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Sample records for acute acid loading

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

    Science.gov (United States)

    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.

  2. Renal response to acute acid loading--an organ physiological approach

    DEFF Research Database (Denmark)

    Osther, P J; Engel, K; Kildeberg, P

    2004-01-01

    performed in 10 healthy men using a randomized, placebo-controlled, crossover design. Arterialized capillary blood, serum and urine were collected hourly during the loading studies for the measurement of electrolytes and acid-base status. Concentrations of non-metabolizable base (NB) and acid (NA) were...

  3. Effect of acute acid loading on acid-base and calcium metabolism

    DEFF Research Database (Denmark)

    Osther, Palle J

    2006-01-01

    male recurrent idiopathic calcium stone-formers and 12 matched healthy men using a randomized, placebo-controlled, cross-over design. Arterialized capillary blood, serum and urine were collected hourly for measurement of electrolytes, ionized calcium, magnesium, phosphate, parathyroid hormone and acid...

  4. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests I. Review of Biochemical Aspects and Poor Specificity of Current Amino Acid Formulations

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    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests are powerful tools for studying the roles of serotonin, dopamine and noradrenaline in normal subjects and those with behavioural disorders. The current amino acid formulations for these tests, however, are associated with undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to competing amino acids resulting in loss of specificity. This could confound biochemical and behavioural findings. Compositions of current formulations are reviewed, the biochemical principles underpinning the tests are revisited and examples of unintended changes in the above ratios and their impact on monoamine function and behaviour will be demonstrated from data in the literature. The presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and Val is responsible for these unintended decreases and the consequent loss of specificity. Strategies for enhancing the specificity of the different formulations are proposed.

  5. Acute effect of folic acid, betaine, and serine supplements on flow-mediated dilation after methionine loading: A randomized trial

    NARCIS (Netherlands)

    Olthof, M.R.; Bots, M.L.; Katan, M.B.; Verhoef, P.

    2006-01-01

    Objectives: We investigated whether reducing post-methionine homocysteine concentrations via various treatments other than folic acid affects vascular function, as measured through flow-mediated dilation (FMD) of the brachial artery. High fasting and post-methionine homocysteine concentrations are a

  6. Citraturic response to oral citric acid load

    Science.gov (United States)

    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.

  7. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests Part II: Normalisation of the Tryptophan and the Tyrosine Plus Phenylalanine to Competing Amino Acid Ratios in a New Control Formulation

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    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available Current formulations for acute tryptophan (Trp or tyrosine (Tyr plus phenylalanine (Phe depletion and loading cause undesirable decreases in ratios of Trp or Tyr + Phe to competing amino acids (CAA, thus undermining the specificities of these tests. Branched-chain amino acids (BCAA cause these unintended decreases, and lowering their content in a new balanced control formulation in the present study led to normalization of all ratios. Four groups (n = 12 each of adults each received one of four 50 g control formulations, with 0% (traditional, 20%, 30%, or 40% less of the BCAA. The free and total [Trp]/[CAA] and [Phe + Tyr]/[BCAA + Trp] ratios all decreased significantly during the first 5 h following the traditional formulation, but were fully normalized by the formulation containing 40% less of the BCAA. We recommend the latter as a balanced control formulation and propose adjustments in the depletion and loading formulations to enhance their specificities for 5-HT and the catecholamines.

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

    NARCIS (Netherlands)

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

    2016-01-01

    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 com

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

    NARCIS (Netherlands)

    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

    2016-01-01

    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 compar

  10. Acute chemical pneumonitis caused by nitric acid inhalation: case report

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Hyung Shim; Lee, In Jae; Ko, Eun Young; Lee, Jae Young; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2003-06-01

    Chemical pneumonitis induced by nitric acid inhalation is a rare clinical condition. The previously reported radiologic findings of this disease include acute permeability pulmonary edema, delayed bronchiolitis obliterans, and bronchiectasis. In very few published rare radiologic reports has this disease manifested as acute alveolar injury; we report a case of acute chemical pneumonitis induced by nitric acid inhalation which at radiography manifested as bilateral perihilar consolidation and ground-glass attenuation, suggesting acute alveolar injury.

  11. Fecal loading in the cecum as a new radiological sign of acute appendicitis

    Institute of Scientific and Technical Information of China (English)

    Andy Petroianu; Luiz Ronaldo Alberti; Renata Indelicato Zac

    2005-01-01

    AIM: Although the radiological features of acute appendicitis have been well documented, the value of plain radiography has not been fully appreciated. The aim of this study was to determine the frequency of the association of acute appendicitis with images of fecal loading in the cecum.METHODS: Plain abdominal radiographs of 400 patients operated upon for acute appendicitis (n = 100), acute cholecystitis (n = 100), right acute pelvic inflammatory disease (n = 100) and right nephrolithiasis (n = 100)were assessed. The presence of fecal loading was recorded and the sensitivity and specificity of this sign for acute appendicitis were calculated.RESULTS: The presence of fecal loading in the cecum occurred in 97 patients with acute appendicitis, 13 patients with acute cholecystitis, 12 patients with acute inflammatory pelvic disease and 19 patients with nephrolithiasis. The sensitivity of this sign for appendicitis was 97% and its specificity to this disease was 85.3%. Its positive predictive value for appendicitis was 68.7%; however, its negative predictive value for appendicitis was 98.8%.CONCLUSION: The present study suggests that the presence of radiological images of fecal loading in the cecum may be a useful sign of acute appendicitis, and the absence of this sign probably excludes this disease.This is the first description of fecal loading as a radiological sign for acute appendicitis.

  12. Influence of Dietary Acid Load on Exercise Performance.

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    Applegate, Catherine; Mueller, Mackenzie; Zuniga, Krystle E

    2017-01-04

    Diet composition can affect systemic pH and acid-base regulation, which may in turn influence exercise performance. An acidic environment in the muscle impairs performance and contributes to fatigue; therefore, current trends in sports nutrition place importance on maximizing the alkalinity of the body with ergogenic aids and dietary strategies. This review examines the evidence on the effects of dietary manipulations on acid load and exercise performance. Ten studies that investigated the effect of high versus low dietary acid loads on athletic performance generally identified that low dietary acid loads increased plasma pH, but did not consistently improve exercise performance at maximal or submaximal exercise intensities. In addition, the few studies conducted have several limitations including lack of female subjects and use of exercise tests exclusive to cycling or treadmill running. Although the research does not strongly support a performance benefit from low dietary acid loads, a more alkaline dietary pattern may be beneficial for overall health, as dietary induced acidosis has been associated with greater risk of cardiovascular disease and bone disease. The review includes dietary recommendations for athletes to reduce dietary acid load while still meeting sports nutrition recommendations.

  13. Novel Polymers with Carboxylic Acid Loading

    DEFF Research Database (Denmark)

    Thomsen, Anders Daugaard; Malmström, Eva; Hvilsted, Søren

    2006-01-01

    Click chemistry has been used to prepare a range of novel polymers with pendant carboxylic acid side groups. Four azido carboxylic acids, either mono- or difunctional and aliphatic or aromatic, have been prepared and thoroughly characterized. Extensive model reactions with 1-ethyl-4-hydroxybenzene......, the simplest model for poly(4-hydroxystyrene), and the four azido carboxylic acids have been conducted to establish the proper reaction conditions and provide an analytical frame for the corresponding polymers. Poly(4-hydroxystyrene) moieties in three different polymers—poly(4-hydroxystyrene), poly(4...... the polymers in general exhibit [when poly(4-hydroxystyrene) is a substantial part] significant changes in the glass-transition temperature from the polar poly(4-hydroxystyrene) (120–130 °C) to the much less polar alkyne polymers (46–60 °C). A direct correlation between the nature of the pendant groups...

  14. Bile Acid Determination after Standardized Glucose Load in Pregnant Women

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    Adams, April; Jacobs, Katherine; Vogel, Rachel Isaksson; Lupo, Virginia

    2015-01-01

    Objective Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disorder, usually manifesting in the third trimester and associated with increased perinatal morbidity and mortality. The hallmark laboratory abnormality in ICP is elevated fasting serum bile acids; however, there are limited data on whether a nonfasting state affects a pregnant woman's total bile acids. This study assesses fasting and nonfasting bile acid levels in 10 healthy pregnant women after a standardized glucose load to provide insight into the effects of a glucose load on bile acid profiles. Study Design Pilot prospective cohort analysis of serum bile acids in pregnant women. A total of 10 healthy pregnant women from 28 to 32 weeks' gestation were recruited for the study before undergoing a glucose tolerance test. Total serum bile acids were collected for each subject in the overnight fasting state, and 1 and 3 hours after the 100-g glucose load. Results There was a statistically significant difference between fasting versus 3-hour values. There was no statistically significant difference between fasting versus 1-hour and 1-hour versus 3-hour values. Conclusion There is a difference between fasting and nonfasting total serum bile acids after a 100-g glucose load in healthy pregnant women. PMID:26495178

  15. Dietary acid load and risk of hypertension : the Rotterdam Study

    NARCIS (Netherlands)

    Engberink, Marielle F.; Bakker, Stephan J. L.; Brink, Elizabeth J.; van Baak, Marleen A.; van Rooij, Frank J. A.; Hofman, Albert; Witteman, Jacqueline C. M.; Geleijnse, Johanna M.

    2012-01-01

    Background: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP). Objective: The objective was to examine whether dietary acid load was associated with incident hypertension in a cohort of older Dutch adults from the Rotterdam Study. Design: The analyses i

  16. Dietary acid load and risk of hypertension: The Rotterdam study

    NARCIS (Netherlands)

    M.F. Engberink (Marielle); S.J.L. Bakker (Stephan); E.J. Brink (Elizabeth); M.A. van Baak (Marleen); F.J.A. van Rooij (Frank); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); J.M. Geleijnse (Marianne)

    2012-01-01

    textabstractBackground: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP). Objective: The objective was to examine whether dietary acid load was associated with incident hypertension in a cohort of older Dutch adults from the Rotterdam Study. Design: Th

  17. Dietary acid load and risk of hypertension: The Rotterdam study

    NARCIS (Netherlands)

    Engberink, M.F.; Bakker, S.J.L.; Brink, E.J.; Baak, M.A. van; Rooij, F.J.A. van; Hofman, A.; Witteman, J.C.M.; Geleijnse, J.M.

    2012-01-01

    Background: Mild metabolic acidosis, which can be caused by diet, may result in elevated blood pressure (BP). Objective: The objective was to examine whether dietary acid load was associated with incident hypertension in a cohort of older Dutch adults from the Rotterdam Study. Design: The analyses i

  18. Pancreatic ductal bicarbonate secretion: challenge of the acinar acid load

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    Peter eHegyi

    2011-07-01

    Full Text Available Acinar and ductal cells of the exocrine pancreas form a close functional unit. Although most studies contain data either on acinar or ductal cells, an increasing number of evidence highlights the importance of the pancreatic acinar-ductal functional unit. One of the best examples for this functional unit is the regulation of luminal pH by both cell types. Protons co-released during exocytosis from acini cause significant acidosis, whereas, bicarbonate secreted by ductal cells cause alkalization in the lumen. This suggests that the first and probably one of the most important role of bicarbonate secretion by pancreatic ductal cells is not only to neutralize the acid chyme entering into the duodenum from the stomach, but to neutralize acidic content secreted by acinar cells. To accomplish this role, it is more than likely that ductal cells have physiological sensing mechanisms which would allow them to regulate luminal pH. To date, four different classes of acid-sensing ion channels have been identified in the gastrointestinal tract (transient receptor potential ion channels, two-pore domain potassium channel, ionotropic purinoceptor and acid-sensing ion channel, however, none of these have been studied in pancreatic ductal cells. In this mini-review, we summarize our current knowledge of these channels and urge scientists to characterize ductal acid-sensing mechanisms and also to investigate the challenge of the acinar acid load on ductal cells.

  19. INTERRELATIONS BETWEEN IMMUNOLOGICAL ALTERATIONS AND VIRAL LOAD IN ACUTE HEPATITIS B

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    A. A. Savchenko

    2011-01-01

    Full Text Available Abstract. A group of seventy-six patients with acute viral hepatitis B (HB was under study, in order to evaluate immunological parameters, and ability of blood mononuclear cells to produce cytokines, as dependent on individual viral loads. The immune parameters were less affected in cases of low viral load. Meanwhile, the immune profiles exhibited maximal alterations in the patients with medium and high viral loads. Most expressed changes of immune parameters are found in patients with moderate and high  virus load. Meanwhile, moderate  HB  viral  loads  are  associated  with  higher  functional  activity  of  B-cells  and  lower  NK  numbers, whereas high viral loads correlated with increased amounts of peripheral B cells and higher CD25+ lymphocyte levels. Increased background cytokine synthesis is revealed in mononuclear cells of the patients with acute HB, being, however, suppressed upon additional functional induction. An increased viral load is associated with decreased basal levels of TNFα synthesis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 181-188 

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

    Science.gov (United States)

    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.

  1. Safety and Efficacy of Acute Clopidogrel Load in Patients with Moderate and Severe Ischemic Strokes

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    Amir Shaban

    2016-01-01

    Full Text Available Objective. To study the safety and efficacy of a clopidogrel loading dose in patients with moderate and severe acute ischemic strokes. Background. The safety of clopidogrel loading has been extensively investigated in patients with minor strokes and transient ischemic attacks. Methods. Acute ischemic stroke patients presenting consecutively to our center from 07/01/08 to 07/31/13 were screened. Clopidogrel loading was defined as at least 300 mg dose (with or without aspirin given within 6 hours of admission. We compared outcomes in patients with baseline NIHSS > 3 with and without clopidogrel loading. Results. Inclusion criteria were met for 1011 patients (43.6% females, 69.1% black, median age 63. Patients with clopidogrel loading had lower baseline NIHSS than patients who were not loaded (8 versus 9, p=0.005. The two groups had similar risk for hemorrhagic transformation (p=0.918 and symptomatic hemorrhage (p=0.599. Patients who were loaded had a lower rate of neurological worsening (38.9% versus 48.3%, p=0.031 and less in-hospital mortality (4.3% versus 13.4%, p=0.001 compared to those who were not loaded. The likelihood of having a poor functional outcome did not differ between the two groups after adjusting for NIHSS on admission (OR = 0.71, 95% CI 0.4633–1.0906, p=0.118. Conclusion. Clopidogrel loading dose was not associated with increased risk for hemorrhagic transformation or symptomatic intracranial hemorrhage in our retrospective study and was associated with reduced rates of neuroworsening following moderate and severe stroke.

  2. Safety and Efficacy of Acute Clopidogrel Load in Patients with Moderate and Severe Ischemic Strokes

    Science.gov (United States)

    Monlezun, Dominique J.; Rincon, Natalia; Tiu, Jonathan; Valmoria, Melisa

    2016-01-01

    Objective. To study the safety and efficacy of a clopidogrel loading dose in patients with moderate and severe acute ischemic strokes. Background. The safety of clopidogrel loading has been extensively investigated in patients with minor strokes and transient ischemic attacks. Methods. Acute ischemic stroke patients presenting consecutively to our center from 07/01/08 to 07/31/13 were screened. Clopidogrel loading was defined as at least 300 mg dose (with or without aspirin) given within 6 hours of admission. We compared outcomes in patients with baseline NIHSS > 3 with and without clopidogrel loading. Results. Inclusion criteria were met for 1011 patients (43.6% females, 69.1% black, median age 63). Patients with clopidogrel loading had lower baseline NIHSS than patients who were not loaded (8 versus 9, p = 0.005). The two groups had similar risk for hemorrhagic transformation (p = 0.918) and symptomatic hemorrhage (p = 0.599). Patients who were loaded had a lower rate of neurological worsening (38.9% versus 48.3%, p = 0.031) and less in-hospital mortality (4.3% versus 13.4%, p = 0.001) compared to those who were not loaded. The likelihood of having a poor functional outcome did not differ between the two groups after adjusting for NIHSS on admission (OR = 0.71, 95% CI 0.4633–1.0906, p = 0.118). Conclusion. Clopidogrel loading dose was not associated with increased risk for hemorrhagic transformation or symptomatic intracranial hemorrhage in our retrospective study and was associated with reduced rates of neuroworsening following moderate and severe stroke.

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

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    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.

  4. STANDARDIZING TERMINOLOGY FOR ESTIMATING THE DIET-DEPENDENT NET ACID LOAD TO THE METABOLIC SYSTEM

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    Contemporary Western diets contain acid precursors in excess of base precursors, yielding a daily systemic net acid load of varying amounts, depending on the specific composition of the diet. Increasing evidence suggests that differences in daily net acid load, resulting predominantly from differen...

  5. FORMULATION DEVELOPMENT AND EVALUATION OF ABACAVIR LOADED POLYMETHACRYLIC ACID NANOPARTICLES

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    S.L. Dheivanai

    2012-03-01

    Full Text Available Nanoparticles render a promising drug delivery system of controlled and targeted drug release. These are specially designed to release the drug in the vicinity of target tissue. The aim of this present study was to develop and evaluate polymethacrylic acid nanoparticles containing nanoparticles abacavir in different drug to polymer ratio by nanoprecipitation method. SEM indicates that nanoparticles have a discrete spherical structure without aggregation. The average particle size was accurately found to be 120 ±9 - 403 ±3 nm. The particle size of the nanoparticles was gradually increased with increase in the proportion of polymethacrylic acid polymer. The drug containing nanoparticles was increasing on increasing polymer concentration up to a particular concentration ratio. No difference was observed in the extent of degradation of product during sixty days in which, nanoparticles were stored at various temperatures. FT-IR studies indicated that there were no chemical interaction between drug and polymer and stability of drug. The in-vitro release character from all the drug loaded batches was found to be zero order and rendered sustained release over a period of 24 h. The prepared formulations overcome and breakup the drawbacks and limitations of abacavir sustained release formulations and could possibility be advantageous in terms of increased bioavailability and efficacy of abacavir.

  6. Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

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    Zhang, Zhen; Qian, Hanqing; Yang, Mi; Li, Rutian; Hu, Jing; Li, Li; Yu, Lixia; Liu, Baorui; Qian, Xiaoping

    2017-01-01

    Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier.

  7. Loading of acute myeloid leukemia cells with poly(I:C) by electroporation

    NARCIS (Netherlands)

    Lion, E.; Winde, C.M. de; Tendeloo, V.F. Van; Smits, E.L.

    2014-01-01

    In this chapter, we describe the technique of electroporation as an efficient method to load primary leukemic cells with the double-stranded RNA (dsRNA) analogue, polyriboinosinic polyribocytidylic acid (poly(I:C)), and detail on the delicate freezing and thawing procedure of primary leukemic cells.

  8. Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition.

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    Ling Zhang

    Full Text Available Severe acute malnutrition (SAM is a major cause of mortality in children under 5 years and is associated with hepatic steatosis. Bile acids are synthesized in the liver and participate in dietary fat digestion, regulation of energy expenditure, and immune responses. The aim of this work was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis.An initial discovery cohort with 5 healthy controls and 22 SAM-patients was used to identify altered bile acid homeostasis. A follow up cohort of 40 SAM-patients were then studied on admission and 3 days after clinical stabilization to assess recovery in bile acid metabolism. Recruited children were 6-60 months old and admitted for SAM in Malawi. Clinical characteristics, feces and blood were collected on admission and prior to discharge. Bile acids, 7α-hydroxy-4-cholesten-3-one (C4 and FGF-19 were quantified.On admission, total serum bile acids were higher in children with SAM than in healthy controls and glycine-conjugates accounted for most of this accumulation with median and interquartile range (IQR of 24.6 μmol/L [8.6-47.7] compared to 1.9 μmol/L [1.7-3.3] (p = 0.01 in controls. Total serum bile acid concentrations did not decrease prior to discharge. On admission, fecal conjugated bile acids were lower and secondary bile acids higher at admission compared to pre- discharge, suggesting increased bacterial conversion. FGF19 (Fibroblast growth factor 19, a marker of intestinal bile acid signaling, was higher on admission and was associated with decreased C4 concentrations as a marker of bile acid synthesis. Upon recovery, fecal calprotectin, a marker of intestinal inflammation, was lower.SAM is associated with increased serum bile acid levels despite reduced synthesis rates. In SAM, there tends to be increased deconjugation of bile acids and conversion from primary to secondary bile acids, which may contribute to the development of liver disease.

  9. Lack of association between viral load and severity of acute bronchiolitis in infants

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    Ana Paula Duarte de Souza

    Full Text Available ABSTRACT Objective: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. Methods: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period by direct immunofluorescence and (in the second year of the study by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. Results: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9% were positive for a single virus, and 16 (14.5% were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8% were positive for a single virus, and 1 (1.7% was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. Conclusions: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants.

  10. Lack of association between viral load and severity of acute bronchiolitis in infants

    Science.gov (United States)

    de Souza, Ana Paula Duarte; Leitão, Lidiane Alves de Azeredo; Luisi, Fernanda; Souza, Rodrigo Godinho; Coutinho, Sandra Eugênia; da Silva, Jaqueline Ramos; Mattiello, Rita; Pitrez, Paulo Márcio Condessa; Stein, Renato Tetelbom; Pinto, Leonardo Araújo

    2016-01-01

    ABSTRACT Objective: To investigate the correlation between respiratory syncytial viral load and length of hospitalization in infants with acute wheezing episodes. Methods: This was a two-year, cross-sectional study of infants ≤ 12 months of age with bronchiolitis at the time of admission to a tertiary hospital. For the identification of respiratory viruses, nasopharyngeal secretions were collected. Samples were analyzed (throughout the study period) by direct immunofluorescence and (in the second year of the study) by quantitative real-time PCR. We screened for three human viruses: rhinovirus, respiratory syncytial virus, and metapneumovirus. Results: Of 110 samples evaluated by direct immunofluorescence, 56 (50.9%) were positive for a single virus, and 16 (14.5%) were positive for two or more viruses. Among those 72 samples, the most prevalent virus was respiratory syncytial virus, followed by influenza. Of 56 samples evaluated by quantitative real-time PCR, 24 (42.8%) were positive for a single virus, and 1 (1.7%) was positive for two viruses. Among those 25 samples, the most prevalent virus was again respiratory syncytial virus, followed by human rhinovirus. Coinfection did not influence the length of the hospital stay or other outcome s. In addition, there was no association between respiratory syncytial virus load and the length of hospitalization. Conclusions: Neither coinfection nor respiratory syncytial viral load appears to influence the outcomes of acute bronchiolitis in infants. PMID:27832233

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

    Science.gov (United States)

    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.

  12. Dietary potential renal Acid load in venezuelan children.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. Critical acidity loads in France; Charges critiques d`acidite en France

    Energy Technology Data Exchange (ETDEWEB)

    Probst, A.; Party, J.P.; Fevrier, C. [Centre de Geochimie de la Surface (UPR 06251 du CNRS), 67 - Strasbourg (France); Dambrine, E. [Centre de Recherches Forestieres, INRA, 45 - Orleans (France); Thomas, A.L.; King, D. [Institut National de Recherches Agronomique (INRA), 45 - ORDON (France); Stussi, J.M. [Centre National de la Recherche Scientifique (CNRS), 54 - Vandoeuvre-les-Nancy (France)

    1997-12-31

    Based on results from several systematic forest and surface water monitoring programs, carried out in various parts of France as well as in Europe, acidity critical loads have been calculated for soils and surface waters; critical loads are presented for water and soils in crystalline mountainous regions such as Ardennes, Vosges and Massif Central; links with geochemistry, ecosystems and types of trees are discussed and perspectives are given for the calculation of acid and nitrogen critical loads on the whole France

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

    Directory of Open Access Journals (Sweden)

    J. O. Woo

    2014-01-01

    Full Text Available 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.

  17. Are acute effects of maximal dynamic contractions on upper-body ballistic performance load specific?

    Science.gov (United States)

    Markovic, Goran; Simek, Sanja; Bradic, Asim

    2008-11-01

    This study investigated the acute effects of upper-body maximal dynamic contractions on maximal throwing speed with 0.55- and 4-kg medicine balls. It was hypothesized that heavy preloading would transiently improve throwing performance only when overcoming the heavier of the two loads. Twenty-three male volunteers were randomly allocated into experimental (n = 11) and control (n = 12) groups. Both groups performed initial and final seated medicine ball throws from the chest, and the maximal medicine ball speed was measured by means of a radar gun. Between the two measurements, the control group rested passively for 15 minutes, and the experimental group performed three sets of three-repetition maximum bench presses. For the 0.55-kg load, a 2 x 2 repeated-measures analysis of variance revealed no significant effect of time x group interaction (p = 0.22), as well as no significant time (p = 0.22) or group (p = 0.72) effects. In contrast, for the 4-kg load, a significant time x group interaction (p = 0.004) and a significant time (p = 0.035) but not group (p = 0.77) effect were observed. Analysis of simple main effects revealed that the experimental group significantly (8.3%; p ballistic performance might be load specific. In a practical sense, our findings suggest that the use of upper-body heavy resistance exercise before ballistic throwing movements against moderate external loads might be an efficient training strategy for improving an athlete's upper-body explosive performance.

  18. All-trans-retinoic acid-induced pseudotumor cerebri in acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    T. M. Anoop

    2014-01-01

    Full Text Available All-trans-retinoic acid is an integral part in the treatment strategy of acute promyelocytic leukemia (APL. Here we describe a case of pseudotumor cerebri associated with all-trans-retinoic acid (ATRA during the induction therapy in an adult with acute promyelocytic leukemia (APL.

  19. Transport of citrate across renal brush border membrane: effects of dietary acid and alkali loading

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, A.D.; Dousa, T.P.; Smith, L.H.

    1985-10-01

    Dietary acid or alkali loading was given to rats by providing 150 mM NH4Cl or 150 mM NaHCO3 in place of drinking water for 6 days; control animals received 150 mM NaCl. After 6 days, the citrate clearance was 0.04 +/- 0.01 ml/min (mean +/- SE) in the acid-loaded group, 0.9 +/- 0.1 ml/min in the control group, and 2.5 +/- 0.2 ml/min in the alkali-loaded group. At the end of the experiment, the rats were killed, and the Na gradient-dependent citrate uptake was measured in brush border membrane (BBM) vesicles prepared from each group. At 0.3 min, the ( UC)citrate uptake was 198 +/- 8 pmol/mg protein (mean +/- SE) in the acid-loaded group, 94 +/- 16 pmol/mg protein in the control group, and 94 +/- 13 pmol/mg protein in the alkali-loaded group. The rate of Na -independent (NaCl in medium replaced by KCl) ( UC)-citrate uptake by BBM vesicles was the same for acid-loaded, control, and alkali-loaded animals. Thus, the increased capacity of the proximal tubular BBM to transport citrate from the tubular lumen into the cell interior may be an important factor that contributes to decreased urinary citrate in the presence of metabolic acidosis induced by chronic dietary acid loading.

  20. Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

    Directory of Open Access Journals (Sweden)

    Chih-Cheng Lai

    2014-08-01

    Full Text Available Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI in patients with acute respiratory distress syndrome (ARDS. Here, we examined potential benefits of glutamine (GLN on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV of 15 mL/kg and zero positive end-expiratory pressure (PEEP or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology, neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Keum CG

    2011-10-01

    Full Text Available Chang-Gu Keum1*, Young-Wook Noh1*, Jong-Suep Baek1, Ji-Ho Lim1, Chan-Ju Hwang1, Young-Guk Na1, Sang-Chul Shin2, Cheong-Weon Cho11College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Gungdong, Yuseonggu, Daejeon, South Korea; 2College of Pharmacy, Chonnam National University, Yongbongdong, Buggu, Gwangju, South Korea *These authors contributed equally to this work 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

  3. Free fatty acids do not acutely increase asymmetrical dimethylarginine concentrations.

    Science.gov (United States)

    Namiranian, K; Mittermayer, F; Artwohl, M; Pleiner, J; Schaller, G; Mayer, B X; Bayerle-Eder, M; Roden, M; Baumgartner-Parzer, S; Wolzt, M

    2005-12-01

    Concentrations of asymmetrical dimethylarginine (ADMA) and free fatty acids (FFAs) are elevated in insulin resistance which is associated with impaired vascular function. We hypothesized that FFAs could alter vascular tone by affecting ADMA concentrations. Plasma FFA levels were increased in seventeen healthy male volunteers by Intralipid/heparin infusion; hemodynamic and biochemical parameters were measured after 90 minutes. Plasma collected before and during Intralipid/heparin or equivalent synthetic FFAs was incubated with human umbilical vein endothelial cells (HUVECs) in vitro. Intralipid/heparin infusion resulted in an approximately seven-fold increase in plasma FFA levels to 1861 +/- 139 micromol/l, which was paralleled by increased systemic blood pressure and forearm blood flow. Intralipid/heparin did not affect ADMA (baseline mean 0.59 [95 % confidence interval [CI]: 0.54; 0.64] and 0.56 [CI: 0.51; 0.59] after 90 minutes), but slightly decreased SDMA (from 0.76, [CI: 0.70; 0.83] to 0.71 [CI: 0.64; 0.74], p < 0.05), and had no effect on ADMA/SDMA ratio. There was no correlation between ADMA and FFA concentrations or forearm blood flow. Incubation of HUVECs with FFA-rich plasma or synthetic FFAs induced an ADMA release after 24 hours, but not after 90 minutes. Acutely increased FFA levels caused hemodynamic effects but did not affect ADMA. Prolonged elevation of FFA levels might influence vascular function by increasing ADMA levels.

  4. Daily spinal mechanical loading as a risk factor for acute non-specific low back pain: A case-control study using the 24-Hour Schedule

    NARCIS (Netherlands)

    E.W.P. Bakker (Eric); A.P. Verhagen (Arianne); C. Lucas (Cees); H.J.C.M.F. Koning (Hans); R.J. de Haan (Rob); B.W. Koes (Bart)

    2007-01-01

    textabstractA case-control study was conducted to assess the daily loading of the spine as a risk factor for acute non-specific low back pain (acute LBP). Acute LBP is a benign, self-limiting disease, with a recovery rate of 80-90% within 6 weeks irrespective of the treatment type. Unfortunately, re

  5. Novel Polymers with a High Carboxylic Acid Loading

    DEFF Research Database (Denmark)

    Thomsen, Anders Daugaard; Malmström, Eva; Hvilsted, Søren

    2006-01-01

    ABSTRACT: Click chemistry has been used to prepare a range of novel polymers with pendant carboxylic acid side groups. Four azido carboxylic acids, either mono- or difunctional and aliphatic or aromatic, have been prepared and thoroughly characterized. Extensive model reactions with 1-ethyl-4......-hydroxybenzene, the simplest model for poly(4-hydroxystyrene), and the four azido carboxylic acids have been conucted to establish the proper reaction conditions and provide an analytical frame for the corresponding polymers. Poly(4-hydroxystyrene) moieties in three different polymers—poly (4-hydroxystyrene...... investigations of ali the polymers in general exhibit [when poly(4-hydroxystyrene) is a subetantial parti significant changes in the glass-transition temperature from the polar poly(4-hydroxystyr- ene) (120—130 “C) to the much less polar alkyne polymers (46—60 DC). A direct correlation between the nature...

  6. Dust metal loadings and the risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Whitehead, Todd P; Ward, Mary H; Colt, Joanne S; Dahl, Gary; Ducore, Jonathan; Reinier, Kyndaron; Gunier, Robert B; Katharine Hammond, S; Rappaport, Stephen M; Metayer, Catherine

    2015-01-01

    We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in nickel: 0.95 (0.82, 1.09), tin: 0.96 (0.86, 1.08), and zinc: 0.94 (0.84, 1.05)). Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL.

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

    Energy Technology Data Exchange (ETDEWEB)

    McNulty, Steven G., E-mail: steve_mcnulty@ncsu.ed [USDA Forest Service, Eastern Forests Environmental Assessment Threats Center, Southern Global Change Program, 920 Main Campus Dr. Suite 300, Raleigh, NC 27606 (United States); Boggs, Johnny L. [USDA Forest Service, Eastern Forests Environmental Assessment Threats Center, Southern Global Change Program, 920 Main Campus Dr. Suite 300, Raleigh, NC 27606 (United States)

    2010-06-15

    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

  8. Effects of acute creatine loading with or without carbohydrate on repeated bouts of maximal swimming in high-performance swimmers.

    Science.gov (United States)

    Theodorou, Apostolos S; Havenetidis, Konstantinos; Zanker, Cathy L; O'Hara, John P; King, Roderick F G J; Hood, Colin; Paradisis, Giorgios; Cooke, Carlton B

    2005-05-01

    The addition of carbohydrate (CHO) to an acute creatine (Cr) loading regimen has been shown to increase muscle total creatine content significantly beyond that achieved through creatine loading alone. However, the potential ergogenic effects of combined Cr and CHO loading have not been assessed. The purpose of this study was to compare swimming performance, assessed as mean swimming velocity over repeated maximal intervals, in high-performance swimmers before and after an acute loading regimen of either creatine alone (Cr) or combined creatine and carbohydrate (Cr + CHO). Ten swimmers (mean +/- SD of age and body mass: 17.8 +/- 1.8 years and 72.3 +/- 6.8 kg, respectively) of international caliber were recruited and were randomized to 1 of 2 groups. Each swimmer ingested five 5 g doses of creatine for 4 days, with the Cr + CHO group also ingesting approximately 100 g of simple CHO 30 minutes after each dose of creatine. Performance was measured on 5 separate occasions: twice at "baseline" (prior to intervention, to assess the repeatability of the performance test), within 48 hours after intervention, and then 2 and 4 weeks later. All subjects swam faster after either dietary loading regimen (p swimmers continued to produce faster swim times for up to 4 weeks after intervention. Our findings suggest that no performance advantage was gained from the addition of carbohydrate to a creatine-loading regimen in these high-caliber swimmers.

  9. Lack of association between serum uric acid levels and outcome in acute ischemic stroke

    NARCIS (Netherlands)

    Miedema, Irene; Uyttenboogaart, Maarten; Koch, Marcus; Kremer, Berry; de Keyser, Jacques; Luijckx, Gert-Jan

    2012-01-01

    Background: The prognostic value of serum uric acid (UA) in acute ischemic stroke is controversial. The aim of this study is to further analyse the relation between UA and outcome after acute ischemic stroke. Methods: We analysed UA levels in blood samples collected within 6 h of stroke onset from p

  10. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

  11. Effect of saline loading on uranium-induced acute renal failure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hishida, A.; Yonemura, K.; Ohishi, K.; Yamada, M.; Honda, N.

    1988-05-01

    Studies were performed to examine the effect of saline loading on uranium-induced acute renal failure (ARF) in rats. Forty-eight hours after the i.v. injection of uranyl acetate (UA, 5 mg/kg), inulin clearance rate (Cin) decreased to approximately 43% of the control value in water drinking rats (P less than 0.005). Animals receiving continuous isotonic saline infusion following UA showed higher urine flow and Cin (60% of control, P less than 0.01), and lessened intratubular cast formation when compared with water-drinking ARF rats. A short-term saline infusion following UA did not attenuate the decline in Cin (43% of control). An inverse relationship was found between Cin and the number of casts (r = -0.75, P less than 0.01). Multiple regression analysis showed that standardized partial regression coefficient is statistically significant between Cin and cast formation (-0.69, P less than 0.05), but not between Cin and tubular necrosis (-0.07, P greater than 0.05). Renin depletion caused by DOCA plus saline drinking did not attenuate the decline in Cin in ARF (47% of control). No significant difference was found in urinary uranium excretion between water-drinking and saline-infused ARF rats. The findings suggest that continuous saline infusion following UA attenuates the decline in Cin in ARF rats; and that this beneficial effect of saline loading is associated with lessened cast formation rather than with suppressed renin-angiotensin activity or enhanced urinary-uranium excretion.

  12. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone- (ZER- loaded nanostructure lipid carrier (NLC (ZER-NLC prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50 of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

  13. Triclosan and triclosan-loaded liposomal nanoparticles in the treatment of acute experimental toxoplasmosis.

    Science.gov (United States)

    El-Zawawy, Lobna A; El-Said, Doaa; Mossallam, Shereen F; Ramadan, Heba S; Younis, Salwa S

    2015-02-01

    Efficacy of triclosan (TS) and TS-loaded liposomes against the virulent strain of Toxoplasma gondii (T. gondii) was evaluated. Swiss albino mice were intraperitoneally infected with 10(4) tachyzoites of RH HXGPRT(-) strain of T. gondii, then were orally treated with 150 mg/kg TS or 100 mg/kg TS liposomes twice daily for 4 days. Mice mortality, peritoneal and liver parasite burdens, viability, infectivity and ultrastructural changes of peritoneal tachyzoites of infected treated mice were studied, in comparison with those of infected non-treated controls. Drug safety was biochemically assessed by measuring liver enzymes and thyroxin. Both TS and TS liposomes induced significant reduction in mice mortality, parasite burden, viability and infectivity of tachyzoites harvested from infected treated mice. Scanning electron microscopy of treated tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion. Transmission electron microscopy showed that treated tachyzoites were intracellularly distorted, had cytoplasmic vacuolation, discontinuous plasma membranes, nuclear abnormalities and disrupted internal structures. Besides, in TS liposomes-treated subgroup, most tachyzoites were seen intracellularly with complete disintegration of the parasite plasma and nuclear membranes, with complete destruction of the internal structures. Biochemical safety of TS and TS liposomes was proven. Accordingly, TS can be considered as a promising alternative to the standard therapy for treating acute murine toxoplasmosis. Liposomal formulation of TS enhanced its efficacy and allowed its use in a lower dose.

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

    Science.gov (United States)

    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

  15. Synthesis, Characterization, and Evaluation of Radical Scavenging Ability of Ellagic Acid-Loaded Nanogels

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    Gautam Behl

    2011-01-01

    Full Text Available Ellagic acid (EA, a potential antioxidant phytochemical has low aqueous solubility and bioavailability. In this paper, encapsulation of ellagic acid has been carried out into the biodegradable disulfide crosslinked poly (ethylene glycol PEO-based nanogels synthesized via AGET (activator generated electron transfer ATRP (atom transfer radical polymerization, and their radical scavenging ability was evaluated. The encapsulation of the EA was carried out at two drug loading percentages, that is, 10 and 20 wt.% of the nanogels. 1,1-Diphenyl-2-picryldrazyl (DPPH assay was utilized in order to assess the radical scavenging ability of the ellagic acid-loaded nanogels. A drug-loading level of about 2.5 wt.% was achieved with encapsulation efficiency of about 25% at 10 wt.% of the EA w.r.t nanogels, which was found to increase to about 4.7 wt.% with decreased encapsulation efficiency of 23.5% as EA content was increased to 20wt.% of the nanogels. Ellagic acid loading was found to be accompanied with increase in the size of the nanogels from 144.6±39.52 nm for neat nanogels to 217.8±105.5 and 633±160.1 nm at 2.5 and 4.7 wt.% drug loading level. The nanogels were found to be capable of scavenging radicals and biocompatible on human cervical cancer cell lines (HeLa cells at appropriate concentrations.

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

    Science.gov (United States)

    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.

  17. Serum fatty acid in patients with acute myocardial infarction in Gorgan

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    Abdoljalal Marjani

    2012-10-01

    Full Text Available Introduction: The present study aimed to assess serum fatty acid in patients with acute myocardial infarction in Gorgan, Iran. Material and Methods: The study conducted on the thirty and five subjects with acute myocardial infarction who were referred to the intensive Coronary Care Unit in 5th Azar in Gorgan. Results: The content of palmitoleic acid (16:1 was significantly higher in serum fatty acid of the patients than of the control groups (P=0.019, whereas oleic acid (18:1, linoleic acid (18:2, _-linolenic acid (18:3, arachidonic acid (20:4 and Eicosapentaenoic acid (EPA were significantly higher in the control groups than the patients (P<0.0001, P=0.013, P=0.042, P=0,001 and P=0.022 respectively. Conclusion: This study showed that the content of polyunsaturated fatty acids in serum fatty acid component was decreased in acute myocardial infarction patients. These results suggest that there may be some protective effects of poly unsaturated fatty acid against myocardial infarction.

  18. The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading.

    Science.gov (United States)

    Theodorou, A S; Cooke, C B; King, R F; Hood, C; Denison, T; Wainwright, B G; Havenetidis, K

    1999-11-01

    We investigated the effect of an acute creatine loading (25 g per day for 4 days) and longer-term creatine supplementation (5 g of creatine or 5 g of placebo per day for 2 months) on the performance of 22 elite swimmers during maximal interval sessions. After the acute creatine loading, the mean of the average interval swim times for all swimmers (n = 22) improved (44.3+/-16.5 s before vs. 43.7+/-16.3 s after supplementation; Pswimmers did not respond positively to supplementation. After 2 months of longer-term creatine supplementation or placebo, neither group showed a significant change in swimming performance (38.7+/-13.5 s before vs. 38.7+/-14.1 s after for the creatine group; 48.7+/-18.0 s before vs. 48.7+/-18.1 s after for the placebo group). We conclude that, in elite swimmers, 4 days of acute creatine loading improves swimming performance significantly when assessed by maximal interval sessions. However, longer-term supplementation for 2 months (5 g of creatine per day) did not benefit significantly the creatine group compared with the placebo group.

  19. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case.

    Science.gov (United States)

    Ray, Sukanta; Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-08-01

    Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up.

  20. Steady-state critical loads of acidity for forest soils in the Georgia Basin, British Columbia

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    Shaun A. WATMOUGH

    2010-08-01

    Full Text Available There has been growing interest in acid rain research in western Canada where sulphur (S and nitrogen (N emissions are expected to increase during the next two decades. One region of concern is southern British Columbia, specifically the Georgia Basin, where emissions are expected to increase owing to the expansion of industry and urban centres (Vancouver and Victoria. In the current study, weathering rates and critical loads of acidity (S and N for forest soils were estimated at nineteen sites located within the Georgia Basin. A base cation to aluminium ratio of 10 was selected as the critical chemical criterion associated with ecosystem damage. The majority of the sites (58% had low base cation weathering rates (≤50 meq m–2 y–1 based on the PROFILE model. Accordingly, mean critical load for the study sites, estimated using the steady-state mass balance model, ranged between 129–168 meq m–2 y–1. Annual average total (wet and dry S and N deposition during the period 2005–2006 (estimated by the Community Multiscale Air Quality model, exceeded critical load at five–nine of the study sites (mean exceedance = 32–46 meq m–2 y–1. The high-elevation (>1000 m study sites had shallow, acid sensitive, soils with low weathering rates; however, critical loads were predominantly exceeded at sites close to Vancouver under higher modelled deposition loads. The extent of exceedance is similar to other industrial regions in western and eastern Canada.

  1. Acute hormonal and force responses to combined strength and endurance loadings in men and women: the "order effect".

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    Ritva S Taipale

    Full Text Available PURPOSE: To examine acute responses and recovery of serum hormones and muscle force following combined strength (S and endurance (E loading sessions in which the order of exercises is reversed (ES vs. SE. METHODS: This cross-over study design included recreationally endurance trained men and women (age 21-45 years, n = 12 men n = 10 women who performed both loadings. Maximal bilateral isometric strength (MVC, isometric rate of force development (RFD and serum concentrations of testosterone (T, cortisol (C, growth hormone (GH, insulin-like growth factor 1 (IGF-1, binding protein 3 (IGFBP3 and sex hormone binding globulin (SHBG were measured during and after both loadings. RESULTS: Both of the present combined (ES and SE loadings led to a greater acute decrease in MVC in men than in women, while RFD was slightly affected only in men. Recovery of MVC and RFD to baseline was complete at 24 h regardless of the order of exercises. In men, neuromuscular fatigue was accompanied by increased C concentrations observed post SE. This was followed by decreased concentrations of T at 24 h and 48 h that were significantly lower than those observed following ES. GH response in men also differed significantly post loadings. In women, only a significant difference in T between ES and SE loadings was observed at post. CONCLUSION: These observed differences in hormonal responses despite similarities in neuromuscular fatigue in men indicate the presence of an order effect as the body was not fully recovered at 48 h following SE. These findings may be applicable in training prescription in order to optimize specific training adaptations.

  2. Uric acid levels and their relation to incapacities in acute cerebrovascular disease

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    Julio López Argüelles

    2010-02-01

    Full Text Available Background: cerebrovascular disease and ischemic cardiopathy can be considered as an epidemic and constitute the first cause of incapacities in developed countries. Multiple studies have shown the association between uric acid levels and cerebrovascular diseases. Objective: To correlate the levels of serum uric acid and incapacities in the acute phase of cerebrovascular disease. Methods: A correlational study was carried out with 217 patients with acute cerebrovascular disease. The patient’s incapacity level was measured by using the Barthel Index and those results were related with the serum uric acid levels and other variables. Results: Male patients have higher levels of uric acid (p=0, 04; r=0, 13. Age and Barthel index were p < 0,001; r = -0, 30 and uric acid levels and Barthel Index were p=0, 03; r=-0, 14. The principal predicting factors of incapacity in the acute phase of cerebrovascular disease were the high levels of uric acid, age and diabetes mellitus. Conclusions: It is shown that the highest is the level of uric acid at advanced age; the greatest is the risk of suffering from incapacity in acute phases of cerebrovascular diseases.

  3. [Acute neurological disclosure of B12 avitaminosis induced by folic acid administration].

    Science.gov (United States)

    Ammar, N; Martinez Almoyna, L; Husson, H; De Broucker, T

    2005-04-01

    A paradigmatic case of acute combined spinal cord degeneration and delirium due to inappropriate administration of folic acid in the context of chronic cobalamin deficiency is described. Rapid improvement was obtained with immediate cessation of folate administration and parenteral cobalamin supplementation. Folic acid and cobalamin prescription rules are recalled. Pathophysiological hypotheses tentatively explaining the neurotoxicity of folic acid in case of vitamin B12 deficiency are summarized.

  4. Water pollution abatement programme. The Czech Republic. Project 4.2. Assessing critical loads of acidity to surface waters in The Czech Republic. Critical loads of acidity to surface waters, Northern Moravia and Silesia, The Czech Republic

    Energy Technology Data Exchange (ETDEWEB)

    Lien, L.; Raclavsky, K.; Henriksen, A.; Raclavska, H.; Matysek, D.

