalence of nonalcoholic Fatty liver disease in chinese adults in Hong Kong.

    PubMed

    Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto's method and potential renal acid load (PRAL) was calculated using Remer's method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

  7. Increasing precision of turbidity-based suspended sediment concentration and load estimates.

    PubMed

    Jastram, John D; Zipper, Carl E; Zelazny, Lucian W; Hyer, Kenneth E

    2010-01-01

    Turbidity is an effective tool for estimating and monitoring suspended sediments in aquatic systems. Turbidity can be measured in situ remotely and at fine temporal scales as a surrogate for suspended sediment concentration (SSC), providing opportunity for a more complete record of SSC than is possible with physical sampling approaches. However, there is variability in turbidity-based SSC estimates and in sediment loadings calculated from those estimates. This study investigated the potential to improve turbidity-based SSC, and by extension the resulting sediment loading estimates, by incorporating hydrologic variables that can be monitored remotely and continuously (typically 15-min intervals) into the SSC estimation procedure. On the Roanoke River in southwestern Virginia, hydrologic stage, turbidity, and other water-quality parameters were monitored with in situ instrumentation; suspended sediments were sampled manually during elevated turbidity events; samples were analyzed for SSC and physical properties including particle-size distribution and organic C content; and rainfall was quantified by geologic source area. The study identified physical properties of the suspended-sediment samples that contribute to SSC estimation variance and hydrologic variables that explained variability of those physical properties. Results indicated that the inclusion of any of the measured physical properties in turbidity-based SSC estimation models reduces unexplained variance. Further, the use of hydrologic variables to represent these physical properties, along with turbidity, resulted in a model, relying solely on data collected remotely and continuously, that estimated SSC with less variance than a conventional turbidity-based univariate model, allowing a more precise estimate of sediment loading, Modeling results are consistent with known mechanisms governing sediment transport in hydrologic systems.

  8. Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes.

    PubMed

    Popat, Ketul C; Eltgroth, Matthew; Latempa, Thomas J; Grimes, Craig A; Desai, Tejal A

    2007-11-01

    Bacterial infection is one of the most common problems after orthopedic implant surgery. If not prevented, bacterial infection can result in serious and life threatening conditions such as osteomyelitis. Thus, in order to reduce chances of such serious complication, patients are often subjected to antibiotic drug therapy for 6-8 weeks after initial surgery. The antibiotics are systemically delivered either intravenously, intramuscularly or topically. Systemic antibiotic delivery entails certain drawbacks such as systemic toxicity and limited bioavailability. Further, in order for the drug to be effective at the site of implantation, high doses are required, which can result in undesired side effects in patients. Thus, local antibiotic therapy is the preferred way of administering drugs. To that end, we have developed titania nanotubular arrays for local delivery of antibiotics off-implant at the site of implantation. These nanotubes were fabricated on bulk titanium using anodization techniques. The fabrication strategies allow us to precisely control the nanotube length and diameter, thus enabling us to load different amounts of drugs and control the release rates. In this work we have fabricated titania nanotubes with 80 nm diameter and 400 nm length. We have loaded these tubes with 200, 400 and 600 microg of gentamicin. The gentamicin release kinetics from these nanotubes and its effect on Staphylococcus epidermis adhesion were investigated. Further, a preosteoblastic cell line called MC3T3-E1 was cultured on gentamicin-loaded nanotubes to evaluate the effect of nanoarchitecture on cell functionality. Our results indicate that we can effectively fill the nanotubes with the drug and the drug eluting nanotubes significantly reduce bacterial adhesion on the surface. Also, there is enhanced osteoblast differentiation on nanotubes filled with gentamicin. PMID:17697708

  9. Directed evolution increases desaturation of a cyanobacterial fatty acid desaturase in eukaryotic expression systems.

    PubMed

    Bai, Shuangyi; Wallis, James G; Denolf, Peter; Browse, John

    2016-07-01

    Directed evolution of a cyanobacterial Δ9 fatty acid desaturase (DSG) from Synechococcus elongatus, PCC6301 created new, more productive desaturases and revealed the importance of certain amino acid residues to increased desaturation. A codon-optimized DSG open reading frame with an endoplasmic-reticulum retention/retrieval signal appended was used as template for random mutagenesis. Increased desaturation was detected using a novel screen based on complementation of the unsaturated fatty acid auxotrophy of Saccharomyces cerevisiae mutant ole1Δ. Amino acid residues whose importance was discovered by the random processes were further examined by saturation mutation to determine the best amino acid at each identified location in the peptide chain and by combinatorial analysis. One frequently-detected single amino acid change, Q240R, yielded a nearly 25-fold increase in total desaturation in S. cerevisiae. Several other variants of the protein sequence with multiple amino acid changes increased total desaturation more than 60-fold. Many changes leading to increased desaturation were in the vicinity of the canonical histidine-rich regions known to be critical for electron transfer mediated by these di-iron proteins. Expression of these evolved proteins in the seed of Arabidopsis thaliana altered the fatty acid composition, increasing monounsaturated fatty acids and decreasing the level of saturated fatty acid, suggesting a potential application of these desaturases in oilseed crops. Biotechnol. Bioeng. 2016;113: 1522-1530. © 2016 Wiley Periodicals, Inc. PMID:26724425

  10. Fracture characteristics of carbon fibre, ceramic and non-palladium endodontic post systems at monotonously increasing loads.

    PubMed

    Ottl, P; Hahn, L; Lauer, H Ch; Fay, M

    2002-02-01

    A carbon fibre post system, three non-palladium and one palladium metal post systems, two ceramic post systems, and a metal post system with a ceramic core were studied in vitro. The control group consisted of root-filled test teeth without posts. The test teeth were identical artificial roots of an upper central incisor made from a posterior composite whose module of elasticity was similar to that of natural dentine. All posts were cemented in the roots using Panavia 21 TC. Subsequently, standardized full crowns were cemented onto all roots. On a universal testing machine, the test teeth were loaded palatally at monotonously increasing loads until root fracture. The highest mean fracture loads were found for the carbon fibre post system (312.5 +/- 58.8 N). The fracture load of non-palladium metal posts (242.3-300.4 N) did not differ significantly from that of the Perma-dor post (265.9 N), which does contain palladium. Values of 300.3 +/- 89.3 N (aluminium oxide ceramics) and 193.5 +/-57.0 N (zirconia ceramics) were found for the ceramic posts. The control group exhibited a fracture load of 228.8 +/- 35.7 N. The mean distance between the vestibular end of the fracture gap and the point of force application was between 10.1 +/- 2.3 and 14.7 +/- 1.2 mm.

  11. Pantothenic acid deficiency may increase the urinary excretion of 2-oxo acids and nicotinamide catabolites in rats.

    PubMed

    Shibata, Katsumi; Inomoto, Kasumi; Nakata, Chifumi; Fukuwatari, Tsutomu

    2013-01-01

    Pantothenic acid (PaA) is involved in the metabolism of amino acids as well as fatty acid. We investigated the systemic metabolism of amino acids in PaA-deficient rats. For this purpose, urine samples were collected and 2-oxo acids and L-tryptophan (L-Trp) and its metabolites including nicotinamide were measured. Group 1 was freely fed a conventional chemically-defined complete diet and used as an ad lib-fed control, which group was used for showing reference values. Group 2 was freely fed the complete diet without PaA (PaA-free diet) and used as a PaA-deficient group. Group 3 was fed the complete diet, but the daily food amount was equal to the amount of the PaA-deficient group and used as a pair-fed control group. All rats were orally administered 100 mg of L-Trp/kg body weight at 09:00 on day 34 of the experiment and the following 24-h urine samples were collected. The urinary excretion of the sum of pyruvic acid and oxaloacetic acid was higher in rats fed the PaA-free diets than in the rats fed pair-fed the complete diet. PaA deficiency elicited the increased urinary excretion of anthranilic acid and kynurenic acid, while the urinary excretion of xanthurenic acid decreased. The urinary excretion of L-Trp itself, 3-hydroxyanthranilic acid, and quinolinic acid revealed no differences between the rats fed the PaA-free and pair-fed the complete diets. PaA deficiency elicited the increased excretion of N(1)-methylnicotinamide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide. These findings suggest that PaA deficiency disturbs the amino acid catabolism.

  12. A Novel Method for the Preparation of Retinoic Acid-Loaded Nanoparticles

    PubMed Central

    Errico, Cesare; Gazzarri, Matteo; Chiellini, Federica

    2009-01-01

    The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation of nanoparticles based on a copolymer of maleic anhydride and butyl vinyl ether (VAM41) loaded with RA. Nanoparticles with an average diameter size of 70 nm and good morphology were prepared. The activity of the encapsulated RA was evaluated on SK-N-SH human neuroblastoma cells, which are known to undergo inhibition of proliferation and neuronal differentiation upon treatment with RA. The activity of RA was not affected by the encapsulation and purification processes. PMID:19564952

  13. Chlorogenic acid increased 5-hydroxymethylfurfural formation when heating fructose alone or with aspartic acid at two pH levels.

    PubMed

    Zhang, Zhenhua; Zou, Yueyu; Wu, Taigang; Huang, Caihuan; Pei, Kehan; Zhang, Guangwen; Lin, Xiaohua; Bai, Weibin; Ou, Shiyi

    2016-01-01

    Chlorogenic acid (CGA) is a phenolic acid that ubiquitously exists in fruits. This work aims to investigate whether and how CGA influences HMF formation during heating fructose alone, or with an amino acid. The results showed that that CGA increased 5-hydroxymethylfurfural (HMF) formation. At pH 5.5 and 7.0, the addition of 5.0 μmol/ml CGA increased HMF formation by 49.4% and 25.2%, respectively when heating fructose alone, and by 9.0% and 16.7%, respectively when heating fructose with aspartic acid. CGA significantly increased HMF formation by promoting 3-deoxosone formation, and its conversion to HMF by inhibiting HMF elimination, especially in the Maillard reaction system. A comparison of the catalytic capacity of CGA with its six analogous compounds showed that both its di-hydroxyphenyl and carboxyl groups function in increasing HMF formation.

  14. Preparation of Lung-Targeting, Emodin-Loaded Polylactic Acid Microspheres and Their Properties

    PubMed Central

    Chen, Xiaohong; Yang, Zifeng; Sun, Renshan; Mo, Ziyao; Jin, Guangyao; Wei, Fenghuan; Hu, Jianmin; Guan, Wenda; Zhong, Nanshan

    2014-01-01

    Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has been identified to have the potential to improve lung fibrosis and lung cancer. To avoid the liver and kidney toxicities and the fast metabolism of emodin, emodin-loaded polylactic acid microspheres (ED-PLA-MS) were prepared and their characteristics were studied. ED-PLA-MS were prepared by the organic phase dispersion-solvent diffusion method. By applying an orthogonal design, our results indicated that the optimal formulation was 12 mg/mL PLA, 0.5% gelatin, and an organic phase:glycerol ratio of 1:20. Using the optimal experimental conditions, the drug loading and encapsulation efficiencies were (19.0 ± 1.8)% and (62.2 ± 2.6)%, respectively. The average particle size was 9.7 ± 0.7 μm. In vitro studies indicated that the ED-PLA-MS demonstrated a well-sustained release efficacy. The microspheres delivered emodin, primarily to the lungs of mice, upon intravenous injection. It was also detected by microscopy that partial lung inflammation was observed in lung tissues and no pathological changes were found in other tissues of the ED-PLA-MS-treated animals. These results suggested that ED-PLA-MS are of potential value in treating lung diseases in animals. PMID:24733070

  15. Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting.

    PubMed

    Ma, Yanni; He, Shaolong; Ma, Xueqin; Hong, Tongtong; Li, Zhifang; Park, Kinam; Wang, Wenping

    2016-01-01

    Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver.

  16. Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation.

    PubMed

    Wu, Junzi; Williams, Gareth R; Branford-White, Christopher; Li, Heyu; Li, Yan; Zhu, Li-Min

    2016-09-20

    In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections. Reduced blood sugar levels were seen in the microsphere treatment groups, with the results being similar to those obtained with conventional injections between 10 and 25days after the commencement of treatment. After 5 and 30days of treatment, the microspheres seem a little slower to act than the injections. The pathology of the rats' spleen, heart, kidney and lungs was probed after the 30-day treatment period, and the results indicated that the microspheres were safe and had beneficial effects on the liver, reducing the occurrence of fatty deposits seen in untreated diabetic rats. Moreover, in terms of liver, renal and cardiac functions, and blood lipid and antioxidant levels, the microspheres were as effective as the injections. The expression of several proteases linked to the metabolism of aliphatic acids and homocysteine was promoted by the microsphere formulations. Inflammatory markers in the microsphere treatment groups were somewhat higher than the injection group, however. The liraglutide/PLGA microspheres prepared in this work are overall shown to be efficacious in a rat model of diabetes, and we thus believe they have strong potential for clinical use.

  17. Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load.

    PubMed

    Walsh, Lauren K; Restaino, Robert M; Neuringer, Martha; Manrique, Camila; Padilla, Jaume

    2016-11-01

    Postprandial hyperglycaemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. In the present study, we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500 mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycaemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, and at 60 and 120 min after an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized cross-over design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycaemia under the placebo condition (-32% at 60 min and -28% at 120 min post oral glucose load; P<0.05 from baseline) but not under the TUDCA condition (-4% at 60 min and +0.3% at 120 min post oral glucose load; P>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and thiobarbituric acid reactive substance (TBARS) remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycaemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycaemia.

  18. Propagated fixed-bed mixed-acid fermentation: Part I: Effect of volatile solid loading rate and agitation at high pH.

    PubMed

    Golub, Kristina W; Forrest, Andrea K; Mercy, Kevin L; Holtzapple, Mark T

    2011-11-01

    Countercurrent fermentation is a high performing process design for mixed-acid fermentation. However, there are high operating costs associated with moving solids, which is an integral component of this configuration. This study investigated the effect of volatile solid loading rate (VSLR) and agitation in propagated fixed-bed fermentation, a configuration which may be more commercially viable. To evaluate the role of agitation on fixed-bed configuration performance, continuous mixing was compared with periodic mixing. VSLR was also varied and not found to affect acid yields. However, increased VSLR and liquid retention time did result in higher conversions, productivity, acid concentrations, but lower selectivities. Agitation was demonstrated to be important for this fermentor configuration, the periodically-mixed fermentation had the lowest conversion and yields. Operating at a high pH (∼9) contributed to the high selectivity to acetic acid, which might be industrially desirable but at the cost of lower yield compared to a neutral pH.

  19. Volatile fatty acids production from food waste: effects of pH, temperature, and organic loading rate.

    PubMed

    Jiang, Jianguo; Zhang, Yujing; Li, Kaimin; Wang, Quan; Gong, Changxiu; Li, Menglu

    2013-09-01

    The effects of pH, temperature, and organic loading rate (OLR) on the acidogenesis of food waste have been determined. The present study investigated their effects on soluble chemical oxygen demand (SCOD), volatile fatty acids (VFAs), volatile solids (VS), and ammonia nitrogen (NH4(+)-N). Both the concentration and yield of VFAs were highest at pH 6.0, acetate and butyrate accounted for 77% of total VFAs. VFAs concentration and the VFA/SCOD ratio were highest, and VS levels were lowest, at 45 °C, but the differences compared to the values at 35 °C were slight. The concentrations of VFAs, SCOD, and NH4(+)-N increased as OLR increased, whereas the yield of VFAs decreased from 0.504 at 5 g/Ld to 0.306 at 16 g/Ld. Acetate and butyrate accounted for 60% of total VFAs. The percentage of acetate and valerate increased as OLR increased, whereas a high OLR produced a lower percentage of propionate and butyrate.

  20. Increased Biomass Yield of Lactococcus lactis by Reduced Overconsumption of Amino Acids and Increased Catalytic Activities of Enzymes

    PubMed Central

    Adamberg, Kaarel; Seiman, Andrus; Vilu, Raivo

    2012-01-01

    Steady state cultivation and multidimensional data analysis (metabolic fluxes, absolute proteome, and transcriptome) are used to identify parameters that control the increase in biomass yield of Lactococcus lactis from 0.10 to 0.12 C-mol C-mol−1 with an increase in specific growth rate by 5 times from 0.1 to 0.5 h−1. Reorganization of amino acid consumption was expressed by the inactivation of the arginine deiminase pathway at a specific growth rate of 0.35 h−1 followed by reduced over-consumption of pyruvate directed amino acids (asparagine, serine, threonine, alanine and cysteine) until almost all consumed amino acids were used only for protein synthesis at maximal specific growth rate. This balanced growth was characterized by a high glycolytic flux carrying up to 87% of the carbon flow and only amino acids that relate to nucleotide synthesis (glutamine, serine and asparagine) were consumed in higher amounts than required for cellular protein synthesis. Changes in the proteome were minor (mainly increase in the translation apparatus). Instead, the apparent catalytic activities of enzymes and ribosomes increased by 3.5 times (0.1 vs 0.5 h−1). The apparent catalytic activities of glycolytic enzymes and ribosomal proteins were seen to follow this regulation pattern while those of enzymes involved in nucleotide metabolism increased more than the specific growth rate (over 5.5 times). Nucleotide synthesis formed the most abundant biomonomer synthetic pathway in the cells with an expenditure of 6% from the total ATP required for biosynthesis. Due to the increase in apparent catalytic activity, ribosome translation was more efficient at higher growth rates as evidenced by a decrease of protein to mRNA ratios. All these effects resulted in a 30% decrease of calculated ATP spilling (0.1 vs 0.5 h−1). Our results show that bioprocesses can be made more efficient (using a balanced metabolism) by varying the growth conditions. PMID:23133574

  1. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease.

  2. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. PMID:25616451

  3. Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters.

    PubMed

    Oliveira, Camila Areias de; Peres, Daniela D'Almeida; Graziola, Fabiana; Chacra, Nádia Araci Bou; Araújo, Gabriel Lima Barros de; Flórido, Ana Catarina; Mota, Joana; Rosado, Catarina; Velasco, Maria Valéria Robles; Rodrigues, Luís Monteiro; Fernandes, Ana Sofia; Baby, André Rolim

    2016-01-01

    The encapsulation of natural ingredients, such as rutin, can offer improvements in sun protection effectiveness. This strategy can provide enhanced flavonoid content and produces an improved bioactive compound with new physical and functional characteristics. As an alternative to common synthetic-based sunscreens, rutin-entrapped gelatin nanoparticles (GNPs) were designed and associated with ethylhexyl dimethyl PABA (EHDP), ethylhexyl methoxycinnamate (EHMC) and methoxydibenzoylmethane (BMDBM) in sunscreen formulations. The purpose of this study was to develop rutin-loaded gelatin nanoparticles and characterize their physicochemical, thermal, functional and safety properties. Rutin-loaded gelatin nanoparticles increased antioxidant activity by 74% relative to free-rutin (FR) solution. Also, this new ingredient upgraded the Sun Protection Factor (SPF) by 48%, indicating its potential as a raw material for bioactive sunscreens. The safety profile indicated that GNPs and glutaraldehyde (GTA) decreased HaCaT cell viability in a concentration/time-dependent manner. However, both blank nanoparticles (B-NC) and rutin-loaded nanoparticles (R-NC) had good performance on skin compatibility tests. These results functionally characterized rutin-loaded nanoparticles as a safe SPF enhancer in sunscreens, especially in association with UV filters.

  4. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

    PubMed Central

    2010-01-01

    Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209

  5. The strength of attentional biases reduces as visual short-term memory load increases.

    PubMed

    Shimi, A; Astle, D E

    2013-07-01

    Despite our visual system receiving irrelevant input that competes with task-relevant signals, we are able to pursue our perceptual goals. Attention enhances our visual processing by biasing the processing of the input that is relevant to the task at hand. The top-down signals enabling these biases are therefore important for regulating lower level sensory mechanisms. In three experiments, we examined whether we apply similar biases to successfully maintain information in visual short-term memory (VSTM). We presented participants with targets alongside distracters and we graded their perceptual similarity to vary the extent to which they competed. Experiments 1 and 2 showed that the more items held in VSTM before the onset of the distracters, the more perceptually distinct the distracters needed to be for participants to retain the target accurately. Experiment 3 extended these behavioral findings by demonstrating that the perceptual similarity between target and distracters exerted a significantly greater effect on occipital alpha amplitudes, depending on the number of items already held in VSTM. The trade-off between VSTM load and target-distracter competition suggests that VSTM and perceptual competition share a partially overlapping mechanism, namely top-down inputs into sensory areas.

  6. Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice.

    PubMed

    Aspenström-Fagerlund, Bitte; Tallkvist, Jonas; Ilbäck, Nils-Gunnar; Glynn, Anders W

    2015-09-01

    The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120min after exposure, or were exposed to 0.6, 2.4 or 4.8g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.

  7. Metal loading assessment of a small mountainous sub-basin characterized by acid drainage -- Prospect Gulch, upper Animas River watershed, Colorado

    USGS Publications Warehouse

    Wirt, Laurie; Leib, Kenneth J.; Melick, Roger; Bove, Dana J.

    2001-01-01

    iron spring yielded 39% of the discharge and 54%, 73%, and 87% of the SO4, Al, and Fe loads; but only 4% of the total Cu and 30% of the total Zn loads in Prospect Gulch. Base flow from the Prospect Gulch sub-basin contributes about 4.8 percent of the total discharge at the mouth of Cement Creek; compared with sampled instream loads of 1.8%, 8.8%, 15.9%, 28%, and 8.6% for SO4, Al, Fe, Cu and Zn, respectively. Water-shed scale remediation efforts targeted at reducing loads of SO4, Al, and Fe at inactive mine sites are likely to fail because the major sources of these constituents in Prospect Gulch are predominantly discharged from natural sources. Remediation goals aimed at reducing acidity and loads of Cu and other base metals, may succeed, however, because changes in pH and loads are disproportionately greater than increases in discharge over the same reach, and a substantial fraction of the metal loading is from mining-impacted reaches. Whether remediation of abandoned mines in Prospect Gulch can be successful depends on how goals are defined?that is, whether the objective is to reduce loads of SO4, Al, and Fe; or whether loads of Cu and other base metals and pH are targeted.

  8. Long-term toxicity of holmium-loaded poly(L-lactic acid) microspheres in rats.

    PubMed

    Zielhuis, Sander W; Nijsen, J Frank W; Seppenwoolde, Jan-Henry; Bakker, Chris J G; Krijger, Gerard C; Dullens, Hub F J; Zonnenberg, Bernard A; van Rijk, Peter P; Hennink, Wim E; van het Schip, Alfred D

    2007-11-01

    The aim of this study was to get insight into the toxic effects of holmium-166-loaded poly(L-lactic acid) microspheres (Ho-PLLA-MS) which have very interesting features for treatment of liver malignancies. Acute, mid- and long-term effects were studied in healthy Wistar rats by evaluating clinical, biochemical and tissue response. Rats were divided into four treatment groups: sham, decayed neutron-irradiated Ho-PLLA-MS, non-irradiated Ho-PLLA-MS and PLLA-MS. After implantation of the microspheres into the liver of the rats, the animals were monitored (body weight, temperature and liver enzymes) for a period of 14-18 months. Some of the rats that received previously neutron-irradiated Ho-PLLA-MS were periodically scanned with magnetic resonance imaging (MRI) to see if holmium was released from the microspheres. After sacrifice, the liver tissue was histologically evaluated. Bone tissue was subjected to neutron-activation analysis in order to examine whether accumulation of released holmium in the bone had occurred. No measurable clinical and biochemical toxic effects were observed in any of the treatment groups. Furthermore, histological analyses of liver tissue samples only showed signs of a slight chronic inflammation and no significant differences in the tissue reaction between rats of the different treatment groups could be observed. The non-irradiated PLLA-MS and Ho-PLLA-MS stayed intact during the study. In contrast, 14 months after administration, the neutron-irradiated Ho-PLLA-MS was not completely spherical anymore, indicating that degradation had started. However, the holmium loading had not been released as was illustrated with MRI and affirmed by neutron-activation analysis of bone tissue. In conclusion, neutron-irradiated Ho-PLLA-MS does not provoke any toxic reaction and can be applied safely in vivo.

  9. Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic anti-inflammatory formulations.

    PubMed

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning (1)H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved (1)H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may

  10. Magnetoliposomes Loaded with Poly-Unsaturated Fatty Acids as Novel Theranostic Anti-Inflammatory Formulations

    PubMed Central

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become

  11. Invertebrate response to nutrient-driven epiphytic load increase in Posidonia oceanica meadows

    NASA Astrophysics Data System (ADS)

    Castejón-Silvo, Inés; Domínguez, Marta; Terrados, Jorge; Tomas, Fiona; Morales-Nin, Beatriz

    2012-10-01

    Nutrient increases in coastal systems are becoming a world-wide concern since they promote strong structural and functional changes in shallow ecosystems. Increased nutrient availability in the water column may strongly enhance the leaf epiphytic communities of key habitat-forming species such as seagrasses through a bottom-up mechanism, competing for light and nutrients with the leaves. Epiphytes support an abundant and diverse community of resident invertebrates which fuel higher trophic levels in Posidonia oceanica food webs. We evaluated the response of seagrass, epiphytes and the invertebrate community to an experimental increase of water column nutrient availability. Nutrient increase was followed by a rise of epiphyte biomass. The increase in epiphytic biomass promoted invertebrate abundance, but appeared to have negative effects on P. oceanica shoot size. On the other hand, the increase in invertebrate abundance did not seem to control epiphytic biomass, which was not reversed to pre-nutrient enrichment levels. This work suggests that the abundance of invertebrate populations is limited by epiphyte biomass, through food or habitat provision, in P. oceanica systems and points to nutrients as the main driver of epiphyte biomass during summer. The results illustrate the control mechanisms at community level in P. oceanica meadows and the possible responses of a threatened ecosystem to human impact such as eutrophication.

  12. Preparation and characterization of Fe(III)-loaded iminodiacetic acid modified GMA grafted nonwoven fabric adsorbent for anion adsorption

    NASA Astrophysics Data System (ADS)

    Kavaklı, Pınar Akkaş; Kavaklı, Cengiz; Güven, Olgun

    2014-01-01

    An Fe(III)-loaded chelating fabric with iminodiacetic acid (IDA) functional groups was prepared by radiation induced graft polymerization of an epoxy group containing monomer, glycidyl methacrylate, onto a nonwoven fabric made of polypropylene coated by polyethylene (PE/PP) and subsequent Fe(III) loading. Grafting conditions were optimized, and GMA grafted polymer was modified with iminodiacetic acid in isopropyl alcohol/water at 80 °C. In order to prepare the polymeric ligand exchanger (PLE) for the removal of phosphate, IDA fabrics were loaded with Fe(III) ions. Fe(III) loading capacity of IDA fabric was determined to be 2.83 mmol Fe(III)/g of polymer. For removal of phosphate anion, adsorption experiments were performed in batch mode at different pH (2-9) and phosphate concentrations. It was found that phosphate adsorption by the Fe(III)-loaded IDA fabric is maximum at pH 2.00. The effect of initial concentration of phosphate on the adsorption behaviour of Fe(III)-loaded IDA nonwoven fabric was determined at low phosphate concentrations (0.5-25 ppm) and at high phosphate concentrations (50-1000 ppm).

  13. Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery.