    1994-12-31

    The governments of Norway and Czech and Slovak Federal Republic have signed a bilateral environmental protection agreement. This report describes Project 4.2 of the agreement: Assessing critical loads of acidity to surface waters in The Czech Republic. Critical load of acidity to surface waters and exceedance of critical load were estimated by using standard methods modified for the sampling area. Water samples were mainly taken from small forest streams, which were the only available surface waters with negligible pollution from local sources. High critical loads were calculated, averaging 20 times higher than the corresponding value for southern Norway. The deposition of acidifying components in the region was high, but did not exceed the critical load and so there is a reserve for additional acid deposition. Scattered water analyses from several other parts of The Czech Republic indicate both low critical loads and exceedance of critical load in various regions (e.g. Bohemia). 21 refs., 14 figs., 3 tabs.

  5. Influence factors of salt-sensitive hypertension and responses of blood pressure and urinary sodium and potassium excretion to acute oral saline loading among essential hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    刘叶舟

    2014-01-01

    Objective To explore the influence factors of saltsensitive hypertension and to observe changes of blood pressures and urinary sodium and potassium excretion in response to acute oral saline loading among essential hypertensive patients in China.Methods Essential hypertensive patients from Beijing Jinzhan second community were included in this study.Salt-sensitivity was determined via the improved Sullivan’s acute oral saline loading

  6. [Hemoperfusion in the treatment of acute valproic acid intoxication].

    Science.gov (United States)

    Peces, R; Fernández, E J; Sánchez, R J; Peces, C; Montero, A; Selgas, R

    2007-01-01

    Valproic acid is increasingly used in the treatment of epilepsy, and also prescribed for bipolar affective disorders, schizoaffective disorders, schizophrenia and migraine prophylaxis. Valproic acid intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, pancytopenia, hemodynamic instability and death. The drug's relatively low molecular weight, small volume of distribution and saturable protein-binding render it potentially amenable to exracorporeal removal (hemodialysis, hemoperfusion or hemofiltration ), but published experience is scarce. We describe a case report involving valproic acid intoxication with ingestion of ethanol, who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of valproic acid was reduced with rapid lowering of valproic acid levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, charcoal hemoperfusion should be considered for serious valproic acid intoxication because free as well as bound drug fractions are eliminated via this technique.

  7. Successful living donor liver transplantation for acute liver failure after acetylsalicylic acid overdose.

    Science.gov (United States)

    Shirota, Tomoki; Ikegami, Toshihiko; Sugiyama, Satoshi; Kubota, Kouji; Shimizu, Akira; Ohno, Yasunari; Mita, Atsuyoshi; Urata, Koichi; Nakazawa, Yuichi; Kobayashi, Akira; Iwaya, Mai; Miyagawa, Shinichi

    2015-04-01

    A 20-year-old woman was admitted to an emergency hospital after ingesting 66 g of acetylsalicylic acid in a suicide attempt. Although she was treated with gastric lavage, oral activated charcoal, and intravenous hydration with sodium bicarbonate, her hepatic and renal function gradually deteriorated and serum amylase levels increased. Steroid pulse therapy, plasma exchange, and continuous hemodiafiltration did not yield any improvement in her hepatic or renal function, and she was transferred to our hospital for living donor liver transplantation. Nine days after drug ingestion, she developed hepatic encephalopathy: thus, we diagnosed the patient with acute liver failure with hepatic coma accompanied by acute pancreatitis due to the overdose of acetylsalicylic acid. Living donor liver transplantation was immediately performed using a left lobe graft from the patient's mother. Following transplantation, the patient's renal and hepatic function and consciousness improved, and she was discharged. In this report, we describe a rare case of acetylsalicylic acid-induced acute liver failure with acute hepatic coma and concomitant acute pancreatitis and acute renal failure, which were treated successfully with emergency living donor liver transplantation.

  8. Dietary supplementation with omega-3 polyunsaturated fatty acids ameliorates acute pneumonia induced by Klebsiella pneumoniae in BALB/c mice.

    Science.gov (United States)

    Sharma, Sonica; Chhibber, Sanjay; Mohan, Harsh; Sharma, Saroj

    2013-07-01

    The immune benefits associated with the optimal intake of dietary fatty acids are widely known. The objective of the present investigation was to elucidate the role of omega-3 polyunsaturated fatty acids (n-3 PUFA) food source on acute pneumonia induced by Klebsiella pneumoniae. Three different n-3 PUFA preparations (cod liver oil, Maxigard, and flaxseed oil) were orally supplemented and infection was induced in different groups of experimental mice. Mice fed olive oil and normal saline served as oil and saline controls, respectively. After 2 weeks of fatty acid feeding, no effect on the establishment of infection was observed when acute pneumonia was induced in animals. On the other hand, 6 weeks of n-3 PUFA administration was found to improve resistance in mice, as reduced lung bacterial load coupled with significant improvement in pathology was seen in infected mice. Alveolar macrophages collected from all 3 groups of mice fed n-3 PUFA exhibited a significant decrease in the level of apoptosis following infection with K. pneumoniae and an enhanced in vitro phagocytic potential for the pathogen. Lower lung levels of nitric oxide, malondialdehyde, and lactate dehydrogenase were associated with a decrease in the severity of tissue damage. There was a significant increase in the lung levels of pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)). No significant change was observed in the levels of interleukin-10 (IL-10). This study highlights that dietary n-3 PUFA supplementation exerts an overall beneficial effect against acute experimental pneumonia. This mechanism is operative through upregulation of nonspecific and specific immune defenses of the host.

  9. Ibuprofen-loaded poly(lactic-co-glycolic acid films for controlled drug release

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    Pang JM

    2011-04-01

    Full Text Available Jianmei Pang1, Yuxia Luan1, Feifei Li1, Xiaoqing Cai1, Jimin Du2, Zhonghao Li31School of Pharmaceutical Science, Shandong University, Jinan, Shandong Province, PR China; 2School of Chemistry and Chemical Engineering, Anyang Normal University, Henan Province, PR China; 3School of Materials Science and Engineering, Shandong University, Jinan, Shandong Province, PR ChinaAbstract: Ibuprofen- (IBU loaded biocompatible poly(lactic-co-glycolic acid (PLGA films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.Keywords: ibuprofen, controlled release, poly(lactic-co-glycolic acid, films

  10. Metal loading levels influence on REE distribution on humic acid: Experimental and Modelling approach

    Science.gov (United States)

    Marsac, R.; Davranche, M.; Gruau, G.; Dia, A.

    2009-04-01

    In natural organic-rich waters, rare earth elements (REE) speciation is mainly controlled by organic colloids such as humic acid (HA). Different series of REE-HA complexation experiments performed at several metal loading (REE/C) displayed two pattern shapes (i) at high metal loading, a middle-REE (MREE) downward concavity, and (ii) at low metal loading, a regular increase from La to Lu (e.g. Sonke and Salters, 2006; Pourret et al., 2007). Both REE patterns might be related to REE binding with different surface sites on HA. To understand REE-HA binding, REE-HA complexation experiments at various metals loading were carried out using ultrafiltration combined with ICP-MS measurements, for the 14 REE simultaneously. The patterns of the apparent coefficients of REE partition between HA and the inorganic solution (log Kd) evolved regularly according to the metal loading. The REE patterns presented a MREE downward concavity at low loading and a regular increase from La to Lu at high loading. The dataset was modelled with Model VI by adjusting two specific parameters, log KMA, the apparent complexation constant of HA low affinity sites and DLK2, the parameter increasing high affinity sites binding strength. Experiments and modelling provided evidence that HA high affinity sites controlled the REE binding with HA at low metal loading. The REE-HA complex could be as multidentate complexes with carboxylic or phenolic sites or potentially with sites constituted of N, P or S as donor atoms. Moreover, these high affinity sites could be different for light and heavy REE, because heavy REE have higher affinity for these sites, in low density, and could saturate them. These new Model VI parameter sets allowed the prediction of the REE-HA pattern shape evolution on a large range of pH and metal loading. According to the metal loading, the evolution of the calculated REE patterns was similar to the various REE pattern observed in natural acidic organic-rich waters (pH10 mg L-1). As

  11. Acute renal failure due to bilateral uric acid lithiasis in infants.

    Science.gov (United States)

    Kaya, Mete; Boleken, M Emin; Soran, Mustafa; Kanmaz, Turan; Yücesan, Selçuk

    2007-06-01

    Acute renal failure (ARF) is one of the complications of urolithiasis, but the role of medical treatment to relieve urinary obstruction in children with ARF is uncertain. We report on infants with acute obstructive uric acid lithiasis. We describe presentation features as well as diagnosis methods and medical treatment in five infants who were admitted to our institution with ARF due to uric acid lithiasis. The medical treatments for all patients were fluid liberalization, urine alkalinization, and oral allopurinol. Two children underwent urinary diversion. Within 8 h, urine output improved in all patients, and the stones passed spontaneously. All obstructed kidneys were relieved with medical treatment, and no renal sequel remained. So this series has showed a role of medical therapy in acute obstructive uric acid lithiasis.

  12. Effects of different accentuated eccentric loads on acute neuromuscular, growth hormone, and blood lactate responses during a hypertrophic protocol.

    Science.gov (United States)

    Ojasto, Timo; Häkkinen, Keijo

    2009-05-01

    This study monitored acute neuromuscular responses and growth hormone (GH) and blood lactate (La) concentrations in the eccentric-concentric (ECC-CON) hypertrophic protocol by using various dynamic accentuated external resistance (DAER) loads in the bench press exercise. Male subjects (age = 32 +/- 4 years; n = 11) performed 4 sets of 10 repetitions with 2 minutes of recovery between the sets. The loads were 70, 80, 90, and 100% of 1 repetition maximum (RM) for the ECC phase, whereas 70% RM was constantly used for the CON phase. Electromyographic activity (EMG), ECC, CON, and isometric (ISOM) forces, serum GH and blood La, were measured at pre- and postloading. Significant reductions occurred in ISOM and CON pre- to postforces in all loading conditions (p 3.5 +/- 1.5 microgxL in the control condition, but the difference did not reach statistical significance. ECC EMG of the agonists increased with the increase in load but significantly only in the deltoid anterior (p exercise protocols in training for muscle hypertrophy and suggest the importance of individualized load selection for DAER exercises.

  13. Acute formic acid poisoning in a rubber plantation worker

    Directory of Open Access Journals (Sweden)

    Dattatrai Kashinath More

    2014-01-01

    Full Text Available Among the workers in a rubber plantation in South India, ingestion of formic acid either accidentally or with suicidal intention is a common problem. Formic acid is diluted and used for coagulation of rubber latex. Easy availability makes formic acid a common poison. The aim of this article is to study the case of formic acid poisoning, its complications and management. Patient was managed symptomatically. Antidote was not used and no nasogastric aspiration was done. Patient had dysphagia; nutrition was maintained with open gastrostomy done on day 5 and subsequent enteral feeding. Measures to prevent anticipated complications were undertaken. Stricture of the esophagus is a common complication leading to long-term morbidity. After initial management, all patients should be on follow-up for prevention and management of strictures. Workers should be educated on complications of formic acid poisoning and easy availability should be curtailed by enforcing remedial measures.

  14. Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep.

    Science.gov (United States)

    Brown, Laura D; Rozance, Paul J; Thorn, Stephanie R; Friedman, Jacob E; Hay, William W

    2012-08-01

    Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion.

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

    Science.gov (United States)

    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.

  16. A Novel Preparation Method for 5-Aminosalicylic Acid Loaded Eudragit S100 Nanoparticles

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    Sining Li

    2012-05-01

    Full Text Available In this study, solution enhanced dispersion by supercritical fluids (SEDS technique was applied for the preparation of 5-aminosalicylic acid (5-ASA loaded Eudragit S100 (EU S100 nanoparticles. The effects of various process variables including pressure, temperature, 5-ASA concentration and solution flow rate on morphology, particle size, 5-ASA loading and entrapment efficiency of nanoparticles were investigated. Under the appropriate conditions, drug-loaded nanoparticles exhibited a spherical shape and small particle size with narrow particle size distribution. In addition, the nanoparticles prepared were characterized by X-ray diffraction, Differential scanning calorimetry and Fourier transform infrared spectroscopy analyses. The results showed that 5-ASA was imbedded into EU S100 in an amorphous state after SEDS processing and the SEDS process did not induce degradation of 5-ASA.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee-Young; Seok, Hyun-Woo [Department of Civil and Environmental Engineering, Pusan National University, Busan 46241 (Korea, Republic of); Kwon, Hye-Ok; Choi, Sung-Deuk [School of Urban and Environmental Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919 (Korea, Republic of); Seok, Kwang-Seol [Chemical Research Division, National Institute of Environmental Research, Incheon 22689 (Korea, Republic of); Oh, Jeong Eun [Department of Civil and Environmental Engineering, Pusan National University, Busan 46241 (Korea, Republic of)

    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 ∑{sub 11}PFAAs concentrations were detected in the influent and effluent from the paper (median: 411 ng/L) and textile (median: 106 ng/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: 91.0 ng/g) and chemical (median: 81.5 ng/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 0.146 ton/yr. The textile industry had the highest discharge load with 0.055 ton/yr (PFOA: 0.039 ton/yr, PFOS: 0.010 ton/yr). Municipal wastewater contributed more to the overall discharge of PFAAs (0.489 ton/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. - Highlights: • 11 PFAAs in wastewater and sludge from 5 industrial sectors were investigated. • PFOA and PFOS were the dominant in wastewater while PFOS was predominant in sludge. • The total discharge loads from 5 industrial sectors 0.146 ton/yr. • The textile industry showed the highest discharge load with 0.055 ton/yr.

  18. Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy.

    Science.gov (United States)

    Shi, Min; Ma, Liang; Zhou, Li; Fu, Ping

    2016-10-18

    Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment with E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis. In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells), E2 both attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, and cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway.

  19. Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats.

    Science.gov (United States)

    Ishizuka, Toshiaki; Niwa, Atsuko; Tabuchi, Masaki; Ooshima, Kana; Higashino, Hideaki

    2008-03-26

    Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.

  20. A modified approach for estimating the aquatic critical load of acid deposition in northern Saskatchewan, Canada

    Science.gov (United States)

    Whitfield, Colin J.; Mowat, Aidan C.; Scott, Kenneth A.; Watmough, Shaun A.

    2016-12-01

    Acid-sensitive ecosystems are found in northern Saskatchewan, which lies downwind of major sulphur (S) and nitrogen (N) emissions sources associated with the oil sands extraction industry. In order to protect these ecosystems against acidification, tolerance to acid deposition must be quantified. The suitability of the central empirical relationship used in the Steady-State Water Chemistry (SSWC) model to predict historical sulphate (SO4) concentrations was investigated, and an alternate approach for determining aquatic critical loads of acidity (CL(A)) was employed for the study lakes (n = 260). Critical loads of acidity were often low, with median values of 12-16 mmolc m-2 yr-1, with the lower value reflecting a region-specific limit for acid-neutralizing capacity identified in this study. Uncertain levels of atmospheric deposition in the region, however, are problematic for characterizing acidification risk. Accurate S and chloride (Cl) deposition are needed to identify catchment sources (and sinks) of these elements in the new approach for CL(A) calculation. Likewise, accurate depiction of atmospheric deposition levels can prove useful for evaluation of lake runoff estimates on which estimates of CL(A) are contingent. While CL(A) are low and exceedance may occur according to projected increases in S deposition in the near-term, S retention appears to be an important feature in many catchments and risk of acidification may be overstated should long-term S retention be occurring in peatlands.

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

    Science.gov (United States)

    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.

  2. Design and characterization of antimicrobial usnic acid loaded-core/shell magnetic nanoparticles.

    Science.gov (United States)

    Taresco, Vincenzo; Francolini, Iolanda; Padella, Franco; Bellusci, Mariangela; Boni, Adriano; Innocenti, Claudia; Martinelli, Andrea; D'Ilario, Lucio; Piozzi, Antonella

    2015-01-01

    The application of magnetic nanoparticles (MNPs) in medicine is considered much promising especially because they can be handled and directed to specific body sites by external magnetic fields. MNPs have been investigated in magnetic resonance imaging, hyperthermia and drug targeting. In this study, properly functionalized core/shell MNPs with antimicrobial properties were developed to be used for the prevention and treatment of medical device-related infections. Particularly, surface-engineered manganese iron oxide MNPs, produced by a micro-emulsion method, were coated with two different polymers and loaded with usnic acid (UA), a dibenzofuran natural extract possessing antimicrobial activity. Between the two polymer coatings, the one based on an intrinsically antimicrobial cationic polyacrylamide (pAcDED) resulted to be able to provide MNPs with proper magnetic properties and basic groups for UA loading. Thanks to the establishment of acid-base interactions, pAcDED-coated MNPs were able to load and release significant drug amounts resulting in good antimicrobial properties versus Staphylococcus epidermidis (MIC = 0.1 mg/mL). The use of pAcDED having intrinsic antimicrobial activity as MNP coating in combination with UA likely contributed to obtain an enhanced antimicrobial effect. The developed drug-loaded MNPs could be injected in the patient soon after device implantation to prevent biofilm formation, or, later, in presence of signs of infection to treat the biofilm grown on the device surfaces.

  3. The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

    Directory of Open Access Journals (Sweden)

    Angélica Florípedes do Amaral

    2012-01-01

    Full Text Available OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 + 8.3 years old, FEV1: 49.3+19.8% received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l and residual volume (-0.47 l, the mean arterial blood pressure (-5.6 mmHg and the cardiac double product (734.8 mmHg.bpm at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w and the respiratory exchange ratio (0.06 at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l. CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. All-trans retinoic acid in acute promyelocytic leukemia in late pregnancy.

    Science.gov (United States)

    Stentoft, J; Nielsen, J L; Hvidman, L E

    1994-09-01

    All-trans retinoic acid (ATRA) was used in a case of acute promyelocytic leukemia (APL) in late pregnancy. A very prompt maternal risk reduction was achieved with subsequent complete remission and spontaneous delivery of two live children in whom no fetal damage seems to have occurred.

  7. The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia

    DEFF Research Database (Denmark)

    Arteaga, Maria Francisca; Mikesch, Jan-Henrik; Qiu, Jihui

    2013-01-01

    While all-trans retinoic acid (ATRA) treatment in acute promyelocytic leukemia (APL) has been the paradigm of targeted therapy for oncogenic transcription factors, the underlying mechanisms remain largely unknown, and a significant number of patients still relapse and become ATRA resistant. We id...

  8. Exacerbation of alcohol-induced oxidative stress in rats by polyunsaturated fatty acids and iron load

    Directory of Open Access Journals (Sweden)

    S N Patere

    2011-01-01

    Full Text Available 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.

  9. Acid deposition critical loads modeling for the simulation of sulfur exceedance and reduction in Guangdong, China

    Institute of Scientific and Technical Information of China (English)

    QIU Rongliang; WANG Shizhong; QIU Hao; WANG Xuemei; LIAO Jin; ZHANG Zhentian

    2009-01-01

    In this study, the current acid deposition critical loads in Guangdong, China were calculated using the PROFILE model with a 3×3 km resolution.Calculations were carried out for critical loads of potential acidity, actual acidity, sulfur and nitrogen, with values in extents of 0-3.5, 0-14.0, 0-26.0 and 0-3.5 kmol/(hm2·year), respectively.These values were comparable to previously reported results and reflected the influences of vegetation and soil characteristics on the soil acid buffering capacity.Simulations of SO2 emission and sulfur deposition in this study showed that sulfur deposition core areas mirrored SO2 emission centers.The prediction of sulfur deposition after 20% and 40% reduction of SO2 emission suggested that the reduction of area sources contributed greatly to the decrease of sulfur deposition.Thus, abatement of area source emissions could be the primary way to mitigate sulfur deposition in Guangdong so as to meet both the provincial and national regulations of air pollution control.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li Fengxia [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China); Li Xiaoli, E-mail: lixiaoli0903@163.com [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China); Li Bin, E-mail: libinzh62@163.com [Heilongjiang Key Laboratory of Molecular Design and Preparation of Flame Retarded Materials, College of Science, Northeast Forestry University, Harbin 150040 (China)

    2011-11-15

    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 {mu}m. Magnetic Fe{sub 3}O{sub 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. - Highlights: > We prepare magnetic polylactic acid microspheres loading curcumin. > The classical oil-in-water emulsion solvent-evaporation method is used. > The magnetic microspheres are regularly spherical with a diameter of 0.55-0.75 {mu}m. > They show a certain sustained release effect on in vitro drug releasing.

  11. Acute effects of lysergic acid diethylamide in healthy subjects

    OpenAIRE

    2015-01-01

    After no research in humans for >40 years, there is renewed interest in using lysergic acid diethylamide (LSD) in clinical psychiatric research and practice. There are no modern studies on the subjective and autonomic effects of LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse inhibition (PPI) of the acoustic startle response, and patients with schizophrenia exhibit similar impairments in PPI. However, no data are available on the effects of LSD on PPI in humans.;...

  12. Water pollution abatement programme. The Czech Republic. Project 4.2. Assessing critical loads of acidity to surface waters in the Czech Republic. Critical loads of acidity to surface waters, north-eastern Bohemia and northern Moravia, The Czech Republic

    Energy Technology Data Exchange (ETDEWEB)

    Lien, L.; Raclavsky, K.; Raclavska, H.; Matysek, D.; Hovind, H.

    1996-01-01

    This report discusses estimates of critical loads of acidity to surface waters and their exceedances, for north-eastern Bohemia and Moravia in The Czech Republic. The survey covers 13 400 km{sup 2}, or 17% of the area of the country. Varying critical loads were observed within the examined region. 19% of the examined area showed exceedance of critical load and another 11% was close to exceedance. The survey should continue in Bohemia. 24 refs., 20 figs., 4 tabs.

  13. Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.

    NARCIS (Netherlands)

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Blous, L.; Peters, J.G.P.; Blaney Davidson, E.N.; Kraan, P.M. van der; Swinkels, D.W.; Masereeuw, R.; Russel, F.G.M.

    2012-01-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study wa

  14. Intensive chromic acid burns and acute chromium poisoning with acute renal failure

    Institute of Scientific and Technical Information of China (English)

    XIANG Jun; SUN Zhen; HUAN Jing-ning

    2011-01-01

    In this case report, we describe our experience of managing a patient with chemical burns caused by hot chromic acid that covered over 60% of the patient's body. The patient developed anuria 48 hours after injury. Early excision of burn eschars and hemodialysis were carried out. The patient survived after a series of comprehensive treatments, including allografting and autografting. In patients burned by hot chromic acid, excision of affected skin down to the muscle fascia should be carried out as soon as possible after injury. Dialysis to remove circulating chromium in the first 24 hours after injury is also recommended.

  15. Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment.

    Science.gov (United States)

    Silva, João P; Gonçalves, Carine; Costa, César; Sousa, Jeremy; Silva-Gomes, Rita; Castro, António G; Pedrosa, Jorge; Appelberg, Rui; Gama, F Miguel

    2016-08-10

    Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi-drug standard therapies often results in treatment failure and emergence of multi-drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe the ability of the exogenous AMP LLKKK18 to efficiently kill mycobacteria. The peptide's potential was boosted by loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity and degradability, while potentiating peptide targeting to main sites of infection. The nanogels were effectively internalized by macrophages and the peptide presence and co-localization with mycobacteria within host cells was confirmed. This resulted in a significant reduction of the mycobacterial load in macrophages infected in vitro with the opportunistic M. avium or the pathogenic M. tuberculosis, an effect accompanied by lowered pro-inflammatory cytokine levels (IL-6 and TNF-α). Remarkably, intra-tracheal administration of peptide-loaded nanogels significantly reduced infection levels in mice infected with M. avium or M. tuberculosis, after just 5 or 10 every other day administrations. Considering the reported low probability of resistance acquisition, these findings suggest a great potential of LLKKK18-loaded nanogels for TB therapeutics.

  16. Bleomycin Loaded Magnetite Nanoparticles Functionalized by Polyacrylic Acid as a New Antitumoral Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Yue Xu

    2013-01-01

    Full Text Available Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs coated with polyacrylic acid (PAA as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM, vibrating sample magnetometer (VSM, and Fourier transform infrared spectroscopy (FTIR. The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30 nm exhibit a saturation magnetization of 87 emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24 h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23 hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. Characterization and Design of Zeolite Catalysts Solid Acidity, Shape Selectivity and Loading Properties

    CERN Document Server

    Niwa, Miki; Okumura, Kazu

    2010-01-01

    Zeolites are microporous, aluminosilicate minerals commonly used as commercial adsorbents. Zeolite-based catalysts are used by industrial chemical companies in the interconversion of hydrocarbons and the alkylation of aromatic compounds. The current book deals with the characterization of specific properties of Zeolites and calculations for the design of catalysts. Measurements and utilization of solid acidity, shape selectivity, and loading properties, that are three prominent properties of a Zeolite catalyst, are treated in detail. These features concern chemical vapor deposition of silica, shape selectivity, loading properties, solid activity, Brønsted or Lewis character, ammonia temperature programmed desorption, control of the pore-opening size by chemical vapor deposition of silica and XAFS analysis of metals being highly dispersed inside and outside a framework.

  20. Poly(acrylic acid) microspheres loaded with lidocaine: preparation and characterization for arterial embolization.

    Science.gov (United States)

    Cui, Dai-Chao; Lu, Wan-Liang; Sa, Er-A; Gu, Meng-Jie; Lu, Xiao-Jing; Fan, Tian-Yuan

    2012-10-15

    A new embolic agent, poly(acrylic acid) microspheres (PMs), was synthesized and the cytocompatibility was proved by mouse L929 fibroblast cells. An analgesic drug, lidocaine, was loaded on the PMs to relief pain caused by embolization. PMs and lidocaine loaded microspheres (LMs) were characterized by investigating infrared spectrum, morphology, particle size, and equilibrium water contents (EWC). A series of tests were employed to evaluate the elasticity of PMs, LMs and Embosphere™, including once compression, twice compression, and stress relaxation test. The pressures of PMs and LMs passing through a catheter were measured on line by our new designed device. Drug release was studied with T-cell apparatus. The properties of PMs and LMs were proved to be suitable for embolization. Both PMs and LMs in this study might be potential embolic agents in the future.

  1. Studies of Heterogeneous Hydrothermal Stripping from Iron-loaded Naphthenic Acid-Alcohol-Kerosen

    Institute of Scientific and Technical Information of China (English)

    王兴尧; 康晓红; 谢慧琴; 卢立柱

    2003-01-01

    The technique of hydrothermal stripping from mixed aqueous-organic systems is a promising method for synthesizing oxide ceramic powders for high-performance applications. Some factors influencing heterogeneous hydrothermal stripping with water from iron-loaded organic phase of naphthenic acid-isooctyl alcohol-kerosene, such as initial concentrations of iron and naphthenic acid, concentration of Fe2O3 "seed", temperature and time, were investigated. Based on the experimental results, the rate equation was established. Nano-ferric oxide powders were obtained by the technique of hydrothermal stripping from the iron-loaded organic phase. The results suggest that the heterogeneous hydrothermal stripping proceeds in 3 steps: adsorption of naphthenic acid dimers and naphthenic complex of iron onto the surface of "seed", hydrolysis of adsorbed complex of iron, and condensation of hydrolyzed complex. The process activation energy is 115 kJ/mol and the heterogeneous hydrothermal stripping is controlled by a chemical reaction(the hydrolysis of naphthenic complex of iron).

  2. Acute Effects of Low-Load/High-Repetition Single-Limb Resistance Training in COPD.

    Science.gov (United States)

    Nyberg, André; Saey, Didier; Martin, Mickaël; Maltais, François

    2016-12-01

    Exercising small muscle groups at a time allows higher muscle specific workloads compared with whole body aerobic exercises in people with chronic obstructive pulmonary disease (COPD). Whether similar effects also occur with partitioning exercise during low load/high-repetition resistance exercises is uncertain.

  3. The fluctuation of free amino acids in serum during acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Szpetnar Maria

    2016-12-01

    Full Text Available Currently, little data exists regarding the involvement of free amino acids (AA in the pathogenesis of ischemic stroke (IS. Thus, our objective was to study the degree of the degree of fluctuation of free amino acids level in serum during the acute phase of IS. The study consisted of eighteen patients (female/male: 10/8; age: 73.1 ± 4.1 with acute IS that was confirmed by way of computed tomography, while twelve sex and age matched individuals were assigned as control group. During the study period, the patients did not receive any supplemental amino acids therapy that could affect the obtained results. The venous blood was obtained after >3 hours fasting at two time-points; time-point 1 – at admission to the hospital; time-point 2 – on day 5 from stroke onset. The blood for control purposes was collected only once, and the blood collection at time-point 1 was done before thrombolytic treatment (nine patients. The amino acids were identified using the Amino Acids Analyser (AAA 400 by INGOS Corp., Praha, Czech Republic. Our results revealed a statistically significant increase of glutamate, cystine and methionine on day 1 of stroke, in comparison to control, whereas, proline level was decreased on day 1 of stroke – in comparison to control serum. On comparing day 5 to the initial day of IS, elevation was observed of levels of asparagine, glycine, tyrosine, arginine, threonine, valine, leucine and phenylalanine. It can be said, then, that ischemic stroke induces both essential and nonessential amino acid fluctuations. Moreover, the decrease in proline and glutamine serum level with the simultaneous increase in the concentration of branch chain amino acids, Glu and Thr suggests a violent mobilization of the body’s proteins. Thus, a decrease of Pro and a simultaneous increase of Glu serum level could be considered as a marker of acute IS.

  4. Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas, E-mail: shoja-sa@modares.ac.ir [Tarbiat Modares University, Biotechnology Group, Faculty of Chemical Engineering (Iran, Islamic Republic of); Morshedi, Dina; Arpanaei, Ayyoob [National Institute of Genetic Engineering and Biotechnology, Department of Industrial and Environmental Biotechnology (Iran, Islamic Republic of); Marvian, Amir Tayaranian [Aarhus University, Department of Biomedicine (Denmark)

    2015-04-15

    Gallic acid (GA), as an antioxidant and antiparkinson agent, was loaded onto cationic human serum albumin nanoparticles (HSA NPs). Polyethylenimine (PEI)-coated HSA (PEI-HSA) NPs were prepared using three different methods: (I) coating negatively charged HSA NPs with positively charged PEI through attractive electrostatic interactions, (II) coating HSA NPs with PEI via covalent amide bond formation using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, and (III) coating HSA NPs with PEI via covalent bonding using glutaraldehyde for linking amine groups of PEI and amine groups of albumin NPs. Method II was selected since it resulted in a higher shift in the zeta potential value (mV) and less zeta potential value deviation, and also less size polydispersity. GA was loaded by adsorption onto the surface of PEI-HSA NPs of two different sizes: 117 ± 2.9 nm (PEI-P1) and 180 ± 3.1 nm (PEI-P2) NPs. Both GA-entrapment and GA-loading efficiencies increased slightly with the increasing size of NPs, and were affected intensely by the mass ratio of GA to PEI-HSA NPs. Free radical scavenging of GA was quantified based on the 2,2-diphenyl-1-picrylhydrazyl method. The obtained results showed that GA remains active during the preparation of GA-loaded PEI-HSA NPs. The cytotoxicities of HSA, PEI-HSA, and GA-loaded PEI-HSA NPs on the PC-12 cells, as the neuroendocrine cell line, were measured. Our results indicate that positively charged PEI-HSA NPs are good candidates for efficient and safe delivery of GA to the brain.

  5. Vulnerability for nitrate loading and acid deposition as represented by geohydrochemical districts in The Netherlands

    Energy Technology Data Exchange (ETDEWEB)

    Beek, C.G.E.M. van; Hesen, P.L.G.M. [Kiwa Water Research, Nieuwegein (Netherlands); Willems, W.J. [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands)

    2004-07-01

    Geohydrochemical districts are areas which behave similarly with regard to pollution, resulting in comparable groundwater chemistries. Recognition of geohydrochemical districts gives a quick assessment of effects of pollution on the chemical composition of groundwater, and conversely also in effects of remedial measures. Moreover, geohydrochemical districts may serve as a starting point for predicting the future chemical composition of groundwater abstracted from phreatic aquifers by waterworks for the public drinking water supply. In this contribution geohydrochemical districts are distinguished in The Netherlands with respect to nitrate loading and acid deposition, but the same approach may be used for estimating the vulnerability of (abstracted) groundwater for pesticides and other chemical pollutants.

  6. Preparation and release kinetics of betulinic acid/ CS drug-loaded microspheres

    Directory of Open Access Journals (Sweden)

    Zhou Hao Ran

    2016-01-01

    Full Text Available Chitosan(CS is the unique alkaline polysaccharide in nature, because of its perfect biocompatibility and degradability, it is widely used in medicine, soft release and control release. The betulinic acid is the derivative of betulin, it has many pharmacological activities, such as anti- inflammatory, antitumor, anti-malaria and anti-HIV. In this paper, the Span-80 was used as emulsifiers, the glutaraldehyde was used as crosslinker. With the method of orthogonal experiment, the preparation technology was optimized. The microspheres were characterized by SEM and its degree of crosslinking, drug-loading rate and encapsulation efficiency were tested at the same time.

  7. The Pharmacokinetics and Pharmacodynamics of Lidocaine- Loaded Biodegradable Poly(lactic-co-glycolic acid) Microspheres

    OpenAIRE

    Jianming Liu; Xin Lv

    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...

  8. Synthesis of glycerin triacetate over molding zirconia-loaded sulfuric acid catalyst

    Institute of Scientific and Technical Information of China (English)

    Lian Wang; Qun Liu; Minghao Zhou; Guomin Xiao

    2012-01-01

    Zirconia-loaded sulfuric acid (SO2-4/ZrO2) catalysts were prepared by impregnation method,molded by punch tablet machine and characterized by X-ray diffraction.SO2-4/ZrO2 catalyst was used to obtain glycerol triacetate (GTA) directly from glycerin.The effect of some factors,such as different temperatures of calcination and catalysts molded or not,on the reusable times of catalysts and the yield of GTA were investigated.The optimum reaction conditions were shown as follows:the reaction temperature was 403 K; the reaction time continued for 8 h; the amount of molded catalysts was 5 wt% of glycerin and the molar ratio of glycerin to acetic acid was 1 ∶ 8.The yield of GTA was 97.93% under the optimum condition.

  9. Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

    Directory of Open Access Journals (Sweden)

    Li Guan

    2015-01-01

    Full Text Available Carbon monoxide (CO poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct, plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA levels in red blood cells (RBCs. These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.

  10. Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys

    Science.gov (United States)

    Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol; insulin; adiponectin) responsiveness to acute stress (AS) were assessed in a ...

  11. Clinical significance of sialic acid in acute rheumatic fever with and without carditis

    OpenAIRE

    Maher H. Gomaa; Halah Salah Al-Din Hamza; Mamdouh M. Ali; Ahmed Abd-Allah Ali; Osama Abd Al-Motaal Mansour; Ahmed M. Ibrahim

    2012-01-01

    Objective: In Egypt, acute rheumatic fever (ARF) is the most common cause of acquired heart disease. ARF is a clinical syndrome without a specific diagnostic test or single pathognomonic feature, so the aim of this study is to investigate the utility of using serum total sialic acid (TSA) in differentiation between children suffering from ARF with and without carditis. Methods: In the present study, 62 children were divided into three groups: first group, 16 healthy children; second group, 20...

  12. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  13. Acute extracellular ethanol load does not produce hyponatremia by internal osmoregulation

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, J.E.; Tzamaloukas, A.H.; Long, D.A.

    1986-03-05

    Hyponatremia is frequently present in subjects intoxicated with ethanol. To study whether an acute increase in extracellular osmolality by addition of ethanol creates any clinically appreciable osmotic shift of intracellular water extracellularly, they infused over 20 sec 11 mmol/kg of ethanol intravenously into 5 anesthetized dogs (2 with intact renal function, 3 anuric) and measured plasma sodium and ethanol concentrations and osmolality at frequent intervals for 100 min after the end of the infusion. For a range of ethanol concentration between 4 and 120 mmol/l, changes in osmolality were equal to ethanol concentration in plasma water (y = -0.49 + 1.06 x mosm/kg per mmol/l, r = 0.981, p < 0.01). Plasma sodium concentration remained unchanged from baseline throughout the experiments, even at 1 min post-infusion, when osmolality was 78 +/- 25 mosm/kg above the baseline. An acute increase in extracellular osmolality created by rapid intravenous infusion of a large dose of ethanol does not create any osmotic shift of intracellular water extracellularly, that can be detected by dilution of extracellular sodium. The mechanism of hyponatremia in ethanol intoxication is not internal osmoregulation, but abnormalities in external balance of body water and/or solute.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Tian, E-mail: phdlitian@163.com; Lin, Oulian; Lu, Zhiyuan; He, Liuimei; Wang, Xiaosheng

    2014-06-01

    The Na{sup +} 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.

  15. Application of Capmul MCM and caprylic acid for the development of danazol-loaded SEDDS.

    Science.gov (United States)

    Li, Suhua; Madan, Parshotam; Lin, Senshang

    2014-07-25

    Abstract The feasibility of using Capmul MCM and caprylic acid (medium-chain triglyceride pre-digestion products) as the lipid phase was investigated for the development of self-emulsifying drug delivery system (SEDDS) as a carrier system to enhance solubilization of poorly water-soluble danazol. The composition of SEDDS was first evaluated by phase diagrams of lipid/surfactant/water systems. Thereafter, danazol-loaded SEDDS was formulated and subjected to dispersion/precipitation study in distilled water, HCl buffer, phosphate buffer, or biorelevant aqueous media. The mechanism of danazol dispersion was investigated by comparing the solubilization capacity of blank SEDDS dispersed in various aqueous media with respective dispersion/precipitation profiles obtained. Phase diagrams showed that at least 30% (w/w) Cremophor RH40, as the surfactant, was needed to properly emulsify Capmul MCM:caprylic acid (1:1), as the lipid phase. Different extent of danazol precipitation was observed upon the dispersion of danazol-loaded SEDDS in different aqueous media. Danazol precipitation was dominated by the solubilization capacity of danazol, which was influenced by the ratio of Capmul MCM:CA and Cremophor RH40, pH of aqueous media, gastrointestinal composition, and blank SEDDS concentration.

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

    Science.gov (United States)

    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.

  17. ATRA (all-trans-retinoic acid) syndrome in acute promyelocytic leukemia: clinical and radiologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keon Ha; Goo, Jin Mo; Im, Jung Gi; Chung, Myung Jin; Do, Kyung Hyun; Park, Seon Yang [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Seo, Joon Beom [Gachon Univ. Medical School, Gil Medical Center, Seoul (Korea, Republic of)

    2001-03-01

    To describe the clinical and radiologic findings of all-trans-retinoic acid (ATRA) syndrome in acute promyelocytic leukemia. Among 21 patients with acute promyelocytic leukemia who were treated with all-trans-retinoic acid between 1995 and 1998, we retrospectively evaluated the cases of four with ATRA syndrome. Two were male and two were female, and their mean age was 58 years. The clinical and radiologic findings of chest radiography (n=4) and HRCT (n=1) were analyzed. Between seven and 13 days after ATRA treatment, dry cough, dyspnea and high fever developed in all patients. The WBC count in peripheral blood was significantly higher [2.9-25.3(mean, 10.8)-fold] than before ATRA treatment, and in all patients, chest radiography revealed ill-defined consolidation and pleural effusion. Kerley's B line (n=3) and hilar enlargement (n=3) were also seen, and in one patient, HRCT demonstrated septal line thickening. Among four patients treated with prednisolone and Ara-C, three recovered and one died. In acute promyelocytic patients treated with all-trans-retinoic acid, radiologic findings of ill-de-fined consolidation, pleural effusion, hilar prominence and Kerley's B line may suggest ATRA syndrome. The early diagnosis of this will improve the patients' prognosis.

  18. Paclitaxel loaded biodegradable poly (sebacic acid-co-ricinoleic acid cylindrical implants for local delivery-in vitro characterization

    Directory of Open Access Journals (Sweden)

    Jagadeesh G Hiremath

    2013-01-01

    Full Text Available The aim of the present research work was to develop the biodegradable polymeric implant for the delivery of antineoplastic drug, paclitaxel (PTX using poly (sebacic-co-recinoleic acid 70:30 w/w. PTX loaded implants were prepared by indigenously developed melt molding technique. Implants were characterized in terms of physico-chemical evaluations, drug content, drug stability and intactness, thermal analysis, drug physical state and crystallinity, surface morphology, hydrolytic degradation, drug release and its kinetics. Prepared implants were yellow and cylindrical in shape with smooth surfaces. Drug in the implants was found to be stable, intact and uniformly dispersed as amorphous state within the polymer matrix. In vitro release, kinetic studies showed zero order and Korsmeyer-Peppas model release being exhibited. Drug release from the polymeric implants was occurred could be as results of diffusion.

  19. Preparation and characterization of paclitaxel-loaded poly lactic acid-co-glycolic acid coating tracheal stent

    Institute of Scientific and Technical Information of China (English)

    Kong Yingying; Zhang Jie; Wang Ting; Qiu Xiaojian; Wang Yuling

    2014-01-01

    Background In-stent restenosis caused by airway granulation poses a challenge due to the high incidence of recurrence after treatment.Weekly applications of anti-proliferative drugs have potential value in delaying the recurrence of airway obstruction.However,it is not practical to subject patients to repeated bronchoscopy and topical drug applications.We fabricated novel pacilitaxel-eluting tracheal stents with sustained and slow pacilitaxel release,which could inhibit the formation of granulation tissue.And we assessed the quality and drug release behaviors of drug-eluting stents (DESs) in vitro.Methods Stents were dipped vertically into a coating solution prepared by dissolving 0.5 g (2% w/v) of poly lactic acid-coglycolic acid (PLGA) and 0.025 g (0.1% w/v) of pacilitaxel in 25 ml of dichloromethane.DES morphology was examined by scanning electron microscopy (SEM).Pacilitaxel release kinetics from these DESs was investigated in vitro by shaking in PBS buffer followed by high performance liquid chromatography (HPLC).Results Using an orthogonal experimental design,we fabricated numerous pacilitaxel/PLGA eluting tracheal stents to assess optimum coating proportions.The optimum coating proportion was 0.1% (w/v) pacilitaxel and 2% (w/v) PLGA,which resulted in total pacilitaxel loading of (16.380 6±0.002 1) mg/stent.By SEM the coating was very smooth and uniform.Pacilitaxel released from DES was at (0.376 3±0.003 8) mg/d,which is a therapeutic level.There was a prolonged,sustained release of pacilitaxel of >40 days.Conclusions Paclitaxel-loaded PLGA coating tracheal stents were successfully developed and evaluated.Quality assessments demonstrated favorable surface morphology as well as sustained and effective drug release behavior,which provides an experimental reference for clinical practitioners.

  20. Acute Effects of Loaded Half-Squat Jumps on Sprint Running Speed in Track and Field Athletes and Soccer Players.

    Science.gov (United States)

    Vanderka, Marián; Krčmár, Matúš; Longová, Katarína; Walker, Simon

    2016-06-01

    The purpose of the study was to determine the acute responses to a jump squat protocol designed to induce postactivation potentiation on sprint running performance in experienced track and field athletes and soccer players. Twenty-five regional level athletes (12 track and field: ∼17 years; ∼177 cm; ∼73 kg and 13 soccer: ∼18 years; ∼175 cm; ∼72 kg) performed 2 test sessions assessing 40-m sprint running performance in a balanced, crossover design. Dual-beam light timing gates measured 0-20 and 20-40 m sprint times before and after either 9 minutes of sitting (control) or 2 sets of 6 repetition half-squat jump with the load eliciting maximum power (experimental) conditions. Sprint performance was significantly enhanced over both 0-20 m (3.09 ± 0.07 to 3.04 ± 0.08 seconds; Δ ∼1.5%; p ≤ 0.05) and 20-40 m (2.42 ± 0.09 to 2.39 ± 0.09 seconds; Δ ∼1%; p ≤ 0.05) in track and field athletes only. Also, the magnitude of enhanced sprint performance was related to baseline 0-20 m sprint performance (r = 0.44; p = 0.028; n = 25). It seems that using loaded half-squat jumps to enhance sprint performance could be used in training of high-level young athletes.

  1. Influence of Fe loadings on desulfurization performance of activated carbon treated by nitric acid.

    Science.gov (United States)

    Guo, Jia-Xiu; Shu, Song; Liu, Xiao-Li; Wang, Xue-Jiao; Yin, Hua-Qiang; Chu, Ying-Hao

    2017-02-01

    A series of Fe supported on activated carbon treated by nitric acid are prepared by incipient wetness impregnation with ultrasonic assistance and characterized by N2 adsorption-desorption, X-ray diffraction, Fourier transform infrared spectrum and X-ray photoelectron spectroscopy. It has shown that Fe loadings significantly influence the desulfurization activity. Fe/NAC5 exhibits an excellent removal ability of SO2, corresponding to breakthrough sulfur capacity of 323 mg/g. With the increasing Fe loadings, the generated Fe3O4 and Fe2SiO4 increase, but Fe2(SO4)3 is observed after desulfurization. Fe/NAC1 has a Brunauer-Emmett-Teller (BET) surface area of 925 m(2)/g with micropore surface area of 843 m(2)/g and total pore volume of 0.562 cm(3)/g including a micropore volume of 0.300 cm(3)/g. With the increasing Fe loadings, BET surface area and micropore volume decrease, and those of Fe/NAC10 decrease to 706 m(2)/g and 0.249 cm(3)/g. The Fe loadings influence the pore-size distribution, and SO2 adsorption mainly reacts in micropores at about 0.70 nm. C=O and C-O are observed for all samples before SO2 removal. After desulfurization, the C-O stretching is still detected, but the C=O stretching vibration of carbonyl groups disappears. The stretching of S-O or S=O in sulfate is observed at 592 cm(-1) for the used sample, proving that the existence of [Formula: see text].

  2. Acute effects of N-terminal progastrin fragments on gastric acid secretion in man.

    Science.gov (United States)

    Goetze, Jens P; Hansen, Carsten P; Rehfeld, Jens F

    2017-03-01

    We previously identified an N-terminal fragment of progastrin in human antrum and plasma, where it circulates in high concentrations. In this study, we examined the effects of N-terminal progastrin fragments on gastric acid secretion by infusion in healthy individuals. Increasing doses of progastrin fragment 1-35 were infused intravenously during constant gastric acid stimulation by gastrin-17. In addition, the effects of progastrin fragment 1-35, fragment 6-35, and fragment 1-19 on gastrin-17 stimulated acid secretion were tested. The gastrin-17 stimulated acid secretion decreased 30% after administration of a high dose of progastrin fragment 1-35 (P < 0.05). In extension, a 1-h infusion of fragment 1-35 also decreased gastric acid output. In contrast, fragment 6-35 did not affect acid secretion, and a single infusion of gastrin-17 alone did not reveal fading of gastric acid output during the time course of the experiments. The results show that N-terminal fragments of progastrin may acutely affect gastrin-stimulated gastric acid secretion in vivo. Structure-function analysis suggests that the N-terminal pentapeptide of progastrin is required for the effect.