    PubMed

    Chen, Xingtao; Lv, Guoyu; Zhang, Jue; Tang, Songchao; Yan, Yonggang; Wu, Zhaoying; Su, Jiacan; Wei, Jie

    2014-01-01

    A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 μm to 79.7 μm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery.

  14. In vitro antimicrobial activity of solution blow spun poly(lactic acid)/ polyvinylpyrrolidone nanofibers loaded with Copaiba (Copaifera sp.) oil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study poly(lactic acid)(PLA) and polyvinylpyrrolidone (PVP) micro and nanofibers mats loaded with copaiba (Copaifera sp.) oil were produced by solution blow spinning (SBS). The copaiba (Copaifera sp.) oil was characterized by gas chromatography (GC). Neat PLA and four PLA/ PVP blends contain...

  15. Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid.

    PubMed

    Sriraman, Shravan Kumar; Salzano, Giusseppina; Sarisozen, Can; Torchilin, Vladimir

    2016-08-01

    Cancer-specific drug delivery represents an attractive approach to prevent undesirable side-effects and increase the accumulation of the drug in the tumor. Surface modification of nanoparticles such as liposomes with targeting moieties specific to the up-regulated receptors on the surface of tumor cells thus represents an effective strategy. Furthermore, since this receptor expression can be heterogeneous, using a dual-combination of targeting moieties may prove advantageous. With this in mind, the anti-cancer activity of PEGylated doxorubicin-loaded liposomes targeted with folic acid (F), transferrin (Tf) or both (F+Tf) was evaluated. The dual-targeted liposomes showed a 7-fold increase in cell association compared to either of the single-ligand targeted ones in human cervical carcinoma (HeLa) cell monolayers. The increased penetration and cell association of the dual-targeted liposomes were also demonstrated using HeLa cell spheroids. The in vitro cytotoxicity of the doxorubicin liposomes (LD) was then evaluated using HeLa and A2780-ADR ovarian carcinoma cell monolayers. In both these cell lines, the (F+Tf) LD showed significantly higher cytotoxic effects than the untargeted, or single-ligand targeted liposomes. In a HeLa xenograft model in nude mice, compared to the untreated group, though the untargeted LD showed 42% tumor growth inhibition, both the (F) LD and (F+Tf) LD showed 75% and 79% tumor growth inhibition respectively. These results thus highlight that though the dual-targeted liposomes represent an effective cytotoxic formulation in the in vitro setting, they were equally effective as the folic acid-targeted liposomes in reducing tumor burden in the more complex in vivo setting in this particular model. PMID:27264717

  16. A simulating analysis of the effects of increased joint stiffness on muscle loading in a thumb

    PubMed Central

    2009-01-01

    Background The development of osteoarthritis (OA) in the hand results in increased joint stiffness, which in turn affects the grip strength. The goal of the present study is to theoretically analyze the muscle forces in a thumb in response to the increased joint stiffness. Methods The thumb was modeled as a linkage system consisting of a trapezium, a metacarpal bone, a proximal and a distal phalanx. Nine muscles were included in the model: flexor pollicis longus (FPL), extensor pollicis longus (EPL), extensor pollicis brevis (EPB), abductor pollicis longus (APL), flexor pollicis brevis (FPB), abductor pollicis brevis (APB), the transverse head of the adductor pollicis (ADPt), the oblique head of the adductor pollicis (ADPo), and opponens pollicis (OPP). Numerical tests were performed using an inverse dynamic approach. The joints were prescribed to an angular motion at one degree-of-freedom (DOF) each time with all other DOFs of the joints being mechanically constrained, while the muscle forces in response to the joint motions were predicted. The normal joint stiffness was assumed to be 0.05, 0.10, and 0.15 N m/rad for interphalangeal (IP), metacarpophalangeal (MCP), and carpometacarpal (CMC) joint, respectively. The joint stiffness was assumed to increase by 50% and 100%, simulating the biomechanical consequences of OA. Results Our simulations indicated that the increase in joint stiffness induced substantial increases in muscle forces, especially in the EPL and FPL muscles in response to IP, MCP, or CMC extension/flexion motions. Conclusions Because the strength of the muscles in the fingers is limited, the muscles will not be able to overcome joint resistance if joint stiffness is increased to its limit due to OA. This may contribute to the reduced range of motion typically seen in OA. PMID:20015378

  17. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice.

    PubMed

    Fu, Zidong Donna; Klaassen, Curtis D

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a "dose-response" model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR "dose-dependently" increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum.

  18. Dietary oleic acid increases M2 macrophages in the mesenteric adipose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding in...

  19. Retinoic acid increases the sensitivity of the rat embryo fibroblast transformation assay.

    PubMed Central

    Halazonetis, T D; Daugherty, C; Leder, P

    1988-01-01

    The rat embryo fibroblast focus assay is used to evaluate the transforming potential of several oncogenes. The sensitivity of this assay increased fivefold when retinoic acid was added to tissue culture media. Retinoic acid probably acts by selectively inhibiting the proliferation of nontransformed cells. Images PMID:3380100

  20. Using Content Acquisition Podcasts to Increase Student Knowledge and to Reduce Perceived Cognitive Load

    ERIC Educational Resources Information Center

    Kennedy, Michael J.; Hirsch, Shanna Eisner; Dillon, Sarah E.; Rabideaux, Lindsey; Alves, Kathryn D.; Driver, Melissa K.

    2016-01-01

    The use of multimedia-driven instruction in college courses is an emerging practice designed to increase students' knowledge. However, limited research has validated the effectiveness of using multimedia to teach students about functional behavioral assessments (FBAs). To test the effectiveness of a multimedia tool called Content Acquisition…

  1. The Criteria of Adaptation of Primary School Pupils to the Academic Load of the Increased Intensity

    ERIC Educational Resources Information Center

    Telegina, Nadezhda V.; Belicheva, Tatyana V.

    2016-01-01

    The relevance of the research problem is due to applying various training programs in the modern education system which are supposed to increase teaching efficiency. In-depth study of some subjects at schools, lyceums and gymnasiums which starts in the elementary school quite often leads to tension and failures of adaptation process in innovative…

  2. Childhood-Onset Bipolar Disorder: Evidence for Increased Familial Loading of Psychiatric Illness

    ERIC Educational Resources Information Center

    Rende, Richard; Birmaher, Boris; Axelson, David; Strober, Michael; Gill, Mary Kay; Valeri, Sylvia; Chiappetta, Laurel; Ryan, Neal; Leonard, Henrietta; Hunt, Jeffrey; Iyengar, Satish; Keller, Martin

    2007-01-01

    Objective: To determine whether childhood-onset bipolar disorder (BP) is associated with an increased psychiatric family history compared with adolescent-onset BP. Method: Semistructured psychiatric interviews were conducted for 438 youth with BP spectrum disorders. To evaluate the effects of age at onset and psychiatric family history, the sample…

  3. Electric field assisted transdermal drug delivery from salicylic acid-loaded polyacrylamide hydrogels.

    PubMed

    Niamlang, Sumonman; Sirivat, Anuvat

    2009-10-01

    The apparent diffusion coefficients, D(app), and the release mechanisms of salicylic acid from polyacrylamide hydrogels through pigskin were investigated. D(app) increases with increasing electric field strength and reaches the maximum value at electric field strength of 0.1 V; beyond that it decreases with increasing electric field strength and becomes saturated at 5 V. The increase in D(app) at low electric field strength can be attributed to the combination of iontophoresis, electroporation of matrix pore, and induced pathway in pigskin. D(app) obeys the scaling behavior D(app)/D(o) = (drug size/pore size)m with m equal to 0.67 and 0.49 at the electric field strengths of 0 and 0.1 V, respectively.

  4. Aggravated phosphorus limitation on biomass production under increasing nitrogen loading: a meta-analysis.

    PubMed

    Li, Yong; Niu, Shuli; Yu, Guirui

    2016-02-01

    Nitrogen (N) and phosphorus (P), either individually or in combination, have been demonstrated to limit biomass production in terrestrial ecosystems. Field studies have been extensively synthesized to assess global patterns of N impacts on terrestrial ecosystem processes. However, to our knowledge, no synthesis has been done so far to reveal global patterns of P impacts on terrestrial ecosystems, especially under different nitrogen (N) levels. Here, we conducted a meta-analysis of impacts of P addition, either alone or with N addition, on aboveground (AGB) and belowground biomass production (BGB), plant and soil P concentrations, and N : P ratio in terrestrial ecosystems. Overall, our meta-analysis quantitatively confirmed existing notions: (i) colimitation of N and P on biomass production and (ii) more P limitation in tropical forest than other ecosystems. More importantly, our analysis revealed new findings: (i) P limitation on biomass production was aggravated by N enrichment and (ii) plant P concentration was a better indicator of P limitation than soil P availability. Specifically, P addition increased AGB and BGB by 34% and 13%, respectively. The effect size of P addition on biomass production was larger in tropical forest than grassland, wetland, and tundra and varied with P fertilizer forms, P addition rates, or experimental durations. The P-induced increase in biomass production and plant P concentration was larger under elevated than ambient N. Our findings suggest that the global limitation of P on biomass production will become severer under increasing N fertilizer and deposition in the future.

  5. Achieving Peak Flow and Sediment Loading Reductions through Increased Water Storage in the Le Sueur Watershed, Minnesota: A Modeling Approach

    NASA Astrophysics Data System (ADS)

    Mitchell, N. A.; Gran, K. B.; Cho, S. J.; Dalzell, B. J.; Kumarasamy, K.

    2015-12-01

    A combination of factors including climate change, land clearing, and artificial drainage have increased many agricultural regions' stream flows and rates at which channel banks and bluffs are eroded. Increasing erosion rates within the Minnesota River Basin have contributed to higher sediment-loading rates, excess turbidity levels, and increases in sedimentation rates in Lake Pepin further downstream. Water storage sites (e.g., wetlands) have been discussed as a means to address these issues. This study uses the Soil and Water Assessment Tool (SWAT) to assess a range of water retention site (WRS) implementation scenarios in the Le Sueur watershed in south-central Minnesota, a subwatershed of the Minnesota River Basin. Sediment loading from bluffs was assessed through an empirical relationship developed from gauging data. Sites were delineated as topographic depressions with specific land uses, minimum areas (3000 m2), and high compound topographic index values. Contributing areas for the WRS were manually measured and used with different site characteristics to create 210 initial WRS scenarios. A generalized relationship between WRS area and contributing area was identified from measurements, and this relationship was used with different site characteristics (e.g., depth, hydraulic conductivity (K), and placement) to create 225 generalized WRS scenarios. Reductions in peak flow volumes and sediment-loading rates are generally maximized by placing site with high K values in the upper half of the watershed. High K values allow sites to lose more water through seepage, emptying their storages between precipitation events and preventing frequent overflowing. Reductions in peak flow volumes and sediment-loading rates also level off at high WRS extents due to the decreasing frequencies of high-magnitude events. The generalized WRS scenarios were also used to create a simplified empirical model capable of generating peak flows and sediment-loading rates from near

  6. Valproic Acid Increases the Hepatic Differentiation Potential of Salivary Gland Cells.

    PubMed

    Petrakova, O S; Ashapkin, V V; Shtratnikova, V Y; Kutueva, L I; Vorotelyak, E A; Borisov, M A; Terskikh, V V; Gvazava, I G; Vasiliev, A V

    2015-01-01

    The studies of cell plasticity and differentiation abilities are important problems in modern cellular biology. The use of histone deacetylase inhibitor - valproic acid is a promising approach to increasing the differentiation efficiency of various cell types. In this paper we investigate the ability of mouse submandibular salivary gland cells to differentiate into the hepatic direction and the effect of valproic acid on the efficiency of this differentiation. It was shown that the gene expression levels of hepatocyte markers (Aat, Afp, G6p, Pepck, Tat, Cyp3a13) and liver-enriched transcription factors (Hnf-3α, Hnf-3β, Hnf-4α, Hnf-6) were increased after differentiation in salivary gland cells. Valproic acid increases the specificity of hepatic differentiation, reducing the expression levels of the ductal (Krt19, Hhex1, Cyp7a1) and acinar (Ptf1a) markers. After valproic acid exposure, the efficiency of hepatic differentiation also increases, as evidenced by the increase in the gene expression level of Alb and Tdo, and increase in urea production by differentiated cells. No change was found in DNA methylation of the promoter regions of the genes; however, valproic acid treatment and subsequent hepatic differentiation largely affected the histone H3 methylation of liver-enriched genes. Thus, mouse submandibular salivary gland cells are capable of effective differentiation in the hepatic direction. Valproic acid increases the specificity and efficiency of the hepatic differentiation of these cells.

  7. Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

    PubMed

    Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

    2006-12-11

    In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection. PMID:17045253

  8. The pharmacokinetics and pharmacodynamics of lidocaine- loaded biodegradable poly(lactic-co-glycolic acid) microspheres.

    PubMed

    Liu, Jianming; Lv, Xin

    2014-01-01

    The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(D,L-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34±0.3 μm. The poly disperse index was 0.21±0.03, and the zeta potential was +0.34±0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5%±4.3% and 11.2%±1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02-2.06-fold that of lidocaine injection (p<0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency.

  9. Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading

    NASA Technical Reports Server (NTRS)

    Adams, G. R.

    1998-01-01

    Adaptations in muscle mass stimulated by changes in muscle loading state entail alternations in the synthesis and degradation of myofiber proteins and the modulation of myonuclear number such that the ratio between the number of myonuclei and the size of the myofibers remains relatively constant. As depicted schematically in Figure 2.6, the literature regarding the role of IGF-in mediating muscle adaptation to alterations in loading state suggests the following conclusions: During periods of increased loading, myofibers upregulate the expression and secretion of IGF-I. Acting as an autocrine and/or paracrine growth factor, IGF-I stimulates myofiber anabolic processes. Acting as a paracrine growth factor, IGF-I also stimulates adjacent satellite cells to enter the cell cycle and proliferate. Continued myofiber production of IGF-I stimulates some satellite cells to differentiate and then fuse with myofibers, thus providing additional myonuclei in order to maintain or reestablish the myonucleus to myofiber size ratios of the enlarged myofibers.

  10. Connecting Source with Sink: The Role of Arabidopsis AAP8 in Phloem Loading of Amino Acids1[OPEN

    PubMed Central

    Santiago, James P.; Tegeder, Mechthild

    2016-01-01

    Allocation of large amounts of nitrogen to developing organs occurs in the phloem and is essential for plant growth and seed development. In Arabidopsis (Arabidopsis thaliana) and many other plant species, amino acids represent the dominant nitrogen transport forms in the phloem, and they are mainly synthesized in photosynthetically active source leaves. Following their synthesis, a broad spectrum of the amino nitrogen is actively loaded into the phloem of leaf minor veins and transported within the phloem sap to sinks such as developing leaves, fruits, or seeds. Controlled regulation of the source-to-sink transport of amino acids has long been postulated; however, the molecular mechanism of amino acid phloem loading was still unknown. In this study, Arabidopsis AMINO ACID PERMEASE8 (AAP8) was shown to be expressed in the source leaf phloem and localized to the plasma membrane, suggesting its function in phloem loading. This was further supported by transport studies with aap8 mutants fed with radiolabeled amino acids and by leaf exudate analyses. In addition, biochemical and molecular analyses revealed alterations in leaf nitrogen pools and metabolism dependent on the developmental stage of the mutants. Decreased amino acid phloem loading and partitioning to sinks led to decreased silique and seed numbers, but seed protein levels were unchanged, demonstrating the importance of AAP8 function for sink development rather than seed quality. Overall, these results show that AAP8 plays an important role in source-to-sink partitioning of nitrogen and that its function affects source leaf physiology and seed yield. PMID:27016446

  11. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    SciTech Connect

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A. )

    1990-03-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. (3H) gamma-aminobutyric acid, (14C) butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of (3H) gamma-aminobutyric acid and (113mIn) transferrin were calculated using (14C) butanol as the highly extracted reference compound. The (113mIn) transferrin data were also used to correct the brain uptake index of (3H) gamma-aminobutyric acid for intravascular retention of (3H) gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid (3H) gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy.

  12. Doxorubicin-loaded microgels composed of cinnamic acid-gelatin conjugate and cinnamic acid-Pluronic F127 conjugate.

    PubMed

    Zhang, Hong; Kim, Jin-Chul

    2016-01-01

    Microgels were prepared by cinnamic acid-gelatin (type B) conjugate (CA-GelB) and cinnamic acid-Pluronic F127 conjugate (CA-Plur). (1)H NMR confirmed that CA was conjugated to gelatin and the gelatin to CA residue molar ratio was estimated to be 1:4.7 by a colorimetric method. CA-Plur of which the CA residue to Plur molar ratio was 1.2:1 was used as a thermo-sensitive polymer. The CA residues of CA-Plur/CA-GelB mixture were readily photo-dimerized to form microgels by UV irradiation. The isoelectric point of the microgel was found to be pH 5.8 and the hydrodynamic diameter decreased when the suspension temperature increased. The microgel could hardly retard the release of doxorubicin (DOX) at pH 3.0 and pH 5.0, but it could suppress and control the release at pH 7.4 possibly due to electrostatic attraction. Meanwhile, the release of DOX at pH 7.4 was less suppressed when the medium temperature was higher, possibly because of thermal thinning of Pluronic chain layer.

  13. Poly(lactic) acid fibers loaded with mesoporous silica for potential applications in the active food packaging

    NASA Astrophysics Data System (ADS)

    Cacciotti, Ilaria; Nanni, Francesca

    2016-06-01

    Multifunctional fibrous systems based on poly(lactic) acid (PLA), mesoporous silica (SiO2) and ascorbic acid (AA) were produced by means of electrospinning technique, for potential applications in the active food packaging sector, as platform for the controlled release of antioxidant and/or antimicrobial agents with the additional filtering function. The ascorbic acid was physisorbed on the surface of mesoporous silica in order to stabilize it and to extend its antioxidant action. The influence of mesoporous silica and ascorbic acid on the microstructural and mechanical properties was investigated, revealing a revelant mechanical reinforcement in the case of fibers loaded only with SiO2 and a decrement in the case of SiO2 with physisorbed ascorbic acid, due to the worse interface between the fillers and the polymeric matrix.

  14. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli

    PubMed Central

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M.; Baerga-Ortiz, Abel

    2014-01-01

    Increasing the production of fatty acids by microbial fermentation remains an important step towards the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations towards accessible biodiesel precursors. PMID:24411456

  15. Increased oxygen load in the prefrontal cortex from mouth breathing: a vector-based near-infrared spectroscopy study.

    PubMed

    Sano, Masahiro; Sano, Sayaka; Oka, Noriyuki; Yoshino, Kayoko; Kato, Toshinori

    2013-12-01

    Individuals who habitually breathe through the mouth are more likely than nasal breathers to have sleep disorders and attention deficit hyperactive disorder. We hypothesized that brain hemodynamic responses in the prefrontal cortex might be different for mouth and nasal breathing. To test this hypothesis, we measured changes in oxyhemoglobin and deoxyhemoglobin in the prefrontal cortex during mouth breathing and nasal breathing in healthy adults (n=9) using vector-based near-infrared spectroscopy. The angle k, calculated from changes in oxyhemoglobin and deoxyhemoglobin and indicating the degree of oxygen exchange, was significantly higher during mouth breathing (P<0.05), indicating an increased oxygen load. Mouth breathing also caused a significant increase in deoxyhemoglobin, but oxyhemoglobin did not increase. This difference in oxygen load in the brain arising from different breathing routes can be evaluated quantitatively using vector-based near-infrared spectroscopy. Phase responses could help to provide an earlier and more reliable diagnosis of a patient's habitual breathing route than a patient interview.

  16. Effects of incremental increases in silt load on the cardiovascular performance of riverine and lacustrine rock bass, Ambloplites rupestris.

    PubMed

    Bunt, Christopher M; Cooke, Steven J; Schreer, Jason F; Philipp, David P

    2004-01-01

    Rock bass (Ambloplites rupestris) are a widespread centrarchid species with both riverine and lacustrine populations. After precipitation events, rivers often carry elevated silt loads, where as lakes generally remain free from suspended silt and sediment. To examine the physiological effects of silt on rock bass, we conducted a series of experiments using fish from Lake Opinicon and the Grand River in Ontario. Ultrasonic Doppler flow probes were surgically affixed around the ventral aorta to monitor cardiovascular performance. After recovery from surgery replicated treatment groups were exposed to incremental increases in silt load (made from bentonite slurry), while cardiac output and its two components, heart rate and stroke volume, were measured simultaneously. Although both groups of rock bass responded significantly to low concentrations of silt (10 NTU), the response by riverine rock bass was rapidly extinguished by acclimation or physiological adjustment. Compensatory mechanisms to minimize cardiac (and respiratory) disruption attributable to increases in suspended silt appear to be inherent in rock bass of riverine origin. These fish appear to fully compensate for interference in gas exchange at the gill surfaces 60 min after initial exposure. In contrast, individual lacustrine rock bass were highly variable in their response to elevated silt concentrations. Changes in stroke volume and cardiac output suggested no clear compensatory mechanism or strategy to cope with increased silt levels.

  17. Robot applied stance loading increases hindlimb muscle mass and stepping kinetics in a rat model of spinal cord injury.

    PubMed

    Nessler, Jeff A; Moustafa-Bayoumi, Moustafa; Soto, Dalziel; Duhon, Jessica E; Schmitt, Ryan

    2011-01-01

    Following spinal cord injury (SCI) reduced limb usage typically results in muscle atrophy. While robotic locomotor training has been shown to improve several aspects of stepping ability following SCI, little is known regarding the effects of automated training on the preservation of muscle function. The purpose of this study was to evaluate the effects of two robotic locomotor training algorithms on hindlimb strength and muscle mass in a rat model of SCI. Eighteen Sprague-Dawley rats received a mid-thoracic spinal cord transection at 5 days of age, and were randomly assigned to one of three groups: control (no training), standard robotic training, and robotic training with a downward force applied to the shank during the stance phase of gait. Training occurred 5 days/week for 5 min/day, and animals received 90% body weight support for all sessions. Following 4 weeks of training, vertical and propulsive ground reaction force during stepping and en vitro mass of two plantarflexor muscles were significantly increased for all of the trained animals when compared to the untrained control group. Post hoc analysis revealed that standard robotic training did not appear to increase ground reaction force and muscle mass to the same extent as the loaded condition. These results indicate that automated robotic training helps to preserve hindlimb muscle function in rats following SCI. Further, the addition of a plantarflexion stance load appears to promote greater increases in muscle mass and stepping kinetics.

  18. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility.

    PubMed

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M

    2016-01-01

    Mice lacking three epidermal barrier proteins-envoplakin, periplakin, and involucrin (EPI-/- mice)-have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4(+) T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance.

  19. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility

    PubMed Central

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M.

    2016-01-01

    Mice lacking three epidermal barrier proteins—envoplakin, periplakin, and involucrin (EPI-/- mice)—have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4+ T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance. PMID:26763429

  20. Chlorogenic acid increased acrylamide formation through promotion of HMF formation and 3-aminopropionamide deamination.

    PubMed

    Cai, Yun; Zhang, Zhenhua; Jiang, Shanshan; Yu, Miao; Huang, Caihuan; Qiu, Ruixia; Zou, Yueyu; Zhang, Qirui; Ou, Shiyi; Zhou, Hua; Wang, Yong; Bai, Weibing; Li, Yiqun

    2014-03-15

    This research was aimed to investigate why chlorogenic acid, presents at high concentrations in some food raw material, influences acrylamide formation. In the asparagine/glucose Maillard reaction system (pH=6.8), addition of chlorogenic acid significantly increased acrylamide formation and inhibited its elimination. In contrast, the quinone derivative of chlorogenic acid decreased acrylamide formation. Three mechanisms may be involved for increasing acrylamide formation by chlorogenic acid. Firstly, it increased the formation of HMF, which acts as a more efficient precursor than glucose to form acrylamide. Secondly, it decreased activation energy for conversion of 3-aminopropionamide (3-APA) to acrylamide (from 173.2 to 136.6kJ/mol), and enhances deamination from 3-APA. And thirdly, it prevented attack of the produced acrylamide from free radicals by keeping high redox potential during the Maillard reaction.

  1. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

  2. Tetradecylthioacetic acid increases fat metabolism and improves cardiac function in experimental heart failure.

    PubMed

    Øie, Erik; Berge, Rolf K; Ueland, Thor; Dahl, Christen P; Edvardsen, Thor; Beitnes, Jan Otto; Bohov, Pavol; Aukrust, Pål; Yndestad, Arne

    2013-02-01

    Changes in myocardial metabolism, including a shift from fatty acid to glucose utilization and changes in fatty acid availability and composition are characteristics of heart failure development. Tetradecylthioacetic acid (TTA) is a fatty acid analogue lacking the ability to undergo mitochondrial β-oxidation. TTA promotes hepatic proliferation of mitochondria and peroxisomes and also decreases serum triglycerides and cholesterol in animals. We investigated the effect of TTA, in combination with a high-fat or regular diet, in a rat model of post-myocardial infarction heart failure. TTA had a beneficial effect on cardiac function in post-myocardial infarction heart failure without affecting myocardial remodeling. These effects of TTA on myocardial function were accompanied by decreased free fatty acids in plasma, increased myocardial proportion of n-3 polyunsaturated fatty acids (PUFA) and a decreased proportion of n-6 PUFA. Myocardial enzyme gene expression during TTA treatment suggested that the increase in n-3 PUFA could reflect increased n-3 PUFA synthesis and inadequately increased n-3 PUFA β-oxidation. Based on our data, it is unlikely that the changes are secondary to alterations in other tissues as plasma and liver showed an opposite pattern with decreased n-3 PUFA during TTA treatment. The present study suggests that TTA may improve myocardial function in heart failure, potentially involving its ability to decrease the availability of FFA and increase the myocardial proportion of n-3 PUFA. PMID:23266898

  3. High hydrostatic pressure increases amino acid requirements in the piezo-hyperthermophilic archaeon Thermococcus barophilus.

    PubMed

    Cario, Anaïs; Lormières, Florence; Xiang, Xiao; Oger, Philippe

    2015-11-01

    We have established a defined growth medium for the piezophilic hyperthermophilic archaeon Thermococcus barophilus, which allows growth yields of ca. 10(8) cells/ml under both atmospheric and high hydrostatic pressure. Our results demonstrate a major impact of hydrostatic pressure on amino acid metabolism, with increases from 3 amino acids required at atmospheric pressure to 17 at 40 MPa. We observe in T. barophilus and other Thermococcales a similar discrepancy between the presence/absence of amino acid synthesis pathways and amino acid requirements, which supports the existence of alternate, but yet unknown, amino acid synthesis pathways, and may explain the low number of essential amino acids observed in T. barophilus and other Thermococcales. T. barophilus displays a strong metabolic preference for organic polymers such as polypeptides and chitin, which may constitute a more readily available resource of carbon and energy in situ in deep-sea hydrothermal vents. We hypothesize that the low energy yields of fermentation of organic polymers, together with energetic constraints imposed by high hydrostatic pressure, may render de novo synthesis of amino acids ecologically unfavorable. Induction of this metabolic switch to amino acid recycling can explain the requirement for non-essential amino acids by Thermococcales for efficient growth in defined medium. PMID:26226334

  4. High hydrostatic pressure increases amino acid requirements in the piezo-hyperthermophilic archaeon Thermococcus barophilus.

    PubMed

    Cario, Anaïs; Lormières, Florence; Xiang, Xiao; Oger, Philippe

    2015-11-01

    We have established a defined growth medium for the piezophilic hyperthermophilic archaeon Thermococcus barophilus, which allows growth yields of ca. 10(8) cells/ml under both atmospheric and high hydrostatic pressure. Our results demonstrate a major impact of hydrostatic pressure on amino acid metabolism, with increases from 3 amino acids required at atmospheric pressure to 17 at 40 MPa. We observe in T. barophilus and other Thermococcales a similar discrepancy between the presence/absence of amino acid synthesis pathways and amino acid requirements, which supports the existence of alternate, but yet unknown, amino acid synthesis pathways, and may explain the low number of essential amino acids observed in T. barophilus and other Thermococcales. T. barophilus displays a strong metabolic preference for organic polymers such as polypeptides and chitin, which may constitute a more readily available resource of carbon and energy in situ in deep-sea hydrothermal vents. We hypothesize that the low energy yields of fermentation of organic polymers, together with energetic constraints imposed by high hydrostatic pressure, may render de novo synthesis of amino acids ecologically unfavorable. Induction of this metabolic switch to amino acid recycling can explain the requirement for non-essential amino acids by Thermococcales for efficient growth in defined medium.

  5. Synthesis of nanosilver loaded chitosan/poly(acrylamide-co-itaconic acid) based inter-polyelectrolyte complex films for antimicrobial applications.

    PubMed

    Bajpai, S K; Jyotishi, Pooja; Bajpai, M

    2016-12-10

    In the present work, AgNPs loaded chitosan/poly(acrylamide-co-itaconic acid) inter-polyelectrolyte complex (IPC) films have been prepared for antimicrobial applications. The AgNPs-loaded IPC films have been characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA) and Surface plasmon resonance (SPR). Particle size of synthesized AgNPs was found to be in the range 10-30nm. These films exhibited a remarkable antibacterial property against strong pathogen E.Coli, thus offering their candidature for antimicrobial applications. PMID:27577913

  6. Steady state critical loads of acidity for sulphur and nitrogen: a multi-receptor, multi-criterion approach.

    PubMed

    Aherne, J; Farrell, E P

    2002-04-15

    The critical load approach to emission reductions has become an important element of the United Nations Economic Commission for Europe (UNECE) Convention on Long-Range Transboundary Air Pollution (CLRTAP). The steady state mass balance approach (SSMB) is the most widely used method in Europe for estimating critical loads, typically applied to forest ecosystems on mineral soils in conjunction with a base cation to aluminium (Bc:Al) ratio using a default critical limit of 1.0. The 'typical' approach has been expanded in this paper by: inclusion of a broader range of natural and semi-natural receptor ecosystems; inclusion of multiple chemical criterion for each receptor; and an attempt to include organic soils (peatlands). Critical loads of acidity were estimated for the Republic of Ireland using four receptor ecosystems (coniferous forest, deciduous forest, natural grasslands and moors and heathlands) and seven chemical criteria. The dominant chemical criteria, in the determination of critical loads, were based on a critical pH limit for mineral soils or a critical pH shift in relation to pristine conditions for organic soils. Approximately 68 and 26% of the final distribution of critical loads were estimated using these criteria, respectively. The 5th-percentile critical loads of acidity were more sensitive than those previously estimated for Ireland due to the inclusion of organic soils. Furthermore, coniferous ecosystems had the lowest critical loads due to the high percentage occurring on organic soils, and the removal of base cations through harvesting. The results demonstrate that it may be more appropriate to use multiple criteria and receptors to ensure adequate protection of biological indicators. However, it is important that appropriate critical limits are chosen to protect the biological indicators and receptor ecosystems from long-term damage.

  7. Increased intestinal amino-acid retention from the addition of carbohydrates to a meal.

    PubMed

    Deutz, N E; Ten Have, G A; Soeters, P B; Moughan, P J

    1995-12-01

    Carbohydrates, added to a protein meal, are known to enhance the efficiency of dietary protein utilisation. However, the respective roles of the gut and liver in relation to this enhanced efficiency are not known. Therefore, we studied amino-acid, ammonia, urea, glucose and lactate fluxes for 6 h across the portal drained viscera and liver in conscious, multi-catheterised pigs of approximately 25 kg body weight after receiving a protein meal with added carbohydrates, a pure protein meal or a control meal. Additional carbohydrate caused a net glucose efflux in the portal drained viscera and increased arterial blood insulin levels. The appearance of amino-acids in the portal blood declined by some 30%, in spite of the dietary true amino-acid digestibility being approximately 95%. Liver uptake of most amino-acids was lower and there was a lower liver urea production. Finally, there was a smaller postprandial increase in the arterial blood concentration for most of the amino-acids. The results of this study suggest that inclusion of maltodextrin in the diet increases the net retention of meal-derived amino-acids in the portal drained viscera. The lower urea production and liver amino-acid uptake suggest a lower nitrogen loss. The gut could be an important site for nitrogen retention induced by the addition of carbohydrates to a protein meal.

  8. Effect of the Organic Loading Rate Increase and the Presence of Zeolite on Microbial Community Composition and Process Stability During Anaerobic Digestion of Chicken Wastes.

    PubMed

    Ziganshina, Elvira E; Belostotskiy, Dmitry E; Ilinskaya, Olga N; Boulygina, Eugenia A; Grigoryeva, Tatiana V; Ziganshin, Ayrat M

    2015-11-01

    This study investigates the effect of the organic loading rate (OLR) increase from 1.0 to 3.5 g VS L(-1) day(-1) at constant hydraulic retention time (HRT) of 35 days on anaerobic reactors' performance and microbial diversity during mesophilic anaerobic digestion of ammonium-rich chicken wastes in the absence/presence of zeolite. The effects of anaerobic process parameters on microbial community structure and dynamics were evaluated using a 16S ribosomal RNA gene-based pyrosequencing approach. Maximum 12 % of the total ammonia nitrogen (TAN) was efficiently removed by zeolite in the fixed zeolite reactor (day 87). In addition, volatile fatty acids (VFA) in the fixed zeolite reactor accumulated in lower concentrations at high OLR of 3.2-3.5 g VS L(-1) day(-1). Microbial communities in the fixed zeolite reactor and reactor without zeolite were dominated by various members of Bacteroidales and Methanobacterium sp. at moderate TAN and VFA levels. The increase of the OLR accompanied by TAN and VFA accumulation and increase in pH led to the predominance of representatives of the family Erysipelotrichaceae and genera Clostridium and Methanosarcina. Methanosarcina sp. reached relative abundances of 94 and 57 % in the fixed zeolite reactor and reactor without zeolite at the end of the experimental period, respectively. In addition, the diminution of Synergistaceae and Crenarchaeota and increase in the abundance of Acholeplasmataceae in parallel with the increase of TAN, VFA, and pH values were observed.

  9. Developing Critical Loads of acidity for streams in the Great Smoky Mountains National Park, using PnET-BGC model

    NASA Astrophysics Data System (ADS)

    Fakhraei, H.

    2015-12-01

    Acid deposition has impaired acid-sensitive streams and reduced aquatic biotic integrity in Great Smoky Mountains National Park (GRSM) by decreasing pH and acid neutralizing capacity (ANC). Twelve streams in GRSM are listed by the state of Tennessee as impaired due to low stream pH (pH<6.0) under Section 303(d) of the Clean Water Act. A dynamic biogeochemical model, PnET-BGC, was used to evaluate past, current and potential future changes in soil and water chemistry of watersheds of GRSM in response to changes in acid deposition. Calibrating 30 stream-watersheds in GRSM (including 12 listed impaired streams) to the long-term stream chemistry observations, the model was parameterized for the Park. The calibrated model was used to evaluate the level of atmospheric deposition above which harmful effects occur, known as "critical loads", for individual study watersheds. Estimated critical loads and exceedances (levels of deposition above the critical load) of atmospheric sulfur and nitrogen deposition were depicted through geographic information system maps. Accuracy of model simulations in the presence of uncertainties in the estimated model parameters and inputs was assessed using three uncertainty and sensitivity techniques.

  10. Poly(ε-caprolactone)/triclosan loaded polylactic acid nanoparticles composite: A long-term antibacterial bionanocomposite with sustained release.

    PubMed

    Kaffashi, Babak; Davoodi, Saeed; Oliaei, Erfan

    2016-07-11

    In this study, the antibacterial bionanocomposites of poly(ε-caprolactone) (PCL) with different concentrations of triclosan (TC) loaded polylactic acid (PLA) nanoparticles (30wt% triclosan) (LATC30) were fabricated via a melt mixing process in order to lower the burst release of PCL and to extend the antibacterial activity during its performance. Due to the PLA's higher glass transition temperature (Tg) and less flexibility compared with PCL; the PLA nanoparticles efficiently trapped the TC particles, reduced the burst release of TC from the bionanocomposites; and extended the antibacterial property of the samples up to two years. The melt mixing temperature was adjusted to a temperature lower than the melting point of LATC30 nanoparticles; therefore, these nanoparticles were dispersed in the PCL matrix without any chemical reaction and/or drug extraction. The sustained release behavior of TC from PCL remained unchanged since no significant changes occurred in the samples' crystallinity compared with that in the neat PCL. The elastic moduli of samples were enhanced once LATC30 is included. This is necessary since the elastic modulus is decreased with water absorption. The rheological behaviors of samples showed appropriate properties for melt electro-spinning. A stable process was established as the relaxation time of the bionanocomposites was increased. The hydrophilic properties of samples were increased with increasing LATC30. The proliferation rate of the fibroblast (L929) cells was enhanced as the content of nanoparticles was increased. A system similar to this could be implemented to prepare long-term antibacterial and drug delivery systems based on PCL and various low molecular weight drugs. The prepared bionanocomposites are considered as candidates for the soft connective tissue engineering and long-term drug delivery.

  11. Antitumor Activity of Doxorubicin-Loaded Carbon Nanotubes Incorporated Poly(Lactic-Co-Glycolic Acid) Electrospun Composite Nanofibers

    NASA Astrophysics Data System (ADS)

    Yu, Yuan; Kong, Lijun; Li, Lan; Li, Naie; Yan, Peng

    2015-08-01

    The drug-loaded composite electrospun nanofiber has attracted more attention in biomedical field, especially in cancer therapy. In this study, a composite nanofiber was fabricated by electrospinning for cancer treatment. Firstly, the carbon nanotubes (CNTs) were selected as carriers to load the anticancer drug—doxorubicin (DOX) hydrochloride. Secondly, the DOX-loaded CNTs (DOX@CNTs) were incorporated into the poly(lactic-co-glycolic acid) (PLGA) nanofibers via electrospinning. Finally, a new drug-loaded nanofibrous scaffold (PLGA/DOX@CNTs) was formed. The properties of the prepared composite nanofibrous mats were characterized by various techniques. The release profiles of the different DOX-loaded nanofibers were measured, and the in vitro antitumor efficacy against HeLa cells was also evaluated. The results showed that DOX-loaded CNTs can be readily incorporated into the nanofibers with relatively uniform distribution within the nanofibers. More importantly, the drug from the composite nanofibers can be released in a sustained and prolonged manner, and thereby, a significant antitumor efficacy in vitro is obtained. Thus, the prepared composite nanofibrous mats are a promising alternative for cancer treatment.

  12. Radiosensitization of TPGS-emulsified docetaxel-loaded poly(lactic-co-glycolic acid) nanoparticles in CNE-1 and A549 cells.

    PubMed

    Shi, Wei; Yuan, Yin; Chu, Min; Zhao, Shuang; Song, Qingle; Mu, Xiaoqian; Xu, Shuangbing; Zhang, Zhiping; Yang, Kunyu

    2016-03-01

    Docetaxel is among the most effective radiosensitizers. It is widely used as radiosensitizer in many tumors, including head and neck carcinoma. Nevertheless, poor solubility and severe hypersensitivity limit its clinical use and its therapeutic effect remains to be improved. In this study, docetaxel-loaded polymeric nanoparticles were prepared by nanoprecipitation method to be new radiosensitizer with lower side effects and higher efficacy. The physiochemical characteristics of the nanoparticles were studied. Two human tumor cell lines which are resistant to radiotherapy were used in this research. We have compared the radioenhancement efficacy of docetaxel-loaded nanoparticles with docetaxel in A549 and CNE-1 cells. Compared with docetaxel, radiosensitization of docetaxel-loaded nanoparticles was improved significantly (sensitization enhancement ratio in A549 increased 1.24-fold to 1.68-fold when the radiation was applied 2 h after the drug, p < 0.01, sensitization enhancement ratio in CNE-1 increased 1.32-fold to 1.61-fold, p < 0.05). We explored the mechanisms for the radiosensitization efficiency and the difference between docetaxel and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, promoted apoptosis and the role of D-alpha-tocopheryl polyethylene glycol 1000 succinate which will enhance the cell uptake and inhibit the multiple drug resistance. Moreover, the radiosensitization efficacy of docetaxel-loaded nanoparticles was more prominent than docetaxel. In conclusion, tocopheryl polyethylene glycol 1000 succinate-emulsified docetaxel-loaded PLGA nanoparticles were more efficacious and fewer adverse effects were observed than with the commercial docetaxel formulation. Thus, PLGA nanoparticles hold promise as a radiosensitizing agent. PMID:26608458

  13. Comparable Cerebral Oxygenation Patterns in Younger and Older Adults during Dual-Task Walking with Increasing Load

    PubMed Central

    Fraser, Sarah A.; Dupuy, Olivier; Pouliot, Philippe; Lesage, Frédéric; Bherer, Louis

    2016-01-01

    The neuroimaging literature on dual-task gait clearly demonstrates increased prefrontal cortex (PFC) involvement when performing a cognitive task while walking. However, findings from direct comparisons of the cerebral oxygenation patterns of younger (YA) and older (OA) adults during dual-task walking are mixed and it is unclear how YA and OA respond to increasing cognitive load (difficulty) while walking. This functional near infra-red (fNIRS) study examined cerebral oxygenation of YA and OA during self-paced dual-task treadmill walking at two different levels of cognitive load (auditory n-back). Changes in accuracy (%) as well as oxygenated (HbO) and deoxygenated (HbR) hemoglobin were examined. For the HbO and HbR measures, eight regions of interest (ROIs) were assessed: the anterior and posterior dorsolateral and ventrolateral PFC (aDLPFC, pDLPFC, aVLPFC, pVLPFC) in each hemisphere. Nineteen YA (M = 21.83 years) and 14 OA (M = 66.85 years) walked at a self-selected pace while performing auditory 1-back and 2-back tasks. Walking alone (single motor: SM) and performing the cognitive tasks alone (single cognitive: SC) were compared to dual-task walking (DT = SM + SC). In the behavioural data, participants were more accurate in the lowest level of load (1-back) compared to the highest (2-back; p < 0.001). YA were more accurate than OA overall (p = 0.009), and particularly in the 2-back task (p = 0.048). In the fNIRS data, both younger and older adults had task effects (SM < DT) in specific ROIs for ΔHbO (three YA, one OA) and ΔHbR (seven YA, eight OA). After controlling for walk speed differences, direct comparisons between YA and OA did not reveal significant age differences, but did reveal a difficulty effect in HbO in the left aDLPFC (p = 0.028) and significant task effects (SM < DT) in HbR for six of the eight ROIs. Findings suggest that YA and OA respond similarly to manipulations of cognitive load when walking on a treadmill at a self-selected pace. PMID

  14. Maximum power output and load matching of a phosphoric acid fuel cell-thermoelectric generator hybrid system

    NASA Astrophysics Data System (ADS)

    Chen, Xiaohang; Wang, Yuan; Cai, Ling; Zhou, Yinghui

    2015-10-01

    Based on the current models of phosphoric acid fuel cells (PAFCs) and thermoelectric generators (TGs), a new hybrid system is proposed, in which the effects of multi-irreversibilities resulting from the activation, concentration, and ohmic overpotentials in the PAFC, Joule heat and heat leak in the TG, finite-rate heat transfer between the TG and the heat reservoirs, and heat leak from the PAFC to the environment are taken into account. Expressions for the power output and efficiency of the PAFC, TG, and hybrid system are analytically derived and directly used to discuss the performance characteristics of the hybrid system. The optimal relationship between the electric currents in the PAFC and TG is obtained. The maximum power output is numerically calculated. It is found that the maximum power output density of the hybrid system will increase about 150 Wm-2, compared with that of a single PAFC. The problem how to optimally match the load resistances of two subsystems is discussed. Some significant results for practical hybrid systems are obtained.

  15. Propagated fixed-bed mixed-acid fermentation: effect of volatile solid loading rate and agitation at near-neutral pH.

    PubMed

    Golub, Kristina W; Golub, Stacey R; Meysing, Daniel M; Holtzapple, Mark T

    2012-11-01

    To increase conversion and product concentration, mixed-acid fermentation can use a countercurrent strategy where solids and liquids pass in opposite directions through a series of fermentors. To limit the requirement for moving solids, this study employed a propagated fixed-bed fermentation, where solids were stationary and only liquid was transferred. To evaluate the role of agitation, continuous mixing was compared with periodic mixing. The periodically mixed fermentation had similar conversion, but lower yield and selectivity. Increasing volatile solid loading rate from 1.5 to 5.1g non-acid volatile solids/(L(liq)·d) and increasing liquid retention time decreased yield, conversion, selectivity, but increased product concentrations. Compared to a previous study at high pH (~9), this study achieved higher performance at near neutral pH (~6.5) and optimal C-N ratios. Compared to countercurrent fermentation, propagated fixed-bed fermentations have similar selectivities and produce similar proportions of acetic acid, but have lower yields, conversion, productivities, and acid concentrations. PMID:22995159

  16. Propagated fixed-bed mixed-acid fermentation: effect of volatile solid loading rate and agitation at near-neutral pH.

    PubMed

    Golub, Kristina W; Golub, Stacey R; Meysing, Daniel M; Holtzapple, Mark T

    2012-11-01

    To increase conversion and product concentration, mixed-acid fermentation can use a countercurrent strategy where solids and liquids pass in opposite directions through a series of fermentors. To limit the requirement for moving solids, this study employed a propagated fixed-bed fermentation, where solids were stationary and only liquid was transferred. To evaluate the role of agitation, continuous mixing was compared with periodic mixing. The periodically mixed fermentation had similar conversion, but lower yield and selectivity. Increasing volatile solid loading rate from 1.5 to 5.1g non-acid volatile solids/(L(liq)·d) and increasing liquid retention time decreased yield, conversion, selectivity, but increased product concentrations. Compared to a previous study at high pH (~9), this study achieved higher performance at near neutral pH (~6.5) and optimal C-N ratios. Compared to countercurrent fermentation, propagated fixed-bed fermentations have similar selectivities and produce similar proportions of acetic acid, but have lower yields, conversion, productivities, and acid concentrations.

  17. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    PubMed Central

    Oraldi, Manuela; Trombetta, Antonella; Biasi, Fiorella; Canuto, Rosa A.; Maggiora, Marina; Muzio, Giuliana

    2009-01-01

    Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s). Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis. PMID:19841681

  18. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking.

    PubMed

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-10-24

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression.

  19. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability.

    PubMed

    Sequeira, Ivana R; Kruger, Marlena C; Hurst, Roger D; Lentle, Roger G

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways.

  20. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking

    PubMed Central

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-01-01

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression. PMID:21964384

  1. Palmitate Induces mRNA Translation and Increases ER Protein Load in Islet β-Cells via Activation of the Mammalian Target of Rapamycin Pathway

    PubMed Central

    Hatanaka, Masayuki; Maier, Bernhard; Sims, Emily K.; Templin, Andrew T.; Kulkarni, Rohit N.; Evans-Molina, Carmella

    2014-01-01

    Saturated free fatty acids (FFAs) have complex effects on the islet β-cell, acutely promoting adaptive hyperplasia but chronically impairing insulin release. The acute effects of FFAs remain incompletely defined. To elucidate these early molecular events, we incubated mouse β-cells and islets with palmitate and then studied mRNA translation by polyribosomal profiling and analyzed signaling pathways by immunoblot analysis. We found that palmitate acutely increases polyribosome occupancy of total RNA, consistent with an increase in mRNA translation. This effect on translation was attributable to activation of mammalian target of rapamycin (mTOR) pathways via L-type Ca2+ channels but was independent of insulin signaling. Longer incubations led to depletion of polyribosome-associated RNA, consistent with activation of the unfolded protein response (UPR). Pharmacologic inhibition of mTOR suppressed both the acute effects of palmitate on mRNA translation and the chronic effects on the UPR. Islets from mice fed a high-fat diet for 7 days showed increases in polyribosome-associated RNA and phosphorylation of S6K, both consistent with activation of mTOR. Our results suggest that palmitate acutely activates mRNA translation and that this increase in protein load contributes to the later UPR. PMID:24834975

  2. Microbial population dynamics in response to increasing loadings of pre-hydrolyzed pig manure in an expanded granular sludge bed.

    PubMed

    Wang, Haoyu; Tao, Yu; Gao, Dawen; Liu, Gang; Chen, Chunhong; Ren, Nanqi; van Lier, Jules B; de Kreuk, Merle

    2015-12-15

    In recent years, pig manure (PM) has been regarded as a valuable substrate for energy and resource recovery via bioprocesses such as anaerobic digestion (AD), however, the efficiency of digesting raw PM is limited by the presence of refractory compounds. In this study, we applied a series of pretreatment on raw PM, consisting of subsequent thermochemical pretreatment, enzymatic hydrolysis, tyndallization and filtration. The liquid PM hydrolysates were fed to an expanded granular sludge bed (EGSB) for the production of biogas. The general performance and population dynamics of the EGSB reactor were assessed during an extended operational period of 339 days. An efficient and stable digestion process was achieved under high organic loading rates (OLRs) up to 21 kg-COD/(m(3)·d), agreeing with a sludge loading rate of 0.75 kg-COD/(kg-VSS·d), 1600 mg-NH4(+)-N/L and 17 mg/L of free ammonia nitrogen. The tyndallization decreased the total amount of active cells from 1 × 10(8) to 1 × 10(2) CFU/ml. Hence, bio-augmentation with pigs' intestinal microbiota was absent and the community dynamics were mainly credited to the composition of the substrate (i.e. PM hydrolysates) and the environmental conditions inside the reactor. The results showed the influence of both the seed community and the imposed loading rates on the evolutionary trajectory of the EGSB microbial community. Four bacterial genera (Clostridium, Cytophaga, Bacillus and Bacteroides) and two methanogenic genera (Methanosaeta and Methanobacterium) dominated the communities. An obvious shift from aceticlastic Methanosaeta to hydrogenotrophic Methanobacterium appeared when the OLR was increased to over 10 kg-COD/(m(3)·d). PMID:26378729

  3. Comparison among model estimates of critical loads of acidic deposition using different sources and scales of input data.

    PubMed

    McDonnell, T C; Cosby, B J; Sullivan, T J; McNulty, S G; Cohen, E C

    2010-09-01

    The critical load (CL) of acidic atmospheric deposition represents the load of acidity deposited from the atmosphere to the earth's surface at which harmful acidification effects on sensitive biological receptors are thought to occur. In this study, the CL for forest soils was estimated for 27 watersheds throughout the United States using a steady-state mass balance approach based on both national and site-specific data and using different approaches for estimating base cation weathering. Results suggested that the scale and source of input data can have large effects on the calculated CL and that the most important parameter in the steady-state model used to estimate CL is base cation weathering. These results suggest that the data and approach used to estimate weathering must be robust if the calculated CL is to be useful for its intended purpose.

  4. Comparison among model estimates of critical loads of acidic deposition using different sources and scales of input data.

    PubMed

    McDonnell, T C; Cosby, B J; Sullivan, T J; McNulty, S G; Cohen, E C

    2010-09-01

    The critical load (CL) of acidic atmospheric deposition represents the load of acidity deposited from the atmosphere to the earth's surface at which harmful acidification effects on sensitive biological receptors are thought to occur. In this study, the CL for forest soils was estimated for 27 watersheds throughout the United States using a steady-state mass balance approach based on both national and site-specific data and using different approaches for estimating base cation weathering. Results suggested that the scale and source of input data can have large effects on the calculated CL and that the most important parameter in the steady-state model used to estimate CL is base cation weathering. These results suggest that the data and approach used to estimate weathering must be robust if the calculated CL is to be useful for its intended purpose. PMID:20609503

  5. Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

    PubMed Central

    Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

    2013-01-01

    The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

  6. A West Nile virus mutant with increased resistance to acid-induced inactivation.

    PubMed

    Martín-Acebes, Miguel A; Saiz, Juan-Carlos

    2011-04-01

    West Nile virus (WNV) is a mosquito-borne flavivirus responsible for epidemics of febrile illness, meningitis, encephalitis and flaccid paralysis. WNV gains entry into host cells through endocytosis. The acid pH inside endosomes triggers rapid conformational rearrangements of the flavivirus envelope (E) glycoprotein that result in fusion of the endosomal membrane with the virion envelope. Conformational rearrangements of the E glycoprotein can be induced by acid exposure in solution in the absence of target membranes, thus causing a loss of infectivity. Following a genetic approach to study this process, a WNV mutant with increased resistance to acid-induced inactivation was isolated and its complete genome was sequenced. A single amino acid substitution, T70I, in the E glycoprotein was found to be responsible for the increased acid resistance, which was linked to an increase in the sensitivity of infection to the chemical rise of endosomal pH, suggesting that the mutant required a more acid pH inside the endosomes for fusion. No alterations in viral infection kinetics, plaque size or induced mortality rates in mice of the mutant were noted. However, by means of virus competition assays, a reduction in viral fitness under standard culture conditions was observed for the mutant. These results provide new evidence of the adaptive flexibility to environmental factors--pH variation in this case--of WNV populations. Implications of the T70I replacement on the E glycoprotein structure-function relationship are discussed.

  7. Design and optimization of oleanolic/ursolic acid-loaded nanoplatforms for ocular anti-inflammatory applications.

    PubMed

    Alvarado, Helen L; Abrego, Guadalupe; Garduño-Ramirez, María L; Clares, Beatriz; Calpena, Ana C; García, María L

    2015-04-01

    Oleanolic acid (OA) and ursolic acid (UA) are ubiquitous pentacyclic triterpenes compounds in plants with great interest as anti-inflammatory therapeutics. The aim of this study was the design and optimization of polymeric nanoparticles (NPs) loaded with natural and synthetic mixtures (NM, SM) of these drugs for ophthalmic administration. A 2(3) + star central rotatable composite design was employed to perform the experiments. Results showed optimal and stable formulations with suitable physicochemical properties (mean diameter<225 nm), homogeneous distribution (polydispersity index∼0.1), negatively charged surface (∼-27 mV) and high entrapment efficiency (∼77%). Release and corneal permeation studies showed that NM release was faster than SM. Amounts of drug retained in the corneal tissue were also higher for NM. In vitro and in vivo tests showed no signs of irritation or toxicity and successful in vivo anti-inflammatory efficacy for both formulations, being NM-OA/UA NPs the most effective. From the clinical editor: Oleanolic acid (OA) and ursolic acid (UA) are compounds found in plants with anti-inflammatory properties. The authors in this paper designed nanoparticles (NPs) using poly(dl-lactide-coglycolide) acid (PLGA) loaded with these compounds for ophthalmic administration. Both in vitro and in vivo experiments showed no toxicity and significant anti-inflammatory efficacy. This may provide new drugs for ocular anti-inflammatory treatment.