  3. Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results.

    Science.gov (United States)

    Wilson, Robert; Anzueto, Antonio; Miravitlles, Marc; Arvis, Pierre; Alder, Jeff; Haverstock, Daniel; Trajanovic, Mila; Sethi, Sanjay

    2012-07-01

    Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study. Patients were aged ≥ 60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population. Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral corticosteroids had more severe disease and higher failure rates. The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD. Both therapies were well tolerated.

  4. The development of an approach to assess critical loads of acidity for woodland habitats in Great Britain

    Directory of Open Access Journals (Sweden)

    S. J. Langan

    2004-01-01

    Full Text Available Alongside other countries that are signatories to the UNECE Convention Long Range Transboundary on Air Pollution, the UK is committed to reducing the impact of air pollution on the environment. To advise and guide this policy in relation to atmospheric emissions of sulphur and nitrogen, a critical load approach has been developed. To assess the potential impact of these pollutants on woodland habitats a steady state, simple mass balance model has been parameterised. For mineral soils, a Ca:Al ratio in soil solution has been used as the critical load indicator for potential damage. For peat and organic soils critical loads have been set according to a pH criterion. Together these approaches have been used with national datasets to examine the potential scale of acidification in woodland habitats across the UK. The results can be mapped to show the spatial variability in critical loads of the three principal woodland habitat types (managed coniferous, managed broadleaved/ mixed woodland and unmanaged woodland. The results suggest that there is a wide range of critical loads. The most sensitive (lowest critical loads are associated with managed coniferous followed by unmanaged woodland on peat soils. Calculations indicate that at steady state, acid deposition inputs reported for 1995–1997 result in a large proportion of all the woodland habitats identified receiving deposition loads in excess of their critical load; i.e. critical loads are exceeded. These are discussed in relation to future modelled depositions for 2010. Whilst significant widespread negative impacts of such deposition on UK woodland habitats have not been reported, the work serves to illustrate that if acid deposition inputs were maintained and projected emissions reductions not achieved, the long-term sustainability of large areas of woodland in the UK could be compromised. Keywords: critical loads, acid deposition, acidification, woodland, simple mass balance model

  5. Enhanced proton conductivity of Nafion composite membrane by incorporating phosphoric acid-loaded covalent organic framework

    Science.gov (United States)

    Yin, Yongheng; Li, Zhen; Yang, Xin; Cao, Li; Wang, Chongbin; Zhang, Bei; Wu, Hong; Jiang, Zhongyi

    2016-11-01

    Design and fabrication of efficient proton transport channels within solid electrolytes is crucial and challenging to new energy-relevant devices such as proton exchange membrane fuel cells (PEMFCs). In this study, the phosphoric acid (H3PO4) molecules are impregnated into SNW-1-type covalent organic frameworks (COFs) via vacuum assisted method. High loading of H3PO4 in SNW-1 and low guest leaching rate are achieved due to the similar diameter between H3PO4 and micropores in SNW-1. Then the COF-based composite membranes are fabricated for the first time with impregnated COFs (H3PO4@SNW-1) and Nafion matrix. For the composite membranes, the acid-base pairs formed between H3PO4@SNW-1 networks and Nafion optimize the interfacial interactions and hydrophilic domains. The acidic -PO3H2 groups in pores of H3PO4@SNW-1 provide abundant proton transfer sites. As a result, the continuous proton transfer channels with low energy barrier are created. At the filler content of 15 wt%, the composite membrane exhibits a superior proton conductivity of 0.0604 S cm-1 at 51% relative humidity and 80 °C. At the same time, the maximum power density of single fuel cell is 60.3% higher than that of the recast Nafion membrane.

  6. Relationships between static foot alignment and dynamic plantar loads in runners with acute and chronic stages of plantar fasciitis: a cross-sectional study

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    Ana P. Ribeiro

    2016-02-01

    Full Text Available BACKGROUND: The risk factors for the development of plantar fasciitis (PF have been associated with the medial longitudinal arch (MLA, rearfoot alignment and calcaneal overload. However, the relationships between the biomechanical variables have yet to be determined. OBJECTIVE: The goal of this study was to investigate the relationships between the MLA, rearfoot alignment, and dynamic plantar loads in runners with unilateral PF in acute and chronic phases. METHOD: Cross-sectional study which thirty-five runners with unilateral PF were evaluated: 20 in the acute phase (with pain and 15 with previous chronic PF (without pain. The MLA index and rearfoot alignment were calculated using digital images. The contact area, maximum force, peak pressure, and force-time integral over three plantar areas were acquired with Pedar X insoles while running at 12 km/h, and the loading rates were calculated from the vertical forces. RESULTS: The multiple regression analyses indicated that both the force-time integral (R2=0.15 for acute phase PF; R2=0.17 for chronic PF and maximum force (R2=0.35 for chronic PF over the forefoot were predicted by an elevated MLA index. The rearfoot valgus alignment predicted the maximum force over the rearfoot in both PF groups: acute (R2=0.18 and chronic (R2=0.45. The rearfoot valgus alignment also predicted higher loading rates in the PF groups: acute (R2=0.19 and chronic (R2=0.40. CONCLUSION: The MLA index and the rearfoot alignment were good predictors of plantar loads over the forefoot and rearfoot areas in runners with PF. However, rearfoot valgus was demonstrated to be an important clinical measure, since it was able to predict the maximum force and both loading rates over the rearfoot.

  7. Relationships between static foot alignment and dynamic plantar loads in runners with acute and chronic stages of plantar fasciitis: a cross-sectional study

    Science.gov (United States)

    Ribeiro, Ana P.; Sacco, Isabel C. N.; Dinato, Roberto C.; João, Silvia M. A.

    2016-01-01

    BACKGROUND: The risk factors for the development of plantar fasciitis (PF) have been associated with the medial longitudinal arch (MLA), rearfoot alignment and calcaneal overload. However, the relationships between the biomechanical variables have yet to be determined. OBJECTIVE: The goal of this study was to investigate the relationships between the MLA, rearfoot alignment, and dynamic plantar loads in runners with unilateral PF in acute and chronic phases. METHOD: Cross-sectional study which thirty-five runners with unilateral PF were evaluated: 20 in the acute phase (with pain) and 15 with previous chronic PF (without pain). The MLA index and rearfoot alignment were calculated using digital images. The contact area, maximum force, peak pressure, and force-time integral over three plantar areas were acquired with Pedar X insoles while running at 12 km/h, and the loading rates were calculated from the vertical forces. RESULTS: The multiple regression analyses indicated that both the force-time integral (R 2=0.15 for acute phase PF; R 2=0.17 for chronic PF) and maximum force (R 2=0.35 for chronic PF) over the forefoot were predicted by an elevated MLA index. The rearfoot valgus alignment predicted the maximum force over the rearfoot in both PF groups: acute (R 2=0.18) and chronic (R 2=0.45). The rearfoot valgus alignment also predicted higher loading rates in the PF groups: acute (R 2=0.19) and chronic (R 2=0.40). CONCLUSION: The MLA index and the rearfoot alignment were good predictors of plantar loads over the forefoot and rearfoot areas in runners with PF. However, rearfoot valgus was demonstrated to be an important clinical measure, since it was able to predict the maximum force and both loading rates over the rearfoot. PMID:26786073

  8. SUPPRESSION OF ANGⅡ AFTER ACUTE SALINE LOAD ASSOCIATED WITH THE CHANGES OF PLASMA ANP AND SODIUM METABOLISM IN SALT-SENSITIVE HYPERTENSION PATIENTS

    Institute of Scientific and Technical Information of China (English)

    王永兴; 刘治全; 刘艳; 侯嵘; 叶涛

    2003-01-01

    Objective To observe the changes of plasma AngⅡ,ANP and their relationship with urine sodium excretion in salt sensitive hypertension. Methods The salt sensitivity was determined by acute saline loading test in 173 primary hypertensives of Stage Ⅰ or Stage Ⅱ. Plasma AngⅡand ANP was determined by radioimmunoassay. Results After acute salt load, AngⅡ was suppressed inadequately. The plasma ANP secretion was not increased. The urine sodiun excretion was delayed, Na+ in RBC was increased in salt sensitive subjects. The plasma ANP was decreased in the salt sensitive subjects without AngⅡ suppressed. The 24 hours urine sodium excretion was lower than those AngⅡ suppressed.Conclusion The changes of plasma RAS are not homogeneous after salt load. Those without the plasma AngⅡ suppressed have more severe sodium metabolism abnormalities and the endogenous ANP secretion is impaired in salt sensitive patients.

  9. Metal loading effect on rare earth element binding to humic acid: Experimental and modelling evidence

    Science.gov (United States)

    Marsac, Rémi; Davranche, Mélanie; Gruau, Gérard; Dia, Aline

    2010-03-01

    The effect of metal loading on the binding of rare earth elements (REE) to humic acid (HA) was studied by combining ultrafiltration and Inductively Coupled Plasma Mass Spectrometry techniques. REE-HA complexation experiments were performed at pH 3 for REE/C molar ratios ranging from ca 4 × 10 -4 to 2.7 × 10 -2. Results show that the relative amount of REE bound to HA strongly increases with decreasing REE/C. A middle-REE (MREE) downward concavity is shown by patterns at high metal loading, whereas patterns at low metal loading display a regular increase from La to Lu. Humic Ion Model VI modelling are close to the experimental data variations, provided that (i) the ΔLK 2 parameter (i.e. the Model VI parameter taken into account the presence of strong but low density binding sites) is allowed to increase regularly from La to Lu (from 1.1 to 2.1) and (ii) the published log KMA values (i.e. the REE-HA binding constants specific to Model VI) are slightly modified, in particular with respect to heavy REE. Modelling approach provided evidence that logKdREE patterns with varying REE/C likely arises because REE binding to HA occurs through two types of binding sites in different density: (i) a few strong sites that preferentially complex the heavy REE and thus control the logKdREE atterns at low REE/C; (ii) a larger amount of weaker binding sites that preferentially complex the middle-REE and thus control the logKdREE pattern at high REE/C. Hence, metal loading exerts a major effect on HA-mediated REE binding, which could explain the diversity of published conditional constants for REE binding with HA. A literature survey suggests that the few strong sites activated at low REE/C could be multidentate carboxylic sites, or perhaps N-, or P-functional groups. Finally, an examination of the literature field data proposed that the described loading effect could account for much of the variation in REE patterns observed in natural organic-rich waters (DOC > 5 mg L -1 and 4

  10. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

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    Patrícia Fernanda Schuck

    Full Text Available Ethylmalonic acid (EMA accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers, and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  11. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    Science.gov (United States)

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.

  12. Acute arterial thrombosis associated with inadvertent high dose of tranexamic acid

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    Surjya Prasad Upadhyay

    2013-01-01

    Full Text Available Tranexamic acid (TA act as anti-fibrinolytic agent and is widely used to limit bleeding in clinical practice. Tranexemic acid bind with plasminogen and prevent its conversion to plasmin, which limits the fibrinolytic pathway, so there is a theoretical risk of increasing thrombosis with high or prolonged therapy with TA. We encountered a case of acute arterial thrombosis following inadvertent administration of high dose of TA. A 27-years-old male with no other co-morbidity was ordered intravenous 1 gm TA to control excessive bleeding from previous bladder injury, but by mistake, he received 10 gm of TA. The patient developed signs and symptoms of acute ischemia in the right lower limb, which was diagnosed as acute iliac arterial thrombosis by computed tomography (CT angiography. The patient was managed with systemic heparinization, fasciotomy for impending gangrene and other supportive care following which he recovered fully within a few days. Caution should be exercised for all prophylactic use, especially with high dosage or prolonged therapy with TA.

  13. Stable emulsions prepared by self-assembly of hyaluronic acid and chitosan for papain loading.

    Science.gov (United States)

    Zhao, Donghua; Wei, Wei; Zhu, Ye; Sun, Jianhua; Hu, Qiong; Liu, Xiaoya

    2015-04-01

    A simple, green and effective process is developed to fabricate hyaluronic acid (HA)/chitosan (CS) complex colloidal particles through electrostatic interactions. The obtained complexes can be used as biocompatible emulsifiers and novel potential carriers for papain loading. An HA/CS mass ratio of 2 is the optimal condition leading to the smallest Dh (420.9 nm). The complexes with eight different mass ratios are used to stabilize white oil/water emulsions. The structure of the complexes at the oil-water interface varies in response to the mass ratio and can be classified into two typical structures, similar to typical polymeric surfactants and solid particulate emulsifiers. Furthermore, papain is introduced into the complex systems. Formation of the papain/HA/CS complexes in a compact form can protect the enzyme. Here, a novel strategy is introduced to fabricate a biocompatible emulsion from the HA/CS complexes and demonstrate that the stable complex is a suitable enzyme delivery system.

  14. Acid Denaturation Inducing Self-Assembly of Curcumin-Loaded Hemoglobin Nanoparticles

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    Kaikai Wang

    2015-12-01

    Full Text Available Hemoglobin is a promising drug carrier but lacks extensive investigation. The chemical conjugation of hemoglobin and drugs is costly and complex, so we have developed curcumin-loaded hemoglobin nanoparticles (CCM-Hb-NPs via self-assembly for the first time. Using the acid-denaturing method, we avoid introducing denaturants and organic solvents. The nanoparticles are stable with uniform size. We have conducted a series of experiments to examine the interaction of hemoglobin and CCM, including hydrophobic characterization, SDS-PAGE. These experiments substantiate that this self-assembly process is mainly driven by hydrophobic forces. Our nanoparticles achieve much higher cell uptake efficiency and cytotoxicity than free CCM solution in vitro. The uptake inhibition experiments also demonstrate that our nanoparticles were incorporated via the classic clathrin-mediated endocytosis pathway. These results indicate that hemoglobin nanoparticles formed by self-assembly are a promising drug delivery system for cancer therapy.

  15. Preparation and evaluation of ofloxacin-loaded palmitic acid solid lipid nanoparticles

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    Shuyu Xie

    2011-03-01

    Full Text Available Shuyu Xie, Luyan Zhu, Zhao Dong, Yan Wang, Xiaofang Wang, WenZhong ZhouDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of ChinaAbstract: The purpose of this study was to use solid lipid nanoparticles (SLN to improve the pharmacological activity of ofloxacin. Ofloxacin-loaded SLN were prepared using palmitic acid as lipid matrix and poly vinyl alcohol (PVA as emulsifier by a hot homogenization and ultrasonication method. The physicochemical characteristics of SLN were investigated by optical microscope, scanning electron microscopy, and photon correlation spectroscopy. Pharmacokinetics was studied after oral administration in mice. In vitro antibacterial activity and in vivo antibacterial efficacy of the SLN were investigated using minimal inhibitory concentrations (MIC and a mouse protection model. The results demonstrated that the encapsulation efficiency, loading capacity, diameter, polydispersivity index, and zeta potential of the nanoparticles were 41.36% ± 1.50%, 4.40% ± 0.16%, 156.33 ± 7.51 nm, 0.26 ± 0.04, and –22.70 ± 1.40 mv, respectively. The SLN showed sustained release and enhanced antibacterial activity in vitro. Pharmacokinetic results demonstrated that SLN increased the bioavailability of ofloxacin by 2.27-fold, and extended the mean residence time of the drug from 10.50 to 43.44 hours. Single oral administrations of ofloxacin-loaded nanoparticles at 3 drug doses, 5 mg/kg, 10 mg/kg, and 20 mg/kg, all produced higher survival rates of lethal infected mice compared with native ofloxacin. These results indicate that SLN might be a promising delivery system to enhance the pharmacological activity of ofloxacin.Keywords: ofloxacin, pharmacological activity, solid lipid nanoparticles, antibacterial activity

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

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

    2015-06-01

    Full Text Available 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.

  17. In vitro evaluation of 5-aminolevulinic acid (ALA loaded PLGA nanoparticles

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    Shi L

    2013-07-01

    Full Text Available Lei Shi,1 Xiuli Wang,1 Feng Zhao,2 Hansen Luan,2 Qingfeng Tu,1 Zheng Huang,3 Hao Wang,2 Hongwei Wang1,41Shanghai Skin Disease Hospital, Shanghai, People's Republic of China; 2National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China; 3Ministry of Education (MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Normal University, Fuzhou, People's Republic of China; 4Huadong Hospital, Fudan University, Shanghai, People's Republic of ChinaBackground: 5-Aminolevulinic acid (ALA is a prodrug for topical photodynamic therapy. The effectiveness of topical ALA can be limited by its bioavailability. The aim of this study was to develop a novel ALA delivery approach using poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs.Methods: A modified double emulsion solvent evaporation method was used to prepare ALA loaded PLGA NPs (ALA PLGA NPs. The characteristics, uptake, protoporphyrin IX fluorescence kinetics, and cytotoxicity of ALA PLGA NPs toward a human skin squamous cell carcinoma cell line were examined.Results: The mean particle size of spherical ALA PLGA NPs was 65.6 nm ± 26 nm with a polydispersity index of 0.62. The encapsulation efficiency was 65.8% ± 7.2% and ALA loading capacity was 0.62% ± 0.27%. When ALA was dispersed in PLGA NPs, it turned into an amorphous phase. ALA PLGA NPs could be taken up by squamous cell carcinoma cells and localized in the cytoplasm. The protoporphyrin IX fluorescence kinetics and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay showed that ALA PLGA NPs were more effective than free ALA of the same concentration.Conclusion: PLGA NPs provide a promising ALA delivery strategy for topical ALA-photodynamic therapy of skin squamous cell carcinoma.Keywords: 5-Aminolevulinic acid (ALA, nanoparticles, poly(lactic-co-glycolic acid (PLGA, skin squamous cell carcinoma, photodynamic therapy (PDT

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

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    Xiaohong Chen

    2014-04-01

    Full Text Available 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.

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

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    Yanni Ma

    2016-02-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-02-29

    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.

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

    Science.gov (United States)

    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.

  2. Developing Critical Loads of acidity for streams in the Great Smoky Mountains National Park, using PnET-BGC model

    Science.gov (United States)

    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 (pHdeposition. 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.

  3. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice

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    Ong YS

    2016-11-01

    Full Text Available Yong Sze Ong,1 Latifah Saiful Yazan,1,2 Wei Keat Ng,1 Mustapha M Noordin,3 Sarah Sapuan,1 Jhi Biau Foo,1 Yin Sim Tor1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Biomedical Science, Faculty of Medicine and Health Sciences, 3Department of Pathology and Veterinary Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Background: Thymoquinone (TQ, the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ. Materials and methods: The in vivo toxicity (acute and subacute toxicity study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed. Results: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ

  4. [Effect of acute stress on the fatty acid composition of lipids of adrenal and heart mitochondria in rabbits].

    Science.gov (United States)

    Mandrik, K A; Doroshkevich, N A; Buko, V U; Vinogradov, V V

    1985-01-01

    A comparative study of changes in the fatty acid composition of rabbit heart and adrenal mitochondria was carried out after acute (1h) immobilization stress. In heart mitochondria the stress induced a decrease in the content of capric, lauric, myristic and pentadecanic acids. A statistically significant reduction of the amount of heptadecanoic, linoleic, arachidonic acids and an increase in the level of palmitic acid was noted in adrenal mitochondria. The acute stress resulted in differently directed shifts in the saturation of fatty acids. An elevation of the sum of unsaturated fatty acids was observed in the heart, and a decrease was detected in the adrenal glands. The above shifts in the fatty acid composition of adrenal and heart mitochondria provide evidence for different directions of lipid metabolism in these organs following stress.

  5. The acute effect of lower-body training on average power output measured by loaded half-squat jump exercise

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    Matúš Krčmár

    2015-09-01

    Full Text Available Background: High muscular power output is required in many athletic endeavors in order for success to be achieved. In the scientific community postactivation potentiation and its effect on performance are often discussed. There are many studies where the effect of resistance exercise on motor performance (such as vertical jump performance and running speed has been investigated but only a few of them studied power output. Objective: The purpose of this study was to determine the acute responses to a 2 set loaded half-squat jumps and 2 set loaded back half-squat protocols designed to induce the acute maximum average power output during loaded half-squat jumps. Methods: A randomized cross-over design was used. 11 participants of this study performed 3 trials in randomized order separated by at least 48 hours where maximum average power output was measured. The specific conditioning activities were comprised of 2 sets and 4 repetitions of half-squat jumps, 2 sets and 4 repetitions of back half-squat exercises and a control protocol without an intervention by specific a conditioning activity. Participants were strength trained athletes with different sport specializations (e.g. ice-hockey, volleyball. Mean age of the athletes was 22 ± 1.8 years, body mass 80 ± 7.1 kg and body height 185 ± 6.5 cm. Analysis of variance with repeated measures was used to determine differences between pre- and post-condition in each protocol, as well as between conditioning protocols, and also effect size was used to evaluate practical significance. Results: Maximum average power was significantly enhanced after application of the half-squat jump condition protocol (1496.2 ± 194.5 to 1552 ± 196.1 W, Δ ~ 3.72%, p < .001 and after application of the back half-squat protocol (1500.7 ± 193.2 to 1556 ± 191.2 W, Δ ~ 3.68%, p < .001 after 10 min of rest. Power output after control protocol was

  6. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  7. Impaired Increase of Plasma Abscisic Acid in Response to Oral Glucose Load in Type 2 Diabetes and in Gestational Diabetes

    OpenAIRE

    Pietro Ameri; Santina Bruzzone; Elena Mannino; Giovanna Sociali; Gabriella Andraghetti; Annalisa Salis; Monica Laura Ponta; Lucia Briatore; Adami, Giovanni F.; Antonella Ferraiolo; Pier Luigi Venturini; Davide Maggi; Renzo Cordera; Giovanni Murialdo; Elena Zocchi

    2015-01-01

    The plant hormone abscisic acid (ABA) is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT) human subjects, plasma ABA (ABAp) increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D) subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i) 9 treatment-naive T2D subjects, and ii) 9 pregnant women with gestati...

  8. [Acute fatty liver in pregnancy: revealing fetal fatty acid oxidation disorders].

    Science.gov (United States)

    Lamireau, D; Feghali, H; Redonnet-Vernhet, I; Mesli, S; Carles, D; Brissaud, O

    2012-03-01

    Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome are serious maternal illnesses occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. AFLP may result from mitochondrial defects in the beta-oxidation of fatty acids, in particular a deficiency of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) in the fetus. Clinical findings in AFLP vary and its diagnosis is complicated by a significant overlap in clinical and biochemical features with HELLP syndrome. We report the case of 2 siblings who died, the first one in the neonatal period of asphyxia with multivisceral presentation and the second one from sudden death at 7 months. Autopsy of the latter infant revealed hepatic steatosis associated with cardiomyopathy, which led to suspicion of a fatty acid oxidation deficiency. Mutation analysis demonstrated that both children were homozygous for the common mutation c.1528G>C and the parents were heterozygous for this same mutation. This case demonstrates the importance of screening mothers with acute fatty liver disease of pregnancy and their children at birth for a metabolic disease. This article proposes several metabolic tests for mother and child suspected of having beta-oxidation of a fatty acid disorder.

  9. Disseminated Exfoliative Dermatitis Associated with All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Yonal Ipek

    2012-01-01

    Full Text Available Acute promyelocytic leukemia (APL is a biologically and clinically separate type of acute myeloid leukemia characterized by a translocation involving the retinoic acid receptor-alpha (RARa locus on chromosome 17, the great majority of which is t(15; 17(q24.1; q21.1 (Collins (1998, Melnick and Licht (1999, and Grimwade (1999. Retinoic acid is a critical ligand in the differentiation pathway of multiple tissues, mediated through binding to an RAR. All-trans retinoic acid (ATRA is a subgroup of the retinoid family, which induces complete remission (CR in APL by causing differentiation and apoptosis in immature malignant promyelocytes rather than inducing cell death by cytotoxicity (Warrell et al. (1993, Liu et al. (2000, and Cassinat et al. (2001. ATRA-associated toxicity consisting of headache, fever, weakness, fatigue, dry skin, dermatitis, gastrointestinal disorders, and hypertriglyceridemia has been shown to be mild (Kurzrock et al. (1993. Herein, we describe a patient with APL that developed an erythematous reaction of the whole body followed by desquamation and exfoliation during ATRA therapy.

  10. A novel, stable and reproducible acute lung injury model induced by oleic acid in immature piglet

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; LING Feng; ZHANG Yan-bo; LIU Ai-jun; LIU Dong-hai; QIAO Chen-hui; WANG Qiang; LIU Ying-long

    2011-01-01

    Background Young children are susceptible to pulmonary injury,and acute lung injury (ALl) often results in a high mortality and financial costs in pediatric patients.A good ALl model will help us to gain a better understanding of the real pathophysiological picture and to evaluate novel treatment approaches to acute respiratory distress syndrome (ARDS) more accurately and liberally.This study aimed to establish a hemodynamically stable and reproducible model with ALl in piglet induced by oleic acid.Methods Six Chinese mini-piglets were used to establish ALl models by oleic acid.Hemodynamic and pulmonary function data were measured.Histopathological assessment was performed.Results Mean blood pressure,heart rate (HR),cardiac output (CO),central venous pressure (CVP) and left atrial pressure (LAP) were sharply decreased after oleic acid given,while the mean pulmonary arterial pressure (MPAP) was increased in comparison with baseline (P <0.05).pH,arterial partial pressure of O2 (PaO2),PaO2/inspired O2 fraction (FiO2) and lung compliance decreased,while PaCO2 and airway pressure increased in comparison with baseline (P <0.05).The lung histology showed severe inflammation,hyaline membranes,intra-alveolar and interstitial hemorrhage.Conclusion This experiment established a stable model which allows for a diversity of studies on early lung injury.

  11. Critical loads of acidity for 90,000 lakes in northern Saskatchewan: A novel approach for mapping regional sensitivity to acidic deposition

    Science.gov (United States)

    Cathcart, H.; Aherne, J.; Jeffries, D. S.; Scott, K. A.

    2016-12-01

    Atmospheric emissions of sulphur dioxide (SO2) from large point sources are the primary concern for acidic deposition in western Canada, particularly in the Athabasca Oil Sands Region (AOSR) where prevailing winds may potentially carry SO2 over acid-sensitive lakes in northern Saskatchewan. A novel catchment-scale regression kriging approach was used to assess regional sensitivity and critical loads of acidity for the total lake population of northern Saskatchewan (89,947 lakes). Lake catchments were delineated using Thiessen polygons, and surface water chemistry was predicted for sensitivity indicators (calcium, pH, alkalinity, and acid neutralizing capacity). Critical loads were calculated with the steady state water chemistry model using regression-kriged base cations, sulphate, and dissolved organic carbon concentrations modelled from surface water observations (n > 800) and digital landscape-scale characteristics, e.g., climate, soil, vegetation, landcover, and geology maps. A large region (>13,726 km2) of two or more indicators of acid sensitivity (pH acid neutralizing capacity, alkalinity, calcium acidic deposition in excess of their critical loads and many of them may be at risk of ecosystem damage owing to their sensitivity.

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

    Science.gov (United States)

    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.

  13. Scrotal ulceration following all-trans retinoic acid therapy for acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Illias Tazi

    2011-01-01

    Full Text Available All-trans retinoic acid (ATRA induces complete remission in most cases of acute promyelocytic leukemia. Toxicity of ATRA has been shown to be mild, consisting of headache, dry skin, dermatitis, and gastrointestinal disorders. We describe a case of scrotal ulceration with ATRA use in a Moroccan patient, an occurrence that has been rarely reported in the medical literature. The pathogenesis of scrotal ulceration remains unknown. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

  14. Acute toxicity and sublethal effects of gallic and pelargonic acids on the zebrafish Danio rerio.

    Science.gov (United States)

    Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

    2015-04-01

    Gallic and pelargonic acids are naturally found in a variety of plants and food products. Despite their extensive use in man-made applications, little is known regarding their potential risks to aquatic vertebrates. The aim of this work was to assess the acute toxicity of these polyphenolic and fatty acid compounds to the zebrafish. In order to get insights into sublethal effects, the enzyme activity of usual biomarkers related to oxidative stress and biotransformation were also assessed in fish. These latter included total superoxide dismutase, catalase as well as total glutathione peroxidase for antioxidant defence mechanisms and glutathione S-transferase for biotransformation related enzyme. Gallic acid was practically non-toxic (96-h lethal concentration (LC50) > 100 mg/L) whereas pelargonic acid was slightly toxic (96-h LC50 of 81.2 mg/L). Moreover, biomarker analyses indicated enhanced superoxide dismutase activity in fish exposed to 20, 40 and 100 mg/L of gallic acid compared to control. A dose-dependent induction of glutathione peroxidase and glutathione S-transferase was reported following gallic acid exposure at the tested concentrations of 10, 20 and 40 mg/L, with the exception of 100 mg/L of substance where basal activity levels were reported. In the case of pelargonic acid, there was no change in antioxidant enzyme activity while an inhibition of glutathione S-transferase was observed from organisms exposed to 45, 58 and 76 mg/L of test solution. The results concerning sublethal effects on biological parameters of zebrafish highlighted thereby the need for further investigations following chronic exposure to both organic acids.

  15. Recently surveyed lakes in northern Manitoba and Saskatchewan, Canada: characteristics and critical loads of acidity

    Directory of Open Access Journals (Sweden)

    Isaac WONG

    2010-08-01

    Full Text Available Based on minimal information, lakes in the western Canadian provinces of Manitoba (MB and Saskatchewan (SK have long been considered unaffected by acid rain. However, emissions of acidifying pollutants from MB smelters and oil sand processing in Alberta (AB may pose a developing threat. Surveys of 347 lakes located on geologically sensitive terrain in northern MB and SK were conducted to assess their acidification sensitivity and status. The survey domain (~193,000 km2 contained 81,494 lakes ≥1 ha in area. Small lakes dominated the inventory in terms of numbers, and large lakes dominated in terms of area. Survey lakes were selected using a stratified-random sampling design in 10 sampling blocks within the overall survey domain. Few lakes had pH <6, and only three (all in SK were acidic, i.e., Gran Alkalinity (Alk <0 μeq L–1. A broad range in lake sensitivity was apparent, and very sensitive lakes (low specific conductance, base cations and Alk were present in all sampling blocks. Dissolved organic carbon (DOC was an important constituent of many lakes. Critical loads (CL of acidity calculated using the Steady-State Water Chemistry model (SSWC revealed extremely low 5th percentile values for every block (range 1.9 to 52.7 eq ha–1 y–1. Block CL exceedances calculated using estimated S and N deposition for 2002 ranged from 54.5 to 909 eq ha–1 y–1. The largest exceedances were for sampling blocks located near smelter sources or downwind of the oil sands. Lake chemistry revealed by our surveys was compared to others conducted both nearby and outside Canada.

  16. Primary and secondary genetic responses after folic acid-induced acute renal injury in the mouse.

    Science.gov (United States)

    Calvet, J P; Chadwick, L J

    1994-12-01

    Folic acid-induced acute renal injury results in dramatic changes in gene expression. Among the genes affected by folic acid treatment are the primary response genes, c-fos and c-myc, which are thought to function to initiate cell cycle events. In this report, changes in the expression of three other genes in response to folic acid injury have been investigated: ornithine decarboxylase, epidermal growth factor (EGF), and sulfated glycoprotein-2 (SGP-2). Renal injury was found to cause a rapid decrease in EGF mRNA, which remained absent for several days after the initial injury, gradually returning to normal levels over an approximately 3-wk regeneration and recovery period. Ornithine decarboxylase mRNA showed a similar decrease. In contrast, folic acid caused a rapid increase in SGP-2 mRNA, which peaked several days after treatment, decreasing to normal levels over the 3-wk period. The mRNAs for the primary response genes were superinduced in the injured kidneys in the presence of the protein synthesis inhibitor cycloheximide. In contrast, the changes in EGF and SGP-2 mRNA levels were blocked by cycloheximide, indicating that these responses required new protein synthesis during the first few hours after folic acid injury. The opposite but parallel responses in the expression of the EGF and SGP-2 genes suggest that their regulation is coupled to the initial injury-induced dedifferentiation and subsequent return to the fully differentiated state.

  17. Presence of viral nucleic acids in the middle ear: acute otitis media pathogen or bystander?

    Science.gov (United States)

    Chonmaitree, Tasnee; Ruohola, Aino; Hendley, J Owen

    2012-04-01

    Viruses play an important role in acute otitis media (AOM) pathogenesis, and live viruses may cause AOM in the absence of pathogenic bacteria. Detection of AOM pathogens generally relies on bacterial culture of middle ear fluid. When viral culture is used and live viruses are detected in the middle ear fluid of children with AOM, the viruses are generally accepted as AOM pathogens. Because viral culture is not sensitive and does not detect the comprehensive spectrum of respiratory viruses, polymerase chain reaction assays are commonly used to detect viral nucleic acids in the middle ear fluid. Although polymerase chain reaction assays have greatly increased the viral detection rate, new questions arise on the significance of viral nucleic acids detected in the middle ear because nucleic acids of multiple viruses are detected simultaneously, and nucleic acids of specific viruses are detected repeatedly and in a high proportion of asymptomatic children. This article first reviews the role of live viruses in AOM and presents the point-counterpoint arguments on whether viral nucleic acids in the middle ear represent an AOM pathogen or a bystander status. Although there is evidence to support both directions, helpful information for interpretation of the data and future research direction is outlined.

  18. Effects of acut and chronic doses of methoxy acetic acid on hamster sperm fertilising ability

    Institute of Scientific and Technical Information of China (English)

    L. D.C. Peiris; H.D.M. Moore

    2001-01-01

    Aim: To evaluate the effects of acute and chronic doses of methoxy acetic acid (MAA) on in vitro fertilisation by hamster sperm and to correlate the data with the testicular damage. Methods: Adult male hamsters were gavaged with 3 single doses (0, 80, 160 and 650 mg/kg) and 3 chronic doses (0, 8, 32 and 64 mg/kg daily for 5 weeks) of MAA in distilled water. After treatment hamsters were killed at weekly intervals and spermatozoa recovered from the distal cauda epididymides were used to assess the fertilising capacity in vitro. The testes were processed for histological examination. Results: Acute doses showed a significant reduction in sperm fertilising ability from week 3 and 4 after treatment and with the chronic doses, the effects were more extensive and persistent. The results were in correpondence with the testicular damages observed. Conclusion: It is evident that both acute and chronic doses of MAA can impair the sperm function by damaging one or more cell populations in the testis.

  19. Serum vitamin B12 and folic Acid levels in acute cerebral atherothrombotic infarction.

    Science.gov (United States)

    Kocer, Abdulkadir; Ince, Nurhan; Canbulat, Cuneyt E; Sargin, Mehmet

    2004-10-01

    Hyperhomocysteinemia is an independent risk factor for atherothrombotic cerebral stroke. Vitamin B12 and folic acid are important determinants of homocysteine metabolism. We aimed to evaluate the relationship, if present, between vitamin B12 and folic acid levels and acute cerebral stroke in this study. Blood aliquots drawn within 24 hours after the stroke from hospitalized patients (n=66) with the diagnosis of acute ischemic cerebrovascular episode and also blood samples from 38 healthy controls without any vascular risk factor were analyzed. With a competitive, chemoluminescence assay, serum levels of vitamin B12 and folic acid were measured in blood samples taken within 24 hours after the stroke. The differences and correlations were tested using frequency test, student-t test and multivariate analysis. Mean serum vitamin B12 levels were significantly lower in the patients than in the control subjects, 245.40 (S.D.: 72.9) and 343.2 (S.D.: 113.0) pg/ml respectively (p=0.0001). This difference was independent from other risk factors. Likewise, mean serum folic acid levels were lower in the patients than in the control subjects, 4.62 (S.D.: 1.94) and 5.97 (S.D.: 1.19) ng/ml, respectively (p=0.003). Mean serum levels of vitamin B12 and folate at the convalescence phase were 253.05 (S.D.: 68.78) pg/ml and 4.48 (S.D.: 2.08) ng/ml, respectively; the values obtained at the acute phase were not significantly different from the values obtained at the convalescence phase. We conclude that low vitamin B12 and folic acid concentrations are associated with an increased risk of stroke, and the relationship for vitamin B12 is independent from the other known modifiable stroke risk factors. For understanding the effects of B12 and folate in stroke patients, more detailed follow-up studies with long period are needed.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  2. Lowering the platinum loading of high temperature polymer electrolyte membrane fuel cells with acid doped polybenzimidazole membranes

    DEFF Research Database (Denmark)

    Fernandez, Santiago Martin; Li, Qingfeng; Jensen, Jens Oluf

    2015-01-01

    Membrane electrode assemblies (MEAs) with ultra-low Pt loading electrodes were prepared for high temperature polymer electrolyte membrane fuel cells (HT-PEMFCs) based on acid doped polybenzimidazole. With no electrode binders or ionomers, the triple phase boundary of the catalyst layer...

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

    Science.gov (United States)

    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.

  4. Preparation and characterization of protein loaded microspheres based on a hydroxylated aliphatic polyester, poly (lactic-co-hydroxymethyl glycolic acid)

    NARCIS (Netherlands)

    Ghassemi, A.H.; van Steenbergen, M.J.; Talsma, H.; van Nostrum, C.F.; Jiskoot, W.; Crommelin, D.J.A.; Hennink, W.E.

    2009-01-01

    The purpose of this study was to investigate the suitability of a novel hydroxylated aliphatic polyester, poly (lactic-co-hydroxymethyl glycolic acid) (PLHMGA), as controlled release system for pharmaceutical proteins. Dextran Blue (as a macromolecular model compound) and lysozyme-loaded PLHMGA and

  5. Critical loads for acidity and nitrogen for Dutch forests on a 1 km x 1 km grid

    NARCIS (Netherlands)

    Vries, de W.

    1996-01-01

    Critical loads were derived using a one-layer steady-state model that includes mineral weathering, nutrient uptake, nitrogen transformations, and an acceptable leaching rate of acidity or nitrogen. Values were calculated for combinations of 12 tree species and 23 soil types. Acceptable leaching rate

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

    Science.gov (United States)

    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...

  7. Nitric Acid Deposition following an Astrophysical Ionizing Radiation Event is below Critical Loads for Terrestrial and Freshwater Ecosystems

    CERN Document Server

    Melott, Ben Neuenswander Adrian

    2014-01-01

    Nitric acid rainout is one of the effects of an astrophysical ionizing radiation event. The predicted values of nitrate rainout from previous work for a typical gamma ray burst (GRB) within our galaxy serve as an extreme example and are shown to be below critical loads of eutrophication and acidification for ecoregions in Europe and the US.

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

    DEFF Research Database (Denmark)

    Garcia Diaz, Maria; Foged, Camilla; Nielsen, Hanne Mørck

    2015-01-01

    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...... 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....

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

    Science.gov (United States)

    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.

  10. Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection

    Directory of Open Access Journals (Sweden)

    Megan L. Lawlor

    2016-01-01

    Full Text Available Intrahepatic cholestasis of pregnancy (ICP is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing was performed. Patient delivered vaginally at 33-week gestation following preterm rupture of membranes. Neonates were admitted to NICU and had uncomplicated neonatal courses. In the setting of ICP with significant transaminitis and severe elevation of bile acids, consideration of acute viral hepatitis is important, especially considering the worsening opioid epidemic and concurrent increase in intravenous drug use in the United States. Further study is needed regarding the acute form of HCV infection and its effect on ICP and associated bile acids.

  11. Admission Serum Uric Acid Levels and In-Hospital Outcomes in Patients with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Abu Sadique Abdullah

    2015-05-01

    Full Text Available Background: Uric acid is an independent risk factor for cardiovascular disease. Hospital admission for ischemic heart disease (IHD is increasing rapidly in our country. Although studies were conducted abroad regarding association of serum uric acid with in-hospital outcomes in patients with acute coronary syndrome (ACS, no data is yet available to show the association in our country. Objective: The objective of this study was to assess the association of serum uric acid level on admission with in-hospital outcomes of the patients with ACS. Materials and Methods: This cross sectional comparative study was done in the Department of Cardiology, Dhaka Medical College Hospital (DMCH from January to December 2012. After proper ethical consideration total 93 ACS patients were enrolled in the study by nonrandom sampling. Serum uric acid of all subjects was measured within 24 hours of admission. Then in-hospital outcomes were observed in all subjects. Results: The frequency of hyperuricemia among ACS patients was 24.7% (22.54% in male and 31.82% in female. Hyperuricemic patients significantly developed heart failure (30.4% vs 11.4%, p=0.032 and conduction defect (13.0% vs 1.4%, p=0.017 than normouricemic subjects. The mean ejection fraction was significantly lower in hyperuricemic patients than patients with normal uric acid level (50.87 ± 10.27% vs 55.94 ± 6.66%. The mean ± SD duration of hospital stay of hyperuricemic group was significantly longer in patients with ACS (8.26 ± 1.18 vs 7.51±1.18 days, p=0.010. Conclusion: The measurement of serum uric acid level, an easily available and inexpensive biochemical tool, might turn out as a valuable risk marker for prediction of in-hospital outcomes in patients with ACS.

  12. Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability

    Directory of Open Access Journals (Sweden)

    Ilaiyaraja Nallamuthu

    2015-06-01

    Full Text Available In this study, chlorogenic acid (CGA, a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of Cmax, longer Tmax, longer MRT, larger AUC0–t and AUC0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

  13. Adsorptive desulfurization of model oil using untreated, acid activated and magnetite nanoparticle loaded bentonite as adsorbent

    Directory of Open Access Journals (Sweden)

    Muhammad Ishaq

    2017-02-01

    Full Text Available The present research work focuses on a novel ultraclean desulfurization process of model oil by the adsorption method using untreated, acid activated and magnetite nanoparticle loaded bentonite as adsorbent. The parameters investigated are effect of contact time, adsorbent dose, initial dibenzothiophene (DBT concentration and temperature. Experimental tests were conducted in batch process. Pseudo first and second order kinetic equations were used to examine the experimental data. It was found that pseudo second order kinetic equation described the data of the DBT adsorption onto all types of adsorbents very well. The isotherm data were analyzed using Langmuir and Freundlich isotherm models. The Langmuir isotherm model fits the data very well for the adsorption of DBT onto all three forms of adsorbents. The adsorption of DBT was also investigated at different adsorbent doses and was found that the percentage adsorption of DBT was increased with increasing the adsorbent dose, while the adsorption in mg/g was decreased with increasing the adsorbent dose. The prepared adsorbents were analyzed by scanning electron microscopy (SEM, energy dispersive X-ray spectrometry (EDX and X-ray diffraction (XRD.

  14. Cisplatin Loaded Hyaluronic Acid Modified TiO2 Nanoparticles for Neoadjuvant Chemotherapy of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Enling Liu

    2015-01-01

    Full Text Available Novel tumor-targeting titanium dioxide (TiO2 nanoparticles modified with hyaluronic acid (HA were developed to explore the feasibility of exploiting the pH-responsive drug release property of TiO2 and the tumor-targeting ability of HA to construct a tumor-targeting cisplatin (CDDP delivery system (HA-TiO2 for potential neoadjuvant chemotherapy of ovarian cancer. The experimental results indicated that CDDP release from the HA-TiO2 nanoparticles was significantly accelerated by decreasing pH from 7.4 to 5.0, which is of particular benefit to cancer therapy. CDDP-loaded HA-TiO2 nanoparticles increased the accumulation of CDDP in A2780 ovarian cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo real-time imaging assay revealed that HA-TiO2 nanoparticles possessed preferable tumor-targeting ability which might potentially minimize the toxic side effects of CDDP in clinical application.

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

    Science.gov (United States)

    Liu, Jianming; Lv, Xin

    2014-09-29

    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 (ppharmacodynamics 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.

  16. The Pharmacokinetics and Pharmacodynamics of Lidocaine- Loaded Biodegradable Poly(lactic-co-glycolic acid Microspheres

    Directory of Open Access Journals (Sweden)

    Jianming Liu

    2014-09-01

    Full Text Available 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.

  17. Preparation and In Vitro Evaluation of Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carriers

    Directory of Open Access Journals (Sweden)

    Yang Chu

    2014-02-01

    Full Text Available Curcumin, a phenolic antioxidant compound derived from the rhizome of the turmeric plant Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion and apoptosis, revealing its anticancer potential. In this study, a Glycyrrhetinic Acid-Modified Curcumin-Loaded Nanostructured Lipid Carrier (Cur-GA-PEG-NLC was prepared by the film ultrasound method to improve the tumor-targeting ability. The drug content was detected by an UV spectrophotometry method. The encapsulation efficiency of curcumin in the nanostructured lipid carriers (NLCs was determined using a mini-column centrifugation method. The encapsulation efficiency for various Cur-GA-PEG-NLC was within the range of 90.06%–95.31% and particle size was between 123.1 nm and 132.7 nm. An in vitro MTT assay showed that Cur-GA10%-PEG-NLC had significantly high cellular uptake and cytotoxicity against HepG2 cells compared with other groups.

  18. Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model.

    Science.gov (United States)

    Mohanty, Chandana; Das, Manasi; Sahoo, Sanjeeb K

    2012-10-01

    Wound healing is an intricate multistage process that includes inflammation, cell proliferation, matrix deposition and remodeling phases. It is often associated with oxidative stress and consequent prolonged inflammation, resulting in impaired wound healing. Curcumin has been reported to improve wound healing in different animal models. In order to increase the efficacy of curcumin in the healing arena a curcumin loaded oleic acid based polymeric (COP) bandage was formulated. The in vivo wound healing potency was compared with void bandage and control (cotton gauze treatment) in a rat model. Biochemical parameters and histological analysis revealed increased wound reduction and enhanced cell proliferation in COP bandage treated groups due to its efficient free radical scavenging properties. Comparative acceleration in wound healing was due to early implementation of fibroblasts and its differentiation (increased level of α-smooth muscle actin). Western blotting and semiquantitative PCR analysis clearly indicate that COP bandage can efficiently quench free radicals leading to reduced antioxidative enzyme activity. Further evidence at mRNA and protein level indicates that our system is potent enough to reduce the inflammatory response mediated by the NFκB pathway during wound healing. With this background, we anticipate that such a versatile approach may seed new arena for topical wound healing in the near future.