  8. Preparation and drug-loading properties of Fe3O4/Poly(styrene-co-acrylic acid) magnetic polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Lu, Wensheng; Shen, Yuhua; Xie, Anjian; Zhang, Weiqiang

    2013-11-01

    Fe3O4/poly(styrene-co-acrylic acid) magnetic polymer nanocomposites were synthesized by the dispersion polymerization method using styrene as hard monomer, acrylic acid as functional monomer, Fe3O4 nanoparticles modified with oleic acid as core, and poly(styrene-co-acrylic acid) as shell. Drug-loading properties of magnetic polymer nanocomposites with curcumin as a model drug were also studied. The results indicated that magnetic polymer nanocomposites with monodisperse were obtained, the particle size distribution was 50-120 nm, and the average size was about 100 nm. The contents of poly(styrene-co-acrylic acid) and Fe3O4 nanoparticles in magnetic polymer nanocomposites were 74% and 24.7%, respectively. The drug-loading capacity and entrapment efficiency were 2.5% and 44.4%, respectively. The saturation magnetization of magnetic polymer nanocomposites at 300 K was 20.2 emu/g without coercivity and remanence. The as-prepared magnetic polymer nanocomposites have not only lots of functional carboxyl groups but also stronger magnetic response, which might have potential applications in drug carrier and targeted drug release.

  9. Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles.

    PubMed

    Pradhan, Roshan; Poudel, Bijay Kumar; Choi, Ju Yeon; Choi, Im Soon; Shin, Beom Soo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2015-01-01

    In the present study, we developed the novel 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate and poloxamer 407 as the anionic and non-ionic surfactant for stabilization. The PLGA NPs were prepared by emulsification/solvent evaporation method. Both the drug/polymer ratio and phase ratio were 1:10 (w/w). The optimized formulation of 17-AAG-loaded PLGA NPs had a particle size and polydispersity index of 151.6 ± 2.0 and 0.152 ± 0.010 nm, respectively, which was further supported by TEM image. The encapsulation efficiency and drug loading capacity were 69.9 and 7.0%, respectively. In vitro release study showed sustained release. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.468, which suggested that the drug was released by anomalous or non-Fickian diffusion. In addition, 17-AAG-loaded PLGA NPs in 72 h, displayed approximately 60% cell viability reduction at 10 µg/ml 17-AAG concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of 17-AAG into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

  10. Evaluation of five biocarriers as supports for immobilized bacteria: Comparative performance during high chemical loading, acid shocking, drying and heat shocking

    SciTech Connect

    Heitkamp, M.A.; Adams, W.J. . Environmental Sciences Center); Camel, V. )

    1993-06-01

    Immobilized bacteria technology (IBT) utilizes inert biocarriers to support high concentrations of chemical-degrading bacteria in reactors designed to provide optimal conditions for microbial activity. This study evaluated IBT performance inpacked bed reactors (PBRs) using a porous inorganic biocarrier (diatomaceous earth), nonporous biocarriers (glass beads), and organic biocarriers having carbon adsorption properties (granular activated carbon) with different porosity. Each reactor was challenged with high chemical loading, acid, dryness, and heat shock conditions. Benchtop PBSs inoculated with a p-nitrophenol (PNP)-degrading Pseudomonas sp. and fed a synthetic waste containing 100 to 1,300 mg/L of PNP showed removal of PNP from effluents within 24 h of start-up. Chemical loading studies showed maximum PNP removal rates of 6.45 to 7.35 kg/m[sup 3]/d for bacteria in PBRs containing diatomaceous earth beads, glass beads, and activated coconut carbon. A lower PNP removal rate of 1.47 kg/m[sup 3]/d was determined for the activated anthracite carbon, and this PBR responded more slowly to increases in chemical loading. The PBR containing bacteria immobilized on activated coconut carbon showed exceptional tolerance to acid shocking, drying, and heat shocking by maintaining PNP removal rates > 85% throughout the entire study. The other biocarriers showed nearly complete loss of PNP degradation during the perturbations, but all recovered high rates of PNP degradation (> 98% removal) within 48 h after an acid shock at pH2, within 8 d after an acid shock at pH 1.0, within 24 h after drying for 72 h, and within 48 h of heat shocking. The resiliency and high chemical removal efficiency demonstrated by immobilized bacteria in this study support the concept of using IBT for the biotreatment of industrial wastes..

  11. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it. PMID:26634573

  12. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

  13. C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle.

    PubMed

    Olson, Aaron K; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly Priddy, Colleen; Isern, Nancy; Portman, Michael A

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and (13)Carbon ((13)C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing (13)C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the

  14. Increased acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis.

    PubMed

    Hu, Youtian; Liu, Zhenyu; Yu, Xiaoyun; Pasricha, Pankaj J; Undem, Bradley J; Yu, Shaoyong

    2014-07-15

    Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE.

  15. Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis.

    PubMed

    Farese, R V; Konda, T S; Davis, J S; Standaert, M L; Pollet, R J; Cooper, D R

    1987-05-01

    The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [3H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [3H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [3H]glycerol labeling as an indicator of de novo phospholipid synthesis, [3H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [3H]Glycerol-labeled diacylglycerol was largely derived directly from phosphatidic acid. Insulin increased de novo phosphatidic acid synthesis within 5 to 10 seconds; within 1 minute, this synthesis was 60 times greater than that of controls. Thus, the initial increase in diacylglycerol is due to both increased hydrolysis of phospholipids and a burst of de novo phosphatidic acid synthesis. After 5 to 10 minutes, de novo phosphatidic acid synthesis continues as a major source of diacylglycerol. Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipid-derived intracellular signaling substances.

  16. Higher Estimated Net Endogenous Acid Production May Be Associated with Increased Prevalence of Nonalcoholic Fatty Liver Disease in Chinese Adults in Hong Kong

    PubMed Central

    Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

  17. Increase of geometrical and positional fatty acid isomers in dark meat from broilers fed heated oils.

    PubMed

    Bou, R; Tres, R Codony A; Baucells, M D; Guardiola, F

    2005-12-01

    Oxidation of polyunsaturated fatty acids leads to primary and secondary oxidation products. Compounds and amounts of these products vary, depending on the oxidative conditions. Because these oxidation products have different absorption and biological effects, we performed 2 different heating treatments on sunflower oil. The first was heating the oil at 190 to 195 degrees C for 28 h (i.e., very oxidized oil), and the other was heating at 60 degrees C for 12 d (i.e., peroxidized oil). In the frame of this study, we compared the fatty acid composition of a refined sunflower oil (fresh oil), peroxidized oil, very oxidized oil, and a mixture (1:1) of fresh and very oxidized oil (i.e., oxidized oil). Oil fatty acid compositions were affected by the heating treatments. In addition, different fatty acid isomers were formed during heating at 190 to 195 degrees C, and significant differences were found between their contents in the sunflower oils. We also studied the effect of feeding broilers with these oils and Zn and tocopherol supplements on the fatty acid composition of their raw dark meat. Various trans fatty acid isomers increased in dark meat from broilers fed oxidized and very oxidized oils. In addition, discriminant analysis showed that ditrans-conjugated linoleic acid content was able to distinguish dark chicken meat from chickens fed sunflower oils heated at 190 to 195 degrees C.

  18. Production of Siderophores Increases Resistance to Fusaric Acid in Pseudomonas protegens Pf-5

    PubMed Central

    Ruiz, Jimena A.; Bernar, Evangelina M.; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  19. Production of siderophores increases resistance to fusaric acid in Pseudomonas protegens Pf-5.

    PubMed

    Ruiz, Jimena A; Bernar, Evangelina M; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  20. Novel Simvastatin-Loaded Nanoparticles Based on Cholic Acid-Core Star-Shaped PLGA for Breast Cancer Treatment.

    PubMed

    Wu, Yanping; Wang, Zhongyuan; Liu, Gan; Zeng, Xiaowei; Wang, Xusheng; Gao, Yongfeng; Jiang, Lijuan; Shi, Xiaojun; Tao, Wei; Huang, Laiqiang; Mei, Lin

    2015-07-01

    A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma. The star-shaped polymer CA-PLGA with three branch arms was synthesized successfully through the core-first approach. The simvastatin-loaded star-shaped CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method. The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein cyclin D1 was dramatically inhibited by simvastatin in both cells, with simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect. MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin-loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth of tumor over a longer period of time than pristine simvastatin and simvastatin-loaded linear PLGA nanoformulations at the same dose. In agreement with these, the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star-shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups through tumor frozen section immunohistochemistry. In conclusion, the star-shaped CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer chemotherapy.

  1. Deficiency of Ube3a in Huntington's disease mice brain increases aggregate load and accelerates disease pathology.

    PubMed

    Maheshwari, Megha; Shekhar, Shashi; Singh, Brijesh Kumar; Jamal, Imran; Vatsa, Naman; Kumar, Vipendra; Sharma, Ankit; Jana, Nihar Ranjan

    2014-12-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal expansion of CAG repeats in the gene encoding huntingtin. Mutant huntingtin undergoes proteolytic processing and its N-terminal fragment containing polyglutamine repeat accumulates as inclusion not only in nucleus but also in cytoplasm and neuronal processes. Here, we demonstrate that removal of ubiquitin ligase Ube3a selectively from HD mice brain resulted in accelerated disease phenotype and shorter lifespan in comparison with HD mice. The deficiency of Ube3a in HD mice brain also caused significant increase in global aggregates load, and these aggregates were less ubiquitinated when compared with age-matched HD mice. These Ube3a-maternal deficient HD mice also showed drastic reduction of DARPP-32, a dopamine-regulated phoshphoprotein in their striatum. These results emphasize the crucial role of Ube3a in the progression of HD and its immense potential as therapeutic target. PMID:25027318

  2. Short branched-chain C6 carboxylic acids result in increased growth, novel 'unnatural' fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant.

    PubMed

    Sen, Suranjana; Sirobhushanam, Sirisha; Hantak, Michael P; Lawrence, Peter; Brenna, J Thomas; Gatto, Craig; Wilkinson, Brian J

    2015-10-01

    Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique 'unnatural' fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant.

  3. Short branched-chain C6 carboxylic acids result in increased growth, novel 'unnatural' fatty acids and increased membrane fluidity in a Listeria monocytogenes branched-chain fatty acid-deficient mutant.

    PubMed

    Sen, Suranjana; Sirobhushanam, Sirisha; Hantak, Michael P; Lawrence, Peter; Brenna, J Thomas; Gatto, Craig; Wilkinson, Brian J

    2015-10-01

    Listeria monocytogenes is a psychrotolerant food borne pathogen, responsible for the high fatality disease listeriosis, and expensive food product recalls. Branched-chain fatty acids (BCFAs) of the membrane play a critical role in providing appropriate membrane fluidity and optimum membrane biophysics. The fatty acid composition of a BCFA-deficient mutant is characterized by high amounts of straight-chain fatty acids and even-numbered iso fatty acids, in contrast to the parent strain where odd-numbered anteiso fatty acids predominate. The presence of 2-methylbutyrate (C5) stimulated growth of the mutant at 37°C and restored growth at 10°C along with the content of odd-numbered anteiso fatty acids. The C6 branched-chain carboxylic acids 2-ethylbutyrate and 2-methylpentanoate also stimulated growth to a similar extent as 2-methylbutyrate. However, 3-methylpentanoate was ineffective in rescuing growth. 2-Ethylbutyrate and 2-methylpentanoate led to novel major fatty acids in the lipid profile of the membrane that were identified as 12-ethyltetradecanoic acid and 12-methylpentadecanoic acid respectively. Membrane anisotropy studies indicated that growth of strain MOR401 in the presence of these precursors increased its membrane fluidity to levels of the wild type. Cells supplemented with 2-methylpentanoate or 2-ethylbutyrate at 10°C shortened the chain length of novel fatty acids, thus showing homeoviscous adaptation. These experiments use the mutant as a tool to modulate the membrane fatty acid compositions through synthetic precursor supplementation, and show how existing enzymes in L. monocytogenes adapt to exhibit non-native activity yielding unique 'unnatural' fatty acid molecules, which nevertheless possess the correct biophysical properties for proper membrane function in the BCFA-deficient mutant. PMID:26225744

  4. Development of a total maximum daily load (TMDL) for acid-impaired lakes in the Adirondack region of New York

    NASA Astrophysics Data System (ADS)

    Fakhraei, Habibollah; Driscoll, Charles T.; Selvendiran, Pranesh; DePinto, Joseph V.; Bloomfield, Jay; Quinn, Scott; Rowell, H. Chandler

    2014-10-01

    Acidic deposition has impaired acid-sensitive surface waters in the Adirondack region of New York by decreasing pH and acid neutralizing capacity (ANC). In spite of air quality programs over past decades, 128 lakes in the Adirondacks were classified as “impaired” under Section 303(d) of the Clean Water Act in 2010 due to elevated acidity. The biogeochemical model, PnET-BGC, was used to relate decreases in atmospheric sulfur (S) and nitrogen (N) deposition to changes in lake water chemistry. The model was calibrated and confirmed using observed soil and lake water chemistry data and then was applied to calculate the maximum atmospheric deposition that the impaired lakes can receive while still achieving ANC targets. Two targets of ANC were used to characterize the recovery of acid-impaired lakes: 11 and 20 μeq L-1. Of the 128 acid-impaired lakes, 97 currently have ANC values below the target value of 20 μeq L-1 and 83 are below 11 μeq L-1. This study indicates that a moderate control scenario (i.e., 60% decrease from the current atmospheric S load) is projected to recover the ANC of lakes at a mean rate of 0.18 and 0.05 μeq L-1 yr-1 during the periods 2022-2050 and 2050-2200, respectively. The total maximum daily load (TMDL) of acidity corresponding to this moderate control scenario was estimated to be 7.9 meq S m-2 yr-1 which includes a 10% margin of safety.

  5. Trying to Put the Puzzle Together: Age and Performance Level Modulate the Neural Response to Increasing Task Load within Left Rostral Prefrontal Cortex.

    PubMed

    Bauer, Eva; Sammer, Gebhard; Toepper, Max

    2015-01-01

    Age-related working memory decline is associated with functional cerebral changes within prefrontal cortex (PFC). Kind and meaning of these changes are heavily discussed since they depend on performance level and task load. Hence, we investigated the effects of age, performance level, and load on spatial working memory retrieval-related brain activation in different subregions of the PFC. 19 younger (Y) and 21 older (O) adults who were further subdivided into high performers (HP) and low performers (LP) performed a modified version of the Corsi Block-Tapping test during fMRI. Brain data was analyzed by a 4 (groups: YHP, OHP, YLP, and OLP) × 3 (load levels: loads 4, 5, and 6) ANOVA. Results revealed significant group × load interaction effects within rostral dorsolateral and ventrolateral PFC. YHP showed a flexible neural upregulation with increasing load, whereas YLP reached a resource ceiling at a moderate load level. OHP showed a similar (though less intense) pattern as YHP and may have compensated age-effects at high task load. OLP showed neural inefficiency at low and no upregulation at higher load. Our findings highlight the relevance of age and performance level for load-dependent activation within rostral PFC. Results are discussed in the context of the compensation-related utilization of neural circuits hypothesis (CRUNCH) and functional PFC organization.

  6. Edge loading does not increase wear rates of ceramic-on-ceramic and metal-on-polyethylene articulations.

    PubMed

    Halma, Jelle J; Señaris, Jose; Delfosse, Daniel; Lerf, Reto; Oberbach, Thomas; van Gaalen, Steven M; de Gast, Arthur

    2014-11-01

    The mal-positioning of total hip arthroplasty components can result in edge loading conditions. Purpose of this study was to determine if the wear rate of ceramic-on-ceramic and metal-on-polyethylene increases under edge loading conditions. The literature was reviewed to determine which of the commonly used hip bearings is the most forgiving to implant mal-orientation. Two 28-mm ceramic-on-ceramic articulations were tested in vitro: pure alumina (PAL) ceramic versus the new alumina-toughened zirconia (ATZ). Two 28-mm metal-on-polyethylene articulations were tested in vitro: conventional ultrahigh molecular weight polyethylene (UHMWPE) versus highly crosslinked polyethylene (HXLPE) stabilized with vitamin E. All bearings were tested at standard and at highest possible inclination angles. Hip simulator tests were run for five million cycles based on N = 3 tests per condition. The average wear rate of ATZ-on-ATZ is 0.024 mm(3) /Mcycles at 45° and 0.018 mm(3) /Mcycles at 65°. Wear rate of PAL-on-PAL is between 0.02 and 0.03 mm(3) /Mcycles at 45°, as well as 65°. The wear rate of UHMWPE was 31 ± 1 mm(3) /Mcycles at an inclination angle of 45° and 26 ± 1 mm(3) /Mcycles at 80°. The wear rate of vitamin E stabilized HXLPE was 5.9 ± 0.2 mm(3) /Mcycles at 45° and 5.8 ± 0.2 mm(3) /Mcycles at 80°. Edge loading does not increase the wear rate of ceramic-on-ceramic and metal-on-polyethylene articulations. The newest biomaterials showed markedly lower wear rates compared with their conventional counterparts. ATZ-on-ATZ showed the lowest wear rate of all tested pairings, but the vitamin E stabilized HXLPE seems to be the most forgiving material when it comes to implant mal-orientation.

  7. The Potential Impact of Increased Phosphorus Loads in Lakes Acting as Heavy Metal Reservoirs: A case study from west-central Indiana

    NASA Astrophysics Data System (ADS)

    McLennan, D. A.; Latimer, J. C.; Smith, E.; Stone, J.

    2015-12-01

    Green Valley Lake is a designated state fishing area in west-central Indiana. Prior to this designation, the lake was a water supply reservoir for the adjacent and now abandoned Green Valley Coal Mine (Operating from 1948-1963). The Green Valley Coal Mine property continues to produce excess acidity despite reclamation efforts. The former mine property and the lake are connected by a channel that discharges acidic drainage directly into Green Valley Lake. To evaluate temporal variability in metal and phosphorus (P) geochemistry, two short cores were collected in spring 2014 (38cm) and spring 2015 (39cm). Metal concentrations were determined by a hand-held X-ray fluorescence analyzer after the samples had been dried and crushed. Approximately 20% of these metal concentrations will be verified by ICP-OES following extraction in 50% aqua regia. Detailed P geochemistry was determined using a sequential extraction technique (SEDEX). The sediments in Green Valley Lake are characterized by heavy metal concentrations that are elevated above typical background levels. These metals tend to be concentrated near the sediment water interface, often 3-5 times greater than the average concentration for the rest of the core, which suggests that they are diagenetically mobile and possibly diffusing out of the sediments under dysoxic to anoxic conditions and returning to the sediments under oxic conditions. Total sedimentary P averages 57 umol/g, but oscillates between 20 - 110 umol/g. The most dramatic shift in the detailed P geochemistry is the significant reduction of mineral P at 15 cm and the increasing importance of oxide-associated and adsorbed P upcore. Diatom assemblages suggest that the lake has become increasingly more eutrophic over time. As nutrient loads continue to increase, the oxygen depleted zone may expand impacting fish populations and changing water geochemistry significantly, in particular, mobilizing heavy metals.

  8. Using CD-ROM technology to increase folic acid knowledge among physician assistant students.

    PubMed

    Morgan, Christine; Klein, Diane Austrin; Selbst, Melissa

    2004-01-01

    The purpose of this study was to examine the effectiveness of incorporating CD-ROM technology to increase the knowledge of folic acid among physician assistant students. Participants included 76 first-year physician assistant students enrolled in a Women's Health course. A pretest and posttest was used to evaluate the knowledge gain after viewing the CD-ROM over a 2-week period. Of the 76 students in the course, 73 completed the pretest and the post-test. Posttest scores were significantly better than pretest scores (t = -11.83; p < or = 0.001), with means 68.63% and 46.18%. Knowledge scores increased by 22.45% from pre-test to posttest. Student evaluation results suggested that the CD-ROM (1) provided folic acid information in a clear and effective manner, (2) adequately covered the folic acid information, (3) increased student awareness and knowledge about folic acid, and (4) may promote early commitment by students to recommend daily folic acid intake to their patients.

  9. Linoleic acid supplementation results in increased arachidonic acid and eicosanoid production in CF airway cells and in cftr−/− transgenic mice

    PubMed Central

    Zaman, Munir M.; Martin, Camilia R.; Andersson, Charlotte; Bhutta, Abdul Q.; Cluette-Brown, Joanne E.; Laposata, Michael

    2010-01-01

    Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o− sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/− transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE2, and PGF2α secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr−/− Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators. PMID:20656894

  10. Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity.

    PubMed

    Horowitz, J F; Klein, S

    2000-12-01

    We evaluated plasma fatty acid availability and plasma and whole body fatty acid oxidation during exercise in five lean and five abdominally obese women (body mass index = 21 +/- 1 vs. 38 +/- 1 kg/m(2)), who were matched on aerobic fitness, to test the hypothesis that obesity alters the relative contribution of plasma and nonplasma fatty acids to total energy production during exercise. Subjects exercised on a recumbent cycle ergometer for 90 min at 54% of their peak oxygen consumption. Stable isotope tracer methods ([(13)C]palmitate) were used to measure fatty acid rate of appearance in plasma and the rate of plasma fatty acid oxidation, and indirect calorimetry was used to measure whole body substrate oxidation. During exercise, palmitate rate of appearance increased progressively and was similar in obese and lean groups between 60 and 90 min of exercise [3.9 +/- 0.4 vs. 4.0 +/- 0.3 micromol. kg fat free mass (FFM)(-1). min(-1)]. The rate of plasma fatty acid oxidation was also similar in obese and lean subjects (12.8 +/- 1.7 vs. 14.5 +/- 1.8 micromol. kg FFM(-1). min(-1); P = not significant). However, whole body fatty acid oxidation during exercise was 25% greater in obese than in lean subjects (21.9 +/- 1.2 vs. 17.5 +/- 1.6 micromol. kg FFM(-1). min(-1); P < 0.05). These results demonstrate that, although plasma fatty acid availability and oxidation are similar during exercise in lean and obese women, women with abdominal obesity use more fat as a fuel by oxidizing more nonplasma fatty acids.

  11. Assessment of zinc loading in an acid rock drainage alpine catchment using a tracer-injection and synoptic-sampling study

    NASA Astrophysics Data System (ADS)

    Crouch, C. M.; McKnight, D. M.; Todd, A.

    2010-12-01

    Seasonal low flow conditions in acid rock drainage (ARD) streams result in increased acidity and metal ion concentrations - changes that have been shown to become more pronounced with longer dry periods. These resulting increases in acidity and metals concentrations may pose an increasing danger to aquatic ecosystems and drinking water supplies. For example, in many ARD-impacted mountain streams, fish populations are not self-sustaining. The study site in the Upper Snake River watershed in Colorado is an alpine catchment impacted by acid rock drainage thought to originate from the natural weathering of pyrite whereas the main stem of the Snake River and its other tributaries are impacted by accelerated ARD resulting from historic mining activities. Because concentrations toxic to aquatic life persist well downstream of the ARD inputs, dissolved zinc is the primary metal of concern in this study. A compilation of historic data from the Snake River Watershed during the low flow months of September and October indicates that zinc concentrations have increased four-fold over the past 30 years. We hypothesize that this increase is due to changes in groundwater flow patterns caused by climate change and associated earlier peak snowmelt (by 2-3 weeks), resulting in lower stream flows and drier soils in late summer. The observed increase in background metals concentrations has implications for mitigation of former mining sites. A synoptic study to identify discrete surface water sources of zinc loading indicated a significant input from a tributary on the north side of the catchment. Zinc concentrations here measured an order of magnitude higher than in the main stem of the stream, and were correlated with increases in sulfate, hardness, and total metals, supporting our contention that increasing zinc concentrations are driven by the acceleration of ARD in the watershed. The current research further investigates sources of metal-rich inflows to the tributary using a tracer

  12. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    SciTech Connect

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  13. Extremely fast increase in the organic loading rate during the co-digestion of rapeseed oil and sewage sludge in a CSTR--characterization of granules formed due to CaO addition to maintain process stability.

    PubMed

    Kasina, M; Kleyböcker, A; Michalik, M; Würdemann, H

    2015-01-01

    In a co-digestion system running with rapeseed oil and sewage sludge, an extremely fast increase in the organic loading rate was studied to develop a procedure to allow for flexible and demand-driven energy production. The over-acidification of the digestate was successfully prevented by calcium oxide dosage, which resulted in granule formation. Mineralogical analyses revealed that the granules were composed of insoluble salts of long chain fatty acids and calcium and had a porous structure. Long chain fatty acids and calcium formed the outer cover of granules and offered interfaces on the inside thereby enhancing the growth of biofilms. With granule size and age, the pore size increased and indicated degradation of granular interfaces. A stable biogas production up to the organic loading rate of 10.4 kg volatile solids m(-3) d(-1) was achieved although the hydrogen concentration was not favorable for propionic acid degradation. However, at higher organic loading rates, unbalanced granule formation and degradation were observed. Obviously, the adaption time for biofilm growth was too short to maintain the balance, thereby resulting in a low methane yield.

  14. An acid/alkaline stress and the addition of amino acids induce a prolonged viability of Lactobacillus plantarum loaded into alginate gel.

    PubMed

    Bevilacqua, Antonio; Sinigaglia, Milena; Corbo, Maria Rosaria

    2010-08-15

    This study reports on the investigation on the effects of the conditions used throughout the step of biomass production on the survival of Lactobacillus plantarum loaded into alginate gels. L. plantarum was grown under different conditions (MRS or a laboratory medium-LB(2)-at acidic or alkaline pHs, with NaCl, phenols, vitamins or amino acids) and immobilized in sodium alginate; cell number was evaluated throughout the storage and death (delta(stand)) and first-reduction times (delta) were calculated. The storage of alginate gels at 4 degrees C prolonged cell viability up to 60 days (ca. 20 days for cells produced in MRS and stored at 30 degrees C); however, a similar prolongation was achieved for cells produced in LB(2) adjusted to pH 5.0 and 9.0 or added with amino acids (death time>50-60 days).

  15. Tobacco mosaic virus-directed reprogramming of auxin/indole acetic acid protein transcriptional responses enhances virus phloem loading.