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

    Science.gov (United States)

    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.

  20. Citric acid as the last therapeutic approach in an acute life-threatening metabolic decompensation of propionic acidaemia.

    Science.gov (United States)

    Siekmeyer, Manuela; Petzold-Quinque, Stefanie; Terpe, Friederike; Beblo, Skadi; Gebhardt, Rolf; Schlensog-Schuster, Franziska; Kiess, Wieland; Siekmeyer, Werner

    2013-01-01

    The tricarboxylic acid (TCA) cycle represents the key enzymatic steps in cellular energy metabolism. Once the TCA cycle is impaired in case of inherited metabolic disorders, life-threatening episodes of metabolic decompensation and severe organ failure can arise. We present the case of a 6 ½-year-old girl with propionic acidaemia during an episode of acute life-threatening metabolic decompensation and severe lactic acidosis. Citric acid given as an oral formulation showed the potential to sustain the TCA cycle flux. This therapeutic approach may become a treatment option in a situation of acute metabolic crisis, possibly preventing severe disturbance of energy metabolism.

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

    Science.gov (United States)

    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.

  2. Impact of acute vivax malaria on the immune system and viral load of HIV-positive subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 肖斌权; 施文钧; 徐慧芳; 高凯; 饶纪礼; 张周斌

    2003-01-01

    Objective To explore the mechanisms of malariotherapy for human immunodeficiency virus (HIV)-infected patients and to identify which stage(s) of HIV infection is suitable for the treatment of malariotherapy.Methods Therapeutic acute vivax malaria was induced and terminated after 10 fever episodes in 12 HIV-1-infected subjects: Group 1 (G1) had 5 patients with CD4 T-cell counts500/μl at baseline, Group 2 (G2) had 5 patients with CD4 at 499-200/μl and Group 3 had 2 patients with CD4<200/μl (not included in statistical analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma levels of cytokines and soluble activation markers. Flow cytometry was used to measure levels of lymphocyte subsets and phenotypes and CD4 cell apoptosis. Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load). Samples were taken and tested twice before malaria (baselines), three times during malaria and seven times after termination of malaria (at day 10 and 1, 3, 6, 12, 18 and 24 months). Results Levels of plasma tumor necrosis factor-α (TNF-α), soluble TNF-α receptor-2 (sTNF-RII), neopterin (NPT) and soluble IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced to baselines post malaria in all groups. Stronger responses of the aforementioned factors were seen in G2 than in G1 during malaria (P=0.081, 0.001, 0.013, 0.020). CD4 count and percentage; CD4/CD8 ratio and CD25+ and CD4+CD25+ percentages increased but HLA DR+ percentage decreased either during or post malaria in G2. Most G2 patients experienced sustained increase but most G1 patients underwent natural history decline of CD4 counts and percentages during 2-year follow-up. Percentage of apoptotic CD4 cells decreased post malaria in all groups. G3 patients had weaker immune responses, however, one advanced AIDS patient in this group experienced clinical improvement after malariotherapy. Most of the 12 patients experienced increase of HIV viral load during

  3. Complete remission of t(11;17) positive acute promyelocytic leukemia induced by all-trans retinoic acid and granulocyte colony-stimulating factor

    NARCIS (Netherlands)

    J.H. Jansen (Joop); M.C. de Breems-de Ridder (Marleen); W.M. Geertsma; C.A.J. Erpelinck (Claudia); K. van Lom (Kirsten); R. Slater (Rosalyn); B.A. van der Reijden (Bert); G.E. de Greef (Georgine); P. Sonneveld (Pieter); B. Löwenberg (Bob); E.M.E. Smit (Elisabeth)

    1999-01-01

    textabstractThe combined use of retinoic acid and chemotherapy has led to an important improvement of cure rates in acute promyelocytic leukemia. Retinoic acid forces terminal maturation of the malignant cells and this application represents the first generally accepted

  4. Mechanisms of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells

    Indian Academy of Sciences (India)

    Ji-Wang Zhang; Jian Gu; Zhen-Yi Wang; Sai-Juan Chen; Zhu Chen

    2000-09-01

    Retinoic acids (RA) play a key role in myeloid differentiation through their agonistic nuclear receptors (RAR/RXR) to modulate the expression of target genes. In acute promyelocytic leukemia (APL) cells with rearrangement of retinoic acid receptor (RAR) (including: PML-RAR, PLZF-RAR, NPM-RAR, NuMA-RAR or STAT5b-RAR) as a result of chromosomal translocations, the RA signal pathway is disrupted and myeloid differentiation is arrested at the promyelocytic stage. Pharmacologic dosage of all-trans retinoic acid (ATRA) directly modulates PML-RAR and its interaction with the nuclear receptor co-repressor complex, which restores the wild-type RAR/RXR regulatory pathway and induces the transcriptional expression of downstream genes. Analysing gene expression profiles in APL cells before and after ATRA treatment represents a useful approach to identify genes whose functions are involved in this new cancer treatment. A chronologically well coordinated modulation of ATRA-regulated genes has thus been revealed which seems to constitute a balanced functional network underlying decreased cellular proliferation, initiation and progression of maturation, and maintenance of cell survival before terminal differentiation.

  5. Bioavailability Enhancement of Paclitaxel via a Novel Oral Drug Delivery System: Paclitaxel-Loaded Glycyrrhizic Acid Micelles

    Directory of Open Access Journals (Sweden)

    Fu-Heng Yang

    2015-03-01

    Full Text Available Paclitaxel (PTX, taxol, a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05. The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

  6. Antitumor Activity of Doxorubicin-Loaded Carbon Nanotubes Incorporated Poly(Lactic-Co-Glycolic Acid) Electrospun Composite Nanofibers

    Science.gov (United States)

    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.

  7. Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

    Science.gov (United States)

    Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

    2016-03-01

    Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance.

  8. Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

    Directory of Open Access Journals (Sweden)

    Chen Chien-Ju

    2009-01-01

    Full Text Available Abstract Background Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3 in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of ASIC3 knockout (ASIC3-/- or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation. Results Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in ASIC3-/- mice induced by complete Freund's adjuvant (CFA or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the ASIC3+/+ controls, ASIC3-/- mice showed normal thermal and mechanical hyperalgesia with acute (4-h intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an ASIC3-dependent Nav1.9 up-regulation and increase of tetrodotoxin (TTX-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in ASIC3-/- or ASIC3+/+ mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in ASIC3-/- mice, as previously described. However, ASIC3-/- mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with ASIC3+/+ mice. Conclusion We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.

  9. Pharm GKB: Leukemia, Myeloid, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym AML - Acute... myeloblastic leukaemia; Acute Myeloblastic Leukemia; Acute Myeloblastic Leukemias; Acute... Myelocytic Leukemia; Acute Myelocytic Leukemias; Acute Myelogenous Leukemia; Acute Myelogenous Leukemias; Acute... granulocytic leukaemia; Acute myeloblastic leukemia; Acute myeloid leukaemia; Acute myeloid leukaemia - category; Acute... myeloid leukaemia, disease; Acute myeloid leukemia; Acute myelo

  10. Corosolic acid ameliorates acute inflammation through inhibition of IRAK-1 phosphorylation in macrophages

    Science.gov (United States)

    Kim, Seung-Jae; Cha, Ji-Young; Kang, Hye Suk; Lee, Jae-Ho; Lee, Ji Yoon; Park, Jae-Hyung; Bae, Jae-Hoon; Song, Dae-Kyu; Im, Seung-Soon

    2016-01-01

    Corosolic acid (CA), a triterpenoid compound isolated from Lagerstroemia speciosa L. (Banaba) leaves, exerts anti-inflammatory effects by regulating phosphorylation of interleukin receptor- associated kinase (IRAK)-2 via the NF-κB cascade. However, the protective effect of CA against endotoxic shock has not been reported. LPS (200 ng/mL, 30 min) induced phosphorylation of IRAK-1 and treatment with CA (10 μM) significantly attenuated this effect. In addition, CA also reduced protein levels of NLRP3 and ASC which are the main components of the inflammasome in BMDMs. LPS-induced inflammasome assembly through activation of IRAK-1 was down-regulated by CA challenge. Treatment with Bay11-7082, an inhibitor of IκB-α, had no effect on CA-mediated inhibition of IRAK-1 activation, indicating that CA-mediated attenuation of IRAK-1 phosphorylation was independent of NF-κB signaling. These results demonstrate that CA ameliorates acute inflammation in mouse BMDMs and CA may be useful as a pharmacological agent to prevent acute inflammation. [BMB Reports 2016; 49(5): 276-281] PMID:26615974

  11. Therapeutic effect of caffeic acid phenethyl ester on cerulein-induced acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Mehmet Buyukberber; M Cemil Savas; Cahit Bagci; Mehmet Koruk; Murat T Gulsen; Ediz Tutar; Tugba Bilgic; Nurdan (O) Ceylan

    2009-01-01

    AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of ceruleaninduced acute pancreatitis (AP). METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 μg/kg) four times at 1-h intervals. CAPE (30 mg/kg) was given by subcutaneous injection at the beginning (CAPE 1 group) and 12 h after the last cerulein injection (CAPE 2 group). Serum amylase, lipase, white blood cell count, and tumor necrosis factor (TNF)-α levels were measured, and pancreatic histopathology was assessed. RESULTS: In the AP group, amylase and lipase levels were found to be elevated and the histopathological evaluation showed massive edema and inflammation of the pancreas, with less fatty necrosis when compared with sham and control groups. Amylase and lipase levels and edema formation decreased significantly in the CAPE therapy groups (P < 0001); especially in the CAPE 2 group, edema was improved nearly completely (P = 0001). Inflammation and fatty necrosis were partially recovered by CAPE treatment. The pathological results and amylase level in the placebo groups were similar to those in the AP group. White blood cell count and TNF-α concentration was nearly the same in the CAPE and placebo groups. CONCLUSION: CAPE may be useful agent in treatment of AP but more experimental and clinical studies are needed to support our observation of beneficial effects of CAPE before clinical usage of this agent.

  12. NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia.

    Science.gov (United States)

    Nichol, Jessica N; Galbraith, Matthew D; Kleinman, Claudia L; Espinosa, Joaquín M; Miller, Wilson H

    2016-03-29

    Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Surprisingly, RA stimulation in these cells results in enhanced chromatin association of the nucleosome remodeler BRG1. Inhibition of NPM or TOP2B abrogated BRG1 recruitment. Furthermore, NPM inhibition and targeting BRG1 restored differentiation when combined with RA. Here, we demonstrate a role for NPM and BRG1 in obstructing RA differentiation and implicate chromatin remodeling in mediating therapeutic resistance in malignancies. NPM mutations are the most common genetic change in patients with acute leukemia (AML); therefore, our model may be applicable to other more common leukemias driven by NPM.

  13. The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia.

    Science.gov (United States)

    Arteaga, Maria Francisca; Mikesch, Jan-Henrik; Qiu, Jihui; Christensen, Jesper; Helin, Kristian; Kogan, Scott C; Dong, Shuo; So, Chi Wai Eric

    2013-03-18

    While all-trans retinoic acid (ATRA) treatment in acute promyelocytic leukemia (APL) has been the paradigm of targeted therapy for oncogenic transcription factors, the underlying mechanisms remain largely unknown, and a significant number of patients still relapse and become ATRA resistant. We identified the histone demethylase PHF8 as a coactivator that is specifically recruited by RARα fusions to activate expression of their downstream targets upon ATRA treatment. Forced expression of PHF8 resensitizes ATRA-resistant APL cells, whereas its downregulation confers resistance. ATRA sensitivity depends on the enzymatic activity and phosphorylation status of PHF8, which can be pharmacologically manipulated to resurrect ATRA sensitivity to resistant cells. These findings provide important molecular insights into ATRA response and a promising avenue for overcoming ATRA resistance.

  14. Polyunsaturated Fatty Acid Status and Physical Activity Level in Children Admitted with Severe Acute Malnutrition

    DEFF Research Database (Denmark)

    Babirekere-Iriso, Esther

    of blood cells. Despite advances in the management of SAM, current therapeutic feeds do not correct whole-blood LCPUFA composition, particularly n-3 LCPUFA, in children with SAM. The level of physical activity at discharge among children with SAM is very low perhaps indicating inadequate recovery from SAM.......Severe acute malnutrition (SAM) is a worldwide problem although it commonly occurs in children living in low-income countries. SAM may be associated with reduced relative contribution of whole-blood polyunsaturated fatty acids (PUFA) yet PUFA play very important roles in the body such as immune...... modulation, growth and development as well as maintenance of skin water barrier among others. The reduced relative contribution of PUFA may be linked to some of the clinical presentations in children with SAM. Treatment of SAM may be improved by better understanding of most of the nutritional deficiencies...

  15. Clavulanic acid does not affect convulsions in acute seizure tests in mice.

    Science.gov (United States)

    Gasior, Maciej; Socała, Katarzyna; Nieoczym, Dorota; Wlaź, Piotr

    2012-01-01

    Clavulanic acid (CLAV) inhibits bacterial β-lactamases and is commonly used to aid antibiotic therapy. Prompted by the initial evidence suggestive of the potential anticonvulsant and neuroprotective properties of CLAV, the present study was undertaken to systematically evaluate its acute effects on seizure thresholds in seizure tests typically used in primary screening of potential antiepileptic drugs (AEDs). In the present study, 6-Hz seizure threshold, maximal electroshock seizure threshold (MEST) test, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests were used to determine anticonvulsant effects of intraperitoneally (i.p.) administered CLAV in mice. Acute effects on motor coordination and muscle strength were assessed in the chimney and grip-strength tests, respectively. Doses of CLAV studied in the present study were either comparable or extended the doses reported in the literature to be effective against kainic acid-induced convulsions in mice or behaviorally active in rodents and monkeys. CLAV had no effect on seizure thresholds in the 6-Hz (64 ng/kg to 1 mg/kg) and MEST (64 ng/kg to 5 mg/kg) seizure tests. Similarly, CLAV had no effect on seizure thresholds for i.v. PTZ-induced myoclonic twitch, clonic convulsions, and tonic convulsions (64 ng/kg to 5 mg/kg). Finally, CLAV (64 ng/kg to 5 mg/kg) had no effect on the motor performance and muscle strength in the chimney and grip-strength tests, respectively. In summary, CLAV failed to affect seizure thresholds in three seizure tests in mice. Although the results of the present study do not support further development of CLAV as an AED, its beneficial effects in chronic epilepsy models warrant further evaluation owing to its, for example, potential neuroprotective properties.

  16. Acute Generalized Exanthematous Pustulosis Induced by Amoxicillin/Clavulanic Acid: Report of a Case Presenting With Generalized Lymphadenopathy.

    Science.gov (United States)

    Syrigou, Ekaterini; Grapsa, Dimitra; Charpidou, Andriani; Syrigos, Konstantinos

    2015-01-01

    Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin reaction, most commonly triggered by antibiotics. Although its diagnosis is based primarily on the presence of specific clinical and histopathologic features, additional in vivo (patch testing) or in vitro testing may be required, especially in atypical cases, to more accurately determine the causative agent. The authors report a histologically confirmed case of acute generalized exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as documented by subsequent patch testing, and presented with generalized painful lymphadenopathy, mimicking an acute infectious process. This is a very rare and diagnostically challenging clinical presentation of acute generalized exanthematous pustulosis, which has been reported, to the best of our knowledge, only once previously.

  17. Alleviative effects of α-lipoic acid supplementation on acute heat stress-induced thermal panting and the level of plasma nonesterified fatty acids in hypothyroid broiler chickens.

    Science.gov (United States)

    Hamano, Y

    2012-01-01

    1. The present study was conducted to examine the effects of α-lipoic acid on hypothyroidism-induced negative growth performance and whether α-lipoic acid alleviates acute heat stress in relation to hypothyroid status. 2. Female broiler chickens (14 d-old) were fed diets supplemented with α-lipoic acid (100 mg/kg) and an antithyroid substance, propylthiouracil (200 mg/kg), for 20 d under thermoneutral conditions (25°C). At 42 d of age, chickens were exposed to a high ambient temperature (36°C, 60% RH) for 4 h. 3. Under the thermoneutral condition, propylthiouracil administration decreased feed efficiency and concomitantly increased adipose tissue and thyroid gland weights. Plasma nonesterified fatty acids and triacylglycerol were also increased by propylthiouracil administration. However, α-lipoic acid supplementation did not affect the hypothyroidism-induced effects. 4. In hypothyroid chickens, the rise in respiratory rate induced by heat exposure was greatly inhibited by α-lipoic acid administration at 1 h, but this effect had disappeared at 4 h. In addition, a similar inhibitory effect on the concentrations of plasma nonesterified fatty acids was subsequently observed at 4 h. 5. Therefore, the present study suggested that α-lipoic acid alleviates acute heat stress if chickens are in a hypothyroid status.

  18. Effect of loading-dose ticagrelor on coronary blood flow, left ventricular remodeling and myocardial enzyme spectrum in patients with acute myocardial infarction after interventional therapy

    Institute of Scientific and Technical Information of China (English)

    Xiao-Rui Xie; Pu Yang

    2016-01-01

    Objective:To study the effect of loading-dose ticagrelor on coronary blood flow, left ventricular remodeling and myocardial enzyme spectrum in patients with acute myocardial infarction after interventional therapy.Methods: A total of 86 patients with acute myocardial infarction who received emergency PCI in our hospital between May 2013 and May 2016 were selected and randomly divided into two groups, ticagrelor group received perioperative ticagrelor therapy and clopidogrel group received perioperative clopidogrel therapy. After PCI, coronary blood flow reperfusion was evaluated, serum myocardial remodeling indexes and myocardial enzymes were determined, and cardiac color Doppler ultrasonography was conducted to determine the cardiac function indexes.Results:TIMI grading and TMPG grading of ticagrelor group after PCI were significantly higher than those of clopidogrel group; serum MMP9, BNP, CITP, PICP, PIIINP, CK, CK-MB, cTnI and cTnT content of ticagrelor group 24h after operation were significantly lower than those of clopidogrel group; LVEDD, LVSED and LVMI of ticagrelor group 2 weeks after operation were significantly lower than those of clopidogrel group while LVEF was significantly higher than that of clopidogrel group.Conclusion:Peri-PCI loading-dose ticagrelor can improve coronary blood perfusion and reduce ventricular remodeling and myocardial injury in patients with acute myocardial infarction.

  19. Facile Synthesis of Gold Nanoparticle-loaded Carbon Nanofiber Composites and Their Electrocatalytic Activity Towards Dopamine, Ascorbic Acid and Uric Acid

    Institute of Scientific and Technical Information of China (English)

    TENG Hong; LIU Yang; YOU Tian-yan

    2011-01-01

    A facile approach for the synthesis of gold nanoparticle-loaded carbon nanofibcr(Au/CNF) composites was developed. When applied to electrochemistry, these composites showed attractive performances such as high conductivity and facile electron transfer kinetics. Under physiological conditions, the Au/CNF composite modified electrode exhibits highly electrocatalytic activity for the oxidation of dopamine, ascorbic acid and uric acid. Owing to the good selectivity for the simultaneous detection of these three species, the novel composites are promising for the development of effective electrochemical biosensors.

  20. Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles.

    Science.gov (United States)

    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.

  1. Preparation and drug-loading properties of Fe3O4/Poly(styrene-co-acrylic acid) magnetic polymer nanocomposites

    Science.gov (United States)

    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.

  2. Evaluation of estimation methods and base data uncertainties for critical loads of acid deposition in Japan

    NARCIS (Netherlands)

    Shindo, J.; Bregt, A.K.; Hakamata, T.

    1995-01-01

    A simplified steady-state mass balance model for estimating critical loads was applied to a test area in Japan to evaluate its applicability. Three criteria for acidification limits were used. Mean values and spatial distribution patterns of critical load values calculated by these criteria differed

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

    Science.gov (United States)

    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. Genital ulcers during treatment with ALL-trans retinoic acid for acute promyelocytic leukemia.

    Science.gov (United States)

    Fukuno, Kenji; Tsurumi, Hisashi; Goto, Hideko; Oyama, Masami; Tanabashi, Shinobu; Moriwaki, Hisataka

    2003-11-01

    Scrotal ulcer is a unique adverse effect of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The pathogenesis of scrotal ulceration remains unknown. We describe genital ulcers that developed in four patients with APL who were undergoing ATRA therapy (45 mg/m2 per day p.o.). Two of the patients were female, in whom this condition is quite rare. Genital ulcers with concomitant fever appeared between 17 and 32 days of therapy in all four patients. Genital ulcers healed in three of the patients while another patient developed Fournier's gangrene and underwent left testectomy. Ulcer healing was brought by either local or intravenous corticosteroids. Intravenous dexamethasone actually enabled continued ATRA administration in one patient, while ATRA was discontinued in other two patients. If corticosteroids cannot control progression of genital ulcers nor concomitant fever, ATRA administration should be discontinued so as not to induce Fournier's gangrene nor retionic acid syndrome. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

  5. Is biliary bile acid a good predictor for acute cellular rejection in living donor liver transplantation?

    Institute of Scientific and Technical Information of China (English)

    Mohammed Saied Hedaya; Walid M. El Moghazy; YamamotoYasutomo; Tomioka Kiyoshi; Toshimi Kaido; Hiroto Egawa; Shinji Uemoto; Yasutsugu Takada

    2009-01-01

    BACKGROUND: In liver transplantation, acute cellular rejection (ACR) is still a major complication that can lead to mortality. Bile secretion has been considered as a marker of early graft function. METHODS: The study included 41 adults who received living donor liver transplantation (LDLT) at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR. Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation. Total bile acid (BA) and taurine-conjugated bile acid (TCBA) in bile were measured by magnetic resonance spectroscopy. The recipient/donor (R/D) BA ratio and R/D TCBA ratio were calculated. RESULTS: The ACR group (n=12) showed a greater decrease in BA post-transplantation than the non-ACR group, but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9). The R/D TCBA ratio ≥0.5 on days 7 and 9, and ≥0.38 on day 11 post-transplantation were associated with better ACR-free survival. CONCLUSION: The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post-transplantation day 7.

  6. Vitamin C fails to protect amino acids and lipids from oxidation during acute inflammation.

    Science.gov (United States)

    Gaut, Joseph P; Belaaouaj, Abderrazzaq; Byun, Jaeman; Roberts, L Jackson; Maeda, Nobuyo; Frei, Balz; Heinecke, Jay W

    2006-05-01

    The observation that antioxidant vitamins fail to confer protective benefits in large, well-designed randomized clinical trials has led many to question the role of oxidative stress in the pathogenesis of disease. However, there is little evidence that proposed antioxidants actually scavenge reactive intermediates in vivo. Ascorbate reacts rapidly with oxidants produced by activated neutrophils in vitro, and neutrophils markedly increase their oxidant production when mice are infected intraperitoneally with the gram-negative bacterium Klebsiella pneumoniae. To explore the antioxidant properties of ascorbate in vivo, we therefore used K. pneumoniae infection as a model of oxidative stress. When mice deficient in L-gulono-gamma-lactone oxidase (Gulo(-/-)), the rate-limiting enzyme in ascorbate synthesis, were depleted of ascorbate and infected with K. pneumoniae, they were three times as likely as ascorbate-replete Gulo(-/-)mice to die from infection. Mass spectrometric analysis of peritoneal lavage fluid revealed a marked increase in the levels of oxidized amino acids and of F2-isoprostanes (sensitive and specific markers of lipid oxidation) in infected animals. Surprisingly, there were no significant differences in the levels of the oxidation products in the ascorbate-deficient and -replete Gulo(-/-)mice. Our observations suggest that ascorbate plays a previously unappreciated role in host defense mechanisms against invading pathogens but that the vitamin does not protect amino acids and lipids from oxidative damage during acute inflammation. To examine the oxidation hypothesis of disease, optimal antioxidant regimens that block oxidative reactions in animals and humans need to be identified.

  7. 3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1 response to acute fatty acid exposure.

    Science.gov (United States)

    Dordevic, Aimee L; Konstantopoulos, Nicky; Cameron-Smith, David

    2014-01-01

    Preadipocytes contribute to the inflammatory responses within adipose tissue. Whilst fatty acids are known to elicit an inflammatory response within adipose tissue, the relative contribution of preadipocytes and mature adipocytes to this is yet to be determined. We aimed to examine the actions of common dietary fatty acids on the acute inflammatory and adipokine response in 3T3-L1 preadipocytes and differentiated mature adipocytes. Gene expression levels of key adipokines in 3T3-L1 preadipocytes and adipocytes were determined following incubation with palmitic acid, myristic acid or oleic acid and positive inflammatory control, lipopolysaccharide for 2 and 4 h. Inflammatory kinase signalling was assessed by analysis of nuclear factor-κB, p38-mitogen-activated protein kinase and c-jun amino-terminal kinase phosphorylation. Under basal conditions, intracellular monocyte chemoattractant protein-1 and interleukin-6 gene expression levels were increased in preadipocytes, whereas mature adipocytes expressed increased gene expression levels of leptin and adiponectin. Fatty acid exposure at 2 and 4 h increased both monocyte chemoattractant protein-1 and interleukin-6 gene expression levels in preadipocytes to greater levels than in mature adipocytes. There was an accompanying increase of inhibitor of κB-α degradation and nuclear factor-κB (p65) (Ser536) phosphorylation with fatty acid exposure in the preadipocytes only. The current study points to preadipocytes rather than the adipocytes as the contributors to both immune cell recruitment and inflammatory adipokine secretion with acute increases in fatty acids.

  8. Comparison of Acute Recoil between Bioabsorbable Poly-L-lactic Acid XINSORB Stent and Metallic Stent in Porcine Model

    Directory of Open Access Journals (Sweden)

    Yizhe Wu

    2012-01-01

    Full Text Available Objective. To investigate acute recoil of bioabsorbable poly-L-lactic acid (PLLA stent. Background. As newly developed coronary stent, bioabsorbable PLLA stent still encountered concern of acute stent recoil. Methods. Sixteen minipigs were enrolled in our study. Eight PLLA XINSORB stents (Weite Biotechnology Co., Ltd., China and eight metallic stents (EXCEL, Jiwei Co., Ltd. China were implanted into coronary arteries. Upon quantitative coronary angiography analysis, acute absolute recoil was defined as the difference between mean diameter of inflated balloon (X and mean lumen diameter of stent immediately after deployment (Y, while acute percent recoil was defined as (X−Y/X and expressed as a percentage. Intravascular ultrasound (IVUS was performed immediately after implantation and 24 hours later to compare cross-sectional area (CSA between two groups and detect stent malapposition or collapse. Results. Acute absolute recoil in XINSORB and EXCEL was 0.02±0.13 mm and −0.08±0.08 mm respectively (P=0.19. Acute percent recoil in XINSORB and EXCEL was 0.66±4.32% and −1.40±3.83%, respectively (P=0.45. CSA of XINSORB was similar to that of EXCEL immediately after implantation, so was CSA of XINSORB at 24-hours followup. Within XINSORB group, no difference existed between CSA after implantation and CSA at 24-hours followup. No sign of acute stent malapposition was detected by IVUS. Conclusions. The acute stent recoil of XINSORB is similar to that of EXCEL. No acute stent malapposition or collapse appeared in both kinds of stent. This preclinical study was designed to provide preliminary data for future studies of long-term efficacy and safety of XINSORB stent.

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

    Science.gov (United States)

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

    2015-11-05

    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 hydrogels as matrix for controlled drug release.

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

    Energy Technology Data Exchange (ETDEWEB)

    Su, Zhongchun; Ma, Huan; Wu, Zhengzheng [Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Key Lab for Genetic Medicine of Guangdong Province, Jinan University, Guangzhou 510632 (China); Zeng, Huilan [Department of Hematology, The First Affiliated Hospital, Jinan University, Guangzhou 510632 (China); Li, Zhizhong [Department of Bone, The First Affiliated Hospital, Jinan University, Guangzhou 510632 (China); Wang, Yuechun; Liu, Gexiu [Department of Physiology, School of Medicine, Jinan University, Guangzhou 510632 (China); Xu, Bin; Lin, Yongliang; Zhang, Peng [Grandhope Biotech Co., Ltd., Building D, #408, Guangzhou International Business Incubator, Guangzhou Science Park, Guangzhou 510663, Guangdong (China); Wei, Xing, E-mail: wei70@hotmail.com [Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Key Lab for Genetic Medicine of Guangdong Province, Jinan University, Guangzhou 510632 (China)

    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. - Highlights: • HA can increase the adsorption of EGF to decellularized scaffolds. • HA can sustain the release of EGF from

  11. Time course of changes in the expression of insulin sensitivity-related genes after an acute load of virgin olive oil.

    Science.gov (United States)

    Konstantinidou, Valentini; Khymenets, Olha; Covas, Maria-Isabel; de la Torre, Rafael; Muñoz-Aguayo, Daniel; Anglada, Roger; Farré, Magi; Fito, Montserrat

    2009-10-01

    Our aim was to examine whether an acute fat load could induce changes in the expression of insulin sensitivity-related genes in human peripheral blood mononuclear cells. Selection of candidate genes was based on previous studies with sustained virgin olive oil (VOO) consumption and biological plausibility in relation to insulin sensitivity. Eleven healthy volunteers ingested raw VOO (50 mL). Blood samples were collected at 0, 1 and 6 h. Plasma glucose, insulin and hydroxytyrosol increased at 1 h and decreased at 6 h. Lipid oxidative damage increased at 6 h (p < 0.05). Gene expression changes were characterized based on quantification of the samples relative to a reference sample [i.e., relative quantification (RQ) method]. A 1 h downregulation was observed in O-linked-N-acetylglucosamine transferase (OGT, RQ: 0.62 +/- 0.32) and arachidonate-5-lipoxygenase-activating protein (ALOX5AP, RQ: 0.64 +/- 0.31) genes (p < 0.005). OGT was upregulated at 6 h (RQ: 1.88 +/- 0.28, p < 0.05). CD36 (thrombospondin receptor) was upregulated at 1 h (RQ: 1.6 +/- 0.8, p < 0.05) returning to the basal values at 6 h. Lipoic acid synthetase (LIAS), peroxisome proliferator-activated receptor binding protein (PPARBP), a disintegrin and metallopeptidase domain 17 (ADAM17), and adrenergic beta-2-receptor (ADRB2) genes were upregulated at 6 h (range for the mean RQ: 1.33-1.56) following an increasing linear trend (p < 0.05) from baseline to 6 h. ALOX5AP and OGT genes inversely correlated with insulin and glucose levels at 1 h. ADAM17 and ADRB2 inversely correlated with oxLDL at 6 h (p < 0.05). Taken together, these observations may inform the future clinical nutrigenomics study designs and indicate that a single dose of VOO can elicit quantifiable and rapid changes in gene expression in targets that are mechanistically relevant for insulin sensitivity and the metabolic syndrome.

  12. Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets

    Institute of Scientific and Technical Information of China (English)

    LING Feng; LIU Ying-long; LIU Ai-jun; WANG Dong; WANG Qiang

    2011-01-01

    Background Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.Methods Oleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n=5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.Results Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio,partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P<0.05or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P<0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P<0.05).Conclusions Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

  13. Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    XU Yu-lin; LIU Ying-long; WANG Qiang; LI Gang; L(U) Xiao-dong; KONG Bo

    2012-01-01

    Background Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units.The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS.Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury.Here,our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS.Methods Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified.ALl was induced in rats byoleic acid (OA),and MSCs were transplanted intravenously.The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours,24 hours and 48 hours after OA-injection.Results The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs.The concentration of tumor necrosis factor-α and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs,whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours,24 hours and 48 hours after OA-challenge.Conclusions Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS.Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.

  14. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients

    DEFF Research Database (Denmark)

    Krag, Mette; Perner, Anders; Wetterslev, Jørn

    2015-01-01

    PURPOSE: To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients. METHODS: We included adults without GI bleeding who were acutely admitted to the intensive care unit (ICU...... bleeding occurred in 2.6 % (95 % confidence interval 1.6-3.6 %) of patients. The following variables at ICU admission were independently associated with clinically important GI bleeding: three or more co-existing diseases (odds ratio 8.9, 2.7-28.8), co-existing liver disease (7.6, 3.3-17.6), use of renal...

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

    Science.gov (United States)

    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. Hydroxysafflor yellow A suppress oleic acid-induced acute lung injury via protein kinase A

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chaoyun [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China); Huang, Qingxian [Department of Hepatobiliary Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000 (China); Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China); Bai, Xianyong, E-mail: xybai2012@163.com [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China)

    2013-11-01

    Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO{sub 2}), carbon dioxide tension, pH, and the PaO{sub 2}/fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22{sup phox} levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI. - Highlights: • Oleic acid (OA) cause acute lung injury (ALI) via inhibiting cAMP/PKA signal pathway. • Blocking protein kinase A (PKA) activation may

  17. Repair of radius defect with bone-morphogenetic-protein loaded hydroxyapatite/collagen-poly(L-lactic acid) composite

    Institute of Scientific and Technical Information of China (English)

    胡蕴玉; 张超; 吕荣; 徐建强; 李丹

    2003-01-01

    Objective: To explore the method to repair bone defect with bone-morphogenetic-protein loaded hydroxyapatite/collagen-poly(L-lactic acid) composite. Methods: 18 adult beagle dogs were randomly divided into 3 groups. In Group A, bone-morphogenetic-protein (BMP) loaded hydroxyapatite/collagen-poly(L-lactic acid) (HAC-PLA) scaffold was implanted in a 2 cm diaphyseal defect in the radius. In Group B, unloaded pure HAC-PLA scaffold was implanted in the defects. No material was implanted in Group C (control group). The dogs were sacrificed 6 months postoperatively. Features of biocompatibility, biodegradability and osteoinduction were evaluated with histological, radiological examinations and bone mineral density (BMD) measurements.Results: In Group A, the radius defect healed after the treatment with BMP loaded HAC-PLA. BMD at the site of the defect was higher than that of the contralateral radius. Fibrous union developed in the animals of the control group. Conclusions: BMP not only promotes osteogenesis but also accelerates degradation of the biomaterials. Optimized design parameters of a three-dimensional porous biomaterial would give full scope to the role of BMP as an osteoinductive growth factor.

  18. Preparation and Characterization of Nimodipine-loaded Methoxy Poly (ethylene glycol)-poly (lactic acid) Diblock Copolymer Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    ZHA Liu-sheng; LI Lan; ZHAO Hui-peng

    2006-01-01

    Amphiphilic diblock copolymers, methoxy poly (ethylene glycol)-poly(lactic acid) (MePEG-PLA), were synthesized from monomers of DL-lactide and methoxy poly (ethylene glycol) by a ring opening bulk polymerization in the presence of stannous octoate. Their chemical structure and physical properties were investigated using FTIR, NMR, GPC, and fluorescence spectroscopy. To estimate the feasibility as colloidal drug carrier, nimodipine (ND) was loaded into MePEG-PLA block copolymer nanoparticles by phaseseparation/dialysis method. The mean diameter and drug loading efficiency of ND-loaded MePEG-PLA copolymer nanoparticles depended on PLA/MePEG block composition of the copolymer and drug/polymer feed ratio in preparation. NMR study confirmed that nimodipine was entrapped into the hydrophobic inner core of MePEG-PLA copolymer nanoparticles and hydrophilic PEG chains were located on the surface of the drug-loaded polymer nanoparticles. In vitro release experiments exhibited the sustained release behavior of nimodipine from MePEG-PLA copolymer nanoparticles, without any burst effect.

  19. Preparation, characterization of a ceria loaded carbon nanotubes nanocomposites photocatalyst and degradation of azo dye Acid Orange 7

    Directory of Open Access Journals (Sweden)

    Wen Tao

    2016-06-01

    Full Text Available A ceria loaded carbon nanotubes (CeO2/CNTs nanocomposites photocatalyst was prepared by chemical precipitation, and the preparation conditions were optimized using an orthogonal experiment method. HR-TEM, XRD, UV-Vis/DRS, TGA and XPS were used to characterize the photocatalyst. Nitrogen adsorption-desorption was employed to determine the BET specific surface area. The results indicated that the photocatalyst has no obvious impurities. CeO2 was dispersed on the carbon nanotubes with a good loading effect and high loading efficiency without agglomeration. The catalyst exhibits a strong ability to absorb light in the ultraviolet region and some ability to absorb light in the visible light region. The CeO2/CNTs nanocomposites photocatalyst was used to degrade azo dye Acid Orange 7 (40 mg/L. The optical decolorization rate was 66.58% after xenon lamp irradiation for 4 h, which is better than that of commercial CeO2 (43.13%. The results suggested that CeO2 loading on CNTs not only enhanced the optical decolorization rate but also accelerated the separation of CeO2/CNTs and water.

  20. Maximising high solid loading enzymatic saccharification yield from acid-catalysed hydrothermally-pretreated brewers spent grain

    Directory of Open Access Journals (Sweden)

    Stuart Wilkinson

    2016-06-01

    Full Text Available Enzyme saccharification of pretreated brewers spent grains (BSG was investigated, aiming at maximising glucose production. Factors investigated were; variation of the solids loadings at different cellulolytic enzyme doses, reaction time, higher energy mixing methods, supplementation of the cellulolytic enzymes with additional enzymes (and cofactors and use of fed-batch methods. Improved slurry agitation through aerated high-torque mixing offered small but significant enhancements in glucose yields (to 53 ± 2.9 g/L and 45% of theoretical yield compared to only 41 ± 4.0 g/L and 39% of theoretical yield for standard shaking methods (at 15% w/v solids loading. Supplementation of the cellulolytic enzymes with additional enzymes (acetyl xylan esterases, ferulic acid esterases and α-L- arabinofuranosidases also boosted achieved glucose yields to 58 – 69 ± 0.8 - 6.2 g/L which equated to 52 - 58% of theoretical yield. Fed-batch methods also enhanced glucose yields (to 58 ± 2.2 g/L and 35% of theoretical yield at 25% w/v solids loading compared to non-fed-batch methods. From these investigations a novel enzymatic saccharification method was developed (using enhanced mixing, a fed-batch approach and additional carbohydrate degrading enzymes which further increased glucose yields to 78 ± 4.1 g/L and 43% of theoretical yield when operating at high solids loading (25% w/v.

  1. Dynamic flow method to study the CO2 loading capacity of amino acid salt solutions

    DEFF Research Database (Denmark)

    Lerche, Benedicte Mai; Stenby, Erling Halfdan; Thomsen, Kaj

    Due to a number of advantages amino acid salt solutions have emerged as alternatives to the alkanolamine solvents for the chemical absorption of CO2 from flue gas. The use of amino acids in CO2 capture is a bio-mimetic process, as it is similar to CO2 binding by proteins in the blood, such as hem......Due to a number of advantages amino acid salt solutions have emerged as alternatives to the alkanolamine solvents for the chemical absorption of CO2 from flue gas. The use of amino acids in CO2 capture is a bio-mimetic process, as it is similar to CO2 binding by proteins in the blood......, such as hemoglobin. Amino acid salt solutions have the same amine functionality as alkanolamines, and are thus expected to behave similar towards CO2 in flue gas. Despite rising interest, few studies have been performed so far on amino acids as CO2 absorbents....

  2. Associations between Dietary Acid-Base Load and Cardiometabolic Risk Factors in Adults: The Tehran Lipid and Glucose Study

    Directory of Open Access Journals (Sweden)

    Zahra Bahadoran

    2015-06-01

    Full Text Available BackgroundIn this study we investigated the associations of dietary acid-base load, identified by potential renal acid load (PRAL and protein to potassium (Pro:K ratio, with cardiometabolic risk factors in Tehranian adults.MethodsA cross-sectional study was conducted within the framework of the fourth phase of the Tehran Lipid and Glucose Study (2009 to 2011 on 5,620 men and women aged 19 to 70 years. Dietary data were collected by a trained dietitian using a validated, 147-food item, semi-quantitative food frequency questionnaire, and dietary PRAL and Pro:K ratio were calculated. Multiple linear regression models with adjustment for potential confounding variables were used to evaluate the associations of dietary acid-base load with anthropometric measures, blood pressure, serum triglycerides, high density lipoprotein cholesterol (HDL-C, serum creatinine, and fasting blood glucose.ResultsThe mean±SD age of the participants was 39.8±12.8 years and 54% of participants were women. Mean±SD PRAL was -22.0±29.1; mean PRAL was -15.6 in men and -26.8 in women. Dietary PRAL was associated with weight (β=0.098, P<0.001, waist circumference (β=0.062, P<0.01, serum triglycerides (β=0.143, P<0.01, HDL-C (β=-0.11, P<0.01, diastolic blood pressure (β=0.062, P<0.01, and serum creatinine (β=0.142, P<0.001. Pro:K ratio was associated with weight (β=0.055, P<0.001, waist circumference (β=0.04, P<0.01, serum HDL-C (β=-0.06, P<0.01, serum triglycerides (β=0.03, P<0.05, diastolic blood pressure (β=0.026, P<0.05, and serum creatinine (β=0.07, P<0.01.ConclusionA more acidic dietary acid-base load may be a risk factor for the development of metabolic disorders.

  3. "THE ROLE OF PROSTAGLANDINS AND MAST CELLS IN THE MODULATION OF ACUTE ACID-INDUCED TRACHEAL CONTRACTION IN RAT"

    Directory of Open Access Journals (Sweden)

    M. H. Pipelzadeh

    2004-05-01

    Full Text Available The exact role of the epithelial lining of the trachea in modulating the bronchial tone is controversial. The present study was an attempt to verify the role of both prostaglandins and mast cells in the acute phase of acid inspiration in rat. Four groups (n = 6 of N. Mari rats were employed. The first group was used as placebo control, and normal saline was injected. To the second group hydrochloric acid (25 µl with pH of 1.3 was injected into the trachea through the criothyroid membrane. The third and fourth groups were pretreated for three consecutive days either with indomethacin (10 mg/Kg or nebulized sodium cromoglycate (20 mg/Kg, 1 hour prior to installation of the acid. Three minutes after instillation of acid, the trachea was removed. The tracheal spirals were prepared and immediately suspended in an organ bath containing Tyrode’s solution. Dose response curves to acetylcholine (10-9 to 10-3M were constructed. The results showed that the responses to acetylcholine in the acid treated trachea were significantly (P<0.01 reduced compared with the control saline treated trachea due to acute acid-induced tracheal contraction. Incubation with atropine, induced reduction of baseline tension and reversed the responses to acetylcholine. Both indomethacin and sodium cromoglycate, reversed the responses to acetylcholine and were in similar range as the control trachea. In conclusion, it seems that both prostaglandins and mast cells are important mediators in the acute phase of airway smooth muscle contraction following instillation of acid.

  4. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

    Science.gov (United States)

    Fisher, Bernard J; Kraskauskas, Donatas; Martin, Erika J; Farkas, Daniela; Wegelin, Jacob A; Brophy, Donald; Ward, Kevin R; Voelkel, Norbert F; Fowler, Alpha A; Natarajan, Ramesh

    2012-07-01

    Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

  5. Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load

    OpenAIRE

    Kenji Ando; Soo Ryang Kim; Susumu Imoto; Taisuke Nakajima; Keiji Mita; Katsumi Fukuda; Miyuki Taniguchi; Noriko Sasase; Akira Muramatsu; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2009-01-01

    Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 μg) plus a daily oral dose of RBV (60...

  6. Effect of organic load on decolourization of textile wastewater containing acid dyes in upflow anaerobic sludge blanket reactor

    Energy Technology Data Exchange (ETDEWEB)

    Wijetunga, Somasiri, E-mail: swije2001@yahoo.com [Laboratory of Environmental Biotechnology, School of Biotechnology, Southern Yangtze University, 170 Huihe Road, Wuxi 214036 (China); Li Xiufen [Laboratory of Environmental Biotechnology, School of Biotechnology, Southern Yangtze University, 170 Huihe Road, Wuxi 214036 (China); Jian Chen, E-mail: jchen@sytu.edu.cn [Laboratory of Environmental Biotechnology, School of Biotechnology, Southern Yangtze University, 170 Huihe Road, Wuxi 214036 (China)

    2010-05-15

    Textile wastewater (TW) is one of the most hazardous wastewater for the environment when discharged without proper treatment. Biological treatment technologies have shown encouraging results over the treatment of recalcitrant compounds containing wastewaters. Upflow anaerobic sludge blanket reactor (UASB) was evaluated in terms of colour and the reduction of chemical oxygen demand (COD) with different organic loads using TW containing dyes belonging to different chemical groups. The study was performed using six different dye concentrations (10 mg/L, 25 mg/L, 50 mg/L, 100 mg/L, 150 mg/L, 300 mg/L) with three COD levels ({approx}1000 mg/L, {approx}2000 mg/L, {approx}3000 mg/L). Decolourization, COD removal and reactor stability were monitored. Over 85% of colour removal was observed with all dye concentrations with three organic loads. Acid Red 131 and Acid Yellow 79 were decolourized through biodegradation while Acid Blue 204 was decolourized due to adsorption onto anaerobic granules. COD removal was high in all dye concentrations, regardless of co-substrate levels. The reactor did not show any instability during the study. The activity of granules was not affected by the dyes. Methanothrix like bacteria were the dominant group in granules before introducing TW, however, they were reduced and cocci-shape microorganism increased after the treatment of textile wastewater.

  7. Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats.

    Science.gov (United States)

    Chu, JianJun; Zhang, Xiaojun; Jin, Liugen; Chen, Junliang; Du, Bin; Pang, Qingfeng

    2015-03-01

    Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague-Dawley rats were intraperitoneally administered with CAPE (30 mg/kg) for 3 consecutive days before exposing them to a single dose of 30 Gy of β-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-κB p65 subunit, decreased the level of tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury.

  8. Leptin attenuates lipopolysaccharide or oleic acid-induced acute lung injury in mice.

    Science.gov (United States)

    Dong, Hai-Ying; Xu, Min; Ji, Zhen-Yu; Wang, Yan-Xia; Dong, Ming-Qing; Liu, Man-Ling; Xu, Dun-Quan; Zhao, Peng-Tao; Liu, Yi; Luo, Ying; Niu, Wen; Zhang, Bo; Ye, Jing; Li, Zhi-Chao

    2013-12-01

    Leptin is reported to be involved in acute lung injury (ALI). However, the role and underlying mechanisms of leptin in ALI remain unclear. The aim of this study was to determine whether leptin deficiency promoted the development of ALI. LPS or oleic acid (OA) were administered to wild-type and leptin deficient (ob/ob) mice to induce ALI. Leptin level, survival rate, and lung injury were examined. Results showed that leptin levels were predominantly increased in the lung, but also in the heart, liver, kidney, and adipose tissue after LPS adminiatration. Compared with wild-type mice, LPS- or OA-induced lung injury was worse and the survival rate was lower in ob/ob mice. Moreover, leptin deficiency promoted the release of proinflammatory cytokines. Exogenous administration of leptin reduced lethality in ob/ob mice and ameliorated lung injury partly through inhibiting the activation of NF-κB, p38, and ERK pathways. These results indicated that leptin deficiency contributed to the development of lung injury by enhancing inflammatory response, and a high level of leptin improved survival and protected against ALI.