    PubMed

    Collum, Tamara D; Padmanabhan, Meenu S; Hsieh, Yi-Cheng; Culver, James N

    2016-05-10

    Vascular phloem loading has long been recognized as an essential step in the establishment of a systemic virus infection. In this study, an interaction between the replication protein of tobacco mosaic virus (TMV) and phloem-specific auxin/indole acetic acid (Aux/IAA) transcriptional regulators was found to modulate virus phloem loading in an age-dependent manner. Promoter expression studies show that in mature tissues TMV 126/183-kDa-interacting Aux/IAAs predominantly express and accumulate within the nuclei of phloem companion cells (CCs). Furthermore, CC Aux/IAA nuclear localization is disrupted upon infection with an interacting virus. In situ analysis of virus spread shows that the inability to disrupt Aux/IAA CC nuclear localization correlates with a reduced ability to load into the vascular tissue. Subsequent systemic movement assays also demonstrate that a virus capable of disrupting Aux/IAA localization is significantly more competitive at moving out of older plant tissues than a noninteracting virus. Similarly, CC expression and overaccumulation of a degradation-resistant Aux/IAA-interacting protein was found to inhibit TMV accumulation and phloem loading selectively in flowering plants. Transcriptional expression studies demonstrate a role for Aux/IAA-interacting proteins in the regulation of salicylic and jasmonic acid host defense responses as well as virus-specific movement factors, including pectin methylesterase, that are involved in regulating plasmodesmata size-exclusion limits and promoting virus cell-to-cell movement. Combined, these findings indicate that TMV directs the reprogramming of auxin-regulated gene expression within the vascular phloem of mature tissues as a means to enhance phloem loading and systemic spread. PMID:27118842

  16. Effect of high dry solids loading on enzymatic hydrolysis of acid bisulfite pretreated Eastern redcedar.

    PubMed

    Ramachandriya, Karthikeyan D; Wilkins, Mark; Atiyeh, Hasan K; Dunford, Nurhan T; Hiziroglu, Salim

    2013-11-01

    This study investigates hydrolysis of cellulose from Eastern redcedar to glucose at high solids loading. Enzymatic hydrolysis of pretreated redcedar was performed with 0.5 ml Accelerase® 1500/g glucan (46 FPU/g glucan) using dry solids loading from 2% to 20% (w/w). Rheological challenges observed at high solids loading were overcome by adding stainless steel balls to shake flask reactors. The highest glucose concentration, 126 g/L (84% glucan-to-glucose yield), was obtained using 20% solids loading with stainless steel balls as a mixing aid. This enzymatic hydrolyzate was fermented into ethanol using Saccharomyces cerevisiae D5A to produce 52 g/L of ethanol (corresponding to 166 L/dry Mg of redcedar). Reducing enzyme dosage at 16% solids loading from 46 to 11.5 FPU/g glucan reduced glucan-to-glucose yields. This study has demonstrated the possibility of extracting sugars from the invasive species of Eastern redcedar with high solid loadings and their conversion into ethanol.

  17. Hepatitis C Virus Increases Free Fatty Acids Absorption and Promotes its Replication Via Down-Regulating GADD45α Expression

    PubMed Central

    Chen, Wei; Li, Xiao-ming; Li, An-ling; Yang, Gui; Hu, Han-ning

    2016-01-01

    Background Hepatitis C virus (HCV) infection, as a major cause of chronic hepatic diseases, is always accompanied with an abnormality of lipid metabolism. The aim of this study was to investigate the pathogenic role of free fatty acids (FFA) in human HCV infection. Material/Methods Peripheral blood lipid indexes among HCV patients with different viral loads (199 samples) and healthy donors (80 samples) were detected by clinical biochemistry tests. HCV replication and the expression of growth arrest and DNA-damage-inducible gene 45-α (GADD45α) in Huh7 cells and clinical samples were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Lipid accumulation in Huh7 cells was detected by immunofluorescence. Results In this study, we found that FFA showed a significant positive correlation with viral load in peripheral blood of HCV patients, but not total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). GADD45α expression in HCV patients dramatically decreased with the increase of viral load. In Huh7 cells, FFA treatment significantly enhanced HCV replication. HCV infection inhibited GADD45α expression, and this effect was further enhanced with the presence of FFA treatment. Ectopic expression of GADD45α in HCV-infected Huh7 cells markedly inhibited the absorption of FFA and HCV replication. However, FFA significantly elevated GADD45α expression without HCV infection. Conclusions These results demonstrated that HCV down-regulates GADD45α expression to enhance FFA absorption and thus facilitate its replication. GADD45α is an essential mediator for the pathogenesis of HCV infection. Thus, our study provides potential clues in the search for novel therapeutics and fatty lipid control options for HCV patients. PMID:27381636

  18. Tunable self-assembly of Irinotecan-fatty acid prodrugs with increased cytotoxicity to cancer cells†

    PubMed Central

    Xue, Xiangdong; Zhang, Tingbin; Jiang, Yonggang

    2016-01-01

    The development of a clinical chemotherapeutic is not an easy task. One challenge is how to deliver the agent to cancer cells. Nano-formulation of prodrugs, which combines the strengths of nanotechnology and prodrugs, possesses many advantages for chemotherapeutic drug delivery, including high drug loading efficiency, improved drug availability and enhanced accumulation in cancer cells. Here, we have constructed a small library of Irinotecan-derived prodrugs, in which the 20-hydroxyl group was derived with fatty-acid moieties through esterification. This conjugation fine-tuned the polarity of the Irinotecan molecule, thus enhancing the lipophilicity of the prodrugs and inducing their self-assembly into nanoparticles with different morphologies. These nano-formulated prodrugs accumulated at higher levels in cancer cells and were much more cytotoxic than free drugs. The rational design of prodrug-based nano-formulations opens a new avenue for the engineering of more efficient drug-delivery systems. PMID:27239311

  19. Polyunsaturated fatty acid content is increased in the milk of women with pregnancy associated breast cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Pregnancy associated breast cancer (PABC) is aggressive and difficult to diagnose. High intake of most types of dietary fat is thought to increase breast cancer risk, however results in humans supporting this premise remain equivocal. Fatty acid (FA) concentrations in the body comprise b...

  20. Dry deposition and heavy acid loading in the vicinity of Masaya Volcano, a major sulfur and chlorine source in Nicaragua.

    PubMed

    Delmelle, P; Stix, J; Bourque, C P; Baxter, P J; Garcia-Alvarez, J; Barquero, J

    2001-04-01

    Certain volcanoes constitute the world's largest sources of SO2, HCl, and HF emissions and contribute significantly to regional acid deposition. However, the impact of volcanic acid emissions to nearby ecosystems remain poorly documented. In this paper, the spatial pattern of acid dry depositions was monitored within 44 km of Masaya Volcano, Nicaragua, with a network of sulfation plates. Measured SO2 deposition rates were <2-791 mg m(-2) day(-1). The plates also collected the dry deposition of HCI at rates of <1-297 mg m(-2) day(-1). A similar deposition velocity Vd (gas transfer) of 1.6 +/- 0.8 cm/s was calculated for SO2 and HCl above the plate surfaces. Quantities of SO2 and HCI deposited daily within the area surveyed amounted to 1.5 x 10(8) g and 5.7 x 10(7) g, respectively, which correspond to about 10% of the total SO2 and HCl released by the volcano. These depositions may generate an equivalent hydrogen flux ranging from <1 to 30 mg m(-2) day(-1). Our results demonstrate that volcano emissions can dramatically affect acid deposition downwind and in turn cause extreme acid loading of the local ecosystems. This study opens exciting prospects for investigating the sensivity of volcanic ash soils to acid inputs.

  1. Dry deposition and heavy acid loading in the vicinity of Masaya Volcano, a major sulfur and chlorine source in Nicaragua.

    PubMed

    Delmelle, P; Stix, J; Bourque, C P; Baxter, P J; Garcia-Alvarez, J; Barquero, J

    2001-04-01

    Certain volcanoes constitute the world's largest sources of SO2, HCl, and HF emissions and contribute significantly to regional acid deposition. However, the impact of volcanic acid emissions to nearby ecosystems remain poorly documented. In this paper, the spatial pattern of acid dry depositions was monitored within 44 km of Masaya Volcano, Nicaragua, with a network of sulfation plates. Measured SO2 deposition rates were <2-791 mg m(-2) day(-1). The plates also collected the dry deposition of HCI at rates of <1-297 mg m(-2) day(-1). A similar deposition velocity Vd (gas transfer) of 1.6 +/- 0.8 cm/s was calculated for SO2 and HCl above the plate surfaces. Quantities of SO2 and HCI deposited daily within the area surveyed amounted to 1.5 x 10(8) g and 5.7 x 10(7) g, respectively, which correspond to about 10% of the total SO2 and HCl released by the volcano. These depositions may generate an equivalent hydrogen flux ranging from <1 to 30 mg m(-2) day(-1). Our results demonstrate that volcano emissions can dramatically affect acid deposition downwind and in turn cause extreme acid loading of the local ecosystems. This study opens exciting prospects for investigating the sensivity of volcanic ash soils to acid inputs. PMID:11348058

  2. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

    SciTech Connect

    Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W. )

    1991-05-01

    Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.

  3. Increased saccharification yields from aspen biomass upon treatment with enzymatically generated peracetic acid.

    PubMed

    Duncan, Shona; Jing, Qing; Katona, Adrian; Kazlauskas, Romas J; Schilling, Jonathan; Tschirner, Ulrike; Aldajani, Waleed Wafa

    2010-03-01

    The recalcitrance of lignocellulosic biomass to enzymatic release of sugars (saccharification) currently limits its use as feedstock for biofuels. Enzymatic hydrolysis of untreated aspen wood releases only 21.8% of the available sugars due primarily to the lignin barrier. Nature uses oxidative enzymes to selectively degrade lignin in lignocellulosic biomass, but thus far, natural enzymes have been too slow for industrial use. In this study, oxidative pretreatment with commercial peracetic acid (470 mM) removed 40% of the lignin (from 19.9 to 12.0 wt.% lignin) from aspen and enhanced the sugar yields in subsequent enzymatic hydrolysis to about 90%. Increasing the amount of lignin removed correlated with increasing yields of sugar release. Unfortunately, peracetic acid is expensive, and concentrated forms can be hazardous. To reduce costs and hazards associated with using commercial peracetic acid, we used a hydrolase to catalyze the perhydrolysis of ethyl acetate generating 60-70 mM peracetic acid in situ as a pretreatment to remove lignin from aspen wood. A single pretreatment was insufficient, but multiple cycles (up to eight) removed up to 61.7% of the lignin enabling release of >90% of the sugars during saccharification. This value corresponds to a predicted 581 g of fermentable sugars from 1 kg of aspen wood. Improvements in the enzyme stability are needed before the enzymatically generated peracetic acid is a commercially viable alternative.

  4. Memantine increases brain production of kynurenic acid via protein kinase A-dependent mechanism.

    PubMed

    Kloc, Renata; Luchowska, Elzbieta; Wielosz, Marian; Owe-Larsson, Bjorn; Urbanska, Ewa M

    2008-04-18

    We describe a novel aspect of action of memantine ex vivo, in the brain cortical slices and in vitro, in mixed glial cultures. The drug potently increased the production of kynurenic acid, an endogenous tryptophan metabolite blocking N-methyl-D-aspartate (NMDA) and nicotinic alpha7 receptors. In cortical slices memantine, an open-channel NMDA blocker (100-150 microM), but not the competitive NMDA receptor antagonist, LY235959 increased the production of kynurenic acid. Neither SCH23390, D1 receptor antagonist (50 microM) nor raclopride, D2 receptor antagonist (10 microM) changed the memantine-induced effects. Propranolol (100 microM) has partially reduced its action. Selective cAMP-dependent protein kinase (PKA) inhibitor, KT5720 (1 microM), but not selective protein kinase C (PKC) inhibitor, NPC15437 (30 microM) totally reversed the action of memantine. In mixed glial cultures, 2-24 h incubation with memantine (2-50 microM) enhanced the production of kynurenic acid. Memantine (up to 0.5 mM) has not affected the activity of kynurenic acid biosynthetic enzymes. The obtained data suggest that memantine enhances the production of kynurenic acid in PKA-mediated way. This effect may partially contribute to the therapeutic actions of memantine and be of a potential clinical importance.

  5. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide

    PubMed Central

    Yao, Chien-An; Chen, Chin-Chu; Wang, Nai-Phog; Chien, Chiang-Ting

    2016-01-01

    The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids’ oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis. PMID:27043621

  6. Improved Monitoring of Semi-Continuous Anaerobic Digestion of Sugarcane Waste: Effects of Increasing Organic Loading Rate on Methanogenic Community Dynamics.

    PubMed

    Leite, Athaydes Francisco; Janke, Leandro; Lv, Zuopeng; Harms, Hauke; Richnow, Hans-Hermann; Nikolausz, Marcell

    2015-01-01

    The anaerobic digestion of filter cake and its co-digestion with bagasse, and the effect of gradual increase of the organic loading rate (OLR) from start-up to overload were investigated. Understanding the influence of environmental and technical parameters on the development of particular methanogenic pathway in the biogas process was an important aim for the prediction and prevention of process failure. The rapid accumulation of volatile organic acids at high OLR of 3.0 to 4.0 gvs·L⁻¹·day⁻¹ indicated strong process inhibition. Methanogenic community dynamics of the reactors was monitored by stable isotope composition of biogas and molecular biological analysis. A potential shift toward the aceticlastic methanogenesis was observed along with the OLR increase under stable reactor operating conditions. Reactor overloading and process failure were indicated by the tendency to return to a predominance of hydrogenotrophic methanogenesis with rising abundances of the orders Methanobacteriales and Methanomicrobiales and drop of the genus Methanosarcina abundance. PMID:26404240

  7. Improved Monitoring of Semi-Continuous Anaerobic Digestion of Sugarcane Waste: Effects of Increasing Organic Loading Rate on Methanogenic Community Dynamics

    PubMed Central

    Leite, Athaydes Francisco; Janke, Leandro; Lv, Zuopeng; Harms, Hauke; Richnow, Hans-Hermann; Nikolausz, Marcell

    2015-01-01

    The anaerobic digestion of filter cake and its co-digestion with bagasse, and the effect of gradual increase of the organic loading rate (OLR) from start-up to overload were investigated. Understanding the influence of environmental and technical parameters on the development of particular methanogenic pathway in the biogas process was an important aim for the prediction and prevention of process failure. The rapid accumulation of volatile organic acids at high OLR of 3.0 to 4.0 gvs·L−1·day−1 indicated strong process inhibition. Methanogenic community dynamics of the reactors was monitored by stable isotope composition of biogas and molecular biological analysis. A potential shift toward the aceticlastic methanogenesis was observed along with the OLR increase under stable reactor operating conditions. Reactor overloading and process failure were indicated by the tendency to return to a predominance of hydrogenotrophic methanogenesis with rising abundances of the orders Methanobacteriales and Methanomicrobiales and drop of the genus Methanosarcina abundance. PMID:26404240

  8. Mechanisms increasing n-3 highly unsaturated fatty acids in the heart.

    PubMed

    Glück, Tobias; Rupp, Heinz; Alter, Peter

    2016-03-01

    Due to ambiguous findings on cardiovascular benefits of systemic omega-3 fatty acid therapy, endogenous mechanisms contributing to local organ-specific concentrations of highly unsaturated fatty acids (HUFA) were examined. Using gas chromatography, 43 fatty acids were analyzed in atrial and ventricular myocardium and in pericardial fluid of male Wistar rats. To examine the endogenous fatty acid metabolism, precursors were administered into the pericardial sac. Pro- and anti-inflammatory actions were induced by talc or fenofibrate, respectively. Physical exercise and a sedentary obese state were used for increased beta-oxidation. DHA (22:6n-3) was increased in ventricular when compared with atrial myocardium (9.0 ± 2.1% vs. 4.7 ± 1.0%, p < 0.001). Intrapericardial EPA (20:5n-3) application lead to an increase of the succeeding tetracosapentaenoic acid (24:5n-3) in atrial myocardium, which is a key precursor of DHA. In contrast, proinflammatory stimulation of the n-6 HUFA pathway did not influence the n-3 metabolism. Exercise- and obesity-induced increased beta-oxidation, the finalizing step of DHA synthesis, was associated with increased ventricular DHA concentrations (6.7 ± 1.0% vs. 8.4 ± 1.2%, p < 0.01). It is concluded that the endogenous metabolism contributes markedly to myocardial HUFA concentrations. The findings are supposed to influence the efficacy of oral HUFA treatment and provide a rationale for divergent findings of previous trials on omega-3 therapy. PMID:26780261

  9. Does simulated acid rain increase the leaching of cadmium from wood ash to toxic levels to coniferous forest humus microbes?

    PubMed

    Perkiömäki, Jonna; Fritze, Hannu

    2003-05-01

    Abstract Wood ash contains Cd in concentrations not permitted for fertilization use in agriculture (>3 mg kg(-1)). It has been shown that spiking ash with Cd to concentrations of 1000 mg kg(-1) induced no further changes in humus microbial activity and community structure as ash alone. To accelerate the weathering process and thus to liberate the spiked Cd from the ash, three treatments - wood ash (A), Cd spiked wood ash (ACd, 1000 mg Cd kg(-1) ash), both applied at a fertilization rate of 5000 kg ha(-1), together with a control (C) - were performed in microcosms and incubated in field condition under two types of irrigation - water and simulated acid rain. During the incubation period of one growing season the simulated acid rain plots received a sulfur load of 3.64 g S m(-2), which was 15 times more than the S deposition on the water irrigated plots. The treatments resulted in a mean Cd increase of the humus from 0.23 mg kg(-1) of the C treatment to 0.52 and 39.5 mg kg(-1) of the A and ACd treatments, respectively. The irrigation had no further effect on the result. The microbial activity, measured as soil basal respiration, and the microbial community structure, measured as humus phospholipid fatty acid and 16S and 18S polymerase chain reaction/denaturing gradient gel electrophoresis patterns, changed only due to the ash (A and ACd treatments) fertilization irrespective of the irrigation. The bacterial biosensor, emitting light in the presence of bioavailable Cd, did not react to any of the treatments. This result shows that Cd in ash was not leached into the humus due to increased deposition of acidified rain.

  10. Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment.

    PubMed

    Tang, Xiaolong; Cai, Shuyu; Zhang, Rongbo; Liu, Peng; Chen, Hongbo; Zheng, Yi; Sun, Leilei

    2013-01-01

    A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment.

  11. Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment

    PubMed Central

    2013-01-01

    A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment. PMID:24134303

  12. Identification of research relating to the critical loads concept and its potential application to the regulation of acidic deposition

    SciTech Connect

    Bhatti, N.

    1993-12-01

    The overwhelming majority of strategies currently implemented to regulate acidic deposition have focused on source-based or emission-control techniques. In the past few years, however, the fact that such source-based. strategies may not be sufficient to prevent adverse ecological effects and may therefore need to be supplemented with other control options, such as receptor-based strategies, has become apparent. Partly in response to this insufficiency of regulatory controls, the US Congress has required the National Acid Precipitation Assessment Program to determine (1) what deposition levels are needed to prevent such ecological damage, (2) whether such safe deposition levels (i.e., critical loads) can realistically be identified, and (3) what the costs and benefits of attaining such deposition levels are. This report reviews and culls the existing research on these alternative control strategies, emphasizing the critical loads concept, to determine the advantages and limitations and the cost-benefit relationships associated with receptor-based control options. The results of this study indicate that in spite of the significant limitations associated with the critical loads concept, this strategy dominates all discussions of non-source-based control options and offers considerable advantages, including cost-effectiveness, over the more traditional source-based control methods. Summaries of 10 of the most relevant studies dealing with alternative control strategies and the costs and benefits associated with them are also presented in this report.

  13. Homologous electron transport components fail to increase fatty acid hydroxylation in transgenic Arabidopsis thaliana.

    PubMed

    Wayne, Laura L; Browse, John

    2013-01-01

    Ricinoleic acid, a hydroxylated fatty acid (HFA) present in castor ( Ricinus communis) seeds, is an important industrial commodity used in products ranging from inks and paints to polymers and fuels. However, due to the deadly toxin ricin and allergens also present in castor, it would be advantageous to produce ricinoleic acid in a different agricultural crop. Unfortunately, repeated efforts at heterologous expression of the castor fatty acid hydroxylase (RcFAH12) in the model plant Arabidopsis thaliana have produced only 17-19% HFA in the seed triacylglycerols (TAG), whereas castor seeds accumulate up to 90% ricinoleic acid in the endosperm TAG. RcFAH12 requires an electron supply from NADH:cytochrome b5 reductase (CBR1) and cytochrome b5 (Cb5) to synthesize ricinoleic acid. Previously, our laboratory found a mutation in the Arabidopsis CBR1 gene, cbr1-1, that caused an 85% decrease in HFA levels in the RcFAH12 Arabidopsis line. These results raise the possibility that electron supply to the heterologous RcFAH12 may limit the production of HFA. Therefore, we hypothesized that by heterologously expressing RcCb5, the reductant supply to RcFAH12 would be improved and lead to increased HFA accumulation in Arabidopsis seeds. Contrary to this proposal, heterologous expression of the top three RcCb5 candidates did not increase HFA accumulation. Furthermore, coexpression of RcCBR1 and RcCb5 in RcFAH12 Arabidopsis also did not increase in HFA levels compared to the parental lines. These results demonstrate that the Arabidopsis electron transfer system is supplying sufficient reductant to RcFAH12 and that there must be other bottlenecks limiting the accumulation of HFA.

  14. Climate driven release of carbon and mercury from permafrost mires increases mercury loading to sub-arctic lakes.

    PubMed

    Rydberg, Johan; Klaminder, Jonatan; Rosén, Peter; Bindler, Richard

    2010-09-15

    In sub-arctic and arctic regions mercury is an element of concern for both wildlife and humans. Over thousands of years large amounts of atmospherically deposited mercury, both from natural and anthropogenic sources, have been sequestered together with carbon in northern peatlands. Many of these peatlands are currently underlain by permafrost, which controls mire stability and hydrology. With the ongoing climate change there is concern that permafrost thawing will turn large areas of these northern peatlands from carbon/mercury-sinks into much wetter carbon/mercury-sources. Here we can show that such a change in mire structure in the sub-arctic Stordalen mire in northern Sweden actually is responsible for an increased export of mercury to the adjacent lake Inre Harrsjön. We also show that sediment mercury accumulation rates during a warm period in the pre-industrial past were higher than in the 1970s when atmospheric input peaked, indicating that in areas with permafrost, climate can have an effect on mercury loading to lakes as large as anthropogenic emissions. Thawing of permafrost and the subsequent export of carbon is a widespread phenomenon, and the projection is that it will increase even more in the near future. Together with our observations from Stordalen, this makes northern peatlands into a substantial source of mercury, at risk of being released into sensitive arctic freshwater and marine systems.

  15. VASP Increases Hepatic Fatty Acid Oxidation by Activating AMPK in Mice

    PubMed Central

    Tateya, Sanshiro; Rizzo-De Leon, Norma; Handa, Priya; Cheng, Andrew M.; Morgan-Stevenson, Vicki; Ogimoto, Kayoko; Kanter, Jenny E.; Bornfeldt, Karin E.; Daum, Guenter; Clowes, Alexander W.; Chait, Alan; Kim, Francis

    2013-01-01

    Activation of AMP-activated protein kinase (AMPK) signaling reduces hepatic steatosis and hepatic insulin resistance; however, its regulatory mechanisms are not fully understood. In this study, we sought to determine whether vasodilator-stimulated phosphoprotein (VASP) signaling improves lipid metabolism in the liver and, if so, whether VASP’s effects are mediated by AMPK. We show that disruption of VASP results in significant hepatic steatosis as a result of significant impairment of fatty acid oxidation, VLDL-triglyceride (TG) secretion, and AMPK signaling. Overexpression of VASP in hepatocytes increased AMPK phosphorylation and fatty acid oxidation and reduced hepatocyte TG accumulation; however, these responses were suppressed in the presence of an AMPK inhibitor. Restoration of AMPK phosphorylation by administration of 5-aminoimidazole-4-carboxamide riboside in Vasp−/− mice reduced hepatic steatosis and normalized fatty acid oxidation and VLDL-TG secretion. Activation of VASP by the phosphodiesterase-5 inhibitor, sildenafil, in db/db mice reduced hepatic steatosis and increased phosphorylated (p-)AMPK and p-acetyl CoA carboxylase. In Vasp−/− mice, however, sildendafil treatment did not increase p-AMPK or reduce hepatic TG content. These studies identify a role of VASP to enhance hepatic fatty acid oxidation by activating AMPK and to promote VLDL-TG secretion from the liver. PMID:23349495

  16. Development and Optimization of a Doxorubicin Loaded Poly Lactic Acid Contrast Agent for Ultrasound Directed Drug Delivery

    PubMed Central

    Eisenbrey, J.R.; Burstein, O. Mualem; Kambhampati, R.; Forsberg, F.; Liu, J-B.; Wheatley, M.A.

    2010-01-01

    An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly lactic acid (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index = 0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 µg/ml, with a half life of over 15 mins. In vivo, the agent provided ultrasound enhancement of 13.4 ± 1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method. PMID:20060024

  17. Gamma-aminobutyric acid loaded halloysite nanotubes and in vitro-in vivo evaluation for brain delivery.

    PubMed

    Kırımlıoğlu, Gülsel Yurtdaş; Yazan, Yasemin; Erol, Kevser; Çengelli Ünel, Çiğdem

    2015-11-30

    Gamma-aminobutyric acid (GABA) is a key neurotransmitter where it usually inhibits impulse transmission. GABA release blockage or postsynaptic reaction were determined to provoke epileptic convulsions. The aim of the present study was the development of brain-targeted, nanosized, nontoxic, biocompatible, highly specific formulations. Incorporation of GABA into halloysite nanotubes (HNT) was performed using different methods. Particle size, zeta potential and pH measurements, morphological, thermal, XRD, FTIR analyses and GABA quantification by validated HPLC method were used for the characterization of the systems prepared. Release pattern of GABA from the nanotubes was determined using a dialysis membrane. Following successful incorporation of GABA into HNTs for brain delivery, nanotube formulation coded HNT-GABA H1 was selected for in vivo studies. Smaller particle size with narrow size distribution, possible HNT-GABA interaction indicated by thermal, XRD and FTIR analyses and prolonged release were the parameters considered in this selection. Moreover, HNT-GABA H1 remained stable for 3-month storage period and showed higher cell viability values than GABA. Rats were used in in vivo studies and potential of anticonvulsant effect of GABA was determined in the pentylenetetrazole model of seizure. HNT-GABA H1 was found to increase latency of seizure, decrease ending time of the convulsion, duration of severe convulsion and mortality rate significantly compared to pure GABA. After administration of HNT-GABA H1, GABA concentration in Stratum corsatum measured by enzyme immune assay showed that it was not significantly higher than GABA administered alone. These findings suggest that GABA loaded HNTs reduces the duration of all phases of convulsion indicating efficient delivery of GABA to all brain areas to interfere with epileptic mechanism.

  18. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

    NASA Astrophysics Data System (ADS)

    Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

    2016-04-01

    Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

  19. Multifunctional hyaluronic acid modified graphene oxide loaded with mitoxantrone for overcoming drug resistance in cancer

    NASA Astrophysics Data System (ADS)

    Hou, Lin; Feng, Qianhua; Wang, Yating; Yang, Xiaomin; Ren, Junxiao; Shi, Yuyang; Shan, Xiaoning; Yuan, Yujie; Wang, Yongchao; Zhang, Zhenzhong

    2016-01-01

    Multifunctional nanosheets (HA-GO/Pluronic) with targeted chemo-photothermal properties were successfully developed for controlled delivery of mitoxantrone (MIT) to overcome multidrug resistance (MDR). In vitro release profiles displayed that both an acidic environment and a NIR laser could trigger and accelerate the release of a drug, which ensured nanosheets were stable in blood circulation and released MIT within tumor cells under laser irradiation. HA-GO/Pluronic nanosheets were taken up into MCF-7/ADR cells via receptor-mediated endocytosis, which further facilitated escapement of P-gp efflux. Compared with MIT solution, MIT/HA-GO/Pluronic showed greater cytotoxicity and increase in cellular MIT accumulation in MCF-7/ADR cells. Cell apoptosis and cell cycle arrest studies also revealed that MIT/HA-GO/Pluronic was more potent than MIT/GO/Pluronic and MIT solution. The anticancer efficacy in vivo was evaluated in MCF-7 and MCF-7/ADR-bearing mice, and inhibition of tumors by MIT/HA-GO/Pluronic with NIR laser irradiation was the most effective among all MIT formulations. In summary, the MIT/HA-GO/Pluronic system had striking functions such as P-gp reversible inhibitor and anticancer efficacy, and could present a promising platform for drug-resistant cancer treatment.