  9. Gangrenous cheilitis associated with all-trans retinoic acid therapy for acute promyelocytic leukemia.

    Science.gov (United States)

    Tanaka, Mariko; Fukushima, Noriyasu; Itamura, Hidekazu; Urata, Chisako; Yokoo, Masako; Ide, Masaru; Hisatomi, Takashi; Tomimasu, Rika; Sueoka, Eisaburo; Kimura, Shinya

    2010-01-01

    A 67-year-old Japanese woman who presented with erythema on the abdomen and pancytopenia was found to have acute promyelocytic leukemia (APL). A skin biopsy revealed invasion of APL cells. She was started on induction treatment with all-trans retinoic acid (ATRA) at 45 mg/m(2). On day 4, the leukemic cell number had increased to over 1.0 x 10(9)/L. Consequently, chemotherapy with idarubicin and cytarabine was initiated. On day 10, dryness of the lips appeared. The lower lip swelled and developed painful black eschars. A high fever was also present. Despite discontinuing ATRA on day 20 and administering antibiotics, an anti-fungal agent and valaciclovir, these signs did not improve. Histopathologically, the biopsied lip revealed infiltration of neutrophils and vasculitis. The patient was given ATRA on days 29 and 30 due to an increase in APL cell numbers, after which the gangrenous cheilitis extended over the whole lip. On day 49, the patient was started on re-induction treatment with arsenic trioxide. She achieved complete remission and the gangrenous cheilitis slowly healed over the following 8 weeks. Since the clinical features of the gangrenous cheilitis in this case were similar to those of ATRA-associated scrotal ulcers, it appears that activated neutrophils derived from differentiated APL cells may have caused the gangrenous cheilitis. Physicians should be alert to the development of gangrenous cheilitis during treatment with ATRA.

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

    Directory of Open Access Journals (Sweden)

    Guan QG

    2015-02-01

    Full Text Available Qigang Guan,1 Wei Chen,2 Xianming Hu2 1Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Pharmaceutical, Shenyang Institute of Pharmaceutical Industry, Shenyang, People’s Republic of China 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. Keywords: lovastatin, microspheres, PLA, in vitro release, pharmacokinetics 

  11. Content of non-esterified fatty acids in the blood plasma of rabbits with acute arginine pancreatitis and its correction

    Directory of Open Access Journals (Sweden)

    Y. F. Rivis

    2013-01-01

    Full Text Available The aim of this work was to study the content of non-esterified fatty acids in plasma and liver of rabbits with acute arginine pancreatitis and its correction by linseed oil. The experiment was carried out on male rabbits breed gray giant with live weight 3.8–4.0 kg. The material for the study was sampled from blood and liver. Lipids from plasma and liver were extracted with a mixture of chloroform and methanol. After that the non-esterified fatty acids were isolated and methylated. Methyl esters of fatty acids were studied by the gas-liquid chromatography with the chromatograph ''Chrom 5'' (Prague,CzechRepublic. We have found that the content of non-esterified fatty acids decreases in the blood plasma and liver of rabbits with the acute arginine pancreatitis. It takes place at the expense of a reduce of saturated fatty acids with odd and even number of carbon atoms in a chain, monounsaturated fatty acids of the families ω-7 and ω-9 and polyunsaturated fatty acids of the families ω-3 and ω-6. That may indicate a greater use of non-esterified fatty acids for energy metabolism and esterification of lipids. We suppose that this is a consequence of the probable increase in content of non-esterified and esterified cholesterol in the rabbits’ blood plasma. Those processes provoke the cholesterol deposits in blood vessels and therefore cardiovascular diseases. We tried to influence on the processes by addition of linseed oil to the rabbits diet. We have found that in the linseed oil-fed rabbits the content of non-esterified fatty acids decreases at the expense of saturated fatty acids with odd and even number of carbon atoms in a chain and monounsaturated fatty acids of the families ω-7 and ω-9 inblood plasma and liver of the rabbits with acute arginine pancreatitis. Furthermore the levels of non-esterified polyunsaturated fatty acids of ω-3 family increase in the rabbits’ plasma and liver. As this takes place the ratio of non

  12. Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load

    Directory of Open Access Journals (Sweden)

    Kenji Ando

    2009-11-01

    Full Text Available Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α and ribavirin (RBV combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 μg plus a daily oral dose of RBV (600 mg. The therapy was discontinued, however, because of the onset of acute pancreatitis (after 15 weeks, 48 weeks, and 3 weeks respectively. The drug-induced pancreatitis was diagnosed on the basis of elevated levels of amylase and lipase and the absence of other identifiable causes. High tumor necrosis factor-α was found in one patient and high interleukin-6 in the other two. The immune system stimulated by PEG-IFN and RBV combination therapy might have caused the acute pancreatitis. Further study is needed to clarify the mechanism of the onset of drug-induced pancreatitis by PEG-IFN and RBV combination therapy.

  13. Intake of tryptophan-enriched whey protein acutely enhances recall of positive loaded words in patients with multiple sclerosis

    NARCIS (Netherlands)

    Lieben, Cindy K; Blokland, Arjan; Deutz, Nicolaas E; Jansen, Willemijn; Han, Gang; Hupperts, Raymond M

    2017-01-01

    BACKGROUND & AIMS: Multiple sclerosis (MS) has physiological and/or immunological characteristics that diminish serotonin metabolism, a neurotransmitter associated with affective and cognitive functions. The aim was examine the acute and dose-dependent effects of a dietary tryptophan (TRP) enrichmen

  14. Humic Acid Complexation of Th, Hf and Zr in Ligand Competition Experiments: Metal Loading and Ph Effects

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

    Science.gov (United States)

    Yamaguchi, K; Mori, M; Kawai, A; Asano, K; Takasugi, T; Umeda, A; Yokoyama, T

    1992-01-01

    To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a

  18. Therapeutic efficacy of new dimercaptosuccinic acid (DMSA) analogues in acute arsenic trioxide poisoning in mice.

    Science.gov (United States)

    Kreppel, H; Paepcke, U; Thiermann, H; Szinicz, L; Reichl, F X; Singh, P K; Jones, M M

    1993-01-01

    The therapeutic efficacy of six newly synthesized analogues of dimercaptosuccinic acid (DMSA) was investigated in acute arsenic trioxide poisoning in mice. Meso-2,3-di(acetylthio)succinic acid (DATSA) and meso-2,3- di(benzoylthio)succinic acid (DBTSA) are analogues of DMSA with protected thiol groups ("prodrugs"), and DMDMS, DEDMS, DnPDMS, and DiPDMS are various di-esters of DMSA with methyl, ethyl, n-propyl, and isopropyl alcohols, respectively. Thirty minutes after s.c. injection of an LD80 of arsenic trioxide (65 mumol/kg) male NMRI mice were treated with a single equimolar dose (0.7 mmol/kg) of DMSA i.p. or one of the analogues i.p. or via gastric tube (i.g.). Control animals received arsenic trioxide and saline 30 min later. The survival rate was recorded for 30 days. All of the animals treated with DMSA i.p. survived and all controls died within 2 days. Administered i.g., DATSA and DBTSA increased the survival rate to 29% and 43%, and injected i.p. to 86%. Treatment with DMDMS i.p. and i.g., and with DEDMS, DnPDMS, and DiPDMS i.g. did not reduce lethality. Given i.p., DnPDMS increased the survival rate to 72%, and DEDMS and DiPDMS to 86%, respectively. To investigate the efficacy of the DMSA analogues in reducing the tissue content of arsenic, male NMRI mice received an s.c. injection of an LD5 of arsenic trioxide containing a tracer dose of 73-As(III) (42.5 mumol/kg body wt). Thirty minutes later, saline (controls) or a single equimolar dose (0.7 mmol/kg) of DMSA i.p., or one of the analogues i.p. or i.g. was administered. The arsenic content of various organs (blood, liver, kidneys, heart, lungs, spleen, small intestine, large intestine, brain, testes, skeletal muscle, and skin) at 30 min, 2 h, 4 h, 6 h, and 8 h after the arsenic injection was measured using a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Acute and sub-acute effects of 2-butenoic acid-3-(diethoxy phosphinothioyl) methyl ester (RPR-II) on testis of albino rat.

    Science.gov (United States)

    Khan, I A; Reddy, B V; Mahboob, M; Rahman, M F; Jamil, Kaiser

    2002-02-01

    Acute and sub-acute toxic effects of a novel phosphorothionate coded as RPR-II on testis of albino rats were studied. In acute study rats received a single dose of 12.3 mg/kg of RPR-II and sacrificed after 24 hr. For sub-acute study 0.58 mg/kg/day was administered orally to rats for 10 and 21 days. Acute exposure of rats to RPR-II brought no change either in the gonadosomatic index (GSI) or in the structure of testis or in the serum levels of testosterone. Testis glutathione (GSH) level and glutathione S-transferase (GST) activity was significantly decreased whereas, acid phosphatase (AcP) levels increased significantly at 24 hr post-treatment. On 7th day (withdrawal period) after the cessation of the treatment the GSH, GST, AcP, and AkP levels reached to near control. The sub-acute study revealed a significant decrease in GSI on 10th and 21st day of the treatment. In contrast, a time-dependent and significant increased in GSH level and GST activity was observed on 100th and 21st day of post-treatment, except GSH level on 10th day, which was declined. Due to RPR-II treatment the testis AcP and alkaline phosphatase (AkP) levels were significant at both 10th and 21st day of medication but AcP levels were increased whereas AkP levels decreased. The histopathological studies on day 10th showed considerable loss of spermatozoids in testis and at 21st day complete derangement of cellular organization was observed. Testosterone levels decreased significantly on 10th day and remained significantly low at 21st day. However, withdrawal studies showed a recovery in testis of rat treated with RPR-II. GST, GSH, GSI, AcP and AkP values recovered, testosterone levels were also well recovered but recovery in testis structure remained at a low profile. The present study suggests that RPR-II may cause testicular toxicity in rats affecting the normal functioning of testis and it also gave some new information in withdrawal studies.

  20. Functionalized antibiofilm thin coatings based on PLA–PVA microspheres loaded with usnic acid natural compounds fabricated by MAPLE

    Energy Technology Data Exchange (ETDEWEB)

    Grumezescu, Valentina [National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, PO Box MG-36, Bucharest-Magurele, Bucharest (Romania); University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Department of Science and Engineering of Oxidic Materials and Nanomaterials, Polizu Street no 1-7, 011061 Bucharest (Romania); Socol, Gabriel [National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, PO Box MG-36, Bucharest-Magurele, Bucharest (Romania); Grumezescu, Alexandru Mihai, E-mail: grumezescu@yahoo.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Department of Science and Engineering of Oxidic Materials and Nanomaterials, Polizu Street no 1-7, 011061 Bucharest (Romania); Holban, Alina Maria [Faculty of Biology, University of Bucharest, Microbiology Immunology Department, Aleea Portocalelor 1-3, Sector 5, 77206 Bucharest (Romania); Ficai, Anton [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Department of Science and Engineering of Oxidic Materials and Nanomaterials, Polizu Street no 1-7, 011061 Bucharest (Romania); Truşcǎ, Roxana [S.C. Metav-CD S.A., 31Rosetti Str., 020015 Bucharest (Romania); Bleotu, Coralia [Stefan S Nicolau Institute of Virology, Bucharest (Romania); Balaure, Paul Cǎtǎlin [Department of Organic Chemistry, Faculty of Applied Chemistry and Materials Science, Politehnica Universitiy of Bucharest, Polizu Street no 1-7, 011061 Bucharest (Romania); Cristescu, Rodica [National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, PO Box MG-36, Bucharest-Magurele, Bucharest (Romania); Chifiriuc, Mariana Carmen [Faculty of Biology, University of Bucharest, Microbiology Immunology Department, Aleea Portocalelor 1-3, Sector 5, 77206 Bucharest (Romania)

    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.

  1. Preparation, characterization, and antibacterial activity studies of silver-loaded poly(styrene-co-acrylic acid) nanocomposites.

    Science.gov (United States)

    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.

  2. Functionalized antibiofilm thin coatings based on PLA-PVA microspheres loaded with usnic acid natural compounds fabricated by MAPLE

    Science.gov (United States)

    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.

  3. Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. Preparation and functional characterization of tumor-targeted folic acid-chitosan conjugated nanoparticles loaded with mitoxantrone

    Institute of Scientific and Technical Information of China (English)

    王炜; 童春义; 刘星言; 李涛; 刘斌; 熊炜

    2015-01-01

    Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), and then used as a template to prepare folic acid-chitosan (FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles (FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48−58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride (MTX) is (77.5±1.9)%, and the drug loading efficiency is (18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.

  6. Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion

    Science.gov (United States)

    Limberg, Jacqueline K.; Kellawan, J. Mikhail; Harrell, John W.; Johansson, Rebecca E.; Eldridge, Marlowe W.; Proctor, Lester T.; Sebranek, Joshua J.

    2014-01-01

    We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise − rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = −0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. PMID:25038148

  7. LEUKOCYTOSIS AND RETINOIC ACID SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA TREATED WITH ARSENIC TRIOXIDE

    Institute of Scientific and Technical Information of China (English)

    Bo Jin; Ke-zuo Hou; Yun-peng Liu; Ping Yu

    2006-01-01

    Objective To study the incidence of leukocytosis and retinoic acid (RA) syndrome in newly diagnosed and relapsed acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO).Methods Thirty patients with newly diagnosed or relapsed APL received ATO for remission induction at the dose of 10 mg/d. RA syndrome was defined when patient was with one or more of the following signs or symptoms: fever,dyspnea, serous cavity effusion, muscular pain, pulmonary infiltration, weight gain, or pulmonary infiltration on chest X-ray.Results Twenty-three (77%) patients achieved complete remission, mean time to remission was 37.1 days. Leukocytosis was observed in 14 (47%) patients, mean time to leukocytosis was 12.7 days, median baseline leukocyte count for patients with leukocytosis was 3.1 × 109/L, which was higher than that for patients who did not develop leukocytosis (2.6×109/L, z=-2.635, P=0.008). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in 9(30%) patients, mean time to diagnose of RA syndrome was 13.9 days, median baseline leukocyte count for patients with RA syndrome was 3.6×109/L, which was higher than that for patients who did not develop RA syndrome (2.6 × 109/L, z=-1.909, P=0.046). No patient died of RA syndrome.Conclusion Leukocytosis and RA syndrome are associated with ATO and baseline leukocyte count respectively,and there is distinct link between leukocytosis and RA syndrome.

  8. Clinical significance of sialic acid in acute rheumatic fever with and without carditis

    Directory of Open Access Journals (Sweden)

    Maher H. Gomaa

    2012-08-01

    Full Text Available Objective: In Egypt, acute rheumatic fever (ARF is the most common cause of acquired heart disease. ARF is a clinical syndrome without a specific diagnostic test or single pathognomonic feature, so the aim of this study is to investigate the utility of using serum total sialic acid (TSA in differentiation between children suffering from ARF with and without carditis. Methods: In the present study, 62 children were divided into three groups: first group, 16 healthy children; second group, 20 patients suffering from chronic rheumatic heart disease (RHD; and third group, 26 patients suffering from ARF, subdivided into three subgroups as (A 10 patients suffering from arthritis without carditis, (B 10 patients with carditis but without congestive heart failure (CHF, and (C 6 patients with carditis and CHF. Antistreptolysin O titre (ASOT by latex agglutination test, erythrocyte sedimentation rate (ESR by Westergren method, C-reactive protein (CRP by turbidimetric immunoassay method, lactate dehydrogenase (LDH activity by kinetic method, immunoglobulin levels by radial immunodifussion assay (RID, cardiac troponin I (cTnI by ELISA test kit and TSA by diphenylamine (DPA method were performed. Results: Significant elevated values of ESR, CRP, LDH, IgG and IgA were obtained in ARF as compared to both control and RHD groups; significant values of IgM were found between B and C as compared to control and RHD groups; cTnI showed insignificant difference between all groups; values of TSA showed highly significant difference between ARF as compared to both control and RHD groups as well as between RHD and control groups; significant difference was found between B and C groups as compared to group A. Conclusion: The results of the present study point out the possibility that the levels of TSA could be of help in differentiation between ARF patients with and without carditis. [J Exp Integr Med 2012; 2(4: 305-311

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

    Science.gov (United States)

    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.

  10. Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds.

    Science.gov (United States)

    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.

  11. Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin-loaded poly(lactic-co-glycolic acid) microspheres in rats

    Institute of Scientific and Technical Information of China (English)

    Xiang-lian ZHOU; in-tian HE; Hui-juan DU; Yang-yang FAN; Ying WANG; Hong-xia ZHANG; Yang JIANG

    2012-01-01

    To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats.Methods:The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method.Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats.The serum rhEPO level was determined with ELISA.The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres.Results:rhEPO was almost completely released from the PLGA microspheres in vitro,following zero-order release kinetics over approximately 30 d.After intramuscular injection (10 000 or 30 000 IU rhEPO/kg) in the rats,the serum rhEPO concentration reached maximum levels on d 1,then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks.Furthermore,the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism.A good linear correlation (R2=0.98) was obtained between the in vitro and in vivo release data.A single intramuscular injection of the rhEPO-loaded PLGA microspheres (10 000 or 30 000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d.Moreover,the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO.Conclusion:The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month.

  12. Impaired increase of plasma abscisic Acid in response to oral glucose load in type 2 diabetes and in gestational diabetes.

    Science.gov (United States)

    Ameri, Pietro; Bruzzone, Santina; Mannino, Elena; Sociali, Giovanna; Andraghetti, Gabriella; Salis, Annalisa; Ponta, Monica Laura; Briatore, Lucia; Adami, Giovanni F; Ferraiolo, Antonella; Venturini, Pier Luigi; Maggi, Davide; Cordera, Renzo; Murialdo, Giovanni; Zocchi, Elena

    2015-01-01

    The plant hormone abscisic acid (ABA) is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT) human subjects, plasma ABA (ABAp) increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D) subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i) 9 treatment-naive T2D subjects, and ii) 9 pregnant women with gestational diabetes (GDM), who underwent the glucose load before and 8-12 weeks after childbirth. Each group was compared with matched NGT controls. The increase of ABAp in response to glucose was found to be abrogated in T2D patients compared to NGT controls. A similar result was observed in the women with GDM compared to pregnant NGT controls; 8-12 weeks after childbirth, however, fasting ABAp and ABAp response to glucose were restored to normal in the GDM subjects, along with glucose tolerance. We also retrospectively compared fasting ABAp before and after bilio-pancreatic diversion (BPD) in obese, but not diabetic subjects, and in obese T2D patients, in which BPD resulted in the resolution of diabetes. Compared to pre-BPD values, basal ABAp significantly increased 1 month after BPD in T2D as well as in NGT subjects, in parallel with a reduction of fasting plasma glucose. These results indicate an impaired hyperglycemia-induced ABAp increase in T2D and in GDM and suggest a beneficial effect of elevated ABAp on glycemic control.

  13. Impaired increase of plasma abscisic Acid in response to oral glucose load in type 2 diabetes and in gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Pietro Ameri

    Full Text Available The plant hormone abscisic acid (ABA is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT human subjects, plasma ABA (ABAp increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i 9 treatment-naive T2D subjects, and ii 9 pregnant women with gestational diabetes (GDM, who underwent the glucose load before and 8-12 weeks after childbirth. Each group was compared with matched NGT controls. The increase of ABAp in response to glucose was found to be abrogated in T2D patients compared to NGT controls. A similar result was observed in the women with GDM compared to pregnant NGT controls; 8-12 weeks after childbirth, however, fasting ABAp and ABAp response to glucose were restored to normal in the GDM subjects, along with glucose tolerance. We also retrospectively compared fasting ABAp before and after bilio-pancreatic diversion (BPD in obese, but not diabetic subjects, and in obese T2D patients, in which BPD resulted in the resolution of diabetes. Compared to pre-BPD values, basal ABAp significantly increased 1 month after BPD in T2D as well as in NGT subjects, in parallel with a reduction of fasting plasma glucose. These results indicate an impaired hyperglycemia-induced ABAp increase in T2D and in GDM and suggest a beneficial effect of elevated ABAp on glycemic control.

  14. Bactericidal Effect of Lauric Acid-Loaded PCL-PEG-PCL Nano-Sized Micelles on Skin Commensal Propionibacterium acnes

    Directory of Open Access Journals (Sweden)

    Thi-Quynh-Mai Tran

    2016-08-01

    Full Text Available Acne is the over growth of the commensal bacteria Propionibacterium acnes (P. acnes on human skin. Lauric acid (LA has been investigated as an effective candidate to suppress the activity of P. acnes. Although LA is nearly insoluble in water, dimethyl sulfoxide (DMSO has been reported to effectively solubilize LA. However, the toxicity of DMSO can limit the use of LA on the skin. In this study, LA-loaded poly(ɛ-caprolactone-poly(ethylene glycol-poly(ɛ-caprolactone micelles (PCL-PEG-PCL were developed to improve the bactericidal effect of free LA on P. acnes. The block copolymers mPEG-PCL and PCL-PEG-PCL with different molecular weights were synthesized and characterized using 1H Nuclear Magnetic Resonance spectroscopy (1H NMR, Fourier-transform infrared spectroscopy (FT-IR, Gel Permeation Chromatography (GPC, and Differential Scanning Calorimetry (DSC. In the presence of LA, mPEG-PCL diblock copolymers did not self-assemble into nano-sized micelles. On the contrary, the average particle sizes of the PCL-PEG-PCL micelles ranged from 50–198 nm for blank micelles and 27–89 nm for LA-loaded micelles. The drug loading content increased as the molecular weight of PCL-PEG-PCL polymer increased. Additionally, the minimum inhibitory concentration (MIC and the minimum bactericidal concentration (MBC of free LA were 20 and 80 μg/mL, respectively. The MICs and MBCs of the micelles decreased to 10 and 40 μg/mL, respectively. This study demonstrated that the LA-loaded micelles are a potential treatment for acne.

  15. Effect of acute lindane and alcohol intoxication on serum concentration of enzymes and fatty acids in rats.

    Science.gov (United States)

    Radosavljević, T; Mladenović, D; Vucević, D; Petrović, J; Hrncić, D; Djuric, D; Loncar-Stevanović, H; Stanojlović, O

    2008-05-01

    This study examines possible synergistic effects of lindane and ethanol on inducing liver injury and serum fatty acid derangement in adult male Wistar rats. When administered together, ethanol and lindane-induced even more pronounced increase of alanine aminotransferase (165 +/- 10 U/L) and gamma-glutamyltranspeptidase activity (10.3 +/- 0.6 U/L) than after isolated administration of either substance. In addition, separate administration of lindane and ethanol was followed by a significant decrease of linoleic acid level in the serum (301 +/- 38 mg/L, 276 +/- 35 mg/L vs. 416 +/- 48 mg/L). However, when ethanol administration was followed by lindane injection, serum linoleic acid was at the similar level found in the control group (516 +/- 62 mg/L). Ethanol-treated rats that received lindane 30 min after ethanol administration have shown a marked increase of palmitic (421 +/- 27 mg/L) and linolic acid level (43 +/- 5 mg/L) in comparison with rats that have been treated only with ethanol (316+/-26 mg/L for palmitic and 32 +/- 2 mg/L for linolic acid) or lindane (295 +/- 26 mg/L for palmitic and 301 +/- 38 mg/L for linolic acid). Linolic acid level was significantly greater in comparison with control group (29 +/- 1 mg/L). In conclusion, this study found enough evidence to support the hypothesis that acute ethanol intoxication potentiates lindane-induced liver injury and enhances lipid derangement.

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

    Science.gov (United States)

    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.

  17. Low atmospheric nitrogen loads lead to grass encroachment in coastal dunes, but only on acid soils

    NARCIS (Netherlands)

    Remke, E.; Brouwer, E.; Kooijman, A.; Blindow, I.; Roelofs, J.G.M.

    2009-01-01

    The impact of atmospheric N-deposition on succession from open sand to dry, lichen-rich, short grassland, and tall grass vegetation dominated by Carex arenaria was surveyed in 19 coastal dune sites along the Baltic Sea. Coastal dunes with acid or slightly calcareous sand reacted differently to atmos

  18. Metagenomic analysis on thermophilic biogas reactors fed with high load of Long Chain Fatty Acids (LCFA)

    DEFF Research Database (Denmark)

    Zhu, Xinyu; De Francisci, Davide; Treu, Laura;

    In anaerobic digestion systems, the accumulation of long chain fatty acids (LCFA) leads to process instability and decrease of the methane production. This detrimental condition is known to be reversible depending on the concentration of the accumulated LCFAs and mainly on the microbial consortiu...

  19. Experimentally induced acute uric acid nephropathy in rabbits: Findings of high resolution gray scale and doppler ultrasonographies

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ik; Chung, Soo Young; Lee, Kyung Won; Kim, Hong Dae; Ko, Eun Young; Won, Mi Sook; Noh, Jung Woo [Hallym University College of Medicine, Seoul (Korea, Republic of); Park, Moon Hyang [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    To evaluate changes of the high-resolution (HR) gray scale and doppler ultrasonographic (US) characteristics of experimentally induced acute uric acid (UA) nephropathy in rabbits. Acute UA nephropathy was induced in ten rabbits using supersaturated lithium carbonate solution. The rabbits were divided in two groups. Group I consisted of five rabbits, and they were injected with a single dose of 150 ml of saturated UA over one hour. During tis period, serial US studies of the kidneys of these rabbits were performed every ten minutes. Group II consisted of the remaining five rabbits, and three injections of 50 ml of saturated UA solution were given on the first, fifth and eight day and follow-up was done upto twenty fifth day. Sequential HR and Doppler US, renal biopsy and blood sampling were performed on day 1, 5, 8, 21, and 25 in the group II rabbits. In group I, HR and Doppler US examination revealed the normal resistive index without significant abnormality. On the other hand, US studies of group II showed poor renal corticomedullary differentiation, decreased renal blood flow and elevated resistive index. There was statistically significant correlation among US findings, histologic characteristics and chemical index (BUN, creatinine) of renal function. In addition, sequentially increased size and volume of the kidney were noted in both groups. HR gray scale and doppler US characteristics of experimentally induced acute UA nephropathy in rabbits were similar to those of acute renal failure caused by other well-known causes.

  20. Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+).

    Science.gov (United States)

    Georgopoulos, Dimitris; Xirouchaki, Nectaria; Tzanakis, Nikolaos; Younes, Magdy

    2016-09-01

    The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+) after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (ΔP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure), respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual ΔP in these patients and examined how it related to ΔP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy "Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?" [1].

  1. Data on respiratory variables in critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+

    Directory of Open Access Journals (Sweden)

    Dimitris Georgopoulos

    2016-09-01

    Full Text Available The data show respiratory variables in 108 critically ill patients with acute respiratory failure placed on proportional assist ventilation with load adjustable gain factors (PAV+ after at least 36 h on passive mechanical ventilation. PAV+ was continued for 48 h until the patients met pre-defined criteria either for switching to controlled modes or for breathing without ventilator assistance. Data during passive mechanical ventilation and during PAV+ are reported. Data are acquired from the whole population, as well as from patients with and without acute respiratory distress syndrome. The reported variables are tidal volume, driving pressure (ΔP, the difference between static end-inspiratory plateau pressure and positive end-expiratory airway pressure, respiratory system compliance and resistance, and arterial blood gasses. The data are supplemental to our original research article, which described individual ΔP in these patients and examined how it related to ΔP when the same patients were ventilated with passive mechanical ventilation using the currently accepted lung-protective strategy “Driving pressure during assisted mechanical ventilation. Is it controlled by patient brain?” [1].

  2. Acute Delayed or Late Infection of Revision Total Hip Arthroplasty Treated with Debridement/Antibiotic-loaded Cement Beads and Retention of the Prosthesis

    Science.gov (United States)

    Chang, Jun-Dong; Kim, In-Sung; Lee, Sang-Soo

    2017-01-01

    Purpose The treatment of infected revision total hip arthroplasty (THA) is very challenging due to retained revision prosthesis, poor bone stock and soft tissue condition derived from previous revision surgeries, and comorbidities. The purpose of this study was to investigate the effectiveness and short-term outcomes of aggressive debridement and use of antibiotic-loaded cement beads with retention of the prosthesis for acute delayed or late infection of revision THAs. Materials and Methods Ten consecutive patients with symptoms or signs of less than one-week evolution and well-fixed prostheses, were treated with this procedure and a postoperative course of organism-specific antibiotics for a minimum of 6 weeks. All hips presented with acute delayed or late infection of revision THAs. Patients with a mean age of 68.1 years (range, 59-78 years) underwent an average of 1.9 previous revision THAs (1-4) before the index surgery. The minimal follow-up was 2 years with a mean of 46.2 months (range, 24-64 months). Results There were 8 cures (80.0%) and 2 failures with no mortality during the study period. The 2 failures involved the same and resistant bacteria implicated in the primary infection (methicillin-resistant Staphylococcus aureus and Prevotella oralis, respectively). The mean Harris hip score was 65.2 (range, 26-83) and the mean visual analogue scale was 2.6 (range, 1-4) at final follow-up. Conclusion With a favorable success rate and no mortality, our procedure may be considered a safe and effective alternative for the treatment of acute delayed or late infection of revision THAs with well-fixed prostheses. PMID:28316961

  3. Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine

    Directory of Open Access Journals (Sweden)

    Krymchantowski Abouch

    2004-06-01

    Full Text Available Abstract Background Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. Some nonsteroidal anti-inflammatory drugs (NSAID have also demonstrated efficacy in treating migraine attacks. There is evidence that the combination of a triptan and a NSAID decreases migraine recurrence in clinical practice. The primary aim of this randomized open label study was to assess the recurrence rates in migraine sufferers acutely treated with rizatriptan (RI alone vs. rizatriptan plus a COX-2 enzyme inhibitor (rofecoxib, RO vs. rizatriptan plus a traditional NSAID (tolfenamic acid, TO. We were also interested in comparing the efficacy rates within these three groups. Methods We assessed 45 patients from a headache clinic in Rio de Janeiro (35 women and 10 men, ages 18 to 65 years, mean 37 years. Patients with IHS migraine were randomized to one out of 3 groups, where they had to treat 6 consecutive moderate or severe attacks in counterbalanced order. In group 1, patients treated the first two attacks with 10 mg RI, the third and fourth attacks with RI + 50 mg RO and the last attacks with RI + 200 mg of TA. In group 2, we began with RI + TA, followed by RI, and RI + RO. Group 3 treated in the following order: RI + RO, RI + TA, RI alone. The presence of headache, nausea and photophobia at 1, 2 and 4 hours, as well as recurrence and side effects were compared. Results A total of 33 patients finished the study, treating 184 attacks. The pain-free rates at 1 hour were: RI: 15.5%; RI + RO: 22.6%; RI + TA: 20.3%(NS. Pain-free rates at 2 h were: RI: 37.9%; RI + RO: 62.9%, and RI + TA: 40.6% (p = 0.008 for RI vs. RI + RO; p = 0.007 for RI + RO vs. RI + TA, NS for RI vs RI + TA. At 4 h, pain-free rates were: RI: 69%; RI + RO: 82.3%; RI + TA: 78.1% (NS for all comparisons. The combination of RI + RO was superior to RI and to RI + TA in regard of the absense of nausea and photophobia at 4 hours. Recurrence (after being pain-free at 2 h was

  4. Polymeric Framboidal Nanoparticles Loaded with a Carbon Monoxide Donor via Phenylboronic Acid-Catechol Complexation.

    Science.gov (United States)

    van der Vlies, André J; Inubushi, Ryosuke; Uyama, Hiroshi; Hasegawa, Urara

    2016-06-15

    Carbon monoxide (CO) is an essential gaseous signaling molecule in the human body. Toward the controlled delivery of CO to the target tissues or cells, nanomaterial-based CO donors have attracted growing attention. Here, we present CO-releasing polymeric nanoparticles (CONPs) prepared by simple mixing of phenylboronic acid-containing framboidal nanoparticles with the catechol-bearing CO-donor Ru(CO)3Cl(L-DOPA) via phenylboronic acid-catechol complexation. The CONPs release CO in response to cysteine and suppress the production of the pro-inflammatory mediators interleukin 6 (IL-6) and nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophages. This CONP platform may show promise in therapeutic applications of CO.

  5. Influence of solid loading on D-xylose production through dilute sulphuric acid hydrolysis of olive stones

    Directory of Open Access Journals (Sweden)

    Cuevas, M.

    2015-09-01

    Full Text Available The selective hydrolysis of hemicellulose from olive stones was attempted in order to achieve a maximum D-xylose yield. For this aim, batch hydrolysis was conducted under different operating conditions of temperature, acid concentration and solid loading. Firstly, distilled water, sulphuric acid and nitric acid were assessed as hydrolytic agents at different temperatures (200, 205, 210 and 220 °C and at a fixed acid concentration (0.025 M. Sulphuric acid and 200 °C were selected for the subsequent dilute acid hydrolysis optimization based on the obtained D-xylose yields. The combined influence of solid loading (from 29.3 to 170.7 g olive stones into 300 mL acid solution and sulphuric acid concentration (0.006–0.034 M on the release of D-xylose was then estimated by response surface methodology. According to a statistical analysis, both parameters had significant interaction effects on D-xylose production. The results illustrated that the higher the solid loading, the higher the required acid concentration. The decrease in the solid/liquid ratio in the reactor had a positive effect on D-xylose extraction and on the amount of acid used. The optimum solid loading and sulphuric acid concentration were determined to be 50 g (solid/liquid ratio 1/6 and 0.016 M, respectively. Under these conditions, the predicted D-xylose yield (expressed as g of sugar per 100 g of dry matter fed was 20.4 (87.2% of maximum attainable.Se ha desarrollado una hidrólisis selectiva de la fracción hemicelulósica del hueso de aceituna con el fin de obtener el máximo rendimiento de D-xilosa. Para ello las hidrólisis se llevaron a cabo en un reactor discontinuo a distintas condiciones de temperatura, concentración de ácido y carga de sólidos. En primer lugar se evaluó la capacidad hidrolítica del agua destilada y de los ácidos nítrico y sulfúrico a distintas temperaturas (200, 205, 210 y 220°C manteniendo fija la concentración de ácido (0,025 M. A partir de

  6. Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management

    Directory of Open Access Journals (Sweden)

    K. Govind Babu

    2016-01-01

    Full Text Available Background. Acute promyelocytic leukemia is characterized by t(15;17. This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA, a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.

  7. Role of carglumic acid in the treatment of acute hyperammonemia due to N-acetylglutamate synthase deficiency

    Directory of Open Access Journals (Sweden)

    Häberle J

    2011-08-01

    Full Text Available Johannes HäberleKinderspital Zürich, Abteilung Stoffwechsel, Zürich, SwitzerlandAbstract: N-acetylglutamate synthase (NAGS deficiency is a rare inborn error of metabolism affecting ammonia detoxification in the urea cycle. The product of NAGS is N-acetylglutamate which is the absolutely required allosteric activator of the first urea cycle enzyme carbamoylphosphate synthetase 1. In defects of NAGS, the urea cycle function can be severely affected resulting in fatal hyperammonemia in neonatal patients or at any later stage in life. NAGS deficiency can be treated with a structural analog of N-acetylglutamate, N-carbamyl-L-glutamate, which is available for enteral use as a licensed drug. Since NAGS deficiency is an extremely rare disorder, reports on the use of N-carbamyl-L-glutamate are mainly based on single patients. According to these, the drug is very effective in treating acute hyperammonemia by avoiding the need for detoxification during the acute metabolic decompensation. Also during long-term treatment, N-carbamyl-L-glutamate is effective in maintaining normal plasma ammonia levels and avoiding the need for additional drug therapy or protein-restricted diet. Open questions remain which concern the optimal dosage in acute and long-term use of N-carbamyl-L-glutamate and potential additional disorders in which the drug might also be effective in treating acute hyperammonemia. This review focuses on the role of N-carbamyl-L-glutamate for the treatment of acute hyperammonemia due to primary NAGS deficiency but will briefly discuss the current knowledge on the role of N-carbamyl-L-glutamate for treatment of secondary NAGS deficiencies.Keywords: carglumic acid, carbamylglutamate, N-carbamyl-L-glutamate, N-acetylglutamate synthase deficiency, NAGS deficiency, hyperammonemia

  8. Neuroprotective effect of suppression of astrocytic activation by arundic acid on brain injuries in rats with acute subdural hematomas.

    Science.gov (United States)

    Wajima, Daisuke; Nakagawa, Ichiro; Nakase, Hiroyuki; Yonezawa, Taiji

    2013-06-26

    Acute subdural hematoma (ASDH) can cause massive ischemic cerebral blood flow (CBF) underneath the hematoma, but early surgical evacuation of the mass reduces mortality. The aim of this study was to evaluate whether arundic acid improves the secondary ischemic damage induced by ASDH. Our results confirmed that arundic acid decreases the expression of S100 protein produced by activated astrocytes around ischemic lesions due to cytotoxic edema after ASDH as well as reducing infarction volumes and numbers of apoptotic cells around the ischemic lesions. In this study, we also evaluate the relationship of brain edema and the expression of Aquaporin 4 (AQP4) in an ASDH model. The expression of AQP4 was decreased in the acute phase after ASDH. Cytotoxic edema, assumed to be the main cause of ASDH, could also cause ischemic lesions around the edema area. Arundic acid decreased the infarction volume and number of apoptotic cells via suppression of S100 protein expression in ischemic lesions without changing the expression of AQP4.

  9. Core-shell hybrid liposomal vesicles loaded with panax notoginsenoside: preparation, characterization and protective effects on global cerebral ischemia/reperfusion injury and acute myocardial ischemia in rats

    Directory of Open Access Journals (Sweden)

    Zhang J

    2012-08-01

    Full Text Available Jing Zhang,1,* Xizhen Han,1,* Xiang Li,2 Yun Luo,1 Haiping Zhao,1 Ming Yang,1 Bin Ni,1 Zhenggen Liao11Key Laboratory of Modern Preparation of TCM, Ministry of Education, 2National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China*These authors contributed equally to this workPurpose: Novel panax notoginsenoside-loaded core-shell hybrid liposomal vesicles (PNS-HLV were developed to resolve the restricted bioavailability of PNS and to enhance its protective effects in vivo on oral administration.Methods: Physicochemical characterizations of PNS-HLV included assessment of morphology, particle size and zeta potential, encapsulation efficiency (EE%, stability and in vitro release study. In addition, to evaluate its oral treatment potential, we compared the effect of PNS-HLV on global cerebral ischemia/reperfusion and acute myocardial ischemia injury with those of PNS solution, conventional PNS-loaded nanoparticles, and liposomes.Results: In comparison with PNS solution, conventional PNS-loaded nanoparticles and liposomes, PNS-HLV was stable for at least 12 months at 4°C. Satisfactory improvements in the EE% of notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were shown with the differences in EE% shortened and the greater controlled drug release profiles were exhibited from PNS-HLV. The improvements in the physicochemical properties of HLV contributed to the results that PNS-HLV was able to significantly inhibit the edema of brain and reduce the infarct volume, while it could markedly inhibit H2O2, modified Dixon agar, and serum lactate dehydrogenase, and increase superoxide dismutase (P < 0.05.Conclusion: The results of the present study imply that HLV has promising prospects for improving free drug bioactivity on oral administration.Keywords: liposomes, nanoparticles, panax notoginsenoside, physicochemical properties

  10. Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star-shaped poly(lactic-co-glycolic acid

    Directory of Open Access Journals (Sweden)

    Chen Y

    2013-11-01

    Full Text Available Yongxia Chen,1,3,* Ziying Yang,1,* Chao Liu,1 Cuiwei Wang,1 Shunxin Zhao,2 Jing Yang,1 Hongfan Sun,1 Zhengpu Zhang,2 Deling Kong,1 Cunxian Song1 1Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, 2Institute of Polymer Chemistry, Nankai University, 3Center for Medical Device Evaluation of Tianjin, Tianjin, People's Republic of China  *These authors contributed equally to this work 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

  11. Photodynamic therapy of tumors with pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles

    Science.gov (United States)

    Liu, Hui; Zhao, Mei; Wang, Jin; Pang, Mingpei; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan; Hong, Zhangyong

    2016-01-01

    Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light. Systemically delivered NPs were highly enriched in tumor sites, and completely ablated the tumors in a xenograft KB tumor mouse model when illuminated with 680 nm light (156 mW/cm2, 10 minutes). The results suggested that this tumor-specific NP-delivery system for pyropheophorbide-a has the potential to be used in tumor-targeted PDT. PMID:27729788

  12. Preparation and Photodynamic Anti-tumor Activity of Magnetic Polylactic Acid Nanoparticles Loaded with Photosensitizer

    Institute of Scientific and Technical Information of China (English)

    YANG Xiao-xia; HUANG Hui; CHEN Zhi-long; HUANG Peng; SUN Yun; ZHOU Xing-ping

    2010-01-01

    A novel magnetic nanocarrier was strategically designed and successfully prepared. Photosensitizer 2, 7,12, 18-tetramethyl-3, 8-di-(1-propoxyethyl)-13, 17-bis-( 3-hydroxypropyl ) porphyrin ( PHPP ) wasencapsulated into polylactic acid (PLA)-coated Fe3O4nanoparticles. The diameter of nanocarrier is 30-50 nm by transmission electron micrograph ( TEM ). The encapsulation efficiency of photosensitizer is 27.98% calculated from UV-vis absorption spectra. The nanocarrier shows obvious photocytotoxic activity to Hela299 tumor cells in vitro.

  13. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections.

    Science.gov (United States)

    Flores, Claudia; Degoutin, Stephanie; Chai, Feng; Raoul, Gwenael; Hornez, Jean-Chritophe; Martel, Bernard; Siepmann, Juergen; Ferri, Joel; Blanchemain, Nicolas

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60μm, allowing for incorporation inside the macropores (100μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25-30days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions.

  14. Preparation, characterization, and in vivo study of rhein-loaded poly(lactic-co-glycolic acid nanoparticles for oral delivery

    Directory of Open Access Journals (Sweden)

    Yuan Z

    2015-04-01

    Full Text Available Zheng Yuan, Xinhua GuDepartment of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou, People’s Republic of ChinaAbstract: A novel rhein formulation based on poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs suitable for oral administration was developed in this study. The designed nanosystems were obtained by a modified spontaneous emulsification solvent diffusion method. The morphology of rhein-loaded PLGA NPs showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the NPs was 140.5±4.3 nm, and the zeta potential was -16.9±3.1 mV. The average drug loading was 3.9%±0.7%, and encapsulation efficiency was 84.5%±6.2%. Meanwhile, NPs are characterized by the slower release (only about 70% of rhein is released within 5 hours, and the model that fitted best for rhein released from the NPs was Higuchi kinetic model with correlation coefficient r=0.9993, revealing that rhein could be controlled released from the NPs. In vivo, NPs altered the distribution of rhein, and the half-life after oral administration was prolonged remarkably more than those of suspensions (22.6 hours vs 4.3 hours. The pharmacokinetic results indicated that the NPs had sustained-release efficacy. The area under the curve0–∞ of the NPs formulation was 3.07-fold higher than that of suspensions, suggesting that the encapsulated rhein had almost been absorbed in rats over the period of 12 hours. Although rhein-loaded PLGA NP formulations are hopefully used as a chemotherapeutic or adjuvant agent for human gastric cancer (SGC-7901, their in vivo antitumor effect and mechanisms at the molecular level still need further study.Keywords: rhein, PLGA, nanoparticles, release, pharmacokinetics, SGC-7901

  15. Alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine: effect against breast cancer in mice.

    Directory of Open Access Journals (Sweden)

    Ze Liu

    Full Text Available Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5 than did chitosan nanoparticles (C.NPs. Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer's patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl2, which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3(+/CD8(+/CD25(+ when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.

  16. Effects of load-volume on EPOC after acute bouts of resistance training in resistance-trained men.

    Science.gov (United States)

    Abboud, George J; Greer, Beau K; Campbell, Sara C; Panton, Lynn B

    2013-07-01

    Recent investigations have shown excess postexercise oxygen consumption (EPOC) to be elevated for up to 48 hours in both untrained and trained subjects after resistance training (RT). The purpose of this study was to investigate the effect of load-volume on EPOC. Eight trained men (aged 22 ± 3 years) participated in 2 randomized RT bouts separated by at least 1 week with total load-volumes of 10,000 and 20,000 kg, respectively. Intensity of RT (85% 1 repetition maximum) did not differ between trials. Exercise energy expenditure and resting metabolic rate (RMR) were measured by indirect calorimetry at 8.5 hours before, 1.5 hours before, and during RT bouts and 12, 24, 36, and 48 hours after exercise. Creatine kinase (CK) was measured before and after RT, and 12, 24, 36, and 48 hours postexercise; ratings of perceived muscle soreness were measured on a similar time course save the immediate postexercise time point. Analysis of variance with repeated measures was used to analyze dependent variables. During the 20,000 kg trial, subjects expended significantly (p EPOC above baseline RMR.

  17. Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives.

    Science.gov (United States)

    Xie, Tian; Taylor, Lynne S

    2016-03-07

    Amorphous solid dispersions (ASDs) have been extensively exploited as a strategy for improving the dissolution performance of poorly water-soluble drugs. However, factors underpinning the observed dissolution profiles are not clearly understood, and the choice of polymeric carriers is largely empirical. In the current study, the dissolution performance of a high drug loading ASD containing the poorly water-soluble, anti-inflammatory agent, celecoxib, was optimized by using binary polymers combinations. Polyacrylic acid (PAA), a highly water-soluble polymer, was used to substantially increase the dissolution rate of the drug, while hydroxypropyl methyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS) were added to stabilize the solid amorphous matrix against crystallization upon hydration, as well as to maintain supersaturation. Quantitative measurements of the impact of the polymers on the solution nucleation and growth rates of celecoxib revealed that, while the cellulose derivatives are effective nucleation inhibitors, it is more difficult to completely prevent crystal growth in solutions containing seed crystals, in particular at high supersaturations. Therefore, it is critical to prevent the formation of crystals in the dissolving matrix during dissolution. By using certain ratios of HPMC and PAA, both rapid release as well as crystallization inhibition could be achieved, even at high drug loadings. Utilizing combinations of polymers may therefore be useful to tailor release profiles while providing optimized crystallization inhibition.

  18. Effects Of Polylactic Acid Coating and Compression Load on the Delivery of Protein and Steroid from HA Ceramic Devices.

    Science.gov (United States)

    Benghuzzi, Hamed; Tucci, Michelle A; Ibrahim, Jamil

    2015-01-01

    Density variations, due to particle size and time and temperature of sintering, affect the delivery profile of substances from ceramic delivery devices. This investigation was conducted to study the effect of polylactic acid (PLA) impregnation on the porosity of hydroxyapatite (HA) capsules by studying the delivery rate of bovine serum albumin (BSA) and testosterone (TE). HA capsules were fabricated by cold compressing calcined particles at 1000, 3000, and 5000 lbs. Each group was subdivided into PLA-impregnated and non-PLA impregnated capsules. Each capsule was loaded with either 40 mg of TE (impregnated or nonimpregnated with PLA polymer) or BSA. Data obtained in this study suggest that: (1) PLA impregnation of HA ceramic capsules decreases the rate of release of drugs from the ceramic reservoir, (2) Physiochemical characteristics of the drugs to be delivered is an instrumental key in the sustained release profiles, (3) Compression load of HA reservoirs is a key factor in predicting the duration and level of sustained delivery, and (4) Polymer coating of HA ceramic capsules reduces the pore size, as well as, blocking some of the pores on the surface.

  19. Investigation of cutaneous penetration properties of stearic acid loaded to dendritic core-multi-shell (CMS) nanocarriers.

    Science.gov (United States)

    Lohan, S B; Icken, N; Teutloff, C; Saeidpour, S; Bittl, R; Lademann, J; Fleige, E; Haag, R; Haag, S F; Meinke, M C

    2016-03-30

    Dendritic core-multi shell (CMS) particles are polymer based systems consisting of a dendritic polar polyglycerol polymer core surrounded by a two-layer shell of nonpolar C18 alkyl chains and hydrophilic polyethylene glycol. Belonging to nanotransport systems (NTS) they allow the transport and storage of molecules with different chemical characters. Their amphipihilic character CMS-NTS permits good solubility in aqueous and organic solutions. We showed by multifrequency electron paramagnetic resonance (EPR) spectroscopy that spin-labeled 5-doxyl stearic acid (5DSA) can be loaded into the CMS-NTS. Furthermore, the release of 5DSA from the carrier into the stratum corneum of porcine skin was monitored ex vivo by EPR spectroscopy. Additionally, the penetration of the CMS-NTS into the skin was analyzed by fluorescence microscopy using indocarbocyanine (ICC) covalently bound to the nanocarrier. Thereby, no transport into the viable skin was observed, whereas the CMS-NTS had penetrated into the hair follicles down to a depth of 340 μm ± 82 μm. Thus, it could be shown that the combined application of fluorescence microscopy and multi-frequency EPR spectroscopy can be an efficient tool for investigating the loading of spin labeled drugs to nanocarrier systems, drug release and penetration into the skin as well as the localization of the NTS in the skin.

  20. Microbial load, acidity, lipid oxidation and volatile basic nitrogen of irradiated fish and meat-bone meals.

    Science.gov (United States)

    Al-Masri, M R; Al-Bachir, M

    2007-04-01

    Experiments were carried out to study the effect of different doses of gamma irradiation (0, 5, 10, 15 and 20 kilo gray; kGy) on some nutritive components and chemical aspects pertaining to quality of fish meal and meat-bone meal. The radiation doses required to reduce the total microbial load and Salmonella sp. one log cycle (D(10)) in fish meal and meat-bone meal were determined. Results indicated that gamma irradiation of fish meal and meat-bone meal with 5-20 kGy doses had no effects on the total acidity values but increased the values of lipid oxidation and total volatile basic nitrogen. D(10) of total microbial load and Salmonella sp. were 833 and 313 Gy for fish meal and 526 Gy and 278 Gy for meat-bone meal, respectively. It can be concluded that radiation processing could be employed in the recycling of fish and meat-bone meals by using them as feedstuffs in poultry diets with no fear of losing their nutritive components.

  1. Preparation of five 3-MCPD fatty acid esters and the effects of their chemical structures on acute oral toxicity in Swiss mice

    Science.gov (United States)

    Fatty acid esters of 3-monochloro-1, 2-propanediol (3-MCPDEs), including 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters, were synthetized and examined for their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and...

  2. Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?

    DEFF Research Database (Denmark)

    Major-Pedersen, A; Ihlemann, N; Hermann, T S;

    2008-01-01

    The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin....... We found no relationship between postprandial hyperglycemia and post-OGL FMD....

  3. A rapid food screener ranks potential renal acid load of renal stone formers similarly to a diet history questionnaire.

    Science.gov (United States)

    Trinchieri, Alberto

    2013-02-01

    Dietary acid load was reported to be inversely related to urinary citrate excretion. The calcium renal stone formers (RSFs) should be recommended to lower their dietary potential renal acid load (PRAL) to reduce stone recurrence. Reduction of dietary PRAL also showed a promising role for the prevention of other metabolic diseases. However, clinicians often fail to provide nutritional screening and counseling due to lack of simple tools to obtain a reliable dietary history. A one-page food screener (LAKE score) was recently designed to obtain a reliable measure of dietary PRAL in short time. We report the testing of such an instrument in the evaluation of PRAL: in a population of 135 healthy subjects (60 males, 75 females; age range 18-73), living in the area of Milan, Italy. Each participant received both the one-page LAKE food screener and an extensive 24-h dietary questionnaire. We examined agreement between the LAKE food screener scores, and estimates of PRAL and other nutrients produced by the computerized processing of thorough 24-h dietary histories. Spearman rank order correlation coefficient (r > 0.50) showed that LAKE score ranked subjects quite well with respect to dietary PRAL. LAKE positive subscore ranked patients with respect to dietary intake of total protein (r = 0.642) and phosphate (r = 0.648). We also obtained an excellent correlation of LAKE negative subscore with potassium intake (r = -0.531) and vitamin C (r = -0.554) as estimated by 24 h recalls. The LAKE score ranked patients similar to the estimates of 24-h dietary recalls, used as the "gold standard" for the evaluation of dietary PRAL. This rapid, simple and inexpensive food screener for the evaluation of dietary PRAL could provide a "snapshot" of the diet of the RSFs to allow an immediate feedback to the patient during office consultation.

  4. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

    Objective:Impaired active fluid transport of alveolar epithelium may involve in the pathogenesis and resolution of alveolar edema. Thc objective of this study was to explore the changes in alveolar epithelial liquid clearance during lung edema following acute lung injury induced by oleic acid. Methods:Forty-eight Wistar rats were randomly divided into six groups, I.e. , injured, amiloride, ouabain, amiloride plus ouabain and terbutaline groups. Twenty- four hours after the induction of acute lung injury by intravenous oleic acid (0.25 ml/kg), 5% albumin solution with 1.5 μCi 125Ⅰ-labeled albumin (5 ml/kg) was delivered into both lungs via trachea. Alveolar liquid clearance (ALC), extravascular lung water ( EVLW ) content and arterial blood gases were measured one hour thereafter.Results: At 24 h after the infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with EVLW increased by 47.9% and ALC decreased by 49.2%. Addition of either 2 × 10-3 M amiloride or 5 × 10-4 M ouabain to the instillation further reduced ALC and increased EVLW. ALC increased by approximately 63.7% and EVLW decreased by 46.9% with improved hypoxemia in the Terbutaline (10-4 M) group, compared those in injured rats. A significant negative correlation was found between the increment of EVLW and the reduction of ALC. Onclusions:Active fluid transport of alveolar epithelium might play a role in the pathogenesis of lung edema in acute lung injury.

  5. Folic acid mediated solid lipid nanocarriers loaded with docetaxel and oxidized single-walled carbon nanotubes

    Science.gov (United States)

    Zhu, Xiali; Huang, Shengnan; Xie, Yingxia; Zhang, Huijuan; Hou, Lin; Zhang, Yingjie; Huang, Heqing; Shi, Jinjin; Wang, Lei; Zhang, Zhenzhong

    2014-01-01

    Single-walled carbon nanotubes (SWNT) possess high-near-infrared absorption coefficient, large surface area, and have great potential in drug delivery. In this study, we obtained ultrashort oxidized SWNT (OSWNT) using mixed acid oxidation method. Then, docetaxel (DTX) and folic acid (FA) are conjugated with OSWNT via π- π accumulation and amide linkage, respectively. A targeting and photothermal sensitive drug delivery system FA-DTX-OSWNT-SLN was prepared following a microemulsion technique. The size and zeta potential of FA-DTX-OSWNT-SLN were 182.8 ± 2.8 nm and -34.59 ± 1.50 mV, respectively. TEM images indicated that FA-DTX-OSWNT-SLN was spherical and much darker than general solid lipid nanoparticles (SLN). Furthermore, OSWNT may wind round, insert into or be encapsulated into the nanocarriers. Compared with free DTX, FA-DTX-OSWNT-SLN could efficiently cross cell membranes and afford higher antitumor efficacy in MCF-7 cells in vitro. Meanwhile, the combination of near-infrared laser (NIR) irradiation at 808 nm significantly enhanced cell inhibition. In conclusion, FA-DTX-OSWNT-SLN drug delivery system in combination with 808 nm NIR laser irradiation may be promising for targeting and photothermal cancer therapy with multiple mechanisms in future.

  6. Foliar loading and metabolic assimilation of dry deposited nitric acid air pollutants by trees.

    Science.gov (United States)

    Padgett, Pamela E; Cook, Hillary; Bytnerowicz, Andrzej; Heath, Robert L

    2009-01-01

    Dry deposition of nitric acid vapor (HNO(3)) is a major contributor to eutrophication of natural ecosystems. Although soil fertilization by nitrogen deposition is considered to be the primary pathway for changes in plant nutrient status and shifts in ecological structure, the aerial portion of plants offer many times the surface area in which to collect atmospheric HNO(3). As much as 60% of deposited nitrogen may be retained in the canopy and not land on the soil surface below. Although uptake and assimilation appears to contribute to retention, only a small percentage of dry deposition is recovered in assimilated N pools. To test the importance of biological activity on the process and measurements of dry deposition, we used controlled environmental chambers to compare deposition to living and freeze-dried foliage of four tree species using (15)N-labeled HNO(3). In living trees, assimilation was determined by (15)N incorporation into free amino acids and proteins in leaves and roots. From 10% to 60% of the retained HNO(3) was incorporated into the biologically active nitrogen pool. The remainder was bound to foliar surfaces in an insoluble form in either living or freeze-dried foliage. The importance of the boundary layer conditions emerged as a primary factor controlling dry deposition characteristics and measurements.Trade names and commercial enterprises or products are mentioned solely for information. No endorsements by the U.S. Department of Agriculture are implied.

  7. Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold

    Directory of Open Access Journals (Sweden)

    Zhi-Dong Cao

    2016-01-01

    Full Text Available Background: Recently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo. Methods: According to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated. Results: In the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1. The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L, and the function and histomorphology of the liver and kidney were all normal. Conclusion: According to ISO standards, the V-BHA/PAA scaffold

  8. Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold

    Institute of Scientific and Technical Information of China (English)

    Zhi-Dong Cao; Dian-Ming Jiang; Ling Yan; Jun Wu

    2016-01-01

    Background:Recently,local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration,and thereby effectively decrease any systemic toxicity and side effects.A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA) bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA,which was demonstrated to exhibit both porosity and perfect biodegradability.The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo.Methods:According to the ISO rules for medical implant biosafety,for in vitro tests,the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood,with simultaneous creation of positive control and negative control groups.The growth condition ofL929 cells and hemolytic ratio were respectively evaluated after various incubation periods.For in vivo tests,a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established.After bacterial identification,the drug-loaded scaffold,drug-unloaded BHA/PAA,and poly (methyl methacrylate) were implanted,and a blank control group was also set up.Subsequently,the in vivo blood drug concentrations were measured,and the kidney and liver functions were evaluated.Results:In the in vitro tests,the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1.The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%,respectively,both below 5%.In the in vivo tests,the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L),and the function and histomorphology of the liver and kidney were all normal.Conclusion:According to ISO standards,the V-BHA/PAA scaffold is considered to have sufficient safety for

  9. EFFECTS OF ACETYLSALICYLIC ACID AND CLOPIDOGREL ON MORPHOFUNCTIONAL STATUS OF ERYTHROCYTES IN PATIENTS WITH ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    A. L. Alyavi

    2016-01-01

    Full Text Available Aim. In patients with acute coronary syndrome (ACS to study an aggregation activity and morphology of erythrocytes and to assess their changes during therapy with acetylsalicylic acid, clopidogrel and combined antiplatelet therapy (acetylsalicylic acid and clopidogrel.Material and methods. 98 patients (67 men and 31 women, aged 59,6±10,8 y.o. with ACS were included in the study. Patients were split in 3 groups depending on prescribed antiplatelets (acetylsalicylic acid; clopidogrel; acetylsalicylic acid+clopidogrel. Aggregation activity and morphofunctional status of erythrocytes were evaluated at baseline, after 3 and 7 days of treatment.Results. The highest efficacy of antiaggregant therapy was observed in patients receiving antiplatelet combination. In this group there was a maximal reduction of erythrocyte aggregation and a number of pathological erythrocytes in peripheral blood by the 3rd day of therapy. This effect was increasing by the 7th day.Conclusion. The effect of all antiplatelet drugs was significant. The antiaggregant effect of clopidogrel was more significant than this for acetylsalicylic acid. Efficacy of combined therapy was higher than these for each drug alone. 

  10. EFFECTS OF ACETYLSALICYLIC ACID AND CLOPIDOGREL ON MORPHOFUNCTIONAL STATUS OF ERYTHROCYTES IN PATIENTS WITH ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    A. L. Alyavi

    2009-01-01

    Full Text Available Aim. In patients with acute coronary syndrome (ACS to study an aggregation activity and morphology of erythrocytes and to assess their changes during therapy with acetylsalicylic acid, clopidogrel and combined antiplatelet therapy (acetylsalicylic acid and clopidogrel.Material and methods. 98 patients (67 men and 31 women, aged 59,6±10,8 y.o. with ACS were included in the study. Patients were split in 3 groups depending on prescribed antiplatelets (acetylsalicylic acid; clopidogrel; acetylsalicylic acid+clopidogrel. Aggregation activity and morphofunctional status of erythrocytes were evaluated at baseline, after 3 and 7 days of treatment.Results. The highest efficacy of antiaggregant therapy was observed in patients receiving antiplatelet combination. In this group there was a maximal reduction of erythrocyte aggregation and a number of pathological erythrocytes in peripheral blood by the 3rd day of therapy. This effect was increasing by the 7th day.Conclusion. The effect of all antiplatelet drugs was significant. The antiaggregant effect of clopidogrel was more significant than this for acetylsalicylic acid. Efficacy of combined therapy was higher than these for each drug alone. 

  11. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections

    Energy Technology Data Exchange (ETDEWEB)

    Flores, Claudia [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Degoutin, Stephanie [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Chai, Feng [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Raoul, Gwenael [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Hornez, Jean-Chritophe [Laboratoire des Matériaux Céramiques et Procédés Associés (LMCPA), Université de Valenciennes, 59300 Valenciennes (France); Martel, Bernard [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Siepmann, Juergen [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Ferri, Joel [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Blanchemain, Nicolas, E-mail: nicolas.blanchemain@univ-lille2.fr [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France)

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60 μm, allowing for incorporation inside the macropores (100 μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25–30 days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions. - Highlights: • The optimization of microparticle preparation parameters allows to obtain a size compatible with the bone substitute porosity • PDL% has a direct impact on the burst effect, a control release of gentamicin was obtained • The incorporation of microparticles into the

  12. Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy.

    Science.gov (United States)

    Stalmach, Angélique; Steiling, Heike; Williamson, Gary; Crozier, Alan

    2010-09-01

    The intestinal absorption and metabolism of 385 micromol chlorogenic acids following a single intake of 200 mL of instant coffee by human volunteers with an ileostomy was investigated. HPLC-MS(3) analysis of 0-24h post-ingestion ileal effluent revealed the presence of 274+/-28 micromol of chlorogenic acids and their metabolites accounting for 71+/-7% of intake. Of the compounds recovered, 78% comprised parent compounds initially present in the coffee, and 22% were metabolites including free and sulfated caffeic and ferulic acids. Over a 24h period after ingestion of the coffee, excretion of chlorogenic acid metabolites in urine accounted for 8+/-1% of intake, the main compounds being ferulic acid-4-O-sulfate, caffeic acid-3-O-sulfate, isoferulic acid-3-O-glucuronide and dihydrocaffeic acid-3-O-sulfate. In contrast, after drinking a similar coffee, urinary excretion by humans with an intact colon corresponded to 29+/-4% of chlorogenic acid intake. This difference was due to the excretion of higher levels of dihydroferulic acid and feruloylglycine together with sulfate and glucuronide conjugates of dihydrocaffeic and dihydroferulic acids. This highlights the importance of colonic metabolism. Comparison of the data obtained in the current study with that of Stalmach et al. facilitated elucidation of the pathways involved in post-ingestion metabolism of chlorogenic acids and also helped distinguish between compounds absorbed in the small and the large intestine.

  13. Preparation, characterization, and antibacterial activity studies of silver-loaded poly(styrene-co-acrylic acid) nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Song, Cunfeng [Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005 (China); Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China); Chang, Ying; Cheng, Ling; Xu, Yiting [Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005 (China); Chen, Xiaoling, E-mail: tinachen0628@163.com [Department of Endodontics, Xiamen Stomatology Hospital, Teaching Hospital of Fujian Medical University, Xiamen 361003 (China); Zhang, Long; Zhong, Lina [Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005 (China); Dai, Lizong, E-mail: lzdai@xmu.edu.cn [Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005 (China)

    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. - Highlights: • A new type of antibacterial agent (PSA/Ag-NPs nanocomposites) was synthesized. • The antibacterial activity against S. aureus and E. coli was studied. • Inhibition zone, MIC, MBC, and bactericidal kinetics were evaluated. • PSA/Ag-NPs nanocomposites showed excellent antibacterial activity.

  14. Hyaluronic Acid/PLGA Core/Shell Fiber Matrices Loaded with EGCG Beneficial to Diabetic Wound Healing.

    Science.gov (United States)

    Shin, Yong Cheol; Shin, Dong-Myeong; Lee, Eun Ji; Lee, Jong Ho; Kim, Ji Eun; Song, Sung Hwa; Hwang, Dae-Youn; Lee, Jun Jae; Kim, Bongju; Lim, Dohyung; Hyon, Suong-Hyu; Lim, Young-Jun; Han, Dong-Wook

    2016-12-01

    During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration.

  15. Synthesis of multifunctional Ag@Au@phenol formaldehyde resin particles loaded with folic acids for photothermal therapy.

    Science.gov (United States)

    Yang, Ping; Xu, Qi-Zhi; Jin, Sheng-Yu; Lu, Yang; Zhao, Yang; Yu, Shu-Hong

    2012-07-23

    Multifunctional Ag@Au@ phenol formaldehyde resin (PFR) particles loaded with folic acids (FA) have been designed for killing tumor cells through photothermy conversion under the irradiation of near-infrared (NIR) light. Possessing the virtue of good fluorescence, low toxicity, and good targeting, the nanocomposite consists of an Ag core, an Au layer, a PFR shell, and folic acids on the PFR shell. The Ag@PFR core-shell structure can be prepared with a simple hydrothermal method after preheating. We then filled the PFR shell with a layer of Au by heating and modified the shell with polyelectrolyte to change its surface charge state. To capture tumor cells actively, FA molecules were attached onto the surface of the Ag@Au@PFR particles in the presence of 1-ethyl-3-(3-dimethly aminopropyl) carbodiimide (EDAC) and N-hydroxysuccinimide (NHS). Owing to the excellent property of Au NPs and Ag NPs as photothermal conversion agents, the Ag@Au@ PFR@FA particles can be utilized to kill tumor cells when exposed to NIR light.

  16. Discordant findings of dimercaptosuccinic acid scintigraphy in children with multi-detector row computed tomography-proven acute pyelonephritis

    Directory of Open Access Journals (Sweden)

    Jeongmin Lee

    2011-05-01

    Full Text Available Purpose : The diagnosis of acute pyelonephritis (APN is often difficult, as its clinical and biological manifestations are non-specific in children. If not treated quickly and adequately, however, APN may cause irreversible renal damage, possibly leading to hypertension and chronic renal failure. We were suspecting the diagnostic value of 99mTc-dimercaptosuccinic acid (DMSA scan by experiences and so compared the results of DMSA scan to those of multi-detector row computed tomography (MDCT. Methods : We retrospectively selected and analyzed 81 patients who were diagnosed as APN by MDCT during evaluation of their acute abdomen in emergency room and then received DMSA scan also for the diagnostic work-up of APN after admission. We evaluated the results of imaging studies and compared the diagnostic value of each method by age groups, &lt;2 years (n=45 and ?#242; years (n=36. Results : Among total 81 patients with MDCT-proven APN, DMSA scan was diagnostic only in 55 children (68%, while the remaining 26 children (32% showed false negative normal findings. These 26 patients were predominantly male and most of them, 19 (73.1% were &lt;2 years of age. Conclusion : DMSA scan holds obvious limitation compared to MDCT in depicting acute inflammatory lesions of kidney in children with APN, especially in early childhood less than 2 years of age. MDCT showed hidden lesions of APN, those were undetectable through DMSA scan in children.

  17. Physiological study on CT image analysis of acute pulmonary edema by oleic acid and its application to diagnosis of drowning

    Energy Technology Data Exchange (ETDEWEB)

    Nosaka, Mizuho [Wakayama Medical Coll. (Japan)

    1998-05-01

    Recently, various investigations are carried out about the relationship between the pathophysiological changes and the images of the destructive extent in acute lung injury. In present paper, we examined, in progression time, the pathophysiological and histological changes basing upon pulmonary edema model made by administration of oleic acid to beagle dogs, and simultaneously took images of the lung by employing high-resolution X-ray CT and analyzed them. In pathophysiological and histological investigation, V{sub A}/Q heterogeneity and lung water volume increased, and decrease of PO{sub 2} in arterial blood was observed, and also filling of the alveoli with exudate, edema of the alveolar interstitium, congestion of the alveoli were observed histologically. In image analysis, the findings, that is enough to reflect the pathophysiological and histological changes, were obtained from mean CT value and the distribution of CT value histogram. Moreover, the same examination as in acute pulmonary edema model was carried out in drowning model with seawater. Consequently, it became evident that presuming of pathophysiological changes in drowning was possible from results of X-ray CT image analysis. The results described above seem to indicate that X-ray CT image analysis in acute lung injury can use as an index of the damage degree, and also is available for elucidation of the pathophysiological changes. (author)

  18. Genital Ulcer Development in Patients with Acute Promyelocytic Leukaemia Treated with All-Trans Retinoic Acid: A Case Series

    Directory of Open Access Journals (Sweden)

    Mohammed Al Huneini

    2013-05-01

    Full Text Available We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA for the treatment of acute promyelocytic leukemia (APL. Between October 2007 and March 2010, three males and one female (age range 19-35 years were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted.

  19. Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Lei Yu; Yang-De Zhang; Jun Zhou; De-Ming Yao; Xiang Li

    2013-01-01

    Objective: To indentify target genes of transcription factor CCAAT enhancer-binding proteinβ (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid. Methods:A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified. Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA. Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.

  20. Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with acute coronary syndrome: A systematic review and meta-analysis

    Science.gov (United States)

    Su, Qiang; Guo, Wenqin; Dai, Weiran; Li, Hongqing; Yang, Huafeng; Li, Lang

    2017-01-01

    Background Acute coronary syndrome (ACS) is an important disease threatening human life and health. Many studies have shown that the loading dose of atorvastatin can significantly improve the prognosis of patients with ACS, and reduce the mortality. However, this conclusion is not consistent. Thus, we aimed to evaluate the effect of high-dose rosuvastatin loading before percutaneous coronary intervention (PCI) in Chinese patients with ACS using a meta-analysis based on a systematic review of published articles. Methods We systematically reviewed published studies, evaluating the effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with ACS. The retrieval time is limited from inception to 2 November 2016, and the retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database and the Wang Fang database. Two researchers independently assessed the quality of the included studies and then extracted the data. Stata 11.0 was used for data analysis. Results In total, 11 articles, which included 802 patients, were included in our meta-analysis. Among these patients, 398 patients were in the high-dose group (20 mg/day) and 404 patients were in the conventional dose group (10 mg/day). Meta-analysis results showed that compared with the conventional dose group: 1) The loading dose of rosuvastatin can significantly reduce the hs-CRP level after PCI, including at 24 hours (SMD = -0.65, 95%CI -0.84 ~ -0.47, P = 0.000), 48 hours (SMD = -0.40, 95%CI -0.68 ~ -0.11, P = 0.006), and four weeks (SMD = -1.64, 95%CI -2.01 ~ -1.26, P = 0.000). 2) The loading dose of rosuvastatin can significantly reduce the levels of LDL-C and cTnT, including the level of LDL-C at 30 d after PCI (SMD = -0.89, 95%CI -1.10 ~ -0.69, P = 0.000), and the level of cTnT at 24 h after PCI (SMD = -1.93, 95%CI -2.28 ~ -1.59, P = 0.000), and increase the level of HDL-C at 48 h after PCI (SMD = 0.61, 95%CI 0.34 ~ 0.88, P

  1. Large scale load of phosphotungstic acid on multiwalled carbon nanotubes with a grafted poly(4-vinylpyridine) linker

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Junhua, E-mail: jhyuan@zjnu.cn [College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004 (China); Jin Xiaoli; Li Na; Chen Jianrong; Miao Jigen [College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004 (China); Zhang Qixian [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Niu Li, E-mail: lniu@ciac.jl.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Song Jixia [Jilin City Institute of Testing on Product Quality, Jilin 132013 (China)

    2011-11-30

    Highlights: > Carbon nanotubes was grafted with poly(4-vinylpyridine). > Phosphotungstic acid was deposited onto carbon nanotubes with this polymer linker. > This deposition is highly uniform and large scale. > These phosphotungstic acid/carbon nanotubes hybrids can be used as nitrite sensor. > Its linear concentration is 1.2 to 17.5 {mu}M with a detection limit of 0.2 {mu}M. - Abstract: Multiwalled carbon nanotubes (MWCNTs) were grafted with poly(4-vinylpyridine) (PV4P) in aqueous solution by in situ free radical polymerization of 4-vinylpyridine. The as-prepared PV4P-g-MWCNTs hybrids can load phosphotungstic acid (PW) on a large scale by electrostatic interaction, which was characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The as-prepared PWs/PV4P-g-MWCNTs hybrids were modified onto a carbon glassy electrode. Cyclic voltammograms (CVs) show that the electrochemical behavior of the modified electrode follows a four-one-electron surface-confined process of Keggin-type PWs. The modified electrode can be used as a nitrite sensor. The comparison of CVs shows that the response current of nitrite reduction at the electrode modified with PWs/PV4P-g-MWCNTs hybrids is 15 times higher than that of PWs/MWCNTs hybrids in a control experiment at 0.65 V (vs. AgCl). The amperometric i-t curve for the electrode modified with PWs/PV4P-g-MWCNTs hybrids exhibits a linear concentration of NO{sub 2}{sup -} ranged from 1.2 to 17.5 {mu}M with a detection limit of 0.2 {mu}M.

  2. Multifunctional hyaluronic acid modified graphene oxide loaded with mitoxantrone for overcoming drug resistance in cancer

    Science.gov (United States)

    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.

  3. An evaluation of the anti-tumor efficacy of oleanolic acid-loaded PEGylated liposomes

    Science.gov (United States)

    Tang, Shengnan; Gao, Dawei; Zhao, Tingting; Zhou, Jing; Zhao, Xiaoning

    2013-06-01

    The effective delivery of oleanolic acid (OA) to the target site has several benefits in therapy for different pathologies. However, the delivery of OA is challenging due to its poor aqueous solubility. The study aims to evaluate the tumor inhibition effect of the PEGylated OA nanoliposome on the U14 cervical carcinoma cell line. In our previous study, OA was successfully encapsulated into PEGylated liposome with the modified ethanol injection method. Oral administration of PEGylated OA liposome was demonstrated to be more efficient in inhibiting xenograft tumors. The results of organ index indicated that PEG liposome exhibited higher anti-tumor activity and lower cytotoxicity. It was also found that OA and OA liposomes induced tumor cell apoptosis detected by flow cytometry. Furthermore, effects of OA on the morphology of tumor and other tissues were observed by hematoxylin and eosin staining. The histopathology sections did not show pathological changes in kidney or liver in tested mice. In contrast, there was a significant difference in tumor tissues between treatment groups and the negative control group. These observations imply that PEGylated liposomes seem to have advantages for cancer therapy in terms of effective delivery of OA.

  4. Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

    Institute of Scientific and Technical Information of China (English)

    WU Rui-ping; LIANG Xiu-bin; GUO Hui; ZHOU Xiao-shuang; ZHAO Li; WANG Chen; LI Rong-shan

    2012-01-01

    Background Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI).However,LPD solution for treating acute kidney injury secondary to ALI has not been reported.The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.Methods Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups:the placebo group (n=6) pretreated with normal saline and the LPD group (n=6),pretreated with LPD solution.LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.Results All animals survived the experiments with mild histopathological injury to the kidney.There were no significant differences in mean arterial pressure (MAP),creatinin and renal damage scores between the two groups.Compared with the placebo group,the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6)mmHg vs.(284.3±11.3) mmHg at 6 hours after ALI,P<0.01).After 6 hours of treatment with OA,the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group),but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group.And 6 hours after ALl the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg.ml-1.g-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg.ml-1.g-1 protein).Conclusion These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALl piglet model induced by OA injection.

  5. Reverse of Acute and Chronic Morphine Tolerance by Lithocholic Acid via Down-regulating UGT2B7

    Directory of Open Access Journals (Sweden)

    Zizhao Yang

    2016-11-01

    Full Text Available Lithocholic acid (LCA deposited in human livers always induces drastic pains which need analgesic drug, like morphine to release. Our research showed that LCA can effectively inhibit uridine 5'-diphospho-glucuronosyltransferase 2B7 (UGT2B7 in morphine tolerance-like human normal liver cells, HL-7702, then increase μ-opioid receptor (MOR and calcium-calmodulin dependent protein kinase IIα (CaMKIIα expression. In vivo assay, UGT2B7 was significantly repressed in the livers of acute or chronic morphine tolerance mice pretreated with LCA (10, 50 and 100 mg/kg, p.o.. To investigate the connections between LCA function performance and changes of UGT2B7 enzymatic activity in mice livers, two morphine metabolites, morphine-3-glucuronide (M3G and morphine-6-glucuronide (M6G were quantified by solid phase extraction (SPE-HPLC-MS/MS. The result indicated no matter in acute or chronic morphine tolerance, the concentrations of M3G and M6G were all decreased, the later one fell even more. Besides that, 50mg/kg of LCA administration can prevent auto-phosphorylation of CaMKIIα at Thr286 in acute or chronic morphine tolerance mice prefrontal cortexes (mPFCs due to synthesis increase of cyclic adenosine monophosphate (cAMP. As a consequence, UGT2B7 depression mediated by LCA can affect its selective catalysis ability to morphine, that may be responsible to acute or chronic morphine tolerance alleviation. These findings might assist to modify antinociception of morphine in clinic.

  6. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    Science.gov (United States)

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  7. sup 1 H NMR study of renal trimethylamine responses to dehydration and acute volume loading in man

    Energy Technology Data Exchange (ETDEWEB)

    Avison, M.J.; Rothman, D.L.; Nixon, T.W.; Long, W.S.; Siegel, N.J. (Yale Univ. School of Medicine, New Haven, CT (United States))

    1991-07-15

    The authors have used volume-localized {sup 1}H NMR spectroscopy to detect and measure changes in medullary trimethylamines (TMAs) in the human kidney in vivo. Localized water-suppressed {sup 1}H spectra were collected from a volume of interest located within the renal medulla by using a stimulated echo-based localization scheme. The principal resonances in the medullary {sup 1}H spectrum were residual water, lipid, and TMAs. The TMA line width was 7-15 Hz before filtering, and the signal-to-noise ratio was 40:1. In four normal volunteers, 15 hr of dehydration led to a significant increase in urine ismolality and decrease in body weight and an increase in medullary TMAs. A subsequent water load caused a transient water diuresis, a return to euvolemic body weight, and a significant reduction in medullary TMAs within 4 hr. These results suggest that TMAs may play an osmoregulatory role in the medulla of the normal human kidney.

  8. Effect of acute exercise on serum growth hormone and fatty acid levels in elite male water polo players

    Directory of Open Access Journals (Sweden)

    Djelić Marina

    2014-01-01

    Full Text Available The aim of study was to estimate the effect of acute exercise on serum growth hormone (GH and fatty acid (FFA levels in elite water polo players. Twelve male water polo players (20.50 ± 2.02 years and eleven non-athletic male subjects (20.55 ± 1.04 years participated in this study. In order to determine GH and FFA responses to acute exercise, a treadmill-running test was performed following an incremental protocol. Pre-exercise blood samples for both athletes and non-athletes were taken at 9 AM. Post-exercise samples were taken immediately after and 30 min after the treadmill running test. Water polo players had significantly lower baseline values of serum GH concentration compared to controls, whereas serum FFA concentration was significantly higher in water polo players compared to controls (p<0.01; p<0.05, respectively. In both groups, concentration of GH was significantly higher immediately after and after the 30-min of recovery compared to baseline levels (p<0.05. In water polo players, the concentration of FFA was significantly decreased immediately after and after the 30-min of recovery compared to baseline levels (p<0.05. No significant response to maximal exercise test was observed in the control group for serum FFA concentration. Our research indicates that acute exercise resulted in a significant increase in serum GH and reduction in fatty acid levels in elite water polo players. [Projekat Ministarstva nauke Republike Srbije, br. OI 175067

  9. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  10. Randomized comparative study of amoxicillin-clavulanic acid and co-trimoxazole in the treatment of acute urinary tract infections in adults.

    OpenAIRE

    Karachalios, G N

    1985-01-01

    The efficacy and safety of amoxicillin-clavulanic acid were compared with those of co-trimoxazole in the treatment of acute urinary tract infections. A total of 104 patients (mean age, 52 years) with clinical and laboratory evidence of acute urinary tract infection were enrolled in the study. Characteristics and infecting organisms were equivalent in both groups of patients. Escherichia coli was the predominant bacteria pathogen in both groups. Both drugs resulted in clinical improvement in 1...

  11. Study on effects of citric acid induced acid load on salivary secretion%柠檬酸所致酸负荷对唾液分泌影响的研究

    Institute of Scientific and Technical Information of China (English)

    王丽辉; 杨龙; 林传权; 李茹柳; 曾丹; 陈蔚文

    2016-01-01

    目的:考察柠檬酸所致酸负荷对唾液分泌相关指标的影响,以优化柠檬酸负荷方法。方法采集10例健康者第1~90秒(负荷前)、第91~120秒(负荷时)的唾液及第121~210秒(负荷后)的唾液;另混合负荷时和负荷后的唾液进行指标检测。各组均检测唾液淀粉酶(sAA)活性、pH值、唾液流率、总蛋白浓度,并比较各指标酸负荷前后的比值。结果(1)负荷后sAA活性、唾液pH值和总蛋白浓度较负荷前明显增高,且负荷后与负荷前的比值均大于1;(2)但有柠檬酸混合时,sAA活性、唾液pH值、总蛋白浓度均较酸负荷前、后反而降低,其比值均小于1。结论柠檬酸本身明显影响酸负荷唾液分泌结果,建议将酸负荷时的唾液分开处理分析。%Objective To investigate the effects of citric acid on the related indexes of salivary secretion under acid loading in or‐der to optimize the citric acid load method .Methods The saliva samples were collected from 10 young healthy volunteers at 1-90 s before ,at 91-120 s during and at 121-210 s after citric acid loading .The indexes were detected in saliva with mixed loading and after loading .The salivary alpha‐amylase(sAA ) activity ,pH value ,saliva flow rate ,total protein concentration in various groups were detected .The ratio values before and after the acid loading were compared among the groups .Results (1)The sAA activity , saliva pH value and total protein concentrations after acid loading were significantly increased compared before loading (P<0 .05) , moreover the ratio of after loading and before loading was greater than 1(P<0 .05);(2) however in the citric acid mixing ,the sAA activity ,saliva pH value and total protein concentration were decreased compared with before acid loading ,its ratio was less than 1 (P<0 .05) .Conclusion Citric acid affects the secretion result of acid loading saliva secretion ,it is suggested that the

  12. Thyroid hormone reverses aging-induced myocardial fatty acid oxidation defects and improves the response to acutely increased afterload.

    Directory of Open Access Journals (Sweden)

    Dolena Ledee

    Full Text Available BACKGROUND: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to the development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone supplementation reverses these defects. METHODS: Studies were performed on young (Young, 4-6 months and aged (Old, 22-24 months C57/BL6 mice at standard (50 mmHg and high afterload (80 mmHg. Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only. Function was measured in isolated working hearts along with substrate fractional contributions (Fc to the citric acid cycle (CAC using perfusate with (13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. RESULTS: Old mice maintained cardiac function under standard workload conditions, despite a marked decrease in unlabeled (presumably palmitate Fc and relatively similar individual carbohydrate contributions. However, old mice exhibited reduced palmitate oxidation with diastolic dysfunction exemplified by lower -dP/dT. Thyroid hormone abrogated the functional and substrate flux abnormalities in aged mice. CONCLUSION: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  13. Randomized comparative study of amoxicillin-clavulanic acid and co-trimoxazole in the treatment of acute urinary tract infections in adults.

    Science.gov (United States)

    Karachalios, G N

    1985-01-01

    The efficacy and safety of amoxicillin-clavulanic acid were compared with those of co-trimoxazole in the treatment of acute urinary tract infections. A total of 104 patients (mean age, 52 years) with clinical and laboratory evidence of acute urinary tract infection were enrolled in the study. Characteristics and infecting organisms were equivalent in both groups of patients. Escherichia coli was the predominant bacteria pathogen in both groups. Both drugs resulted in clinical improvement in 100% of the patients; bacteriological cure after the termination of therapy was 95% with amoxicillin-clavulanic acid and 83% with co-trimoxazole (P less than 0.001). Side effects were not severe enough to necessitate discontinuation of the antimicrobial agents. Amoxicillin-clavulanic acid is effective and safe therapy for acute urinary tract infections caused by susceptible bacteria. PMID:3911880

  14. Effect of acid secretion blockade on acute gastric mucosal lesions induced by Tityus serrulatus scorpion toxin in anaesthetized rats.

    Science.gov (United States)

    Melo, Júnio Rios; de Araújo, Gnana Keith Marques; da Luz, Magda Maria Profeta; da Conceição, Sérgio Alexandre; Lisboa, Felipe Assis; Moraes-Santos, Tasso; Cunha-Melo, José Renan

    2006-10-01

    Scorpion venom (TX) promotes gastric acid and pepsin secretion leading to acute gastric mucosal lesions (AGML), when injected in animals. The goal of the present study was to observe the effects of acid gastric secretion blockers over the incidence of TX-induced AGML in vivo. To verify this model, we used male albino rats, fasted 18-20 h (n=122) and anaesthetized with urethane (1.4 g/kg, i.p.). Their trachea and left femoral vein were both cannulated; the first to avoid airway obstructions during scorpion intoxication and the second for administration of saline, TX and acid blockers. Following the surgical procedure, the animals were divided in 10 groups of at least 10 animals each. Control groups were injected with NaCl 0.9% 1 ml/kg (n=10) or TX 375 microg/kg (n=32). Test groups (n=10, each) received atropine 5 mg/kg, cimetidine 10mg/kg, ranitidine 2.5mg/kg, ranitidine 5mg/kg, omeprazol 1 mg/kg, omeprazol 4 mg/kg, octreotide 80 and octreotide 100 microg/kg 10 min before the TX was injected. After 1h of intoxication, the stomach was resected for macroscopic study and the gastric secretion was collected for volume, pH and acid output assessment. We observed that all blockers were able to completely or partially prevent the TX-induced acid secretion as well as the AGML (p<0.05). Our data suggest the TX-induced AGML can be prevented by different class of acid blockers injected before the intoxication.

  15. A Diet High in Meat Protein and Potential Renal Acid Load Increases Absorption and Urinary Excretion of Calcium, As Well As Serum IGF-I in Postmenopausal Women

    Science.gov (United States)

    Objective: The objective was to determine the effect of increasing protein and potential renal acid load (PRAL) on Ca retention and markers of bone metabolism. Methods: In a randomized crossover design, twenty postmenopausal women consumed two diets: one low protein, low PRAL (LPLP) and one high pr...

  16. Effect of low severity dilute-acid pretreatment of barley straw and decreased enzyme loading hydrolysis on the production of fermentable substrates and the release of inhibitory compounds

    NARCIS (Netherlands)

    Panagiotopoulos, I.A.; Lignos, G.D.; Bakker, R.R.C.; Koukios, E.G.

    2012-01-01

    The objective of this work was to investigate the feasibility of combining low severity dilute-acid pretreatment of barley straw and decreased enzyme loading hydrolysis for the high production of fermentable substrates and the low release of inhibitory compounds. For most of the pretreatments at 160

  17. Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

    Directory of Open Access Journals (Sweden)

    Li J

    2015-08-01

    Full Text Available Jingjing Li,1 Tong Chen,2 Feng Deng,1 Jingyuan Wan,1 Yalan Tang,1 Pei Yuan,1 Liangke Zhang1 1Chongqing Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, 2School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, People’s Republic of China Abstract: We have designed and developed curcumin (Ccn-loaded albumin nanoparticles (BNPs surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 µg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity. Keywords: glycyrrhetinic acid, albumin, nanoparticles, surface

  18. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test

    Directory of Open Access Journals (Sweden)

    Barros Marcelo P

    2012-06-01

    Full Text Available Abstract Background Dietary creatine has been largely used as an ergogenic aid to improve strength and athletic performance, especially in short-term and high energy-demanding anaerobic exercise. Recent findings have also suggested a possible antioxidant role for creatine in muscle tissues during exercise. Here we evaluate the effects of a 1-week regimen of 20 g/day creatine supplementation on the plasma antioxidant capacity, free and heme iron content, and uric acid and lipid peroxidation levels of young subjects (23.1 ± 5.8 years old immediately before and 5 and 60 min after the exhaustive Wingate test. Results Maximum anaerobic power was improved by acute creatine supplementation (10.5 %, but it was accompanied by a 2.4-fold increase in pro-oxidant free iron ions in the plasma. However, potential iron-driven oxidative insult was adequately counterbalanced by proportional increases in antioxidant ferric-reducing activity in plasma (FRAP, leading to unaltered lipid peroxidation levels. Interestingly, the FRAP index, found to be highly dependent on uric acid levels in the placebo group, also had an additional contribution from other circulating metabolites in creatine-fed subjects. Conclusions Our data suggest that acute creatine supplementation improved the anaerobic performance of athletes and limited short-term oxidative insults, since creatine-induced iron overload was efficiently circumvented by acquired FRAP capacity attributed to: overproduction of uric acid in energy-depleted muscles (as an end-product of purine metabolism and a powerful iron chelating agent and inherent antioxidant activity of creatine.

  19. Effects of lauric acid on upper gut motility, plasma cholecystokinin and peptide YY, and energy intake are load, but not concentration, dependent in humans.

    Science.gov (United States)

    Feltrin, Kate L; Little, Tanya J; Meyer, James H; Horowitz, Michael; Rades, Thomas; Wishart, Judith; Feinle-Bisset, Christine

    2007-06-01

    Animal studies suggest that the effects of fatty acids on gastric emptying and pancreatic secretion are both concentration and load dependent, while their suppressive effect on energy intake is only load dependent. We postulated that, in humans, the modulation of antropyloroduodenal pressure waves, plasma cholecystokinin (CCK) and peptide YY (PYY) concentrations and energy intake by intraduodenal lauric acid, a fatty acid with 12 carbon atoms ('C12') would be load, but not concentration, dependent. Two groups of 12 healthy males were each studied on three separate occasions in double-blind randomized fashion. Antropyloroduodenal pressure waves, plasma CCK and PYY, and appetite perceptions were measured during intraduodenal infusions of C12 at (1) different loads of (i) 0.2, (ii) 0.3 and (iii) 0.4 kcal min(-1) (all 56 mM) for 90 min, and (2) different concentrations of (i) 40, (ii) 56 and (iii) 72 mM (all 0.4 kcal min(-1)) for 60 min. Energy intake at a buffet meal consumed immediately following each infusion was quantified. Suppression of antral and duodenal pressure waves, stimulation of pyloric pressure waves, stimulation of plasma CCK and PYY, and suppression of energy intake, were related to the load of C12 administered (r>0.65, P<0.05). In contrast, there were no concentration-dependent effects of C12 on any of these parameters. In conclusion, in humans, the effects of intraduodenal C12 on antropyloroduodenal motility, plasma CCK and PYY and energy intake appear to be related to load, but not concentration, at least at the loads and concentrations evaluated.

  20. Essential fatty acid composition and correlates in children with severe acute malnutrition

    DEFF Research Database (Denmark)

    Babirekere-Iriso, Esther; Lauritzen, Lotte; Mortensen, Charlotte Gylling;

    2016-01-01

    and HIV-infection status. Multiple linear regression analyses were used to identify correlates of PUFA. Results: The relative contribution of saturated fatty acid to the fatty acids in whole blood (FA%) were lower in 108 children with SAM compared to 24 well-nourished controls whereas most monounsaturated...