  20. Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles

    PubMed Central

    Lojk, Jasna; Bregar, Vladimir B; Rajh, Maruša; Miš, Katarina; Kreft, Mateja Erdani; Pirkmajer, Sergej; Veranič, Peter; Pavlin, Mojca

    2015-01-01

    Magnetic nanoparticles (NPs) are a special type of NP with a ferromagnetic, electron-dense core that enables several applications such as cell tracking, hyperthermia, and magnetic separation, as well as multimodality. So far, superparamagnetic iron oxide NPs (SPIONs) are the only clinically approved type of metal oxide NPs, but cobalt ferrite NPs have properties suitable for biomedical applications as well. In this study, we analyzed the cellular responses to magnetic cobalt ferrite NPs coated with polyacrylic acid (PAA) in three cell types: Chinese Hamster Ovary (CHO), mouse melanoma (B16) cell line, and primary human myoblasts (MYO). We compared the internalization pathway, intracellular trafficking, and intracellular fate of our NPs using fluorescence and transmission electron microscopy (TEM) as well as quantified NP uptake and analyzed uptake dynamics. We determined cell viability after 24 or 96 hours’ exposure to increasing concentrations of NPs, and quantified the generation of reactive oxygen species (ROS) upon 24 and 48 hours’ exposure. Our NPs have been shown to readily enter and accumulate in cells in high quantities using the same two endocytic pathways; mostly by macropinocytosis and partially by clathrin-mediated endocytosis. The cell types differed in their uptake rate, the dynamics of intracellular trafficking, and the uptake capacity, as well as in their response to higher concentrations of internalized NPs. The observed differences in cell responses stress the importance of evaluation of NP–cell interactions on several different cell types for better prediction of possible toxic effects on different cell and tissue types in vivo. PMID:25733835

  1. Research, development, and demonstration of advanced lead-acid batteries for utility load leveling

    NASA Astrophysics Data System (ADS)

    1982-03-01

    A cost and design study was conducted on the production of lead-acid batteries. The major conclusions with regard to a mature level of production, 1000 man-work hours (MWH) per year in 100 MWH installations, are the following: using vertically integrated, automated plants, and a 14 KAH cell design, it is projected that the 100 MWH battery can be manufactured for $76 per kilowatt hour (KWH). The large 10 and 14 kilowatt amphere hour (KAH) cells were found to be more economical than the small 3.4 KAH (6.5 KWH) cell. It is inferred that batteries prepared from large, cell sizes (10 and 14 KAH) will be inherently more reliable due to the reduced number of intercell connections and reduced number of cells requiring maintenance operations, compared to batteries made with small cells (3400 AH). The battery footprint energy density goal can be achieved with tiering of the 14 KAH cell and the specification of somewhat reduced aisle widths on the outside of the strings. Sensitivity studies were performed on the impact of lead price, design cycle life, materials cost reductions, and increase in active materials utilization on the cost of the 100 MWH battery.

  2. Bread enriched with microencapsulated tuna oil increases plasma docosahexaenoic acid and total omega-3 fatty acids in humans.

    PubMed

    Yep, Yolande L; Li, Duo; Mann, Neil J; Bode, Ortwin; Sinclair, Andrew J

    2002-01-01

    The aim of this study was to determine the acute and chronic effects of low doses of long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (<100 mg per day) on plasma LC n-3 PUFA levels using a novel delivery form; bread containing microencapsulated tuna oil (MTO). Six omnivores (three men and three women) participated in the acute study, which involved ingesting a prototype MTO bread containing approximately 80 mg of LC n-3 PUFA/four slices. Plasma triacylglycerol fatty acid compositions were measured after an overnight fast and postprandially at 2 and 4 h. In the chronic study, 10 vegetarian subjects (nine men and one woman) consumed MTO bread at six to eight slices/day (comprising 60 mg of LC n-3 PUFA) as the only dietary source of these PUFA for three weeks. Fasting plasma total and phospholipid fatty acid compositions were measured at baseline and endpoint. In the acute study, the proportions of 22:6 n-3 and total n-3 PUFA in plasma triacylglycerol were significantly increased (P < 0.05). In the chronic study, the proportions of 20:5 n-3, 22:5 n-3, 22:6 n-3, total n-3 PUFA in plasma, and 22:6 n-3 and total n-3 PUFA in plasma phospholipid fractions were significantly increased (P < 0.05) at the endpoint compared with the baseline. This study showed that a low dose of LC n-3 PUFA, consumed as MTO-enriched bread, was bioavailable, as measured by an increase in LC n-3 PUFA levels in the plasma of human subjects.

  3. Fabrication and in vitro release behavior of a novel antibacterial coating containing halogenated furanone-loaded poly(L-lactic acid) nanoparticles on microarc-oxidized titanium

    PubMed Central

    Cheng, Yicheng; Wu, Jiang; Gao, Bo; Zhao, Xianghui; Yao, Junyan; Mei, Shenglin; Zhang, Liang; Ren, Huifang

    2012-01-01

    Background Dental implants have become increasingly common for the management of missing teeth. However, peri-implant infection remains a problem, is usually difficult to treat, and may lead eventually to dental implant failure. The aim of this study was to fabricate a novel antibacterial coating containing a halogenated furanone compound, ie, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF)-loaded poly(L-lactic acid) (PLLA) nanoparticles on microarc-oxidized titanium and to evaluate its release behavior in vitro. Methods BBF-loaded PLLA nanoparticles were prepared using the emulsion solvent-evaporation method, and the antibacterial coating was fabricated by cross-linking BBF-loaded PLLA nanoparticles with gelatin on microarc-oxidized titanium. Results The BBF-loaded PLLA nanoparticles had a small particle size (408 ± 14 nm), a low polydispersity index (0.140 ± 0.008), a high encapsulation efficiency (72.44% ± 1.27%), and a fine spherical shape with a smooth surface. The morphology of the fabricated antibacterial coating showed that the BBF-loaded PLLA nanoparticles were well distributed in the pores of the microarc oxidation coating, and were cross-linked with each other and the wall pores by gelatin. The release study indicated that the antibacterial coating could achieve sustained release of BBF for 60 days, with a slight initial burst release during the first 4 hours. Conclusion The novel antibacterial coating fabricated in this study is a potentially promising method for prevention of early peri-implant infection. PMID:23152682

  4. Prolonged infusion of amino acids increases leucine oxidation in fetal sheep.

    PubMed

    Maliszewski, Anne M; Gadhia, Monika M; O'Meara, Meghan C; Thorn, Stephanie R; Rozance, Paul J; Brown, Laura D

    2012-06-15

    Maternal high-protein supplements designed to increase birth weight have not been successful. We recently showed that maternal amino acid infusion into pregnant sheep resulted in competitive inhibition of amino acid transport across the placenta and did not increase fetal protein accretion rates. To bypass placental transport, singleton fetal sheep were intravenously infused with an amino acid mixture (AA, n = 8) or saline [control (Con), n = 10] for ∼12 days during late gestation. Fetal leucine oxidation rate increased in the AA group (3.1 ± 0.5 vs. 1.4 ± 0.6 μmol·min(-1)·kg(-1), P < 0.05). Fetal protein accretion (2.6 ± 0.5 and 2.2 ± 0.6 μmol·min(-1)·kg(-1) in AA and Con, respectively), synthesis (6.2 ± 0.8 and 7.0 ± 0.9 μmol·min(-1)·kg(-1) in AA and Con, respectively), and degradation (3.6 ± 0.6 and 4.5 ± 1.0 μmol·min(-1)·kg(-1) in AA and Con, respectively) rates were similar between groups. Net fetal glucose uptake decreased in the AA group (2.8 ± 0.4 vs. 3.9 ± 0.1 mg·kg(-1)·min(-1), P < 0.05). The glucose-O(2) quotient also decreased over time in the AA group (P < 0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon increased in the AA group (119 ± 24 vs. 59 ± 9 pg/ml, P < 0.05), and norepinephrine (NE) also tended to increase in the AA group (785 ± 181 vs. 419 ± 76 pg/ml, P = 0.06). Net fetal glucose uptake rates were inversely proportional to fetal glucagon (r(2) = 0.38, P < 0.05), cortisol (r(2) = 0.31, P < 0.05), and NE (r(2) = 0.59, P < 0.05) concentrations. Expressions of components in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle were similar between groups. In summary, prolonged infusion of amino acids directly into normally growing fetal sheep increased leucine oxidation. Amino acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a shift in substrate oxidation by the fetus from glucose to amino acids. PMID:22454287

  5. Discrete carbon nanotubes increase lead acid battery charge acceptance and performance

    NASA Astrophysics Data System (ADS)

    Swogger, Steven W.; Everill, Paul; Dubey, D. P.; Sugumaran, Nanjan

    2014-09-01

    Performance demands placed upon lead acid batteries have outgrown the technology's ability to deliver. These demands, typically leading to Negative Active Material (NAM) failure, include: short, high-current surges; prolonged, minimal, overvoltage charging; repeated, Ah deficit charging; and frequent deep discharges. Research shows these failure mechanisms are attenuated by inclusion of carbon allotropes into the NAM. Addition of significant quantities of carbon, however, produces detrimental changes in paste rheology, leading to lowered industrial throughput. Additionally, capacity, cold-cranking performance, and other battery metrics are negatively affected at high carbon loads. Presented here is Molecular Rebar® Lead Negative, a new battery additive comprising discrete carbon nanotubes (dCNT) which uniformly disperse within battery pastes during mixing. NS40ZL batteries containing dCNT show enhanced charge acceptance, reserve capacity, and cold-cranking performance, decreased risk of polarization, and no detrimental changes to paste properties, when compared to dCNT-free controls. This work focuses on the dCNT as NAM additives only, but early-stage research is underway to test their functionality as a PAM additive. Batteries infused with Molecular Rebar® Lead Negative address the needs of modern lead acid battery applications, produce none of the detrimental side effects associated with carbon additives, and require no change to existing production lines.

  6. Acid mine drainage in the Iberian Pyrite Belt: 1. Hydrochemical characteristics and pollutant load of the Tinto and Odiel rivers.

    PubMed

    Nieto, Jose M; Sarmiento, Aguasanta M; Canovas, Carlos R; Olias, Manuel; Ayora, Carlos

    2013-11-01

    Acid mine drainage in the Iberian Pyrite Belt is probably the worst case in the world of surface water pollution associated with mining of sulphide mineral deposits. The Iberian Pyrite Belt is located in SW Iberian Peninsula, and it has been mined during the last 4,500 years. The central and eastern part of the Iberian Pyrite Belt is drained by the Tinto and Odiel rivers, which receive most of the acidic leachates from the mining areas. As a result, the main channels of the Tinto and Odiel rivers are very rich in metals and highly acidic until reaching the Atlantic Ocean. A significant amount of the pollutant load transported by these two rivers is delivered during the rainy season, as is usual in rivers of Mediterranean climate regions. Therefore, in order to have an accurate estimation of the pollutant loads transported by the Tinto and Odiel rivers, a systematic sampling on a weekly basis and a high temporal resolution sampling of floods events were both performed. Results obtained show that metal fluxes are strongly dependent on the study period, highlighting the importance of inter-annual studies involving dry and wet years.

  7. Fusidic acid and rifampicin co-loaded PLGA nanofibers for the prevention of orthopedic implant associated infections.

    PubMed

    Gilchrist, Samuel E; Lange, Dirk; Letchford, Kevin; Bach, Horacio; Fazli, Ladan; Burt, Helen M

    2013-08-28

    Implant-associated infections following invasive orthopedic surgery are a major clinical problem, and are one of the primary causes of joint failure following total joint arthroplasty. Current strategies using perioperative antibiotics have been met with little clinical success and have resulted in various systemic toxicities and the promotion of antibiotic resistant microorganisms. Here we report the development of a biodegradable localized delivery system using poly(D,L-lactic acid-co-glycolic acid) (PLGA) for the combinatorial release of fusidic acid (FA) (or its sodium salt; SF) and rifampicin (RIF) using electrospinning. The drug-loaded formulations showed good antibiotic encapsulation (~75%-100%), and a biphasic drug release profile. All dual-loaded formulations showed direct antimicrobial activity in vitro against Staphylococcus epidermidis, and two strains of methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, lead formulations containing 10% (w/w) FA/SF and 5% (w/w) RIF were able to prevent the adherence of MRSA to a titanium implant in an in vivo rodent model of subcutaneous implant-associated infection.

  8. Acid mine drainage in the Iberian Pyrite Belt: 1. Hydrochemical characteristics and pollutant load of the Tinto and Odiel rivers.

    PubMed

    Nieto, Jose M; Sarmiento, Aguasanta M; Canovas, Carlos R; Olias, Manuel; Ayora, Carlos

    2013-11-01

    Acid mine drainage in the Iberian Pyrite Belt is probably the worst case in the world of surface water pollution associated with mining of sulphide mineral deposits. The Iberian Pyrite Belt is located in SW Iberian Peninsula, and it has been mined during the last 4,500 years. The central and eastern part of the Iberian Pyrite Belt is drained by the Tinto and Odiel rivers, which receive most of the acidic leachates from the mining areas. As a result, the main channels of the Tinto and Odiel rivers are very rich in metals and highly acidic until reaching the Atlantic Ocean. A significant amount of the pollutant load transported by these two rivers is delivered during the rainy season, as is usual in rivers of Mediterranean climate regions. Therefore, in order to have an accurate estimation of the pollutant loads transported by the Tinto and Odiel rivers, a systematic sampling on a weekly basis and a high temporal resolution sampling of floods events were both performed. Results obtained show that metal fluxes are strongly dependent on the study period, highlighting the importance of inter-annual studies involving dry and wet years. PMID:23589239

  9. Radiofrequency Thermal Ablation: Increase in Lesion Diameter with Continuous Acetic Acid Infusion

    SciTech Connect

    Lubienski, Andreas Duex, Markus; Lubienski, Katrin; Grenacher, Lars; Kauffmann, Guenter

    2005-12-15

    Purpose. To evaluate the influence of continuous infusion of acetic acid 50% during radiofrequency ablation (RFA) on the size of the thermal lesion produced. Methods. Radiofrequency (RF) was applied to excised bovine liver by using an expandable needle electrode with 10 retractable tines (LeVeen Needle Electrode, RadioTherapeutics, Sunnyvale, CA) connected to a commercially available RF generator (RF 2000, RadioTherapeutics, Sunnyvale, CA). Experiments were performed using three different treatment modalities: RF only (n = 15), RF with continuous saline 0.9% infusion (n = 15), and RF with continuous acetic acid 50% infusion (n = 15). RF duration, power output, tissue impedance, and time to a rapid rise in impedance were recorded. The ablated lesions were evaluated both macroscopically and histologically. Results. The ablated lesions appeared as spherical or ellipsoid, well-demarcated pale areas with a surrounding brown rim with both RF only and RF plus saline 0.9% infusion. In contrast, thermolesions generated with RF in combination with acetic acid 50% infusion were irregular in shape and the central portion was jelly-like. Mean diameter of the coagulation necrosis was 22.3 {+-} 2.1 mm (RF only), 29.2 {+-} 4.8 mm (RF + saline 0.9%) and 30.7 {+-} 5.7 mm (RF + acetic acid 50%), with a significant increase in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Time to a rapid rise in impedance was significantly prolonged in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Conclusions. A combination of RF plus acetic acid 50% infusion is able to generate larger thermolesions than RF only or RF combined with saline 0.9% infusion.

  10. Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity.

    PubMed

    Simon, Sharon S; Tusch, Erich S; Holcomb, Phillip J; Daffner, Kirk R

    2016-01-01

    The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models. PMID:27536226

  11. Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity

    PubMed Central

    Simon, Sharon S.; Tusch, Erich S.; Holcomb, Phillip J.; Daffner, Kirk R.

    2016-01-01

    The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models. PMID:27536226

  12. Depletion of Retinoic Acid Receptors Initiates a Novel Positive Feedback Mechanism that Promotes Teratogenic Increases in Retinoic Acid

    PubMed Central

    D'Aniello, Enrico; Rydeen, Ariel B.; Anderson, Jane L.; Mandal, Amrita; Waxman, Joshua S.

    2013-01-01

    Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA) signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1), a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM) specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA. PMID:23990796

  13. Preparation and evaluation of MRI detectable poly (acrylic acid) microspheres loaded with superparamagnetic iron oxide nanoparticles for transcatheter arterial embolization.

    PubMed

    Wang, Huan; Qin, Xiao-Ya; Li, Zi-Yuan; Guo, Li-Ying; Zheng, Zhuo-Zhao; Liu, Li-Si; Fan, Tian-Yuan

    2016-09-25

    To monitor the spatial distribution of embolic particles inside the target tissues during and after embolization, blank poly (acrylic acid) microspheres (PMs) were initially prepared by inverse suspension polymerization method and then loaded with superparamagnetic iron oxide (SPIO) nanoparticles by in situ precipitation method to obtain magnetic resonance imaging (MRI) detectable SPIO-loaded poly (acrylic acid) microspheres (SPMs). The loading of SPIO nanoparticles in SPMs was confirmed by vibrating sample magnetometer, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and infrared spectrum, respectively. The results showed that SPMs exhibited excellent superparamagnetism and the SPIO embedded in SPMs were proved to be inverse spinel magnetite. The content of SPIO loaded in wet SPMs of subgroups of 100-300, 300-500, 500-700 and 700-900μm was measured to be 11.84±0.07, 10.20±0.05, 9.98±0.00 and 8.79±0.01mg/ml, corresponding to the weight percentage in freeze-dried SPMs to be 18.07±0.28%, 18.54±0.13%, 18.66±0.01% and 18.50±0.07%, respectively. The SPMs were spherical in shape, had smooth surface, and were within the size range of clinical demands for embolization. The compression tests indicated that SPMs were more rigid than PMs and commercially used Embospheres (P<0.01). The MRI detectability of SPMs was evaluated with the SPMs embedded in gel phantom in vitro and injected subcutaneously into the back of mice in vivo. Both the results demonstrated that the SPMs could provide distinct negative contrast enhancement and be sensitively detected by T2-weighted MR imaging. All the results show that SPMs are potential MRI detectable embolic microspheres for the future embolotherapy. PMID:27426106

  14. Ionic liquid pretreatment to increase succinic acid production from lignocellulosic biomass.

    PubMed

    Wang, Caixia; Yan, Daojiang; Li, Qiang; Sun, Wei; Xing, Jianmin

    2014-11-01

    In this study, pinewood and corn stover pretreated with the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride (AmimCl) were used as a feedstock for succinic acid production. Results reveal that 5% (v/v) AmimCl inhibited bacterial growth, whereas 0.01% (v/v) AmimCl inhibited succinic acid production. AmimCl was effective in extracting cellulose from pinewood and in degrading pinewood into a uniform pulp, as revealed by scanning electron microscopy (SEM). The rate of enzymatic hydrolysis of pinewood extract reached 72.16%. The combinations of AmimCl pretreatment with steam explosion or with hot compressed water were effective in treating corn stover, whereas AmimCl treatment alone did not result in a significant improvement. Pinewood extract produced 20.7g/L succinic acid with an average yield of 0.37g per gram of biomass. Workflow calculations indicated pine wood pretreated with IL has a theoretical yield of succinic acid of 57.1%. IL pretreatment led to increase in succinic acid yields.

  15. Effect of production variables on the physicochemical characteristics of celecoxib-loaded stearic and alginic acids-based microparticles.

    PubMed

    Shunmugaperumal, Tamilvanan; Sharma, Deepak; Thakur, Ashutosh; Vinaykumar

    2013-12-01

    The objectives of the current investigation were (1) to prepare the microparticles based on stearic and alginic acids from an aqueous system by hot (melt) dispersion method, (2) to achieve a higher drug entrapment efficiency and process yield (%) by changing the production variables such as stirring speed, concentration of stabilizer in aqueous dispersion medium, volume of aqueous dispersion medium, and stirring time, and (3) to see whether or not a retardation in drug release profile was attained from the celecoxib-loaded stearic and alginic acids-based microparticles compared to that of the celecoxib alone. The addition of alginic acid into stearic acid produced spherical-shaped particles with an almost smooth surface. Higher drug entrapment efficiency and process yield (%) values were obtained when the microparticles were prepared at 1000 r/min using 0.1% w/v polyvinyl alcohol in 100 mL aqueous dispersion medium and 30 min stirring time. The in vitro dissolution study in 900 mL of 2% sodium lauryl sulfate (SLS) solution at 75 r/min, however, showed only around 10% retardation in drug release from microparticles compared to the drug release from pure celecoxib alone. This indicated that the gel-like network formed by the alginic acid around the microparticles could not prevent the drug leakage from the microparticles.

  16. The effect of gastric loads of sugars and amino acids on milk intake of suckling pigs.

    PubMed

    Houpt, K A; Houpt, T R; Pond, W G

    1983-08-01

    A 3 h fast of suckling pigs less than a week of age decreased plasma glucose (P less than .005), but did not affect plasma protein, osmolality or hematocrit. After fasting, solutions (40 ml/kg body weight) of 5% glucose, 5% fructose, 5% xylose, 5% mannitol, 5% sorbitol, 2.5% leucine, 2.5% phenylalanine (50 ml/kg), .9% NaCl, 5% lactose, 5% sucrose and a 50% egg yolk-distilled water mixture were administered by stomach tube and the piglet then returned to the sow. Weight gain was used as a measure of sow's milk intake. Milk consumption during the first 3 h after fasting was lower (P less than .05) for pigs given glucose than for sham-loaded controls, but no differences were observed between glucose and mannitol or sorbitol for the same period. Mannitol and sorbitol were more effective than NaCl (P less than .01) in lowering consumption for the 3 h after loading. Also during the first hour after loading, xylose caused lower (P less than .001) food intake than glucose. Egg yolk suppressed intake in comparison to sham-loaded controls (P less than .05). D-phenylalanine suppressed intake more than L-phenylalanine (P less than .05), but no differences were observed between the D and L isomers of leucine.

  17. Increased Fatty Acid β-Oxidation after Glucose Starvation in Maize Root Tips

    PubMed Central

    Dieuaide, Martine; Brouquisse, Renaud; Pradet, Alain; Raymond, Philippe

    1992-01-01

    The effects of glucose starvation on the oxidation of fatty acids were studied in excised maize (Zea mays L.) root tips. After 24 hours of glucose starvation, the rate of oxidation of palmitic acid to CO2 by the root tips was increased 2.5-fold. Different enzyme activities were tested in a crude particulate fraction from nonstarved root tips and those starved for 24 hours. The activities of the β-oxidation enzymes crotonase, hydroxyacyl-coenzyme A (CoA) dehydrogenase, and thiolase and those of catalase, malate synthase, and peroxisomal citrate synthase were higher after starvation. However, no isocitrate lyase activity was detected, thus suggesting that the glyoxylate cycle does not operate. The overall β-oxidation activity was assayed as the formation of [14C]acetyl-CoA from [14C]palmitic acid after high-performance liquid chromatography analysis of the CoA derivatives. An activity was detected in sugar-fed root tips, and it was increased by two-to fivefold in starved roots. Because the recovery of enzyme activities is only marginally better in starved roots compared with nonstarved roots, these results indicate that the β-oxidation activity in the tissues is increased during sugar starvation. This increase is probably an essential part of the response to a situation in which lipids and proteins replace carbohydrates as the major respiratory substrates. These results are discussed in relation to the metabolic changes observed in senescing plant tissues. PMID:16668928

  18. Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster.

    PubMed

    Mora, Marylhi; Medina-Leendertz, Shirley J; Bonilla, Ernesto; Terán, Raikelin E; Paz, Milagros C; Arcaya, José Luis

    2013-06-01

    In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 +/- 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

  19. Metabolic engineering of Aspergillus oryzae NRRL 3488 for increased production of L-malic acid.

    PubMed

    Brown, Stephen H; Bashkirova, Lena; Berka, Randy; Chandler, Tyler; Doty, Tammy; McCall, Keith; McCulloch, Michael; McFarland, Sarah; Thompson, Sheryl; Yaver, Debbie; Berry, Alan

    2013-10-01

    Malic acid, a petroleum-derived C4-dicarboxylic acid that is used in the food and beverage industries, is also produced by a number of microorganisms that follow a variety of metabolic routes. Several members of the genus Aspergillus utilize a two-step cytosolic pathway from pyruvate to malate known as the reductive tricarboxylic acid (rTCA) pathway. This simple and efficient pathway has a maximum theoretical yield of 2 mol malate/mol glucose when the starting pyruvate originates from glycolysis. Production of malic acid by Aspergillus oryzae NRRL 3488 was first improved by overexpression of a native C4-dicarboxylate transporter, leading to a greater than twofold increase in the rate of malate production. Overexpression of the native cytosolic alleles of pyruvate carboxylase and malate dehydrogenase, comprising the rTCA pathway, in conjunction with the transporter resulted in an additional 27 % increase in malate production rate. A strain overexpressing all three genes achieved a malate titer of 154 g/L in 164 h, corresponding to a production rate of 0.94 g/L/h, with an associated yield on glucose of 1.38 mol/mol (69 % of the theoretical maximum). This rate of malate production is the highest reported for any microbial system.

  20. Humic Acid Complexation of Th, Hf and Zr in Ligand Competition Experiments: Metal Loading and Ph Effects

    NASA Technical Reports Server (NTRS)

    Stern, Jennifer C.; Foustoukos, Dionysis I.; Sonke, Jeroen E.; Salters, Vincent J. M.

    2014-01-01

    The mobility of metals in soils and subsurface aquifers is strongly affected by sorption and complexation with dissolved organic matter, oxyhydroxides, clay minerals, and inorganic ligands. Humic substances (HS) are organic macromolecules with functional groups that have a strong affinity for binding metals, such as actinides. Thorium, often studied as an analog for tetravalent actinides, has also been shown to strongly associate with dissolved and colloidal HS in natural waters. The effects of HS on the mobilization dynamics of actinides are of particular interest in risk assessment of nuclear waste repositories. Here, we present conditional equilibrium binding constants (Kc, MHA) of thorium, hafnium, and zirconium-humic acid complexes from ligand competition experiments using capillary electrophoresis coupled with ICP-MS (CE- ICP-MS). Equilibrium dialysis ligand exchange (EDLE) experiments using size exclusion via a 1000 Damembrane were also performed to validate the CE-ICP-MS analysis. Experiments were performed at pH 3.5-7 with solutions containing one tetravalent metal (Th, Hf, or Zr), Elliot soil humic acid (EHA) or Pahokee peat humic acid (PHA), and EDTA. CE-ICP-MS and EDLE experiments yielded nearly identical binding constants for the metal- humic acid complexes, indicating that both methods are appropriate for examining metal speciation at conditions lower than neutral pH. We find that tetravalent metals form strong complexes with humic acids, with Kc, MHA several orders of magnitude above REE-humic complexes. Experiments were conducted at a range of dissolved HA concentrations to examine the effect of [HA]/[Th] molar ratio on Kc, MHA. At low metal loading conditions (i.e. elevated [HA]/[Th] ratios) the ThHA binding constant reached values that were not affected by the relative abundance of humic acid and thorium. The importance of [HA]/[Th] molar ratios on constraining the equilibrium of MHA complexation is apparent when our estimated Kc, MHA values

  1. Acidic pH increases airway surface liquid viscosity in cystic fibrosis.

    PubMed

    Tang, Xiao Xiao; Ostedgaard, Lynda S; Hoegger, Mark J; Moninger, Thomas O; Karp, Philip H; McMenimen, James D; Choudhury, Biswa; Varki, Ajit; Stoltz, David A; Welsh, Michael J

    2016-03-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3- concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator-dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF.