  1. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    Science.gov (United States)

    Rudyk, Olena; Makra, Péter; Jansen, Eugene; Shattock, Michael J; Poston, Lucilla; Taylor, Paul D

    2011-01-01

    Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (pprolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (pobesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

  2. The Effect of Rumen Acid Load on Postpartum Performance and Blood Metabolic Responses in Transition Holstein Cows

    Directory of Open Access Journals (Sweden)

    S. D. Mesgaran

    2011-01-01

    Full Text Available Problem statement: The transition period is the most stressful time in the production cycle of a dairy cow because of depressed feed intake, endocrine and metabolic changes at parturition. The aim was to determine the effect of rumen acid load on postpartum performance and metabolic parameters in transition Holstein cows. Approach: The Acidogenicity Values (AV of the diets were determined using an In-vitro essay. Thirty late pregnant multiparous Holstein cows with the average yielding of 9800 Kg/year were housed. Three weeks before the expected date of calving, cows were randomly assigned to receive either: (a High AV (AV11.9 diet (n = 16 (b Low AV (AV10.7 diet (n=14. Blood samples were collected from the coccygeal vein once a week at a consistent time after morning feeding from d 10 till d 42 postpartum and were analysed for Beta Hydroxybutyrate (BHB, Non-Esterified Fatty Acids (NEFAs, glucose and Blood Urea Nitrogen (BUN. Milk samples were collected from each milking once per week and composited for subsequent analysis of milk composition. Results: Overall subsequent milk yield of animals in high AV was higher compared to the other group (41.9 and 37.8 kg. Although milk fat percentage of the low AV group was higher than the other group (3.7 and 3.5%, however there was no significant effect of the diets on milk protein. Plasma NEFA and BHBA was reduced significantly in animals receiving the high AV diet. Although the concentration of glucose was markedly higher in high AV animals, however the BUN concentration was lower compare to the low AV group. Conclusion: The results of the present study demonstrated that high grain prepartum diets have dramatic impact on postpartum performance and blood metabolic parameters.

  3. Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella

    Science.gov (United States)

    Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

    2017-01-01

    Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06–37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from −8.1 to −24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment. PMID:28112240

  4. Efficacy and safety of single-bolus tenecteplase compared with front-loaded alteplase in Chinese patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction. The purpose of this open-label, randomized, multi-center, angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction. Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October, 2002 to March,2004, in 5 hospitals in Beijing. After giving informed consent, patients were randomly assigned a single-bolus injection of tenecteplase (30-50 mg according to body weight) or front loaded alteplase (100 mg), and underwent coronary angiography at 90 min after starting the study drug. All patients received aspirin and heparin (target activated partial thromboplastin time 50-70 s). The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes. Other efficacy end points included TIMI grade 2/3 flow at 90 minutes. Safety end points included all stroke, intracranial hemorrhage (ICH), moderate/severe hemorrhage (except for ICH), all-cause mortality at 30-days, and major non-fatal cardiac events at 30 days. Results Overall 110 patients were eligible for statistical analysis, with 58 patients assigned to receive tenecteplase and 52 patients to alteplase. Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%) similar to that of alteplase (66.7%, P=1.0); the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase (89.5% versus 80.4%, respectively, P=0.278). At 30 days, rates for all strokes were similar for the two groups (5.17% for tenecteplase and 1.92% for alteplase, P=0.62); rates of ICH were 3.45% and 1.92% (tenecteplase and rt-PA,P=1.00) respectively. The rate of moderate/severe hemorrhage was 8.62% with tenecteplase and 5.77% with alteplase (P=0.72); total

  5. In vitro characteristics of poly(lactic-co-glycolic acid) microspheres incorporating gelatin particles loading basic fibroblast growth factor

    Institute of Scientific and Technical Information of China (English)

    Shao-hong LI; Shao-xi CAI; Bing LIU; Kai-wang MA; Zhen-ping WANG; Xiao-kun LI

    2006-01-01

    Aim: To construct a sustained drug release system for basic fibroblast growth factor (bFGF). With this special system, bFGF can be used to repair an injured peripheral nerve, injured spinal cord, or as a carrier for other drugs that need to be released over a long time. Methods: Microsphere composite was prepared by encapsulating bFGF into gelatin particles with poly(lactic-co-glycolic acid) (PLGA) as its outer-coating. The encapsulation was conducted by a phase separation method. Results: The average diameter of the gelatin particle-PLGA microsphere composite was 5-18 μm, and bFGF-loading efficiency was up to 80.5%. The bFGF releasing experiment indicated that this new composite system could release bFGF continuously and protect bFGF from denaturation. Conclusion: A modified approach was successfully employed to develop a biodegradable system for sustained release of the drug of bFGF in vitro.

  6. Antibacterial and biocompatible properties of vancomycin-loaded nano-hydroxyapatite/collagen/poly (lactic acid) bone substitute

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Lian; Huanye Liu; Xiumei Wang; Suju Xu; Fuzhai Cui; Xizhuang Bai

    2013-01-01

    Infected bone defects are normally regarded as contraindications for bone grafting. In the present study, an antibacterial bone graft substitute was synthesized by loading vancomycin (VCM) in our previously developed mineralized collagen based composite, nano-hydroxyapatite/collagen/poly (lactic acid) (nHAC/PLA), aiming to repair large size bone defects and inhibit related infections simultaneously. The VCM/nHAC/PLA showed typical porous structure with a porosity of (80.776.7)%and compressive strength of 1.52 MPa. The delivery of VCM from VCM/nHAC/PLA was detected in vitro for up to 4 weeks. And their antibacterial properties were determined using inhibition ratio assay and inhibition zone assay. Pretty high level of inhibition ratio (more than 99%) was obtained in VCM/nHAC/PLA group. Additionally, a distinct inhibition zone was clearly formed in Staphylococcus aureus bacterium incubation dish with VCM/nHAC/PLA disc for up to 18 days of incubation. Moreover, both of the nHAC/PLA composites with or without VCM exhibited favorable in vitro and in vivo biocompatibilities for rabbit marrow stromal cells (MSCs) adhesion, spreading, proliferation, and triggering no obvious inflammation responses in subcutaneous implantation. Our results suggested that the VCM/nHAC/PLA performed ideal antibacterial property and biocompatibility and has great promise for the treatment of bone defect-related infections in orthopedic surgeries.

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

    Science.gov (United States)

    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.

  8. Ultrasensitive electrochemical immunosensor based on horseradish peroxidase (HRP)-loaded silica-poly(acrylic acid) brushes for protein biomarker detection.

    Science.gov (United States)

    Zhao, Yan; Zheng, Yiqun; Kong, Rongmei; Xia, Lian; Qu, Fengli

    2016-01-15

    We report an ultrasensitive electrochemical immunosensor designed for the detection of protein biomarkers using horseradish peroxidase (HRP)-loaded silica-poly(acrylic acid) brushes (SiO2-SPAABs) as labels. HRP could be efficiently and stably accommodated in the three-dimensional architecture of the SiO2-SPAABs and the SiO2-SPAABs-HRP exhibited high catalytic performance towards o-phenylenediamine (OPD) oxidation in the presence of H2O2, which resulted in significant differential pulse voltammetric (DPV) response change and color change. Using human IgG (HIgG) as a model analyte, a sandwich-type immunosensor was constructed. In particular, graphene oxide (GO) and SiO2-SPAABs-HRP were used to immobilize capture antibody (Ab1) and bind a layer of detection antibody (Ab2), respectively. The current biosensor exhibited a good linear response of HIgG from 100pg/mL to 100μg/mL with a detection limit of 50pg/mL (S/N=5). The sensitivity was 6.70-fold higher than the conventional enzyme-linked immunosorbent assays. The immunosensor results were validated through the detection of HIgG in serum samples.

  9. Chitosan-functionalised poly(2-hydroxyethyl methacrylate) core-shell microgels as drug delivery carriers: salicylic acid loading and release.

    Science.gov (United States)

    Mahattanadul, Natshisa; Sunintaboon, Panya; Sirithip, Piyawan; Tuchinda, Patoomratana

    2016-09-01

    This work presents the evaluation of chitosan-functionalised poly(2-hydroxyethyl methacrylate) (CS/PHEMA) core-shell microgels as drug delivery carriers. CS/PHEMA microgels were prepared by emulsifier-free emulsion polymerisation with N,N '-methylenebisacrylamide (MBA) as a crosslinker. The study on drug loading, using salicylic acid (SA) as a model drug, was performed. The results showed that the encapsulation efficiency (EE) increased as drug-to-microgel ratio was increased. Higher EE can be achieved with the increase in degree of crosslinking, by increasing the amount of MBA from 0.01 g to 0.03 g. In addition, the highest EE (61.1%) was observed at pH 3. The highest release of SA (60%) was noticed at pH 2.4, while the lowest one (49.4%) was obtained at pH 7.4. Moreover, the highest release of SA was enhanced by the presence of 0.2 M NaCl. The pH- and ionic-sensitivity of CS/PHEMA could be useful as a sustained release delivery device, especially for oral delivery.

  10. Electrospun DOXY-h loaded-poly(acrylic acid) nanofiber mats: in vitro drug release and antibacterial properties investigation.

    Science.gov (United States)

    Khampieng, Thitikan; Wnek, Gary E; Supaphol, Pitt

    2014-01-01

    Electrospun DOXY-h loaded-poly(acrylic acid) (PAA) nanofiber mats (PAA/DOXY-h nanofiber mats) were prepared by the electrospinning technique and post-spinning sorption method at various doses: PAA/DOXY-h125, PAA/DOXY-h250, PAA/DOXY-h500, and PAA/DOXY-h1000. The morphology, drug content, release characteristics, and antibacterial activities of the PAA/DOXY-h nanofiber mats were investigated with scanning electron microscopy, UV-vis spectrophotometry, and disc diffusion methodology. The PAA/DOXY-h nanofiber mats had a diameter range of 285-340 nm, and a smooth surface without beads. Adsorption isotherms of DOXY-h could be described well with the Freundlich model. The amounts of DOXY-h, after the post-spinning sorption process, in the PAA/DOXY-h nanofiber mats ranged between 27.57 and 101.71 mg/g. All of the PAA/DOXY-h nanofiber mats exhibited an initial burst release characteristic with cumulative releasing percentages between 37.14 and 45.97%, which followed the Fickian diffusion mechanism. Based on the antibacterial investigation, the tested gram-positive bacteria, Staphylococcus aureus and Streptococcus agalactiae, seemed to be more sensitive to PAA/DOXY-h nanofiber mats than the tested gram-negative bacteria, Pseudomonas aeruginosa. These PAA/DOXY-h nanofiber mats could be used as an antibacterial wound dressing.

  11. Evaluation of Sialic Acid and Acute Phase Proteins (Haptoglobin and Serum Amyloid A in Clinical and Subclinical Bovine Mastitis

    Directory of Open Access Journals (Sweden)

    S. Nazifi*, M. Haghkhah1, Z. Asadi, M. Ansari-Lari2, M. R. Tabandeh3, Z. Esmailnezhad and M. Aghamiri

    2011-01-01

    Full Text Available The present study was conducted to evaluate the concentrations of sialic acids (total, lipid bound and protein bound and their correlation with acute phase proteins (haptoglobin and serum amyloid A in clinical and subclinical mastitis of cattle. Thirty subclinical mastitic cows with positive California mastitis test (CMT test and no clinical signs of mastitis, 10 clinical mastitic cows and 10 healthy cows with negative CMT test and normal somatic cell count were selected. Milk and blood samples were collected after confirmation of clinical and subclinical mastitis by somatic cell count and bacterial identification. Serum haptoglobin (Hp, serum amyloid A (SAA, total sialic acid (TSA, lipid bound sialic acid (LBSA and protein bound sialic acid (PBSA were measured by validated standard methods. Haptoglobin and SAA increased significantly in both types of mastitis compared with control group (P<0.001. However, the ratio of HP/SAA was significantly different from the control group only in clinical mastitis. The results showed that TSA and LBSA were significantly different in control group compared with clinical and subclinical mastitis (P<0.001. Protein bound sialic acid did not change in subclinical mastitis in comparison with control group (P=0.86. There was positive correlation between LBSA and PBSA in clinical mastitis (r=0.72, P=0.02 whereas significant negative correlation was observed between LBSA and PBSA in subclinical mastitis (r=-0.62, P<0.001. Results also showed no correlation between Hp and SAA with each other or with any other parameters in study groups.

  12. The effects of bud load and regulated deficit irrigation on sugar, organic acid, phenolic compounds and antioxidant activity of Razakı table grape berries

    Directory of Open Access Journals (Sweden)

    Tangolar Semih

    2015-01-01

    Full Text Available This study aims at assessing the effects of increased bud load and irrigation applications on berry quality of the Razakı table grape. Two Regulated Deficit Irrigation (RDI having different irrigation levels (RDI-I and RDI-II based on the growth stages, in addition to a non-irrigated control treatment together with two different bud load practices (K-normal and 2K-two-fold buds of the normal were examined for their effects on quality attributes such as sugar and organic acids contents, phenolic compounds as well as antioxidant capacity of the berries. The non-irrigated vines had highest sugar level (198.86 g/kg in the first year (2013 of the experiment whilst the sugar content of the berries was increased with irrigation (RDI-II in 2014. However the highest organic acid (7.10 g/kg was recorded from the RDI-II treatment in 2013 whereas those of from non-irrigated vines were highest (7.81 g/kg in 2014. Considering the sugar and organic acid content of the berries, bud load effects were not significant. The total phenolic acids were higher under non-irrigated and 2K bud load conditions. Antioxidant activity of berries was increased with RDI-I irrigation and 2K practices in the first year (2013 although no significant effect was recorded in the second year of the experiment. In all applications, glucose among the sugars, tartaric acid among the organic acids, catechin and epicatechin among the phenolic compounds were detected to be higher compared to other components in berries.

  13. Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

    Directory of Open Access Journals (Sweden)

    Lyon Andrew W

    2011-04-01

    Full Text Available Abstract Background Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Methods Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Results Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy. The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism

  14. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

    Science.gov (United States)

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases: Crohn disease and ulcerative colitis. Dietary n-6 fatty acids have been associated with ulcetative colitis in prospective studies. However, the critical d...

  15. Repeat Lumbar Puncture: CSF Lactic Acid Levels are Predictive of Cure with Acute Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    Burke A. Cunha

    2013-12-01

    Full Text Available A common clinical problem concerns the utility of repeat lumbar puncture (LP in adults with acute bacterial meningitis (ABM, e.g., pneumococcal meningitis [1]. An LP is initially done for diagnostic purposes in patients with suspected ABM, i.e., diagnostic lumbar puncture (DLP. A repeat LP (RLP may be done 1–3 days after the initial DLP, if the patient shows no improvement. If a patient with ABM is not doing well after three days, adequacy of antimicrobial therapy is the main concern. Other reasons for RLP is to detect possible intracranial complications of ABM unrelated to adequacy of therapy [1–2].

  16. Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Carneiro G

    2012-12-01

    Full Text Available Guilherme Carneiro,1 Elton Luiz Silva,1 Layssa Alves Pacheco,1 Elaine Maria de Souza-Fagundes,2 Natássia Caroline Resende Corrêa,3 Alfredo Miranda de Goes,3 Mônica Cristina de Oliveira,1 Lucas Antônio Miranda Ferreira11Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil; 2Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil; 3Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilAbstract: This work aims to develop solid lipid nanoparticles (SLNs loaded with retinoic acid (RA to evaluate the influence of two lipophilic amines, stearylamine (SA and benethamine (BA, and one hydrophilic, triethylamine (TA, on drug-encapsulation efficiency (EE and cytotoxicity in cancer cell lines. The SLNs were characterized for EE, size, and zeta potential. The mean particle size decreased from 155 ± 1 nm (SLNs without amine to 104 ± 4, 95 ± 1, and 96 ± 1 nm for SLNs prepared with SA, BA, and TA, respectively. SA-RA-loaded SLNs resulted in positively charged particles, whereas those with TA and BA were negatively charged. The EEs were significantly improved with the addition of the amines, and they increased from 36% ± 6% (without amine to 97% ± 2%, 90% ± 2%, and 100% ± 1% for SA, TA, and BA, respectively. However, stability studies showed higher EE for BA-RA-loaded SLNs than TA-RA-loaded SLNs after 30 days. The formulations containing SA loaded or unloaded (blank SLNs with RA were cytotoxic in normal and cancer cell lines. In contrast, the blank SLNs containing TA or BA did not show cytotoxicity in human breast adenocarcinoma cells (MCF-7, while RA-loaded SLNs with the respective amines were significantly more cytotoxic than free RA. Furthermore, the cytotoxicity of BA-RA-loaded SLNs was significantly higher than TA-RA-loaded SLNs. These

  17. In vitro characterization of pH-sensitive azithromycin-loaded methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) micelles.

    Science.gov (United States)

    Teng, Fangfang; Deng, Peizong; Song, Zhimei; Zhou, Feilong; Feng, Runliang; Liu, Na

    2017-02-09

    In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment.

  18. Effects of β-Hydroxy-β-methylbutyrate Free Acid Ingestion and Resistance Exercise on the Acute Endocrine Response

    Directory of Open Access Journals (Sweden)

    Jeremy R. Townsend

    2015-01-01

    Full Text Available Objective. To examine the endocrine response to a bout of heavy resistance exercise following acute β-hydroxy-β-methylbutyrate free acid (HMB-FA ingestion. Design. Twenty resistance trained men were randomized and consumed either 1 g of HMB-FA (BetaTor or placebo (PL 30 min prior to performing an acute heavy resistance exercise protocol. Blood was obtained before (PRE, immediately after (IP, and 30 min after exercise (30P. Circulating concentrations of testosterone, growth hormone (GH, insulin-like growth factor (IGF-1, and insulin were assayed. Data were analyzed with a repeated measures ANOVA and area under the curve (AUC was analyzed by the trapezoidal rule. Results. The resistance exercise protocol resulted in significant elevations from PRE in testosterone P<0.01, GH P<0.01, and insulin P=0.05 at IP, with GH P<0.01 and insulin P<0.01 remaining elevated at 30P. A significant interaction was noted between groups in the plasma GH response at IP, which was significantly higher following HMB-FA compared to PL P<0.01. AUC analysis revealed an elevated GH and IGF-1 response in the HMB-FA group compared to PL. Conclusion. HMB-FA prior to resistance exercise augments the GH response to high volume resistance exercise compared to PL. These findings provide further support for the potential anabolic benefits associated with HMB supplementation.

  19. Carnosic acid attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway.

    Science.gov (United States)

    Tian, Xinyao; Hu, Yan; Li, Mingzhu; Xia, Kun; Yin, Jiye; Chen, Juan; Liu, Zhaoqian

    2016-04-01

    Ethanol-induced liver injury is associated with oxidative stress and hepatocyte apoptosis. We previously demonstrated that SIRT1/p66Shc pathway activation attenuates hepatocyte apoptosis in liver ischemia/reperfusion. The current study aimed to investigate whether carnosic acid (CA), a natural antioxidant, can inhibit acute ethanol-induced apoptosis of hepatocytes and to determine the effect of SIRT1/p66Shc on this process. Our results showed that CA pretreatment significantly reduced ethanol-induced histologic damage, serum aminotransferase activity, and oxidative stress in rats. Importantly, CA pretreatment increased SIRT1 expression following ethanol exposure. Furthermore, p66Shc expression was negatively correlated with SIRT1 expression. Consistent with the results demonstrating p66Shc inhibition, CA pretreatment inhibited the release of cytochrome C and apoptosis-inducing factor (AIF) from mitochondria. After exposing L02 cells to ethanol, the increased SIRT1 expression induced by CA was abrogated by pharmacologic SIRT1 inhibition or the use of siRNA against SIRT1. Additionally, SIRT1 inhibition significantly abrogated the suppression of p66Shc expression and mitochondrial translocation induced by CA. Accordingly, CA-induced decreases in the release of cytochrome C and AIF and in mitochondrial apoptosis were nearly abolished by SIRT1 knockdown. These data indicated that CA-activated SIRT1 is protective against ethanol treatment. In summary, CA attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway.

  20. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    Science.gov (United States)

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

  1. Effects of dosmalfate, a new cytoprotective agent, on acute and chronic trinitrobenzene sulphonic acid-induced colitis in rats.

    Science.gov (United States)

    Villegas, Isabel; La Casa, Carmen; Orjales, Aurelio; Alarcón de la Lastra, Catalina

    2003-01-24

    Activated neutrophils and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of epidermal growth factor-receptor (EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of dosmalfate, a new flavonoid derivative compound (diosmin heptakis) with antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. The inflammation response was assessed by neutrophil infiltration as evaluated by histology and myeloperoxidase activity. Mucosal TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the EGF receptor inmunohistochemically during the healing of TNBS-induced chronic colitis. A 2-day treatment with 400 or 800 mg/kg of dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased myeloperoxidase activity and colonic mucosal production of TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of dosmalfate also had significant protective effects on TNBS-induced colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of dosmalfate was apparently related to the enhancement of EGF receptor expression. These findings confirm the protective effects of dosmalfate in acute and chronic experimental colitis.

  2. Genital ulcers after treatment with all-trans-retinoic acid in a child with acute promyelocytic leukemia.

    Science.gov (United States)

    Unal, Selma; Gümrük, Fatma; Cetin, Mualla; Hiçsönmez, Gönül

    2005-01-01

    All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment. An 8-year-old girl with APL was treated with ATRA for 21 days and after discontinuation of ATRA treatment she developed genital ulcers. Systemic and local antibiotic pomades were applied and the lesions improved within 15 days. In conclusion, genital ulcers may develop in children with APL as a complication of ATRA treatment and physicians should be alert to this possibility.

  3. [Successful treatment of acute promyelocytic leukemia in a pregnant woman by using all-trans retinoic acid].

    Science.gov (United States)

    Tsuda, H; Doi, H; Inada, T; Shirono, K

    1994-07-01

    A 34-year-old woman was admitted because of pancytopenia with DIC in the 28th week of pregnancy. Bone marrow aspirate demonstrated 81.2% abnormal cells which showed Auer bodies and faggot formation. Chromosomal analysis demonstrated an abnormality, t (15; 17). The patient was diagnosed as having acute promyelocytic leukemia (APL) and started to receive treatment with all-trans retinoic acid (ATRA) 70 mg/body/day per os. She had a cesarean section and gave birth to a female infant in the 29th week of pregnancy. An increase of WBC counts was observed on the 9th hospital day, then chemotherapy with anti-cancer agents was performed additionally. Complete remission was achieved on the 27th hospital day. Management of pregnant patients with APL could be improved by using ATRA instead of conventional combinations of cytotoxic agents.

  4. Malignancy: Case Report: Acute Promyelocytic Leukemia in Late Pregnancy. Successful Treatment with All-Trans-Retinoic Acid (ATRA) and Chemotherapy.

    Science.gov (United States)

    Delgado-Lamas, JOSÉ LUIS; Garcés-Ruiz, OSCAR MIGUEL

    2000-01-01

    The use of all-transretinoic acid (ATRA) in APL is a great advance in the treatment of acute leukemia, driving the maturation steps until adult form. The effect of this medication in pregnant women with APL is being a safe and effective treatment only after the first trimester of pregnancy. If used in the first three months, it can cause fetus malformations due to its potent teratogenicity. The two patients we reported here, gave birth to normal children, yet they received ATRA. After a week with ATRA treatment, fibrinogen level improved and "D" dimers decreased, so as observed slowly maturation of leukemic leucocytes. ATRA used at the same time with chemotherapy; such as Cytarabine and Idarrubicine seems highly useful for induction and long term control of disease. One short discussion about the findings and compare with those found in the literature are presented.

  5. [A neonate born to a mother with acute promyelocytic leukemia treated by all-trans retinoic acid].

    Science.gov (United States)

    Maeda, M; Tyugu, H; Okubo, T; Yamamoto, M; Nakamura, K; Dan, K

    1997-09-01

    We report a female neonate delivered in week 32 of gestation by a mother who had acute promyelocytic leukemia (APL) treated by all-trans retinoic acid (ATRA). APL was diagnosed in week 29 of gestation and was treated with ATRA from week 30. Physical examination and laboratory tests showed no abnormalities at birth. The girl has since shown normal development, with no peripheral blood abnormalities at 2 years old. Hypersegmented neutrophils, which often appear during ATRA treatment, were seen in the peripheral blood of the mother and cord blood but not peripheral blood of the neonate on the day of birth. ATRA is known to cross the placenta, and has been revealed to be teratogenic in animal studies. There have been eight neonates born to the mothers with APL who were treated with ATRA during pregnancy. All infants, including this one, have shown normal growth without any complications.

  6. Acute Promyelocytic Leukemia in Late Pregnancy. Successful Treatment with All-Trans-Retinoic Acid (ATRA) and Chemotherapy.

    Science.gov (United States)

    Delgado-Lamas, J L; GarcéS-Ruiz, O M

    1999-01-01

    The use of all-transretinoic acid (ATRA) in APL is a great advance in the treatment of acute leukemia, driving the maturation steps until adult form. The effect of this medication in pregnant women with APL is being a safe and effective treatment only after the first trimester of pregnancy. If used in the first three months, it can cause fetus malformations due to its potent teratogenicity. The two patients we reported here, gave birth to normal children, yet they received ATRA. After a week with ATRA treatment, fibrinogen level improved and "D" dimers decreased, so as observed slowly maturation of leukemic leucocytes. ATRA used at the same time with chemotherapy; such as Cytarabine and Idarrubicine seems highly useful for induction and long term control of disease. One short discussion about the findings and compare with those found in the literature are presented.

  7. COMPARISON OF CLINICAL OBSERVATIONS BETWEEN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA TREATED WITH ALL-TRANS RETINOIC ACID AND CHEMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    张芬琴; 吴立德; 李秀松; 孙关林; 蔡敬仁; 王振义

    1992-01-01

    Clinical observations were retrospectively compared between 2 matched groups of patients with acute promyelocytic leukemia (APL) each 20. The first group were treated with chemotherapy, the other with all-tram retinoic acid (ATRA) alone at a dose of 45-60mg/M~2/d. The complete remission (CR) rate of ATRA group was significantly higher than that of chemotherapy (90% vs 55%). The time for obtaining CR as well as the duration of fever and hospitalization were shorter and the amount of blood transfused was less in the former than in the latter group. Seven cases were complicated by DIC and 4 died in the group of chemotherapy, while no case was by of DIC or death in the ATRA group. The mechanism was discussed. ATRA is an alternative effective drug for remission induction therapy in APL with high rate of CR.

  8. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.

    Directory of Open Access Journals (Sweden)

    Dev Kumar

    Full Text Available The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI, which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA induced acute kidney injury (AKI characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI. Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.

  9. Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity.

    Science.gov (United States)

    Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

    2011-03-01

    Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of N(ε)-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of N(ε)-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID.

  10. Investigation of the possible protective role of gallic acid on paraoxanase and arylesterase activities in livers of rats with acute alcohol intoxication.

    Science.gov (United States)

    Kartkaya, Kazim; Oğlakçi, Ayşegül; Şentürk, Hakan; Bayramoğlu, Gökhan; Canbek, Mediha; Kanbak, Güngör

    2013-04-01

    Gallic acid, a polyphenyl class natural product from gallnut and green tea, is known to be antioxidant, anti-inflammatory and radical scavenger. In this study, we aimed to investigate the possible protective effects of gallic acid on paraoxonase and arylesterase activities in liver exposed to acute alcohol intoxication. Paraoxonase and arylesterase activities in liver tissue and serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were measured. Histological investigations were also made. In our study, we observed a significant increase of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, which are indicators of liver damage after acute ethanol consumption. Gallic acid therapy has significantly reduced the increase in these biomarkers, indicating a possible hepatoprotective effect of gallic acid. Ethanol consumption caused a significant decrease in liver paraoxonase activity (P Gallic acid treatment partly restored this decreased paraoxonase activity, which resulted from ethanol administration. A gallic acid dose of 100 mg/kg was observed as highest restoring effect for paraoxonase activity (P gallic acid treatment restored the loss of this activity due to ethanol exposure (P gallic acid ameliorates the liver damage caused by excessive alcohol consumption in a dose-dependent way. Our results in this study showed that gallic acid might have a protective effect against alcoholic liver disease.

  11. Mechanism-based pharmacokinetic-pharmacodynamic modeling of salvianolic acid A effects on plasma xanthine oxidase activity and uric acid levels in acute myocardial infarction rats.

    Science.gov (United States)

    Wang, Haidong; Li, Xi; Zhang, Wenting; Liu, Yao; Wang, Shijun; Liu, Xiaoquan; He, Hua

    2017-03-01

    1. Salvianolic acid A (SalA) was found to attenuate plasma uric acid (UA) concentration and xanthine oxidase (XO) activity in acute myocardial infraction (AMI) rats, which was characterized with developed mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model. 2. AMI was induced in rats by coronary artery ligation. Surviving AMI rats received a single intravenous dose of 5 mg/kg of SalA and normal saline. The plasma SalA concentrations were determined by HPLC-MS/MS method. The plasma UA concentrations were determined by HPLC method and plasma XO activity were measured spectrophotometrically. An integrated mathematical model characterized the relationship between plasma UA and SalA. 3. Pharmacokinetics was described using two-compartment model for SalA with linear metabolic process. In post-AMI rats, XO activity and UA concentrations were increased, while SalA dosing palliated this increase. These effects were well captured by using two series of transduction models, simulating the delay of inhibition on XO driven by SalA and UA elevation resulted from the multiple factors, respectively. 4. The effect was well described by the developed PK-PD model, indicating that SalA can exert cardiovascular protective effects by decreasing elevated plasma UA levels induced by AMI.

  12. The impact of acid deposition and forest harvesting on lakes and their forested catchments in south central Ontario: a critical loads approach

    Directory of Open Access Journals (Sweden)

    S. A. Watmough

    2002-01-01

    Full Text Available The impact of acid deposition and tree harvesting on three lakes and their representative sub-catchments in the Muskoka-Haliburton region of south-central Ontario was assessed using a critical loads approach. As nitrogen dynamics in forest soils are complex and poorly understood, for simplicity and to allow comparison among lakes and their catchments, CLs (A for both lakes and forest soils were calculated assuming that nitrate leaching from catchments will not change over time (i.e. a best case scenario. In addition, because soils in the region are shallow, base cation weathering rates for the representative sub-catchments were calculated for the entire soil profile and these estimates were also used to calculate critical loads for the lakes. These results were compared with critical loads obtained by the Steady State Water Chemistry (SSWC model. Using the SSWC model, critical loads for lakes were between 7 and 19 meq m-2yr-1 higher than those obtained from soil measurements. Lakes and forests are much more sensitive to acid deposition if forests are harvested, but two acid-sensitive lakes had much lower critical loads than their respective forested sub-catchments implying that acceptable acid deposition levels should be dictated by the most acid-sensitive lakes in the region. Under conditions that assume harvesting, the CL (A is exceeded at two of the three lakes and five of the six sub-catchments assessed in this study. However, sulphate export from catchments greatly exceeds input in bulk deposition and, to prevent lakes from falling below the critical chemical limit, sulphate inputs to lakes must be reduced by between 37% and 92% if forests are harvested. Similarly, sulphate leaching from forested catchments that are harvested must be reduced by between 16 and 79% to prevent the ANC of water draining the rooting zone from falling below 0 μeq l-1. These calculations assume that extremely low calcium leaching losses (9–27 μeq l-1 from

  13. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  14. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens

    NARCIS (Netherlands)

    Montesinos, Pau; Rayon, Chelo; Vellenga, Edo; Brunet, Salut; Gonzalez, Jose; Gonzalez, Marcos; Holowiecka, Aleksandra; Esteve, Jordi; Bergua, Juan; Gonzalez, Jose D.; Rivas, Concha; Tormo, Mar; Rubio, Vicente; Bueno, Javier; Manso, Felix; Milone, Gustavo; de la Serna, Javier; Perez, Inmaculada; Perez-Encinas, Manuel; Krsnik, Isabel; Ribera, Josep M.; Escoda, Lourdes; Lowenberg, Bob; Sanz, Miguel A.

    2011-01-01

    The expression of CD56 antigen in acute promyelocytic leukemia (APL) blasts has been associated with short remission duration and extramedullary relapse. We investigated the clinical significance of CD56 expression in a large series of patients with APL treated with all-trans retinoic acid and anthr

  15. Selecting against S1P3 enhances the acute cardiovascular tolerability of 3-(N-benzyl)aminopropylphosphonic acid S1P receptor agonists.

    Science.gov (United States)

    Hale, Jeffrey J; Doherty, George; Toth, Leslie; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark; Milligan, James; Shei, Gan-Ju; Chrebet, Gary; Bergstrom, James; Card, Deborah; Forrest, Michael; Sun, Shu-Yu; West, Sarah; Xie, Huijuan; Nomura, Naomi; Rosen, Hugh; Mandala, Suzanne

    2004-07-01

    Structurally modified 3-(N-benzylamino)propylphosphonic acid S1P receptor agonists that maintain affinity for S1P1, and have decreased affinity for S1P3 are efficacious, but exhibit decreased acute cardiovascular toxicity in rodents than do nonselective agonists.

  16. Serum Fatty Acids, Traditional Risk Factors, and Comorbidity as Related to Myocardial Injury in an Elderly Population with Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Laake, Kristian; Seljeflot, Ingebjørg; Schmidt, Erik B;

    2016-01-01

    ), and peak Troponin T (TnT) levels in elderly patients with an acute myocardial infarction (AMI). Materials and Methods. Patients (n = 299) consecutively included in the ongoing Omega-3 fatty acids in elderly patients with myocardial infarction (OMEMI) trial were investigated. Peak TnT was registered during...

  17. Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy

    NARCIS (Netherlands)

    Barragan, Eva; Montesinos, Pau; Camos, Mireia; Gonzalez, Marcos; Calasanz, Maria J.; Roman-Gomez, Jose; Gomez-Casares, Maria T.; Ayala, Rosa; Lopez, Javier; Fuster, Oscar; Colomer, Dolors; Chillon, Carmen; Larrayoz, Maria J.; Sanchez-Godoy, Pedro; Gonzalez-Campos, Jose; Manso, Felix; Amador, Maria L.; Vellenga, Edo; Lowenberg, Bob; Sanz, Miguel A.

    2011-01-01

    Background Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and Methods We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and a

  18. The effect of atorvastatin combined with probucol on contrast-induced acute kidney injury and serum uric acid in elderly patients

    Institute of Scientific and Technical Information of China (English)

    李作成

    2013-01-01

    Objective To observe the effect of different doses of atorvastatin combined with probucol on contrast-induced acute kidney injury(CIAKI) and serum uric acid in elderly patients. Methods Totally 121 cases admitted for coronary angioplasty were randomly divided into three

  19. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

    NARCIS (Netherlands)

    P. Montesinos (Pau); J.M. Bergua (Juan Miguel); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); J. de Serna (Javier); A. León (Angel); J. Esteve (Jordi); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); D.M. Joaquín; J.D. González (José David); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractDifferentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- a

  20. The acute effects of different training loads of whole body vibration on flexibility and explosive strength of lower limbs in divers.

    Science.gov (United States)

    Dallas, G; Paradisis, G; Kirialanis, P; Mellos, V; Argitaki, P; Smirniotou, A

    2015-09-01

    The purpose of this study was to examine the acute effects of different vibration loads (frequency and amplitude) of whole-body vibration (WBV) on flexibility and explosive strength of lower limbs in springboard divers. Eighteen male and female divers, aged 19 ± 2 years, volunteered to perform 3 different WBV protocols in the present study. To assess the vibration effect, flexibility and explosive strength of lower limbs were measured before (Pre), immediately after (Post 1) and 15 min after the end of vibration exposure (Post 15). Three protocols with different frequencies and amplitudes were used in the present study: a) low vibration frequency and amplitude (30 Hz/2 mm); b) high vibration frequency and amplitude (50 Hz/4 mm); c) a control protocol (no vibration). WBV protocols were performed on a Power Plate platform, whereas the no vibration divers performed the same protocol but with the vibration platform turned off. A two-way ANOVA 3 x 3 (protocol × time) with repeated measures on both factors was used. The level of significance was set at p flexibility and explosive strength of lower limbs were significantly higher in both WBV protocols compared to the no vibration group (NVG). The greatest improvement in flexibility and explosive strength, which occurred immediately after vibration treatment, was maintained 15 min later in both WBV protocols, whereas NVG revealed a significant decrease 15 min later, in all examined strength parameters. In conclusion, a bout of WBV significantly increased flexibility and explosive strength in competitive divers compared with the NVG. Therefore, it is recommended to incorporate WBV as a method to increase flexibility and vertical jump height in sports where these parameters play an important role in the success outcome of these sports.

  1. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    Directory of Open Access Journals (Sweden)

    Olena Rudyk

    Full Text Available Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11 or lard-enriched (23.6% fat, n = 16 chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old offspring cardiovascular parameters were measured (radiotelemetry. The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF and controls (OC. However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP and Δheart rate (HR with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week male OF demonstrated higher SBP (p<0.05 in the awake phase (night-time and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

  2. Alteration of podzolized tills by acid load near Ni-Cu smelters at Monchegorsk, Kola Peninsula, Russia

    Directory of Open Access Journals (Sweden)

    Räisänen, M.L.

    1994-06-01

    Full Text Available Mineralogy and geochemistry of podzolized tills was studied in the area of dieback forest near the Ni-Cu smelters at Monchegorsk, and less extensively forest damage near by Apatity and Kirovsk in the Russian Kola Peninsula. The abundances of main elements (Si, Al, Fe, Mg, Ca, K, Na in the <64 μm fraction were determined by the hot aqua regia digestion method and inductively coupled plasma spectrometry. The clay mineralogy of the silt plus clay fraction was examined by X-ray diffraction after selective extraction and heating treatments. At all study sites, trioctahedral mica and chlorite were totally weathered from the silt and clay fraction (<64 μm of the eluvial layer, leaving behind interstratified mica-vermiculite-smectite clays. In general, the mixed-layer clay of the eluvial layer had low levels of hydroxy interlayering. Illuviated layers were characterized by hydroxy interlayered vermiculite-chlorite. The abundance of chlorite and mica was greater, and the degree of interlayering lower, in parent tills than in the overlying illuviated layers. Regardless of differences in bedrock and till geochemistry, the weathering sequence throughout the podzolized till profile was coherent at most of the sampling sites. Exceptionally, in a few profiles sampled at the totally destroyed forest site, the swelling mixed-layer clay of the eluvial layer displayed a neochloritized structure. On the basis of XRD patterns and geochemistry of the samples, it was inferred that a short-term decomposition of plagioclase had promoted, via inputs of Al-hydroxides, the transformation of mica-vermiculite-smectite to a poorly crystalline interstratification of chlorite-aluminous montmorillonite. The accelerated weathering occurring occasionally in exposed places was probably activated by the strongly acidic load in the vicinity of the smelters and the city of Monchegorsk.

  3. Poly(ε-caprolactone)/triclosan loaded polylactic acid nanoparticles composite: A long-term antibacterial bionanocomposite with sustained release.

    Science.gov (United States)

    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.

  4. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

    Science.gov (United States)

    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.

  5. Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The “Nutritional Light Signal” of the Renal Acid Load

    Science.gov (United States)

    Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

    2017-01-01

    Background: Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. Methods: We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T-test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. Results: At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP (p < 0.0001), DBP (p < 0.001), plasma urea (p < 0.0001) protein intake (p < 0.0001), calcemia (p < 0.0001), phosphatemia (p < 0.0001), phosphate intake (p < 0.0001), urinary sodium (p < 0.0001), urinary potassium (p < 0.002), and urinary phosphate (p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. Conclusion: VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks

  6. Acute toxicity and histopathology of channel catfish fry exposed to peracetic acid

    Science.gov (United States)

    Channel catfish Ictalurus punctatus yolk-sac fry and swim-up fry were exposed to peracetic acid (PAA) for 48h in static toxicity bioassays at 23C. The test water was 217 and 126 mg/L (as CaCO3) total alkalinity and total hardness, respectively. Probit LC50 values were estimated with the trimmed Sp...

  7. Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts

    NARCIS (Netherlands)

    Coronel, R.; Wilms-Schopman, F.J.G.; Ruijter, den H.M.; Belterman, C.N.; Schumacher, C.A.; Opthof, T.; Hovernier, R.; Lemmens, A.G.; Terpstra, A.H.M.; Katan, M.B.; Zock, P.L.

    2007-01-01

    Objective Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic

  8. The Acute Effect of Humic Acid on Iron Accumulation in Rats.

    Science.gov (United States)

    Cagin, Yasir Furkan; Sahin, N; Polat, A; Erdogan, M A; Atayan, Y; Eyol, E; Bilgic, Y; Seckin, Y; Colak, C

    2016-05-01

    Free iron leads to the formation of pro-oxidant reactive oxygen species (ROS). Humic acids (HAs) enhance permeability of cellular wall and act as a chelator through electron transferring. This study was designed to test chelator effect of HA on iron as well as its anti-oxidant effect against the iron-induced hepatotoxicity and cardiotoxicity. The rats used were randomly divided into four groups (n = 8/group): group I (the control group); group II (the HA group), humic acid (562 mg/kg) was given over 10 days by oral gavage; group III (the iron group), iron III hydroxide polymaltose (250 mg/kg) was given over 10 days by intraperitoneal route; and group IV (the HA plus iron group), received the iron (similar to group II) plus humic acid (similar to those in groups II and III) group. Blood and two tissue samples both from liver and heart were obtained for biochemical and histopathological evaluations. Iron deposition, the iron-induced hepatotoxicity, and cardiotoxicity were demonstrated by histopathological and biochemical manner. However, no significant differences were observed in the serum biochemical values and the histopathological results among the iron and the HA plus iron groups in the liver tissue but not in the heart tissue. The protective effects of humic acid against iron-induced cardiotoxicity were shown but not against hepatotoxicity in our study.

  9. Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults

    Institute of Scientific and Technical Information of China (English)

    Wei-xing CHEN; Chuan-qin XU; Shao-hua CHEN; Gen-yun XU; Huai-zhuang YE

    2012-01-01

    .05),while there were no significant differences between the latter two treatments.The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption.It may also affect some blood biochemical indicators,but the specific mechanisms need further research.

  10. pACC1 peptide loaded chitosan nanoparticles induces apoptosis via reduced fatty acid synthesis in MDA-MB-231 cells

    Science.gov (United States)

    Kaliaperumal, Jagatheesh; Hari, Natarajan; Pavankumar, Padarthi; Elangovan, Namasivayam

    2016-06-01

    The development of formulations with therapeutic peptides has been restricted to poor cell penetration and in this attempt; we developed pACC1 peptide loaded chitosan nanoparticles. The prepared nanoparticles were characterized with FT-IR, XRD, SEM and TEM. In addition, the suitable formulation was evaluated for hemocompatibility, plasma stability and embryo toxicity using Danio rerio embryo model. The results showed that pACC1 peptide loaded chitosan nanoparticles were compatible with plasma. They possess sustained release pattern and also found to be safe up to 300 mg/L in embryo toxicity tests. Cytotoxicity assays with MDA-MB-231 cell lines suggested that, pACC1 peptide loaded chitosan nanoparticles were capable of enhanced cellular penetration and reduced palmitic acid content, which was confirmed by H1 NMR. Hence, these nanoparticles could be employed as excellent adjuvant therapeutics while treating solid tumors with multi-drug resistance.

  11. [Investigation of viral nucleic acids in middle-ear effusion specimens from children with acute otitis media].

    Science.gov (United States)

    Abu Sitteh, Muhammed H; Sener, Kenan; Yapar, Mehmet; Kiliç, Abdullah; Güney, Cakir; Kubar, Ayhan

    2008-07-01

    Acute otitis media with effusion (OME) is one of the major causes of antibiotic use, indication for operation and hearing loss in children. In two third of the cases the etiologic agents are bacteria. Nonetheless, increasing numbers of reports have implicated viruses as etiologic agents that may have some effect on prognosis of OME. The aim of this study was to investigate the presence of nucleic acids of respiratory syncytial virus (RSV) type A and B, influenza type A virus, adenovirus, cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1), and enteroviruses in the middle ear effusion specimens from children with otitis media by TaqMan real-time PCR. As a result, 18 of 30 (60%) OME samples were found positive in terms of viral nucleic acids by real-time PCR. RSV-A was detected in nine samples (30%), CMV in 3 (10%) samples and HSV-1 in 1 (3.3%) sample. In five of the samples two viruses were detected in the same sample (three were positive for adenovirus and RSV-A, and two were positive for CMV and RSV-A). Our data have supported the importance of viruses as etiologic agents of OME. Additionally, it was thought that TaqMan real-time PCR may be used as a reliable and rapid method for the detection of viruses in the middle ear effusion samples.

  12. Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue.

    Science.gov (United States)

    Polak, Jan; Moro, Cédric; Bessière, David; Hejnova, Jindra; Marquès, Marie A; Bajzova, Magda; Lafontan, Max; Crampes, Francois; Berlan, Michel; Stich, Vladimir

    2007-10-01

    The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

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

    Science.gov (United States)

    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.

  14. Methanesulfonic acid sodium salt protects retina from acute light damage in mice

    Institute of Scientific and Technical Information of China (English)

    WANG Hai-yan; GU Qing; XU Xun

    2012-01-01

    Background Methanesuffonic acid sodium salt (Dipyrone),an antipyretic and analgesic drug,has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades.The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy.Methods One hundred mice were assigned randomly into vehicle (V),methanesulfonic acid sodium salt (D),light damage model plus vehicle (MV) and light damage model plus methanesulfonic acid sodium salt (MD) groups (n=25 each).In the MD group,methanesulfonic acid sodium salt (100 mg/kg) was administered by intraperitoneal injection 30 minutes before light exposure.Twenty-four hours after light exposure,hematoxylin and eosin staining and transmission electron microscopy (TEM) were used for histological evaluation.The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 μm from the optic nerve.Electroretinography (ERG) test was performed to assess the functional change.The morphology of mitochondria was also revealed by TEM.Finally,the expression of cytochrome c (CytC) and the relative apoptotic proteins were detected by Western blotting,and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation.Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group.The thicknesses of the outer plus inner-segment layers and the outer nuclear layer,and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group (P <0.05).TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae.In contrast,the morphology of mitochondria in the MD group was unaffected.Western blotting analysis showed that Cyt

  15. Microwave-Assisted Conversion of Levulinic Acid to γ-Valerolactone Using Low-Loaded Supported Iron Oxide Nanoparticles on Porous Silicates

    Directory of Open Access Journals (Sweden)

    Alfonso Yepez

    2015-09-01

    Full Text Available The microwave-assisted conversion of levulinic acid (LA has been studied using low-loaded supported Fe-based catalysts on porous silicates. A very simple, productive, and highly reproducible continuous flow method has been used for the homogeneous deposition of metal oxide nanoparticles on the silicate supports. Formic acid was used as a hydrogen donating agent for the hydrogenation of LA to effectively replace high pressure H2 mostly reported for LA conversion. Moderate LA conversion was achieved in the case of non-noble metal-based iron oxide catalysts, with a significant potential for further improvements to compete with noble metal-based catalysts.