  2. Acidic pH increases airway surface liquid viscosity in cystic fibrosis

    PubMed Central

    Tang, Xiao Xiao; Ostedgaard, Lynda S.; Hoegger, Mark J.; Moninger, Thomas O.; Karp, Philip H.; McMenimen, James D.; Choudhury, Biswa; Varki, Ajit; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3– concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  3. Polyglycerol as a high-loading support for boronic acids with application in solution-phase Suzuki cross-couplings.

    PubMed

    Hebel, André; Haag, Rainer

    2002-12-27

    In this paper, we describe the usage of a soluble high-loading polyglycerol support for functionalized boronic acids without further linker design. The quantitatively formed polyglycerol boron esters were subsequently employed in homogeneous Suzuki cross-coupling reactions to give high yields (84-91%) of functional biaryls with minimal amounts of the Pd catalyst (0.2 mol %). In situ precipitation and ultrafiltration were used as simple and effective purification protocols. Furthermore, the reaction conditions were optimized by the choice of the solvent and the catalyst.

  4. Dye-loaded zeolite L @silica core-shell composite functionalized with europium(III) complexes for dipicolinic acid detection.

    PubMed

    Wang, Yige; Yue, Yuping; Li, Huanrong; Zhao, Qi; Fang, Yi; Cao, Pengpeng

    2011-01-01

    Novel core-shell composites have been developed by immobilization of non-luminescent europium(III) complexes onto the surface of silica shells that are coated on the surface of luminescent dye-loaded zeolite L nano-crystals. The obtained core-shell composites were used for the ratiometric detection of dipicolinic acid (DPA) molecules. The dyes located in the channels of the zeolite L host are protected from any interaction with the environment of the particles and therefore provide a stable reference signal which can eliminate the need for instrument-specific calibration curves for DPA quantification in an analyte.

  5. Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star-shaped poly(lactic-co-glycolic acid)

    PubMed Central

    Chen, Yongxia; Yang, Ziying; Liu, Chao; Wang, Cuiwei; Zhao, Shunxin; Yang, Jing; Sun, Hongfan; Zhang, Zhengpu; Kong, Deling; Song, Cunxian

    2013-01-01

    Background Star-shaped polymers provide more terminal groups, and are promising for application in drug-delivery systems. Methods A new series of six-arm star-shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles’ encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs). Results The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40°C–50°C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4±6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from

  6. Loading of myoglobin into multilayer films assembled by ZrO2 nanoparticles and phytic acid: electrochemistry and electrocatalysis.

    PubMed

    Yang, Lingzhu; Liu, Hongyun; Hu, Naifei

    2009-04-01

    Small-molecular phytic acid (PA) with its unique structure was successfully assembled with ZrO2 nanoparticles into {PA/ZrO2}n layer-by-layer films on solid surfaces, which was confirmed by quartz crystal microbalance (QCM) and cyclic voltammetry (CV) with K3Fe(CN)6 as the electroactive probe. Myoglobin (Mb) could be gradually "absorbed" or loaded into the films when the films were immersed into Mb solutions. The Mb-loaded films at pyrolytic graphite (PG) electrodes, designated as {PA/ZrO2}n-Mb, demonstrated well-defined and quasi-reversible CV responses for Mb Fe(III)/Fe(II) redox couple and good electrocatalytic properties toward oxygen and H2O2. The driving force of the film assembly and the interaction between Mb and {PA/ZrO2}n films were explored and discussed in detail. The coordination interaction between PA and ZrO2 is believed to be the main driving force for the assembly of {PA/ZrO2}n multilayer films, and the electrostatic attraction between oppositely charged Mb and the film components is the main interaction for Mb loading into the films. The loading behavior of the {PA/ZrO2}n films toward different proteins with different size indicates that while the porosity of the films is necessary for the protein loading, only those proteins with the size smaller than the average pore size of the films can be incorporated in the interior of films. PMID:19437988

  7. Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans

    PubMed Central

    Stephens, Francis B; Wall, Benjamin T; Marimuthu, Kanagaraj; Shannon, Chris E; Constantin-Teodosiu, Dumitru; Macdonald, Ian A; Greenhaff, Paul L

    2013-01-01

    Twelve weeks of daily l-carnitine and carbohydrate feeding in humans increases skeletal muscle total carnitine content, and prevents body mass accrual associated with carbohydrate feeding alone. Here we determined the influence of l-carnitine and carbohydrate feeding on energy metabolism, body fat mass and muscle expression of fuel metabolism genes. Twelve males exercised at 50% maximal oxygen consumption for 30 min once before and once after 12 weeks of twice daily feeding of 80 g carbohydrate (Control, n= 6) or 1.36 g l-carnitine + 80 g carbohydrate (Carnitine, n= 6). Maximal carnitine palmitolytransferase 1 (CPT1) activity remained similar in both groups over 12 weeks. However, whereas muscle total carnitine, long-chain acyl-CoA and whole-body energy expenditure did not change over 12 weeks in Control, they increased in Carnitine by 20%, 200% and 6%, respectively (P < 0.05). Moreover, body mass and whole-body fat mass (dual-energy X-ray absorptiometry) increased over 12 weeks in Control by 1.9 and 1.8 kg, respectively (P < 0.05), but did not change in Carnitine. Seventy-three of 187 genes relating to fuel metabolism were upregulated in Carnitine vs. Control after 12 weeks, with ‘insulin signalling’, ‘peroxisome proliferator-activated receptor signalling’ and ‘fatty acid metabolism’ as the three most enriched pathways in gene functional analysis. In conclusion, increasing muscle total carnitine in healthy humans can modulate muscle metabolism, energy expenditure and body composition over a prolonged period, which is entirely consistent with a carnitine-mediated increase in muscle long-chain acyl-group translocation via CPT1. Implications to health warrant further investigation, particularly in obese individuals who have a reduced reliance on muscle fat oxidation during low-intensity exercise. PMID:23818692

  8. Propagated fixed-bed mixed-acid fermentation: Part I: Effect of volatile solid loading rate and agitation at high pH.

    PubMed

    Golub, Kristina W; Forrest, Andrea K; Mercy, Kevin L; Holtzapple, Mark T

    2011-11-01

    Countercurrent fermentation is a high performing process design for mixed-acid fermentation. However, there are high operating costs associated with moving solids, which is an integral component of this configuration. This study investigated the effect of volatile solid loading rate (VSLR) and agitation in propagated fixed-bed fermentation, a configuration which may be more commercially viable. To evaluate the role of agitation on fixed-bed configuration performance, continuous mixing was compared with periodic mixing. VSLR was also varied and not found to affect acid yields. However, increased VSLR and liquid retention time did result in higher conversions, productivity, acid concentrations, but lower selectivities. Agitation was demonstrated to be important for this fermentor configuration, the periodically-mixed fermentation had the lowest conversion and yields. Operating at a high pH (∼9) contributed to the high selectivity to acetic acid, which might be industrially desirable but at the cost of lower yield compared to a neutral pH. PMID:21963249

  9. Maternal Dietary Loads of Alpha-Tocopherol Increase Synapse Density and Glial Synaptic Coverage in the Hippocampus of Adult Offspring

    PubMed Central

    Salucci, S.; Ambrogini, P.; Lattanzi, D.; Betti, M.; Gobbi, P.; Galati, C.; Galli, F.; Cuppini, R.; Minelli, A.

    2014-01-01

    An increased intake of the antioxidant α-Tocopherol (vitamin E) is recommended in complicated pregnancies, to prevent free radical damage to mother and fetus. However, the anti-PKC and antimitotic activity of α-Tocopherol raises concerns about its potential effects on brain development. Recently, we found that maternal dietary loads of α-Tocopherol through pregnancy and lactation cause developmental deficit in hippocampal synaptic plasticity in rat offspring. The defect persisted into adulthood, with behavioral alterations in hippocampus-dependent learning. Here, using the same rat model of maternal supplementation, ultrastructural morphometric studies were carried out to provide mechanistic interpretation to such a functional impairment in adult offspring by the occurrence of long-term changes in density and morphological features of hippocampal synapses. Higher density of axo-spinous synapses was found in CA1 stratum radiatum of α-Tocopherol-exposed rats compared to controls, pointing to a reduced synapse pruning. No morphometric changes were found in synaptic ultrastructural features, i.e., perimeter of axon terminals, length of synaptic specializations, extension of bouton-spine contact. Gliasynapse anatomical relationship was also affected. Heavier astrocytic coverage of synapses was observed in Tocopherol-treated offspring, notably surrounding axon terminals; moreover, the percentage of synapses contacted by astrocytic endfeet at bouton-spine interface (tripartite synapses) was increased. These findings indicate that gestational and neonatal exposure to supranutritional Tocopherol intake can result in anatomical changes of offspring hippocampus that last through adulthood. These include a surplus of axo-spinous synapses and an aberrant gliasynapse relationship, which may represent the morphological signature of previously described alterations in synaptic plasticity and hippocampus-dependent learning. PMID:24998923

  10. Lovastatin increases arachidonic acid levels and stimulates thromboxane synthesis in human liver and monocytic cell lines.

    PubMed Central

    Hrboticky, N; Tang, L; Zimmer, B; Lux, I; Weber, P C

    1994-01-01

    The effect of lovastatin (LOV), the inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, on linoleic acid (LA, 18:2n-6) metabolism was examined in human monocytic Mono Mac 6 (MM6) and hepatoma Hep G2 cells. The desaturation of LA was examined after LOV (72 h, 10 microM) or dimethylsulfoxide (LOV carrier, < 0.1%) and [14C]LA (last 18 h, 0.3 microCi, 5 microM). In both cell lines, LOV reduced the percentage of 14C label associated with LA and increased the percentage of label in the 20:4n-6 and the 22:5n-6 fractions. In Hep G2 but not MM6 cells, this effect was fully reversible by means of coincubation with mevalonic acid (500 microM), but not with cholesterol or lipoproteins. In both cell lines, the LOV-mediated increase in LA desaturation resulted in dose-dependent reductions of LA and elevations of AA in cellular phospholipids. The lipids secreted by LOV-treated Hep G2 cells were also enriched in arachidonic acid (AA). In the MM6 cells, LOV increased release of thromboxane upon stimulation with the calcium ionophore A23187. In summary, our findings of higher LA desaturation and AA enrichment of lipids secreted by the Hep G2 cells suggest that LOV treatment may increase the delivery of AA from the liver to extrahepatic tissues. The changes in membrane fatty acid composition can influence a variety of cellular functions, such as eicosanoid synthesis in monocytic cells. The mechanism appears to be related to the reduced availability of intermediates of cholesterogenesis. PMID:8282787

  11. Humic substances increase survival of freshwater shrimp Caridina sp. D to acid mine drainage.

    PubMed

    Holland, Aleicia; Duivenvoorden, Leo J; Kinnear, Susan H W

    2013-02-01

    Humic substances (HS) are known to decrease the toxicity of heavy metals to aquatic organisms, and it has been suggested that they can provide buffering protection in low pH conditions. Despite this, little is known about the ability for HS to increase survival to acid mine drainage (AMD). In this study, the ability of HS to increase survival of the freshwater shrimp (Caridina sp. D sensu Page et al. in Biol Lett 1:139-142, 2005) to acid mine drainage was investigated using test waters collected from the Mount Morgan open pit in Central Queensland with the addition of Aldrich humic acid (AHA). The AMD water from the Mount Morgan open pit is highly acidic (pH 2.67) as well as contaminated with heavy metals (1780 mg/L aluminum, 101 mg/L copper [Cu], 173 mg/L manganese, 51.8 mg/L zinc [Zn], and 51.8 mg/L iron). Freshwater shrimp were exposed to dilutions in the range of 0.5 % to 5 % AMD water with and without the addition of 10 or 20 mg/L AHA. In the absence of HS, all shrimp died in the 2.5 % AMD treatment. In contrast, addition of HS increased survival in the 2.5 % AMD treatment by ≤66 % as well as significantly decreased the concentration of dissolved Cu, cobalt, cadmium, and Zn. The decreased toxicity of AMD in the presence of HS is likely to be due to complexation and precipitation of heavy metals with the HS; it is also possible that HS caused changes to the physiological condition of the shrimp, thus increasing their survival. These results are valuable in contributing to an improved understanding of potential role of HS in ameliorating the toxicity of AMD environments. PMID:23135152

  12. Functionalized antibiofilm thin coatings based on PLA-PVA microspheres loaded with usnic acid natural compounds fabricated by MAPLE

    NASA Astrophysics Data System (ADS)

    Grumezescu, Valentina; Socol, Gabriel; Grumezescu, Alexandru Mihai; Holban, Alina Maria; Ficai, Anton; Truşcǎ, Roxana; Bleotu, Coralia; Balaure, Paul Cǎtǎlin; Cristescu, Rodica; Chifiriuc, Mariana Carmen

    2014-05-01

    We report the fabrication of thin coatings of PLA-PVA microspheres loaded with usnic acid by matrix assisted pulsed laser evaporation (MAPLE) onto Ti substrate. The obtained coatings have been physico-chemically characterized by scanning electron microscopy (SEM) and infrared microscopy (IRM). In vitro biological assays have been performed in order to evaluate the influence of fabricated microsphere thin coatings on the Staphylococcus aureus biofilm development as well as their biocompatibility. SEM micrographs have revealed a uniform morphology of thin coatings, while IRM investigations have proved both the homogeneity and functional groups integrity of prepared thin coatings. The obtained microsphere-based thin coatings have proved to be efficient vehicles for usnic acid natural compound with antibiofilm activity, as demonstrated by the inhibitory activity on S. aureus mature biofilm development, opening new perspectives for the prevention and therapy associated to biofilm related infections.

  13. Preparation, characterization, and antibacterial activity studies of silver-loaded poly(styrene-co-acrylic acid) nanocomposites.

    PubMed

    Song, Cunfeng; Chang, Ying; Cheng, Ling; Xu, Yiting; Chen, Xiaoling; Zhang, Long; Zhong, Lina; Dai, Lizong

    2014-03-01

    A simple method for preparing a new type of stable antibacterial agent was presented. Monodisperse poly(styrene-co-acrylic acid) (PSA) nanospheres, serving as matrices, were synthesized via soap-free emulsion polymerization. Field-emission scanning electron microscopy micrographs indicated that PSA nanospheres have interesting surface microstructures and well-controlled particle size distributions. Silver-loaded poly(styrene-co-acrylic acid) (PSA/Ag-NPs) nanocomposites were prepared in situ through interfacial reduction of silver nitrate with sodium borohydride, and further characterized by transmission electron microscopy and X-ray diffraction. Their effects on antibacterial activity including inhibition zone, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bactericidal kinetics were evaluated. In the tests, PSA/Ag-NPs nanocomposites showed excellent antibacterial activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. These nanocomposites are considered to have potential application in antibacterial coatings on biomedical devices to reduce nosocomial infection rates. PMID:24433897

  14. Vitamin B(12) deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid.

    PubMed

    Vaes, Bart L T; Lute, Carolien; Blom, Henk J; Bravenboer, Nathalie; de Vries, Teun J; Everts, Vincent; Dhonukshe-Rutten, Rosalie A; Müller, Michael; de Groot, Lisette C P G M; Steegenga, Wilma T

    2009-05-01

    The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B(12) deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B(12), Hcy, and MMA on differentiation and activity of bone cells. B(12) deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B(12) deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B(12), Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B(12) did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B(12) deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels.

  15. Effect of dietary antioxidant and increasing corn oil inclusion on milk fat yield and fatty acid composition in dairy cattle.

    PubMed

    Boerman, J P; Preseault, C L; Lock, A L

    2014-12-01

    The objective of this study was to examine the effect of a dietary synthetic antioxidant on feed intake, yields of milk and milk components and milk fatty acids (FA), in combination with increasing concentrations of dietary corn oil to provide increasing rumen unsaturated fatty acid load (RUFAL) challenges. Twenty-six Holstein cows (177 ± 57 d in milk; mean ± standard deviation) were assigned to treatment in a randomized complete block design. Treatments were a control diet (CON; n=13 cows) or the same diet supplemented with a synthetic antioxidant (AOX; 6.1g/d; dry blend of ethoxyquin and propyl gallate, Novus International Inc., St. Charles, MO; n=13 cows). In period 1 (21 d), no supplemental corn oil was fed; in periods 2, 3, and 4 (14 d each), corn oil was supplemented at 0.7, 1.4, and 2.8% of the diet [dry matter (DM) basis] to incrementally increase RUFAL. For all variables measured, no significant interactions were detected between treatment and period, indicating no differences between the CON and AOX treatments at all levels of oil inclusion. Intake of DM was lower for AOX compared with CON but AOX had no effect on milk yield or milk fat concentration and yield. Milk protein yield and feed efficiency (energy-corrected milk/DM intake) tended to be greater for AOX compared with CON. Increasing dietary corn oil concentration (RUFAL) decreased DM intake, milk yield, milk fat concentration and yield, and feed efficiency. The AOX treatment increased the concentration and yield of 16-carbon milk FA, with no effect on de novo (<16 carbon) or preformed (>16 carbon) milk FA. Milk FA concentration of trans-10 C18:1, trans-10,cis-12 C18:2, and trans-9,cis-11 C18:2 were unaffected by AOX but increased with increasing RUFAL. In conclusion, supplementation with AOX did not overcome the dietary-induced milk fat depression caused by increased RUFAL.

  16. Effects of small temperature increase and subchronic acid stress on juvenile rainbow trout during winter

    SciTech Connect

    D`Cruz, L.M.; Morgan, I.J.; Wood, C.M.

    1995-12-31

    Increasing water temperatures, as predicted by global warming are potentially problematic to freshwater fish, whose body temperature is set by their environment. In addition, fish living in softwater lakes face the detrimental effects of acid rain. To determine the cost of living in a warmer climate, two ninety day exposures were conducted during the winter in softwater. In the first exposure, fish were fed to satiation twice daily, while in the second exposure, fish were fed 1% of their wet body weight every four days. Monthly sampling was conducted to determine while body energy reserves: protein, lipids and carbohydrates, and changes in plasma Na and Cl concentrations. Oxygen consumption and nitrogen waste excretion rates were also measured. Fish exposed to acid and fed to satiation showed no ionoregulatory disturbances, an atypical result. Moreover, fish exposed to pH 5.2 had increased appetites, resulting in increased growth. In comparison, fish in the second exposure that were fed a limited ration and exposed to pH 5.2 had a greater mortality rate and lower plasma Na and Cl concentrations, with greater detrimental effects observed in fish exposed to +2 C above ambient. The findings suggest that NaCl present in commercial fish food may compensate for bronchial ion loss during acid exposure, as a result of a stimulation of appetite.

  17. Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers.

    PubMed

    Trinchieri, Alberto; Lizzano, Renata; Marchesotti, Federica; Zanetti, Giampaolo

    2006-02-01

    The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/-20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependent from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of

  18. Stearidonic acid-enriched soybean oil increased the omega-3 index, an emerging cardiovascular risk marker.

    PubMed

    Harris, William S; Lemke, Shawna L; Hansen, Susan N; Goldstein, Daniel A; DiRienzo, Maureen A; Su, Hong; Nemeth, Margaret A; Taylor, Mary L; Ahmed, Gulam; George, Cherian

    2008-09-01

    A plant source of omega-3 fatty acid (FA) that can raise tissue eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) is needed. A soybean oil (SBO) containing approximately 20% stearidonic acid [SDA; the delta-6 desaturase product of alpha-linolenic acid (ALA)] derived from genetically modified soybeans is under development. This study compared the effects of EPA to SDA-SBO on erythrocyte EPA+DHA levels (the omega-3 index). Overweight healthy volunteers (n=45) were randomized to SDA-SBO (24 ml/day providing approximately 3.7 g SDA) or to regular SBO (control group) without or with EPA ethyl esters (approximately 1 g/day) for 16 weeks. Serum lipids, blood pressure, heart rate, platelet function and safety laboratory tests were measured along with the omega-3 index. A per-protocol analysis was conducted on 33 subjects (11 per group). Compared to baseline, average omega-3 index levels increased 19.5% in the SDA group and 25.4% in the EPA group (p<0.05 for both, vs. control). DHA did not change in any group. Relative to EPA, SDA increased RBC EPA with about 17% efficiency. No other clinical endpoints were affected by SDA or EPA treatment (vs. control). In conclusion, SDA-enriched SBO significantly raised the omega-3 index. Since EPA supplementation has been shown to raise the omega-3 index and to lower risk for cardiac events, SDA-SBO may be a viable plant-based alternative for providing meaningful intakes of cardioprotective omega-3 FAs.

  19. Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

    PubMed

    van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

    2016-07-01

    Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined. PMID:27038174

  20. Jasmonic acid transient accumulation is needed for abscisic acid increase in citrus roots under drought stress conditions.

    PubMed

    de Ollas, Carlos; Hernando, Bárbara; Arbona, Vicent; Gómez-Cadenas, Aurelio

    2013-03-01

    Phytohormones are central players in sensing and signaling numerous environmental conditions like drought stress. In this work, an experimental system based on severe drought was established and hormone profiling together with gene expression of key enzymes involved in abscisic acid (ABA) and jasmonic acid (JA) biosynthesis was studied in roots of citrumelo CPB 4475 (a commercial citrus rootstock) plants. JA concentration transiently increased after a few hours of stress, returning to control levels 30 h after the onset of the condition. A more progressive ABA accumulation was observed, with the onset of this increase at the same time or right after the JA transient accumulation. Molecular data suggested that, at least, part of the hormonal regulation takes place at the biosynthetic level. These observations also pointed to a possible involvement of JA on ABA biosynthesis under stress. To test this hypothesis, JA and ABA biosynthesis were chemically inhibited and subsequently phenotypes rescued by the addition of exogenous hormones. Results showed that the early JA accumulation was necessary for the subsequent ABA increase in roots under stress whereas the opposite could not be stated. The model includes a burst of JA in roots of citrus under severe drought stress conditions that leads to a more progressive ABA accumulation that will induce later plant responses. The present work adds a new level of interaction between JA and ABA at the biosynthetic level that together with the previously described interaction between signal transduction cascades of the two hormones would allow plants to fine-tune specific responses to different stimuli.

  1. Dicarboxylic acids with limited numbers of hydrocarbons stabilize cell membrane and increase osmotic resistance in rat erythrocytes.

    PubMed

    Mineo, Hitoshi; Amita, Nozomi; Kawawake, Megumi; Higuchi, Ayaka

    2013-11-01

    We examined the effect of dicarboxylic acids having 0 to 6 hydrocarbons and their corresponding monocarboxylic or tricarboxylic acids in changing the osmotic fragility (OF) in rat red blood cells (RBCs). Malonic, succinic, glutaric and adipic acids, which are dicarboxylic acids with 1, 2, 3 and 4 straight hydrocarbons located between two carboxylic groups, decreased the OF in a concentration-dependent manner. Other long-chain dicarboxylic acids did not change the OF in rat RBCs. The benzoic acid derivatives, isophthalic and terephthalic acids, but not phthalic acid, decreased the OF in a concentration-dependent manner. Benzene-1,2,3-tricarboxylic acid, but not benzene-1,3,5-tricarboxylic acid, also decreased the OF in rat RBCs. On the other hand, monocarboxylic acids possessing 2 to 7 straight hydrocarbons and benzoic acid increased the OF in rat RBCs. In short-chain dicarboxylic acids, a limited number of hydrocarbons between the two carboxylic groups are thought to form a V- or U-shaped structure and interact with phospholipids in the RBC membrane. In benzene dicarboxylic and tricarboxylic acids, a part of benzene nucleus between the two carboxylic groups is thought to enter the plasma membrane and act on acyl-chain in phospholipids in the RBC membrane. For dicarboxylic and tricarboxylic acids, limited numbers of hydrocarbons in molecules are speculated to enter the RBC membrane with the hydrophilic carboxylic groups remaining outside, stabilizing the structure of the cell membrane and resulting in an increase in osmotic resistance in rat RBCs.

  2. Increased acid resistance of the archaeon, Metallosphaera sedula by adaptive laboratory evolution.

    PubMed

    Ai, Chenbing; McCarthy, Samuel; Eckrich, Valerie; Rudrappa, Deepak; Qiu, Guanzhou; Blum, Paul

    2016-10-01

    Extremely thermoacidophilic members of the Archaea such as the lithoautotroph, Metallosphaera sedula, are among the most acid resistant forms of life and are of great relevance in bioleaching. Here, adaptive laboratory evolution was used to enhance the acid resistance of this organism while genomics and transcriptomics were used in an effort to understand the molecular basis for this trait. Unlike the parental strain, the evolved derivative, M. sedula SARC-M1, grew well at pH of 0.90. Enargite (Cu3AsS4) bioleaching conducted at pH 1.20 demonstrated SARC-M1 leached 23.78 % more copper relative to the parental strain. Genome re-sequencing identified two mutations in SARC-M1 including a nonsynonymous mutation in Msed_0408 (an amino acid permease) and a deletion in pseudogene Msed_1517. Transcriptomic studies by RNA-seq of wild type and evolved strains at various low pH values demonstrated there was enhanced expression of genes in M. sedula SARC-M1 encoding membrane complexes and enzymes that extrude protons or that catalyze proton-consuming reactions. In addition, M. sedula SARC-M1 exhibited reduced expression of genes encoding enzymes that catalyze proton-generating reactions. These unique genomic and transcriptomic features support a model for increased acid resistance arising from enhanced control over cytoplasmic pH. PMID:27520549

  3. Dietary fatty acid enrichment increases egg size and quality of yellow seahorse Hippocampus kuda.

    PubMed

    Saavedra, M; Masdeu, M; Hale, P; Sibbons, C M; Holt, W V

    2014-02-01

    Seahorses populations in the wild have been declining and to restore them a better knowledge of seahorse reproduction is required. This study examines the effect of dietary quality on seahorse fecundity and egg quality. Two different diets were tested with Hippocampus kuda females: frozen mysis (control) and frozen mysis enriched with a liposome spray containing essential fatty acids. Diets were given to females (two groups of five) over a seven week period. After this period, males (fed the control diet) and females were paired and the eggs dropped by the females were collected. Fatty acid profile were analysed and eggs were counted and measured. Results showed that females fed on enriched mysis had larger eggs and that these had a higher content of total polyunsaturated fatty acids. The size of the egg was especially affected in the first spawn, where egg size for females fed the enriched diet was significantly higher than the egg size from control females. This effect was reduced in the following spawning where no significant differences were found. Egg size is an important quality descriptor as seahorse juveniles originating from smaller eggs and/or eggs of poor quality will have less chances of overcoming adverse conditions in the wild and consequently have lower survival and growth rates. This study shows that enriching frozen mysis with polyunsaturated fatty acids increases egg size and egg quality of H. kuda.

  4. Increased sensitivity and variability of phytotoxicity responses in Arctic soils to a reference toxicant, boric acid.

    PubMed

    Anaka, Alison; Wickstrom, Mark; Siciliano, Steven Douglas

    2008-03-01

    Industrial and human activities in the Arctic regions may pose a risk to terrestrial Arctic ecosystem functions. One of the most common terrestrial toxicological end points, primary productivity, typically is assessed using a plant phytotoxicity test. Because of cryoturbation, a soil mixing process common in polar regions, we hypothesized that phytotoxicity test results in Arctic soils would be highly variable compared to other terrestrial ecosystems. The variability associated with phytotoxicity tests was evaluated using Environment Canada's standardized plant toxicity test in three cryoturbated soils from Canada's Arctic exposed to a reference toxicant, boric acid. Northern wheatgrass (Elymus lanceolatus) not only was more sensitive to toxicants in Arctic soils, its response to toxicants was more variable compared to that in temperate soils. The phytotoxicity of boric acid in cryosols was much greater than commonly reported in other soils, with a boric acid concentration of less than 150 microg/g soil needed to inhibit root and shoot growth by 20%. Large variability also was found in the phytotoxicity test results, with coefficients of variation for 10 samples ranging from 160 to 79%. The increased toxicity of boric acid in cryosols and variability in test response was not explained by soil properties. Based on our admittedly limited data set of three different Arctic soils, we recommend that more than 30 samples be taken from each control and potentially impacted area to accurately assess contaminant effects at sites in northern Canada. Such intensive sampling will insure that false-negative results for toxicant impacts in Arctic soils are minimized.

  5. Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats.

    PubMed

    Toufektsian, Marie-Claire; Salen, Patricia; Laporte, François; Tonelli, Chiara; de Lorgeril, Michel

    2011-01-01

    Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 μL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.

  6. Evaluation of Surfactants-Assisted Folic Acid-Loaded Pectin Submicrospheres: Characterization and Hemocompatibility Assay.

    PubMed

    Varuna Kumara, J B; Ravikumara, N R; Madhusudhan, Basavaraj

    2016-10-01

    Folic acid is used for preventing and treating multiple diseases and disorders, administered in the form of oral supplements. The present research work was aimed to study the influence of two non-ionic surfactants Poloxamer and Tween 80 (Polysorbate 80) on pectin submicrospheres formulations. Typical natural polymer pectin was used to encapsulate folic acid by cross linking method. The resultant submicrospheres contributed to improve the aqueous solubility to enhance the bioavailability of folic acid. During investigation, it was observed that pectin polymers influenced kinetics of the rate of reaction more intensively than the surfactants. The physical phenomenon caused the change in their size, shape and chemistry of pectin polymers transforming into submicrospheres in aqueous condition. The characteristic differences of submicrospheres were assessed by scanning electron microscopy, differential scanning calorimetry and Fourier-transform infrared spectroscopy. The average diameters of the submicrospheres ranged between 250 and 500 nm. The encapsulation efficiency of submicrospheres ranged between 80 and 96 %. The characteristic swelling behavior of lyophilized submicrospheres was influenced by the ratio of pectin polymers and folic acid used in the formulations. The submicrospheres systems exhibited controlled release of folic acid due to the pH-dependent solubility of pectin polymers in aqueous medium. The submicrospheres showed good haemocompatibility suggesting them to be promising candidates for oral delivery. PMID:27605736

  7. Preparation, characterization, and antitumor activity of paclitaxel-loaded folic acid modified and TAT peptide conjugated PEGylated polymeric liposomes.

    PubMed

    Niu, Ruifang; Zhao, Peiqi; Wang, Hanjie; Yu, Man; Cao, Shuzhen; Zhang, Fei; Chang, Jin

    2011-06-01

    Targeting therapy is a promising strategy for enhancing the therapeutic potential of chemotherapeutic agents. In this study, we report the construction of a multifunctional drug delivery system, termed folic acid modified and TAT peptide conjugated PEGylated polymeric liposomes (FA-TATp-PLs), which is originally derived from octadecyl-quaternized lysine modified chitosan and cholesterol. Our data revealed that FA-TATp-PLs have a particle size of about 60 nm with a zeta potential of about 30 mV, a low burst release effect within the first day, a sustained release for the next 14 days in vitro as well as an instant cellular uptake by folate receptor-overexpressing KB human nasopharyngeal carcinoma cells. In vitro cytotoxicity of paclitaxel-loaded FA-TATp-PLs in KB cells was superior to that of Taxol(®). Furthermore, a comparable antitumor efficacy of paclitaxel-loaded FA-TATp-PLs and Taxol(®) was observed at the same doses in murine models bearing nasopharyngeal carcinoma. These results demonstrate that the paclitaxel formulation not only exhibits a higher antitumor activity but also significantly reduces the toxicity and improves the bioavailability as compared to that of free paclitaxel for the treatment of nasopharyngeal carcinoma. Taken together, our findings indicate that paclitaxel-loaded FA-TATp-PLs are a promising nano-sized drug formulation for future cancer therapy. PMID:20677917

  8. Impact of the substrate loading regime and phosphoric acid supplementation on performance of biogas reactors and microbial community dynamics during anaerobic digestion of chicken wastes.

    PubMed

    Belostotskiy, Dmitry E; Ziganshina, Elvira E; Siniagina, Maria; Boulygina, Eugenia A; Miluykov, Vasili A; Ziganshin, Ayrat M

    2015-10-01

    This study evaluates the effects of increasing organic loading rate (OLR) and decreasing hydraulic retention time (HRT) as well as phosphoric acid addition on mesophilic reactors' performance and biogas production from chicken wastes. Furthermore, microbial community composition in reactors was characterized by a 16S rRNA gene-based pyrosequencing analysis. Each step of increasing OLR impacted on the activity of microorganisms what caused a temporary decrease in biogas production. The addition of phosphoric acid resulted in the increased biogas production with values between 361 and 447 mL g(VS)(-1) from day 61 to day 74 compared to control reactor (309-350 mL g(VS)(-1)). With reactors' operation, Bacteroidetes phylotypes were noticeably replaced with Firmicutes representatives, and significant increase of Clostridium sp. was identified. Within Euryarchaeota, Methanosarcina sp. dominated in all analyzed samples, in which high ammonium levels were detected (3.4-4.9 NH4(+)-N g L(-1)). These results can help in better understanding the anaerobic digestion process of simultaneously ammonium/phosphate-rich substrates.

  9. Skin delivery of kojic acid-loaded nanotechnology-based drug delivery systems for the treatment of skin aging.

    PubMed

    Gonçalez, M L; Corrêa, M A; Chorilli, M

    2013-01-01

    The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil-O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery. PMID:24369010

  10. Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

    PubMed Central

    Gonçalez, M. L.; Corrêa, M. A.; Chorilli, M.

    2013-01-01

    The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil—O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery. PMID:24369010

  11. Coffee component 3-caffeoylquinic acid increases antioxidant capacity but not polyphenol content in experimental cerebral infarction.

    PubMed

    Ruiz-Crespo, Silvia; Trejo-Gabriel-Galan, Jose M; Cavia-Saiz, Monica; Muñiz, Pilar

    2012-05-01

    Although coffee has antioxidant capacity, it is not known which of its bioactive compounds is responsible for it, nor has it been analyzed in experimental cerebral infarction. We studied the effect one of its compounds, 3-caffeoylquinic acid (3-CQA), at doses of 4, 25 and 100 μg on plasma antioxidant capacity and plasma polyphenol content, measuring the differences before and after inducing a cerebral infarction in an experimental rat model. We compared them with 3-caffeoylquinic-free controls. The increase in total antioxidant capacity was only higher than in controls in 3-CQA treated animals with the highest dose. This increase in antioxidant capacity was not due to an increase in polyphenols. No differences between the experimental and control group were found regarding polyphenol content and cerebral infarction volume. In conclusion, this increase in antioxidant capacity in the group that received the highest dose of 3-CQA was not able to reduce experimental cerebral infarction.

  12. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    PubMed

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid. PMID:26854723

  13. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    PubMed

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes. PMID:26167409

  14. Trifluoperazine increases fatty acid turnover in phospholipids in cultured human fibroblasts.

    PubMed

    Mazière, C; Mazière, J C; Mora, L; Auclair, M; Polonovski, J

    1988-05-01

    A 24-hr pretreatment of cultured human fibroblasts with trifluoperazine induced a marked increase in incorporation of saturated (stearic, palmitic) and unsaturated (oleic, arachidonic) fatty acids into phospholipids (1.5- to 2-fold for 5.10(-5) M trifluoperazine). Concomitantly, incorporation into cholesteryl esters was strongly inhibited (20% of control for 5.10(-5) M trifluoperazine). The drug did not change the phospholipid composition of treated cells. The effect of trifluoperazine on oleic acid incorporation into phospholipids was time-dependent and reached a maximum after a six-hr preincubation with the drug. Trifluoperazine also induced an increase in the rate of chase of oleic acid from the different phospholipid classes. In vitro preincubation of cell-free extracts with trifluoperazine resulted in activation of phospholipid acyltransferases, whereas cholesterol acyltransferase activity was decreased. The rapid effect of trifluoperazine together with its effect on a cell-free system suggests a direct action of this amphiphilic drug on the acyltransferase activities, probably by modification of the structural organization of cellular membranes.

  15. Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance

    PubMed Central

    Yew Tan, Chong; Virtue, Samuel; Murfitt, Steven; Robert, Lee D.; Phua, Yi Hui; Dale, Martin; Griffin, Julian L.; Tinahones, Francisco; Scherer, Philipp E.; Vidal-Puig, Antonio

    2015-01-01

    The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue. PMID:26679101

  16. The effects of amino acid loading on glomerular filtration in dogs on different protein diets: a controlled study.

    PubMed

    Fine, A

    1988-08-01

    Considerable variation in both the magnitude and pattern of response of glomerular filtration rate (GFR) to protein loading in omnivores has been reported in the literature. These experiments were designed to examine, under carefully controlled conditions, the effects of different acute protein loads given to a group of dogs placed on a normal protein (NP) intake for 4 weeks and to the same dogs when on a low protein (LP) intake for the same duration. GFR did not change when the dogs were changed from NP to LP diets, 3.0 + 0.2 (NP) vs. 3.2 + 0.3 (LP) mL.min-1.kg-1. Intravenous amino acid was infused at 15, 25, and 40 mL/h on different days. Regardless of whether on a low or high protein diet, the GFR did not change. Another set of experiments was performed in another Canadian centre 2000 miles away. In these studies with dogs on a similar normal protein diet, a striking rise in GFR occurred following amino-acid infusion at 25 mL/h, 3.1 + 0.3 vs. 4.8 + 0.6 mL.min-1.kg-1 (p less than 0.001). These results demonstrate, at least in the dog, that contrary to previous reports, dietary protein changes do not affect the GFR. Furthermore, the GFR response to an acute intravenous protein load does not depend on the amount of protein given nor the previous protein diet but appears to be possibly dependent on other factors that may be environmental or congenital.

  17. Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds

    PubMed Central

    Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Doron-Faigenboim, Adi; Blumwald, Eduardo; Sadka, Avi

    2014-01-01

    Many fruit trees undergo cycles of heavy fruit load (ON-Crop) in one year, followed by low fruit load (OFF-Crop) the following year, a phenomenon known as alternate bearing (AB). The mechanism by which fruit load affects flowering induction during the following year (return bloom) is still unclear. Although not proven, it is commonly accepted that the fruit or an organ which senses fruit presence generates an inhibitory signal that moves into the bud and inhibits apical meristem transition. Indeed, fruit removal from ON-Crop trees (de-fruiting) induces return bloom. Identification of regulatory or metabolic processes modified in the bud in association with altered fruit load might shed light on the nature of the AB signalling process. The bud transcriptome of de-fruited citrus trees was compared with those of ON- and OFF-Crop trees. Fruit removal resulted in relatively rapid changes in global gene expression, including induction of photosynthetic genes and proteins. Altered regulatory mechanisms included abscisic acid (ABA) metabolism and auxin polar transport. Genes of ABA biosynthesis were induced; however, hormone analyses showed that the ABA level was reduced in OFF-Crop buds and in buds shortly following fruit removal. Additionally, genes associated with Ca2+-dependent auxin polar transport were remarkably induced in buds of OFF-Crop and de-fruited trees. Hormone analyses showed that auxin levels were reduced in these buds as compared with ON-Crop buds. In view of the auxin transport autoinhibition theory, the possibility that auxin distribution plays a role in determining bud fate is discussed. PMID:24706719

  18. Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds.

    PubMed

    Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Doron-Faigenboim, Adi; Blumwald, Eduardo; Sadka, Avi

    2014-07-01

    Many fruit trees undergo cycles of heavy fruit load (ON-Crop) in one year, followed by low fruit load (OFF-Crop) the following year, a phenomenon known as alternate bearing (AB). The mechanism by which fruit load affects flowering induction during the following year (return bloom) is still unclear. Although not proven, it is commonly accepted that the fruit or an organ which senses fruit presence generates an inhibitory signal that moves into the bud and inhibits apical meristem transition. Indeed, fruit removal from ON-Crop trees (de-fruiting) induces return bloom. Identification of regulatory or metabolic processes modified in the bud in association with altered fruit load might shed light on the nature of the AB signalling process. The bud transcriptome of de-fruited citrus trees was compared with those of ON- and OFF-Crop trees. Fruit removal resulted in relatively rapid changes in global gene expression, including induction of photosynthetic genes and proteins. Altered regulatory mechanisms included abscisic acid (ABA) metabolism and auxin polar transport. Genes of ABA biosynthesis were induced; however, hormone analyses showed that the ABA level was reduced in OFF-Crop buds and in buds shortly following fruit removal. Additionally, genes associated with Ca(2+)-dependent auxin polar transport were remarkably induced in buds of OFF-Crop and de-fruited trees. Hormone analyses showed that auxin levels were reduced in these buds as compared with ON-Crop buds. In view of the auxin transport autoinhibition theory, the possibility that auxin distribution plays a role in determining bud fate is discussed.

  19. Twice-weekly consumption of farmed Atlantic salmon increases plasma content of phospholipid n-3 fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated intake of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is related to risk reduction of cardiovascular and other diseases. Increased consumption of seafood such as farmed Atlantic salmon is an effective way to consume n-3 but there is a paucity of data as ...

  20. Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes.

    PubMed

    Park, Kyoung Sik

    2010-10-01

    Raspberry ketone (RK) is a natural phenolic compound of the red raspberry. The dietary administration of RK to male mice has been reported to prevent high-fat diet-induced elevation in body weight and to increase lipolysis in white adipocytes. To elucidate a possible mechanism for the antiobesity action of RK, its effects on the expression and the secretion of adiponectin, lipolysis, and fatty acid oxidation in 3T3-L1 were investigated. Treatment with 10 µM of RK increased lipolysis significantly in differentiated 3T3-L1 cells. An immunoassay showed that RK increased both the expression and the secretion of adiponectin, an adipocytokine mainly expressed and secreted by adipose tissue. In addition, treatment with 10 µM of RK increased the fatty acid oxidation and suppressed lipid accumulation in 3T3-L1 adipocytes. These findings suggest that RK holds great promise as an herbal medicine since its biological activities alter the lipid metabolism in 3T3-L1 adipocytes.

  1. Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy.

    PubMed Central

    Heindorff, H; Billesbølle, P; Pedersen, S L; Hansen, R; Vilstrup, H

    1995-01-01

    The importance of glucagon on postoperative changes in hepatic amino-nitrogen conversion were investigated in six patients undergoing elective cholecystectomy for uncomplicated gall stones. Patients were given infusions of somatostatin (bolus of 6 micrograms/kg followed by continuous infusion of 6 micrograms/kg/h) from induction of anaesthesia to the end of investigation, the first postoperative day (30 hours). Controls were 16 patients undergoing the same procedures omitting the somatostatin infusion. In all patients blood concentration and plasma clearance of total alpha-amino-nitrogen, and amino acid stimulated rate of urea synthesis were measured. Elective cholecystectomy decreased blood alpha-amino-nitrogen concentration from mean (SEM) 2.9 (0.2) to 2.4 (0.1) mmol/l (p < 0.05), increased the clearance of total alpha-amino-nitrogen from 5.2 (0.3) to 6.6 (0.3) ml/s (p < 0.05), and increased the rate of amino acid stimulated urea synthesis from 27 (1) to 37 (2) mumol/s (p < 0.05) pointing to increased hepatic removal of amino-nitrogen at expense of plasma amino-nitrogen. Infusion of somatostatin prevented increase of glucagon for 24 hours after surgery, and prevented the negative changes in postoperative nitrogen homeostasis resulting from the postoperative changes in hepatic nitrogen conversion, suggesting glucagon as mediator. The exact mechanism remains in doubt, however, because of the multiple effects of somatostatin. PMID:7797129

  2. Reducing Isozyme Competition Increases Target Fatty Acid Accumulation in Seed Triacylglycerols of Transgenic Arabidopsis1[OPEN

    PubMed Central

    van Erp, Harrie; Shockey, Jay; Zhang, Meng; Adhikari, Neil D.; Browse, John

    2015-01-01

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on hydroxy fatty acids (HFAs) and conjugated polyenoic FAs (α-eleostearic acids [ESAs]) using Arabidopsis (Arabidopsis thaliana) as a model. These FAs are found naturally in seed oils of castor (Ricinus communis) and tung tree (Vernicia fordii), respectively, and used for the production of lubricants, nylon, and paints. Transgenic oils typically contain less target FA than that produced in the source species. We hypothesized that competition between endogenous and transgenic isozymes for substrates limits accumulation of unique FAs in Arabidopsis seeds. This hypothesis was tested by introducing a mutation in Arabidopsis diacylglycerol acyltransferase1 (AtDGAT1) in a line expressing castor FA hydroxylase and acyl-Coenzyme A:RcDGAT2 in its seeds. This led to a 17% increase in the proportion of HFA in seed oil. Expression of castor phospholipid:diacylglycerol acyltransferase 1A in this line increased the proportion of HFA by an additional 12%. To determine if our observations are more widely applicable, we investigated if isozyme competition influenced production of ESA. Expression of tung tree FA conjugase/desaturase in Arabidopsis produced approximately 7.5% ESA in seed lipids. Coexpression of VfDGAT2 increased ESA levels to approximately 11%. Overexpression of VfDGAT2 combined with suppression of AtDGAT1 increased ESA accumulation to 14% to 15%. Our results indicate that isozyme competition is a limiting factor in the engineering of unusual FAs in heterologous plant systems and that reduction of competition through mutation and RNA suppression may be a useful component of seed metabolic engineering strategies. PMID:25739701

  3. ESTIMATION OF CRITICAL LOADS OF ACIDITY FOR LAKESIN NORTHEASTERN UNITED STATES AND EASTERN CANADA

    EPA Science Inventory

    The New England Governors and Eastern Canadian Premiers (NEG/ECP) adopted the Acid Rain Action Plan in June 1998, and issued a series of action items to support its work toward a reduction of sulfur dioxide (SO2) and nitrogen oxide (NOx ) emissions in northeastern North Americ...

  4. Organic amendments increase soil solution phosphate concentrations in an acid soil: A controlled environment study

    SciTech Connect

    Schefe, C.R.; Patti, A.F.; Clune, T.S.; Jackson, R.

    2008-04-15

    Soil acidification affects at least 4 million hectares of agricultural land in Victoria, Australia. Low soil pH can inhibit plant growth through increased soluble aluminum (Al) concentrations and decreased available phosphorus (P). The addition of organic amendments may increase P availability through competition for P binding sites, solubilization of poorly soluble P pools, and increased solution pH. The effect of two organic amendments (lignite and compost) on P solubility in an acid soil was determined through controlled environment (incubation) studies. Three days after the addition of lignite and compost, both treatments increased orthophosphate and total P measured in soil solution, with the compost treatments having the greatest positive effect. Increased incubation time (26 days) increased soil solution P concentrations in both untreated and amended soils, with the greatest effect seen in total P concentrations. The measured differences in solution P concentrations between the lignite- and compost-amended treatments were likely caused by differences in solution chemistry, predominantly solution pH and cation dynamics. Soil amendment with lignite or compost also increased microbial activity in the incubation systems, as measured by carbon dioxide respiration. Based on the results presented, it is proposed that the measured increase in soil solution P with amendment addition was likely caused by both chemical and biological processes, including biotic and abiotic P solubilization reactions, and the formation of soluble organic-metal complexes.

  5. Effects of riverine suspended particulate matter on the post-dredging increase in internal phosphorus loading across the sediment-water interface.

    PubMed

    Liu, Cheng; Shao, Shiguang; Shen, Qiushi; Fan, Chengxin; Zhang, Lei; Zhou, Qilin

    2016-04-01

    Dredging is frequently used in the river mouths of eutrophic lakes to reduce internal phosphorus (P) loading from the sediment. However, the accumulation of P-adsorbed suspended particulate matter (SPM) from the inflowing rivers negatively affects the post-dredging sediment-water interface and ultimately increases internal P loading. Here, a 360-d experiment was carried out to investigate the influence of riverine SPM on the efficacy of dredging in reducing internal P loading. SPM was added to dredged and undredged sediments collected from the confluence area of Lake Chaohu. Several parameters related to internal P loading, including oxygen profile, soluble reactive P, and ferrous iron across the sediment-water interface, organic matter, alkaline phosphatase activity, and P fractions, were measured throughout the experimental period. The results showed that the P content (especially mobile P) in the sediment increased to the pre-dredging level with the accumulation of SPM in the dredged sediment. In addition, the P flux across the sediment-water interface increased with the accumulation of SPM. Several characteristics of SPM, including high organic matter content, mobile P, high activity of alkaline phosphatase, and high biological activity, were considered correlated with the post-dredging increase in internal P loading. Overall, this study showed that the heavily contaminated riverine SPM regulates the long-term efficacy of dredging as a nutrient management option in the confluence area. Management is needed to avoid or reduce this phenomenon during dredging projects of this nature.

  6. Impact of organic nutrient load on biomass accumulation, feed channel pressure drop increase and permeate flux decline in membrane systems.

    PubMed

    Bucs, Sz S; Valladares Linares, R; van Loosdrecht, M C M; Kruithof, J C; Vrouwenvelder, J S

    2014-12-15

    The influence of organic nutrient load on biomass accumulation (biofouling) and pressure drop development in membrane filtration systems was investigated. Nutrient load is the product of nutrient concentration and linear flow velocity. Biofouling - excessive growth of microbial biomass in membrane systems - hampers membrane performance. The influence of biodegradable organic nutrient load on biofouling was investigated at varying (i) crossflow velocity, (ii) nutrient concentration, (iii) shear, and (iv) feed spacer thickness. Experimental studies were performed with membrane fouling simulators (MFSs) containing a reverse osmosis (RO) membrane and a 31 mil thick feed spacer, commonly applied in practice in RO and nanofiltration (NF) spiral-wound membrane modules. Numerical modeling studies were done with identical feed spacer geometry differing in thickness (28, 31 and 34 mil). Additionally, experiments were done applying a forward osmosis (FO) membrane with varying spacer thickness (28, 31 and 34 mil), addressing the permeate flux decline and biofilm development. Assessed were the development of feed channel pressure drop (MFS studies), permeate flux (FO studies) and accumulated biomass amount measured by adenosine triphosphate (ATP) and total organic carbon (TOC). Our studies showed that the organic nutrient load determined the accumulated amount of biomass. The same amount of accumulated biomass was found at constant nutrient load irrespective of linear flow velocity, shear, and/or feed spacer thickness. The impact of the same amount of accumulated biomass on feed channel pressure drop and permeate flux was influenced by membrane process design and operational conditions. Reducing the nutrient load by pretreatment slowed-down the biofilm formation. The impact of accumulated biomass on membrane performance was reduced by applying a lower crossflow velocity and/or a thicker and/or a modified geometry feed spacer. The results indicate that cleanings can be delayed

  7. Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

    PubMed Central

    Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness. PMID:22745735

  8. Increasing concentrations of perfluoroalkyl acids in Scandinavian otters (Lutra lutra) between 1972 and 2011: a new threat to the otter population?

    PubMed

    Roos, Anna; Berger, Urs; Järnberg, Ulf; van Dijk, Jiska; Bignert, Anders

    2013-10-15

    Liver samples from 140 otters (Lutra lutra) from Sweden and Norway were analyzed for 10 perfluoroalkyl carboxylic acids (PFCAs; C6-C15), 4 perfluoroalkane sulfonic acids (PFSAs; C4,C6,C8,C10) and perfluorooctane sulfonamide (FOSA). Perfluorooctane sulfonic acid (PFOS) was the dominant compound accounting for approximately 80% of the fluorinated contaminants and showing concentrations up to 16 μg/g wet weight. Perfluorononanoic acid (PFNA) was the dominant PFCA (up to 640 ng/g wet weight) closely followed by the C10 and C11 homologues. A spatial comparison between otters from southwestern Norway, southern and northern Sweden sampled between 2005 and 2011 revealed that the samples from southern Sweden had generally the largest contaminant load, but two PFCAs and FOSA were higher concentrated in the Norwegian samples. A temporal trend study was performed on otters from southern Sweden collected between 1972 and 2011. Seven PFCAs (C8-C14), PFOS and perfluorodecane sulfonic acid (PFDS) showed significantly increasing trends with doubling times between 5.5 and 13 years. The PFCAs also showed significantly increasing trends over the period 2002 to 2011. These findings together with the exceptionally high liver concentrations of PFOS are of great concern for the Scandinavian otter populations.

  9. Stress-induced increases in brainstem amino acid levels are prevented by chronic sodium hydrosulfide treatment.

    PubMed

    Warenycia, M W; Kombian, S B; Reiffenstein, R J

    1990-01-01

    Neurotransmitter amino acid levels were measured in select brain regions of rats and mice after chronic treatment with sublethal doses of sodium hydrosulfide (NaHS). Brainstem aspartate, glutamate, glutamine, taurine and GABA levels increased in chronically but not acutely saline-treated rats. These increases may have been due to stress from frequent handling, and were prevented by chronic NaHS treatment (7.5 mg/kg ip every 8 hr for 3 consecutive days). In contrast, aspartate, glutamate and glutamine increased in female but not in male ICR mouse brainstems after once daily treatment with 7.0 mg/kg NaHS for 5 consecutive days. These effects of NaHS may indicate chronic low level H2S neurotoxicity. Differences between chronic and acute treatments, female and male responses, and treatment paradigms may complicate interpretations of such toxicity studies.

  10. Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats.

    PubMed

    Ferguson, D C; Caffall, Z; Hoenig, M

    2007-08-01

    The obese cat is a model for the study of the progression toward type 2 diabetes. In this study, the impact of obesity on the hypothalamic-pituitary-thyroid axis was examined in 21 domestic shorthair cats before and after the development of obesity, which significantly increased body mass index (BMI), % body fat (BF), and girth (P<0.0001 for all). Serum total thyroxine (TT(4)), tri-iodothyronine, free T(4) (FT(4)) by direct dialysis, nonesterified fatty acids (NEFA), and leptin were measured, and FT(4) fraction (F