  16. Preparation and drug-loading properties of Fe{sub 3}O{sub 4}/Poly(styrene-co-acrylic acid) magnetic polymer nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Wensheng [School of Chemistry and Chemical Engineering, Anhui University, Hefei 230039 (China); Coordination Chemistry Institute, School of Chemistry and Chemical Engineering and Life Science, Chaohu University, Chaohu 238000 (China); Shen, Yuhua, E-mail: s_yuhua@163.com [School of Chemistry and Chemical Engineering, Anhui University, Hefei 230039 (China); Xie, Anjian [School of Chemistry and Chemical Engineering, Anhui University, Hefei 230039 (China); Zhang, Weiqiang [School of Chemistry and Chemical Engineering, Anhui University, Hefei 230039 (China); Coordination Chemistry Institute, School of Chemistry and Chemical Engineering and Life Science, Chaohu University, Chaohu 238000 (China)

    2013-11-15

    Fe{sub 3}O{sub 4}/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, Fe{sub 3}O{sub 4} 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 Fe{sub 3}O{sub 4} 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.

  17. Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler.

    Science.gov (United States)

    Van Dyke, Susan; Hays, Geoffrey P; Caglia, Anthony E; Caglia, Michael

    2010-05-01

    Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic bacteria and mycobacterium. All three cultures were negative. Abscess persistence in all cases necessitated physical removal and/or enzymatic degradation with hyaluronidase. The effects subsided only after the product had been removed. Two of these patients were subsequently treated with other hyaluronic acid-derived dermal fillers without adverse events.

  18. Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler

    OpenAIRE

    Van Dyke, Susan; Hays, Geoffrey P.; Caglia, Anthony E.; Caglia, Michael

    2010-01-01

    Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic...

  19. Arsenic species excretion after dimercaptopropanesulfonic acid (DMPS) treatment of an acute arsenic trioxide poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Heinrich-Ramm, R. [Ordinariat fuer Arbeitsmedizin der Universitaet Hamburg und Zentralinstitut fuer Arbeitsmedizin, Hamburg (Germany); Schaller, K.H.; Angerer, J. [Institut und Poliklinik fuer Arbeits-, Sozial- und Umweltmedizin der Universitaet Erlangen-Nuernberg, Schillerstr. 25, 91054 Erlangen (Germany); Horn, J. [Medizinische Klinik II, Toxikologische-internistische Intensivstation, Klinikum Nuernberg, Nuernberg (Germany)

    2003-02-01

    We studied the urinary excretion of the different arsenic species in urine samples from a young man who tried to commit suicide by ingesting about 0.6 g arsenic trioxide. He received immediate therapy with dimercaptopropanesulfonic acid (DMPS) after his delivery into the hospital. We assessed urinary arsenite (inorganic trivalent arsenic), arsenate (inorganic pentavalent arsenic), pentavalent dimethylarsinic acid (DMA) and pentavalent monomethylarsonic acid (MMA) in urine with ion-exchange chromatography and on-line hydride-technique atomic absorption spectrometry. The predominant amount of the excreted arsenic was unchanged trivalent inorganic arsenic (37.4%), followed by pentavalent inorganic arsenic (2.6%), MMA (2.1%), DMA (0.2%) and one unidentified arsenic species (0.7%, if calculated as DMA). In the first urine voiding in the clinic, the total arsenic concentration was 215 mg/l, which fell 1000-fold after 8 days of DMPS therapy. A most striking finding was the almost complete inhibition of the second methylation step in arsenic metabolism. As mechanisms for the reduced methylation efficiency, the saturation of the enzymatic process of arsenic methylation, the high dosage of antidote DMPS, which might inhibit the activity of the methyl transferases, and analytical reasons are discussed. The high dosage of DMPS is the most likely explanation. The patient left the hospital after a 12-day treatment with antidote. (orig.)

  20. Protective effects of electroacupuncture on acetylsalicylic acid-induced acute gastritis in rats

    Institute of Scientific and Technical Information of China (English)

    Hye Suk Hwang; Kyung-Ju Han; Yeon Hee Ryu; Eun Jin Yang; Yoo Sung Kim; Sang Yong Jeong; Young-Seop Lee; Myeong Soo Lee; Sung Tae Koo; Sun-Mi Choi

    2009-01-01

    AIM: To invest igate the protect ive effects of electroacupuncture (EA) pretreatment on acetylsalicylic acid (ASA)-induced ulceration in rats. METHODS: We randomly divided 72 rats into three groups including control (administered with distilled water), ASA group (administered 100 mg/kg ASA) and EA group (administered EA + 100 mg/kg ASA). Each rat was fasted for 18 to 24 h before experimentation, and lesion scores, gastric acidity, cyclooxygenase (COX)-1 and -2 mRNA levels, and total nitric oxide (NO) concentration were measured. RESULTS: The lesion scores of the EA group were significantly lower than those of the ASA group. Gastric acidity of the ASA and EA groups was reduced compared to the control group. COX-1 and -2 mRNA levels were significantly increased in the EA group as compared to the control and ASA groups, and NO levels were also significantly increased in the EA group as compared to the ASA group. CONCLUSION: These results suggest that EAmediated protection against ASA-induced ulceration in rats may occur via gastric defense components.

  1. Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Guang-ju ZHOU; Hong ZHANG; Sheng-de ZHI; Guo-ping JIANG; Jing WANG; Mao ZHANGI; Jian-xin GAN; Shao-wen XU; Guan-yu JIANG

    2007-01-01

    Aim: To evaluate the protective effect of oral raloxifene on acute lung injury.Methods: Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups: the raloxifene-lipopolysacchadde (LPS)-HC1 group(n=10), the LPS-raloxifene-HCl group (n=10), and the placebo group (n=10). All the rats were injected intraperitoneally (ip) with 5 mg/kg LPS, and raloxifene (30mg/kg) was orally administered 1 h before and 14 h after LPS injection into the raloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebo group received nothing. Sixteen hours after LPS injection, all the animals were anesthetized and the femoral artery was cannulated. All the rats received a direct intratracheal (IT) injection ofHCl (pH 1.2; 0.5 mL/kg). The mean arterial pressure(MAP) and blood gas concentrations were measured. Fifteen rats (5 in each group, respectively) underwent a micro positron emission to mography (microPET)scan of the thorax 4 h after HC1 instillation. The wet/dry (W/D) weight ratio determination and histopathological examination were also performed. Results:The rats in the LPS-raloxifene-HC1 group had a lower [18F]fluorodeoxyglucose uptake compared with the rats in the placebo group (4.67±1.33 vs 9.01±1.58,respectively, P<0.01). The rats in the LPS-raloxifene-HC1 group also had a lower histological lung injury score (8.20±1.23 vs 12.6±0.97, respectively, P<0.01) and W/D weight ratio (5.335±0.198 vs 5.886±0.257, respectively, P<0.01) compared to the placebo group. The rats in this group also showed better pulmonary gas exchange and more stable mean arterial pressure (MAP) compared to the placebo group. Conclusion: Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HC1 IT instillation.

  2. Target loads of atmospheric sulfur and nitrogen deposition for protection of acid sensitive aquatic resources in the Adirondack Mountains, New York

    Science.gov (United States)

    Sullivan, T.J.; Cosby, B.J.; Driscoll, C.T.; McDonnell, T.C.; Herlihy, A.T.; Burns, Douglas A.

    2012-01-01

    The dynamic watershed acid-base chemistry model of acidification of groundwater in catchments (MAGIC) was used to calculate target loads (TLs) of atmospheric sulfur and nitrogen deposition expected to be protective of aquatic health in lakes in the Adirondack ecoregion of New York. The TLs were calculated for two future dates (2050 and 2100) and three levels of protection against lake acidification (acid neutralizing capacity (ANC) of 0, 20, and 50 eq L -1). Regional sulfur and nitrogen deposition estimates were combined with TLs to calculate exceedances. Target load results, and associated exceedances, were extrapolated to the regional population of Adirondack lakes. About 30% of Adirondack lakes had simulated TL of sulfur deposition less than 50 meq m -2 yr to protect lake ANC to 50 eq L -1. About 600 Adirondack lakes receive ambient sulfur deposition that is above this TL, in some cases by more than a factor of 2. Some critical criteria threshold values were simulated to be unobtainable in some lakes even if sulfur deposition was to be decreased to zero and held at zero until the specified endpoint year. We also summarize important lessons for the use of target loads in the management of acid-impacted aquatic ecosystems, such as those in North America, Europe, and Asia. Copyright 2012 by the American Geophysical Union.

  3. Association of serum uric acid level with mortality and morbidity of patients with acute ST-elevation myocardial infarction

    Science.gov (United States)

    Hajizadeh, Reza; Ghaffari, Samad; Salehi, Rezvanieh; Mazani, Sarvin; Aghavali, Sharmin

    2016-01-01

    Introduction: Investigating the clinical impact of serum uric acid (UA) and its lowering agents on the complications and mortality of acute ST-elevation myocardial infarction (STEMI) can open a new era in STEMI treatment. The aim of this study was to evaluate the effect of on admission serum UA level on the mortality and morbidity of patients admitted with STEMI. Methods: A number of 608 patients with STEMI were enrolled in this study from December 21, 2012 until February 19, 2014. Patients were followed for 20 months. Male to female ratio was 2.53, and the mean age of patients was 62.6±13.4. The relationship between the level of UA and patients’ mortality and morbidity, left ventricular ejection fraction (LVEF), atrial and ventricular arrhythmia was analyzed. Results: Patients with high serum UA level had higher Killip class after STEMI (P=0.001). Mean LVEF was measured to be 39.5±9.6 in normal UA group and 34.6±11.6 in high UA group (P=0.001). In comparison with normal UA group, high UA group had significantly higher cTnI (2.68±0.09 vs 4.09±0.42, respectively, P=0.001), increased blood pressure (P=0.009), and higher atrial fibrillation (AF) occurrence (P=0.03), but no association was seen between ventricular tachycardia and serum UA level. Short term and midterm mortality were not different in two groups (P=0.44 and 0.31, respectively). Conclusion: In the current study, high serum UA level in patients with acute myocardial infarction (MI) was not associated with higher in-hospital or midterm mortality, but it was associated with lower LVEF, higher Killip class, elevated cTnI, creatinine, triglyceride, and higher AF. PMID:27489597

  4. Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations.

    Directory of Open Access Journals (Sweden)

    Eduardo O De Souza

    Full Text Available The primary purpose of this investigation was to examine the effects of arachidonic acid (ARA supplementation on functional performance and body composition in trained males. In addition, we performed a secondary study looking at molecular responses of ARA supplementation following an acute exercise bout in rodents.Thirty strength-trained males (age: 20.4 ± 2.1 yrs were randomly divided into two groups: ARA or placebo (i.e. CTL. Then, both groups underwent an 8-week, 3-day per week, non-periodized training protocol. Quadriceps muscle thickness, whole-body composition scan (DEXA, muscle strength, and power were assessed at baseline and post-test. In the rodent model, male Wistar rats (~250 g, ~8 weeks old were pre-fed with either ARA or water (CTL for 8 days and were fed the final dose of ARA prior to being acutely strength trained via electrical stimulation on unilateral plantar flexions. A mixed muscle sample was removed from the exercised and non-exercised leg 3 hours post-exercise.Lean body mass (2.9%, p<0.0005, upper-body strength (8.7%, p<0.0001, and peak power (12.7%, p<0.0001 increased only in the ARA group. For the animal trial, GSK-β (Ser9 phosphorylation (p<0.001 independent of exercise and AMPK phosphorylation after exercise (p-AMPK less in ARA, p = 0.041 were different in ARA-fed versus CTL rats.Our findings suggest that ARA supplementation can positively augment strength-training induced adaptations in resistance-trained males. However, chronic studies at the molecular level are required to further elucidate how ARA combined with strength training affect muscle adaptation.

  5. Acute Copper and Ascorbic Acid Supplementation Inhibits Non-heme Iron Absorption in Humans.

    Science.gov (United States)

    Olivares, Manuel; Figueroa, Constanza; Pizarro, Fernando

    2016-08-01

    The objective of the study is to determine the effect of copper (Cu) plus the reducing agent ascorbic acid (AA) on the absorption of non-heme iron (Fe). Experimental study with block design in which each subject was his own control. After signing an informed consent, 14 adult women using an effective method of contraception and negative pregnancy test received 0.5 mg Fe, as ferrous sulfate, alone or with Cu, as copper sulfate, plus ascorbic acid (AA/Cu 2/1 molar ratio) at 4/1; 6/1 and 8/1 Cu/Fe molar ratios as an aqueous solution on days 1, 2, 14, and 15 of the study. Fe absorption was assessed by erythrocyte incorporation of iron radioisotopes (55)Fe and (59)Fe. Geometric mean (range ± SD) absorption of Fe at 4/1 and 6/1 Cu/Fe molar ratios (and AA/Cu 2/1 molar ratio) and Fe alone was 57.4 % (35.7-92.1 %), 64.2 % (45.8-89.9 %), and 38.8 % (20.4-73.8 %), respectively (ANOVA for repeated measures p absorption; however, Fe absorption at Cu/Fe 8/1 molar ratio was 47.3 % (27.7-80.8) (p = NS compared with Fe alone). It was expected that Fe absorption would have been equal or greater than at 4/1 and 6/1 molar ratios. Copper in the presence of ascorbic acid inhibits non-heme Fe absorption at Cu/Fe 8/1 molar ratio.

  6. Antitumor Effect of Betulinic Acid on Human Acute Leukemia K562 Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    吴秋玲; 何静; 方峻; 洪梅

    2010-01-01

    The effects of betulinic acid (BA), a pentacyclic lupane-type triterpene, on the cell viability, cell cycle and apoptosis in human leukemia K562 cells were investigated. The effects of BA on the growth of K562 cells were studied by MTT assay. Apoptosis was assayed through Annexin V/propidium iodide (PI) double-labeled cytometry. The effects of BA on the cell cycle of K562 cells were studied by a PI method. The expression of Bax and capase-3 was detected by using Western blot. The results showed that BA was ...

  7. Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial.

    LENUS (Irish Health Repository)

    Jones, Kelsey D J

    2015-01-01

    Ready-to-use therapeutic foods (RUTF) are lipid-based pastes widely used in the treatment of acute malnutrition. Current specifications for RUTF permit a high n-6 polyunsaturated fatty acid (PUFA) content and low n-3 PUFA, with no stipulated requirements for preformed long-chain n-3 PUFA. The objective of this study was to develop an RUTF with elevated short-chain n-3 PUFA and measure its impact, with and without fish oil supplementation, on children\\'s PUFA status during treatment of severe acute malnutrition.

  8. A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    R Bharath

    2013-01-01

    Full Text Available Aim: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA of foot in terms of clinical and radiological parameters. Material and Methods: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC. Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1oF. Results: Among the 40 patients, 30 (75% had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. Conclusion: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. 99m Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

  9. Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

    NARCIS (Netherlands)

    Cervera, Jose; Montesinos, Pau; Hernandez-Rivas, Jesus M.; Calasanz, Maria J.; Aventin, Anna; Ferro, Maria T.; Luno, Elisa; Sanchez, Javier; Vellenga, Edo; Rayon, Chelo; Milone, Gustavo; de la Serna, Javier; Rivas, Concha; Gonzalez, Jose D.; Tormo, Mar; Amutio, Elena; Gonzalez, Marcos; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2010-01-01

    Background Acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the t(15;17). The incidence and prognostic significance of additional chromosomal abnormalities in acute promyelocytic leukemia is still a controversial matter. Design and Methods Based on cytogenetic dat

  10. Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

    NARCIS (Netherlands)

    J. Cervera (José); P. Montesinos (Pau); J.M. Hernandez-Rivas (J. M.); M.J. Calasanz (Maria); A. Aventín (Anna); M.T. Ferro (María); E. Luño (Elisa); J. Sánchez (Javier); E. Vellenga (Edo); C. Rayón (Chelo); G. Milone (Gustavo); J. de Serna (Javier); C. Rivas (Concha); J.D. González (José David); M. Tormo (Mar); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2010-01-01

    textabstractBackground: Acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the t(15;17). The incidence and prognostic significance of additional chromosomal abnormalities in acute promyelocytic leukemia is still a controversial matter. Design and Methods: Based on c

  11. Acute effect of lactic acid on tumor-endothelial cell metabolic coupling in the tumor microenvironment

    Science.gov (United States)

    Zhu, Guanqun; Wang, Degui; Li, Shenqian; Yang, Xuecheng; Cao, Yanwei; Wang, Yonghua; Niu, Haitao

    2016-01-01

    The present study aimed to systematically analyze alterations in the expression of mitochondrial-associated proteins in human bladder cancer T24 cells co-cultured with tumor-associated human umbilical vein endothelial cells (HUVECs), and to investigate the characteristics of bladder cancer cell energy metabolism. The present study used the following techniques: A co-culture system of T24 cells and HUVECs was constructed using a microfluidic chip as a 3D co-culture system; the concentration of lactic acid in the medium of the cells was determined using an automatic microplate reader; a qualitative analysis of mitochondria-associated protein expression was performed by immunofluorescent staining; and a quantitative analysis of mitochondrial-associated protein expression was conducted using western blotting. The present results revealed that between the control groups (monoculture of T24 cells or HUVECs), the mitochondrial-associated protein fluorescence intensity was increased in the HUVECs compared with the T24 cells. The fluorescence intensity of mitochondrial-associated proteins in the HUVEC control group was increased compared with the HUVECs in the experimental co-culture group. In the T24 cells, the protein fluorescence intensity was increased in the experimental co-culture group compared with the control group. In addition, the expression of mitochondria-associated proteins was increased in HUVECs compared with T24 cells in the control groups, while T24 cells in the experimental co-culture group had an increased expression compared with HUVECs in the experimental group (P<0.05). For T24 cells, the expression of mitochondrial-associated proteins was increased in the experimental group compared with the control group, and contrasting results were observed for the HUVECs (P<0.05). Determination of lactic acid concentration demonstrated that lactic acid concentration was highest in the experimental co-culture group, followed by the T24 control group and the HUVEC

  12. Degradation of H-acid in aqueous solution by microwave assisted wet air oxidation using Ni-loaded GAC as catalyst

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yao-bin; QUAN Xie; ZHAO Hui-min; CHEN Shuo; YANG Feng-lin

    2005-01-01

    A novel process, microwave assisted catalytic wet air oxidation(MW-CWO), was applied for the degradation of H-acid( 1-amino8-naphthol-3, 6-disulfonic acid) in aqueous solution. Ni-loaded granular activated carbon (GAG), prepared by immersion-calcination method, was used as catalyst. The results showed that the MW-CWO process was very effective for the degradation of H-acid in aqueous solution under atmospheric pressure with 87.4% TOC (total organic carbon) reduction in 20 min. Ni on GAC existed in the form of NiO as specified by XRD. Loss of Ni was significant in the initial stage, and then remained almost constant after 20 min reaction. BET surface area results showed that the surface property of GAC after MW-CWO process was superior to that of blank GAC.

  13. Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid.

    Science.gov (United States)

    Douer, D; Estey, E; Santillana, S; Bennett, J M; Lopez-Bernstein, G; Boehm, K; Williams, T

    2001-01-01

    A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m(2)) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67. 5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.

  14. Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.

    Science.gov (United States)

    Serrano, Pedro; Johnson, Margaret A; Chatterjee, Amarnath; Neuman, Benjamin W; Joseph, Jeremiah S; Buchmeier, Michael J; Kuhn, Peter; Wüthrich, Kurt

    2009-12-01

    The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. Two antiparallel two-strand beta-sheets and two 3(10)-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.

  15. Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

    Directory of Open Access Journals (Sweden)

    B.C. de-Medeiros

    1998-12-01

    Full Text Available Thirty-seven patients with acute promyelocytic leukemia (APL were treated with all-trans retinoic acid (ATRA. Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR was achieved, defined as: a presence of less than 5% blasts in the bone marrow, with b white blood cells >103/mm3, c platelets >105/mm3 and d hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7% patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days, was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS were observed in 7 (19%, 6 (16% and 4 (11% patients, respectively. Thirteen (35% patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3 and six of these presented with new signs of coagulopathy after chemotherapy. Four (11% patients died secondarily to intracerebral hemorrhage (IH and two (5.4% dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity. RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

  16. cis-Urocanic acid attenuates acute dextran sodium sulphate-induced intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Eric Albert

    Full Text Available On exposure to sunlight, urocanic acid (UCA in the skin is converted from trans to the cis form and distributed systemically where it confers systemic immunosuppression. The aim of this study was to determine if administration of cis-UCA would be effective in attenuating colitis and the possible role of IL-10. Colitis was induced in 129/SvEv mice by administering 5% dextran sodium sulfate (DSS for 7 days in drinking water. During this period mice received daily subcutaneously injections of cis-UCA or vehicle. To examine a role for IL-10, 129/SvEv IL-10(-/- mice were injected for 24 days with cis-UCA or vehicle. Clinical disease was assessed by measurement of body weight, stool consistency, and presence of blood. At sacrifice, colonic tissue was collected for histology and measurement of myeloperoxidase and cytokines. Splenocytes were analyzed for CD4+CD25+FoxP3+ T-regulatory cells via flow cytometry. Murine bone-marrow derived antigen-presenting cells were treated with lipopolysaccharide (LPS ± UCA and cytokine secretion measured. Our results demonstrated that cis-UCA at a dose of 50 µg was effective in ameliorating DSS-induced colitis as evidenced by reduced weight loss and attenuated changes in colon weight/length. This protection was associated with reduced colonic expression of CXCL1, an increased expression of IL-17A and a significant preservation of splenic CD4+CD25+FoxP3+ T-regulatory cells. cis-UCA decreased LPS induced CXCL1, but not TNFα secretion, from antigen-presenting cells in vitro. UCA reduced colonic levels of IFNγ in IL-10(-/- mice but did not attenuate colitis. In conclusion, this study demonstrates that cis-urocanic acid is effective in reducing the severity of colitis in a chemically-induced mouse model, indicating that pathways induced by ultraviolet radiation to the skin can influence distal sites of inflammation. This provides further evidence for a possible role for sunlight exposure in modulating inflammatory

  17. [Acute promyelocytic leukemia (APL) resulting in broad cerebral infarction during all-trans retinoic acid (ATRA) treatment].

    Science.gov (United States)

    Ikeda, Y; Yoshinaga, K; Iki, S; Ohbayashi, Y; Urabe, A

    1994-02-01

    A 27-year-old woman visited Kanto Teishin Hospital complaining of fever and petechiae in September, 1992. Her fetus had suddenly died in the uterus two weeks before (in the sixth month of pregnancy). Total white blood cell (WBC) count was 3.2 x 10(3)/microliters with 80% promyelocytes. Bone marrow was hypercellular with 90% promyelocytes. Disseminated intravascular coagulation (DIC) was recognized. She was diagnosed as having acute promyelocytic leukemia (APL), and treatment with daily oral administration of all-trans retinoic acid (ATRA) (70 mg/body/day) was begun. On day 4, hemiplegia and aphasia appeared. Broad cerebral infarction was suspected from computed tomography. On day 9, the WBC count increased rapidly, standard chemotherapy was added and she achieved complete remission. ATRA is known to have stimulatory effects on the differentiation of APL cells, but some reports have described thromboembolic events during the administration of ATRA. In this case, ATRA might have affected coagulability resulting in cerebral infarction.

  18. Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells.

    Science.gov (United States)

    Tabe, Yoko; Yamamoto, Shinichi; Saitoh, Kaori; Sekihara, Kazumasa; Monma, Norikazu; Ikeo, Kazuho; Mogushi, Kaoru; Shikami, Masato; Ruvolo, Vivian; Ishizawa, Jo; Hail, Numsen; Kazuno, Saiko; Igarashi, Mamoru; Matsushita, Hiromichi; Yamanaka, Yasunari; Arai, Hajime; Nagaoka, Isao; Miida, Takashi; Hayashizaki, Yoshihide; Konopleva, Marina; Andreeff, Michael

    2017-03-15

    Leukemia cells in the bone marrow must meet the biochemical demands of increased cell proliferation and also survive by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the bone marrow is a novel therapeutic approach. In this study, we investigated the metabolic role of bone marrow adipocytes in supporting the growth of leukemic blasts. Prevention of nutrient starvation-induced apoptosis of leukemic cells by bone marrow adipocytes, as well as the metabolic and molecular mechanisms involved in this process, was investigated using various analytic techniques. In acute monocytic leukemia (AMoL) cells, the prevention of spontaneous apoptosis by bone marrow adipocytes was associated with an increase in fatty acid β-oxidation (FAO) along with the upregulation of PPARγ, FABP4, CD36, and BCL2 genes. In AMoL cells, bone marrow adipocyte coculture increased adiponectin receptor gene expression and its downstream target stress response kinase AMPK, p38 MAPK with autophagy activation, and upregulated antiapoptotic chaperone HSPs. Inhibition of FAO disrupted metabolic homeostasis, increased reactive oxygen species production, and induced the integrated stress response mediator ATF4 and apoptosis in AMoL cells cocultured with bone marrow adipocytes. Our results suggest that bone marrow adipocytes support AMoL cell survival by regulating their metabolic energy balance and that the disruption of FAO in bone marrow adipocytes may be an alternative, novel therapeutic strategy for AMoL therapy. Cancer Res; 77(6); 1453-64. ©2017 AACR.

  19. Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia.

    Science.gov (United States)

    Boutzen, Héléna; Saland, Estelle; Larrue, Clément; de Toni, Fabienne; Gales, Lara; Castelli, Florence A; Cathebas, Mathilde; Zaghdoudi, Sonia; Stuani, Lucille; Kaoma, Tony; Riscal, Romain; Yang, Guangli; Hirsch, Pierre; David, Marion; De Mas-Mansat, Véronique; Delabesse, Eric; Vallar, Laurent; Delhommeau, François; Jouanin, Isabelle; Ouerfelli, Ouathek; Le Cam, Laurent; Linares, Laetitia K; Junot, Christophe; Portais, Jean-Charles; Vergez, François; Récher, Christian; Sarry, Jean-Emmanuel

    2016-04-04

    Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD-Scid-IL2rγ(null)mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies.

  20. Does acute lead (Pb) contamination influence membrane fatty acid composition and freeze tolerance in intertidal blue mussels in arctic Greenland?

    Science.gov (United States)

    Thyrring, Jakob; Juhl, Bodil Klein; Holmstrup, Martin; Blicher, Martin E; Sejr, Mikael K

    2015-11-01

    In their natural habitats, organisms are exposed to multiple stressors. Heavy metal contamination stresses the cell membrane due to increased peroxidation of lipids. Likewise, sub-zero air temperatures potentially reduce membrane functionality in ectothermal animals. We tested if acute lead (Pb) exposure for 7 days would influence survival in intertidal blue mussels (Mytilus edulis) after exposure to realistic sub-zero air temperatures. A full factorial experiment with five tissue Pb concentrations between 0 and 3500 μg Pb/g and six sub-zero temperatures from 0 to -17 °C were used to test the hypothesis that sub-lethal effects of Pb may increase the lethality caused by freezing in blue mussels exposed to temperatures simulating Greenland winter conditions. We found a significant effect of temperature on mortality. However, the short-term exposure to Pb did not result in any effects of Pb, nor did we find interactions between Pb and temperature. We analysed the relative abundance of major phospholipid fatty acids (PLFAs) in the gill tissue, but we found no significant effect of Pb tissue concentration on PLFA composition. Results suggest that Pb accumulation has limited effects on freeze tolerance and does not induce membrane damage in terms of persistent lipid peroxidation.

  1. Differential efficiency of simvastatin and lipoic acid treatments on Bothrops jararaca envenomation-induced acute kidney injury in mice.

    Science.gov (United States)

    Barone, Juliana Marton; Alponti, Rafaela Fadoni; Frezzatti, Rodrigo; Zambotti-Villela, Leonardo; Silveira, Paulo Flávio

    2011-01-01

    Snake bite accidents by Bothrops genus is an important public health issue in Brazil and one of its most serious complications is the acute kidney injury (AKI). Here we evaluated the effects of Bothrops jararaca venom (vBj) and the treatments with lipoic acid (LA) and simvastatin (SA) on renal function, aminopeptidase (AP) activities and renal redox status. Primordial events for establishment of AKI by vBj were hyperuricemia, hypercreatinemia, urinary hyperosmolality, renal oxidative stress and reduction of hematocrit and protein content in the membrane of renal cortex and medulla and in the plasma. In the renal cortex and medulla the changes caused by vBj in soluble and membrane-bound AP activities had a similar pattern. The beneficial effects of LA and SA on envenomed mice were similar on the hyperuricemia, renal oxidative stress and reduction of hematocrit. LA mitigated the hypercreatinemia, but exacerbated the urinary urea and creatinine, whereas SA mitigated the decrease of plasma urea, urinary hyperosmolality and hypercreatinuria induced by vBj. The beneficial effects of LA and especially of SA on renal effects of vBj open a new perspective for clinical investigations of these drugs as coadjuvant agents in the serotherapy of Bothrops envenomation.

  2. RISK OF REPEATED THROMBOTIC EVENTS IN PATIENTS SURVIVED ACUTE CORONARY SYNDROME AND HAVING LABORATORY PROVEN RESISTANCE TO ACETYLSALICYLIC ACID

    Directory of Open Access Journals (Sweden)

    N. F. Puchinyan

    2009-01-01

    Full Text Available Aim. To evaluate risk of repeated atherothrombotic events in patients survived acute coronary syndrome (ACS and having poorly reduced platelet aggregation (proven by optical aggregometry in response to acetylsalicylic acid (ASA therapy.Material and methods. 200 patients with ACS (aged 56,6±9,2 y.o. were included in the study. Platelet functional activity during ASA therapy was evaluated with laser aggregometer. ASA resistance was defined if the summarizing index of platelet aggregation (induced with ADP, 5 mμml/l was 50% or higher during ASA therapy. Observation period was 18±6 months. Atherothrombotic events (unstable angina, myocardial infarction, stroke, cardiovascular death were considered.Results. Lack ASA response rate was about 12%. Totally 22 repeated atherothrombotic events were registered: 5,6% among ASA sensitive patients and 50% - among ASA resistant patients. Repeated atherothrombotic events were registered in ASA resistance patients during first 14 days. ASA sensitive patients showed repeated atherothrombotic events in some months after ACS. The relative risk of cardiovascular event in ASA resistance patients was 8,92 (CI 95% 4,39; 17,84 р=0,05.Conclusion. The high level of the induced platelet aggregation (proven by laser aggregometry points to high risk of repeated atherothrombotic events in patients with ACS.

  3. An acute dose of gamma-hydroxybutyric acid alters gene expression in multiple mouse brain regions.

    Science.gov (United States)

    Schnackenberg, B J; Saini, U T; Robinson, B L; Ali, S F; Patterson, T A

    2010-10-13

    Gamma-hydroxybutyric acid (GHB) is normally found in the brain in low concentrations and may function as a neurotransmitter, although the mechanism of action has not been completely elucidated. GHB has been used as a general anesthetic and is currently used to treat narcolepsy and alcoholism. Recreational use of GHB is primarily as a "club drug" and a "date rape drug," due to its amnesic effects. For this study, the hypothesis was that behavioral and neurochemical alterations may parallel gene expression changes in the brain after GHB administration. Adult male C57/B6N mice (n=5/group) were administered a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and 4 h after treatment. Control mice were administered saline. Brains were removed and regionally dissected on ice. Total RNA from the hippocampus, cortex and striatum was extracted, amplified and labeled. Gene expression was evaluated using Agilent whole mouse genome 4x44K oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack and differentially expressed genes (DEGs) were identified using P or = 1.7 as the criteria for significance. Principal component analysis (PCA) and Hierarchical Cluster Analysis (HCA) showed that samples from each time point clustered into distinct treatment groups with respect to sacrifice time. Ingenuity pathways analysis (IPA) was used to identify involved pathways. The results show that GHB induces gene expression alterations in hundreds of genes in the hippocampus, cortex and striatum, and the number of affected genes increases throughout a 4-h time course. Many of these DEGs are involved in neurological disease, apoptosis, and oxidative stress.

  4. ASSESSMENT OF HEMATOLOGICAL PARAMETERS, ACID-BASE STATUS AND ARTERIAL BLOOD GAS TEST BEFORE AND AFTER TREATMENT OF ACUTE BRONCHIOLITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Zuvdija Cecunjanin

    2016-08-01

    Full Text Available Objective: The purpose of our retrospective study was to investigate the necessity of some laboratory testing in patients with acute bronchiolitis before and after treatment. Methods: We have taken blood samples of all children puncturing the cubital vein, and analyzed it using the Colter appliances-automatic counter blood count, for analyzes of a number of erythrocytes, leukocytes, platelets, differential blood count, Hct, Hb. CRP concentration in serum of patients determined by laser nephelometry with CardioPhase® high sensitivity C-reactive protein (hsCRP. For assessment of acid-base status and arterial blood gas analysis were used ABL5 and ABL700 Radiometer Copenhagen. We monitored the following parameters: pH, pCO2, HCO3-, total CO2, base excess, pO2, SpO2. Results: There was a significant improvement of hypoxemia after management of acute bronchiolitis in the form of a significant increase in average values of pO2 and SpO2 after treatment of acute bronchiolitis. The average value of the number of leukocytes and value of CRP in children were significantly decreased before and after management of acute bronchiolitis. There was no significant difference in duration of hospitalization in term and preterm newborns. Conclusion: No routine diagnostic tests are used routinely. However, there is an improvement of hypoxemia after management of acute bronchiolitis in children.

  5. Effects of Acute Exposure to Increased Plasma Branched-Chain Amino Acid Concentrations on Insulin-Mediated Plasma Glucose Turnover in Healthy Young Subjects

    OpenAIRE

    Sarah Everman; Mandarino, Lawrence J.; Carroll, Chad C.; Katsanos, Christos S.

    2015-01-01

    Background Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. Objective To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Methods Ten healthy subjects were randomly assigned to...

  6. Changes in rocket salad phytochemicals within the commercial supply chain: Glucosinolates, isothiocyanates, amino acids and bacterial load increase significantly after processing.

    Science.gov (United States)

    Bell, Luke; Yahya, Hanis Nadia; Oloyede, Omobolanle Oluwadamilola; Methven, Lisa; Wagstaff, Carol

    2017-04-15

    Five cultivars of Eruca sativa and a commercial variety of Diplotaxis tenuifolia were grown in the UK (summer) and subjected to commercial growth, harvesting and processing, with subsequent shelf life storage. Glucosinolates (GSL), isothiocyanates (ITC), amino acids (AA), free sugars, and bacterial loads were analysed throughout the supply chain to determine the effects on phytochemical compositions. Bacterial load of leaves increased significantly over time and peaked during shelf life storage. Significant correlations were observed with GSL and AA concentrations, suggesting a previously unknown relationship between plants and endemic leaf bacteria. GSLs, ITCs and AAs increased significantly after processing and during shelf life. The supply chain did not significantly affect glucoraphanin concentrations, and its ITC sulforaphane significantly increased during shelf life in E. sativa cultivars. We hypothesise that commercial processing may increase the nutritional value of the crop, and have added health benefits for the consumer.

  7. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  8. The influence of pendant carboxylic acid loading on surfaces of statistical poly(4-hydroxystyrene)-co-styrene)s

    DEFF Research Database (Denmark)

    Daugaard, Anders Egede; Hvilsted, Søren

    2008-01-01

    synthesis with propargyl bromide and the copolymers were functionalized with pendant aliphatic or aromatic carboxylic acids by click chemistry. Differential scanning calorimetry of the copolymers demonstrates the large influence on Tg ofthe different functional groups and the backbone composition...... of acid groups on the surface....

  9. STREAMWATER ACID-BASED CHEMISTRY AND CRITICAL LOADS OF ATMOSPHERIC SULFUR DEPOSITION IN SHENANDOAH NATIONAL PARK, VIRGINIA

    Science.gov (United States)

    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 neutraliz...

  10. Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.

    Science.gov (United States)

    Liu, James; Boonkaew, Benjawan; Arora, Jaspreet; Mandava, Sree Harsha; Maddox, Michael M; Chava, Srinivas; Callaghan, Cameron; He, Jibao; Dash, Srikanta; John, Vijay T; Lee, Benjamin R

    2015-03-01

    The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.

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

    Science.gov (United States)

    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.

  12. Protective effects of alginate-chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. (Zuojin Pill) against ethanol-induced acute gastric mucosal injury in rats.

    Science.gov (United States)

    Wang, Qiang-Song; Zhu, Xiao-Ning; Jiang, Heng-Li; Wang, Gui-Fang; Cui, Yuan-Lu

    2015-01-01

    Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in "Danxi's experiential therapy" for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1β in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus, these

  13. Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations

    Directory of Open Access Journals (Sweden)

    Sriskandarajah Nadarajah

    2004-09-01

    Full Text Available Abstract Background Elevated non-esterified fatty acids (NEFA concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL, 105 and 135 days gestational age (dGA, term 147+/- 3 days. Methods The plasma concentrations of insulin, growth hormone (GH and ovine placental lactogen (oPL were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA. Results Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p Conclusions Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones

  14. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab.

    Science.gov (United States)

    Abaza, Yasmin; Kantarjian, Hagop; Garcia-Manero, Guillermo; Estey, Elihu; Borthakur, Gautam; Jabbour, Elias; Faderl, Stefan; O'Brien, Susan; Wierda, William; Pierce, Sherry; Brandt, Mark; McCue, Deborah; Luthra, Rajyalakshmi; Patel, Keyur; Kornblau, Steven; Kadia, Tapan; Daver, Naval; DiNardo, Courtney; Jain, Nitin; Verstovsek, Srdan; Ferrajoli, Alessandra; Andreeff, Michael; Konopleva, Marina; Estrov, Zeev; Foudray, Maria; McCue, David; Cortes, Jorge; Ravandi, Farhad

    2017-03-09

    The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m(2) daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m(2) on day 1) added to high-risk patients (white blood cell count, >10 × 10(9)/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

  15. The Role of Omega-3 Fatty Acids in Acute Pancreatitis: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Qiu Cheng Lei

    2015-03-01

    Full Text Available To determine whether treatment with omega-3 fatty acids (ω-3 FA provides benefits to patients with acute pancreatitis (AP. The Cochrane Library, PubMed, Embase, Web of Science, and Chinese Biomedical Literature Database were searched. Data analysis was performed using Revman 5.2 software. A total of eight randomized controlled trials (RCTs were included. Overall, ω-3 FA treatment resulted in a significantly reduced risk of mortality (RR 0.35; 95% CI 0.16 to 0.75, p < 0.05, infectious complications (RR 0.54; 95% CI 0.34 to 0.85, p < 0.05 and length of hospital stay (MD –6.50; 95% CI −9.54 to −3.46, p < 0.05, but not length of ICU stay (MD −1.98; 95% CI −6.92 to 2.96, p > 0.05. In subgroup analysis, only patients who received ω-3 FA parenterally had some statistically significant benefits in terms of mortality (risk ratio (RR 0.37; 95% confidence interval (CI 0.16 to 0.86, p < 0.05, infectious complications (RR 0.5; 95% CI 0.28 to 0.9, p < 0.05 and length of hospital stay (mean difference (MD −8.13; 95% CI −10.39 to −5.87, p < 0.001. The administration of ω-3 FA may be beneficial for decreasing mortality, infectious complications, and length of hospital stay in AP, especially when used parenterally. Large and rigorously designed RCTs are required to elucidate the efficacy of parenteral or enteral ω-3 FA treatment in AP.

  16. Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury.

    Science.gov (United States)

    Negishi, Kousuke; Noiri, Eisei; Doi, Kent; Maeda-Mamiya, Rui; Sugaya, Takeshi; Portilla, Didier; Fujita, Toshiro

    2009-04-01

    The present study aimed to evaluate whether levels of urinary L-type fatty acid-binding protein (L-FABP) could be used to monitor histological injury in acute kidney injury (AKI) induced by cis-platinum (CP) injection and ischemia reperfusion (IR). Different degrees of AKI severity were induced by several renal insults (CP dose and ischemia time) in human L-FABP transgenic mice. Renal histological injury scores increased with both CP dose and ischemic time. In CP-induced AKI, urinary L-FABP levels increased exponentially even in the lowest dose group as early as 2 hours, whereas blood urea nitrogen (BUN) levels increased at 48 hours. In IR-induced AKI, BUN levels increased only in the 30-minute ischemia group 24 hours after reperfusion; however, urinary L-FABP levels increased more than 100-fold, even in the 5-minute ischemia group after 1 hour. In both AKI models, urinary L-FABP levels showed a better correlation with final histological injury scores and glomerular filtration rates measured by fluorescein isothiocyanate-labeled inulin injection than with levels of BUN and urinary N-acetyl-D-glucosaminidase, especially at earlier time points. Receiver operating characteristic curve analysis demonstrated that urinary L-FABP was superior to other biomarkers for the detection of significant histological injuries and functional declines. In conclusion, urinary L-FABP levels are better suited to allow the accurate and earlier detection of both histological and functional insults in ischemic and nephrotoxin-induced AKI compared with conventional renal markers.

  17. Determination of the load state of lead-acid batteries using neural networks; Determinacion del estado de carga de baterias plomo-acido utilizando redes neuronales

    Energy Technology Data Exchange (ETDEWEB)

    Cristin V, Miguel A; Ortega S, Cesar A [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2005-07-01

    The charge of lead-acid batteries (LAB), as in any other type of batteries, consists of replacing the energy consumed during the discharge. Nevertheless, as no physical or chemical process is good enough to totality recharge a battery, it is necessary to supply to it more than the 100% of the energy demanded during its discharge. A critical factor to make a suitable load control of the batteries is to determine its own state of load. That is to say, to have an efficient load control, it is necessary to count on means that allow to accurately determining the residual capacity of the battery to deliver load. This one is the one of the aspects of greater interest in the research centers around world. For this reason, in this work it was pretended to develop a calculation algorithm of the state of load of batteries based on a fuzzy-neural network that could calculate the state of load without using the battery current as an input. This is because one of the main problems for the designers of battery load controllers is the correct supervision of the current that circulates around the system in all the rank of operation of the same one because the sensors do not have a linear behavior. [Spanish] La recarga de baterias plomo-acido (BPA), como cualquier otro tipo de baterias, consiste en reponer la energia consumida durante la descarga. Sin embargo, como ningun proceso fisico o quimico es lo bastante eficiente para recargar a totalidad una bateria, es necesario suministrarle mas del 100% de la energia demandada durante su descarga. Un factor critico para realizar un adecuado control de carga de las baterias, es determinar su propio estado de carga. Es decir, para tener un control de carga eficiente, es necesario contar con un medio que permita determinar con precision la capacidad remanente de la bateria para entregar carga. Este es uno de los aspectos de mayor interes en los centros de investigacion alrededor el mundo. Por tal razon, en este trabajo se propuso

  18. Assessment of metal loads in watersheds affected by acid mine drainage by using tracer injection and synoptic sampling: Cement Creek, Colorado, USA

    Science.gov (United States)

    Kimball, B.A.; Runkel, R.L.; Walton-Day, K.; Bencala, K.E.

    2002-01-01

    Watersheds in mineralized zones may contain many mines, each of which can contribute to acidity and the metal load of a stream. In this study the authors delineate hydrogeologic characteristics determining the transport of metals from the watershed to the stream in the watershed of Cement Creek, Colorado. Combining the injection of a chemical tracer, to determine a discharge, with synoptic sampling, to obtain chemistry of major ions and metals, spatially detailed load profiles are quantified. Using the discharge and load profiles, the authors (1) identified sampled inflow sources which emanate from undisturbed as well as previously mined areas; (2) demonstrate, based on simple hydrologic balance, that unsampled, likely dispersed subsurface, inflows are significant; and (3) estimate attenuation. For example, along the 12-km study reach, 108 kg per day of Zn were added to Cement Creek. Almost half of this load came from 10 well-defined areas that included both mined and non-mined parts of the watershed. However, the combined effect of many smaller inflows also contributed a substantial load that could limit the effectiveness of remediation. Of the total Zn load, 58.3 kg/day came from stream segments with no visible inflow, indicating the importance of contributions from dispersed subsurface inflow. The subsurface inflow mostly occurred in areas with substantial fracturing of the bedrock or in areas downstream from tributaries with large alluvial fans. Despite a pH generally less than 4.5, there was 58.4 kg/day of Zn attenuation that occurred in mixing zones downstream from inflows with high pH. Mixing zones can have local areas of pH that are high enough for sorption and precipitation reactions to have an effect. Principal component analysis classified inflows into 7 groups with distinct chemical signatures that represent water-rock interaction with different mineral-alteration suites in the watershed. The present approach provides a detailed snapshot of metal load

  19. Role of serum sodium in assessing hospital mortality in cancer patients with spontaneous tumour lysis syndrome inducing acute uric acid nephropathy.

    Science.gov (United States)

    Hsu, H-H; Chen, Y-C; Tian, Y-C; Chan, Y-L; Kuo, M-C; Tang, C-C; Fang, J-T; Lee, S-Y; Yang, C-W

    2009-05-01

    Spontaneous tumour lysis syndrome (STLS) inducing acute uric acid nephropathy, a rare and neglected disease, presents more insidiously than conventional post-treatment tumour lysis syndrome. Although STLS is a serious and potentially fatal complication in patients with neoplastic disorders, few investigations have addressed the relevance of clinical and laboratory features in assessing prognosis. A retrospective study was conducted, reviewing the records of all patients who developed acute renal failure (ARF) at Chang Gung memorial hospital between 1 July 1999 and 30 June 2003. STLS-induced acute uric acid nephropathy was identified in 12 of 1072 ARF patients (1.1%) during the study period. All patients had advanced stage tumours with large tumour burden, and 66.7% of cases had abdominal organ involvement. All 12 hyperuricemic patients became oliguric despite conservative therapy, and remained hyperuricemic (21.6 +/- 5.2 mg/dl) before dialysis therapy. Diuresis developed in eight patients (66.7%), with associated resolution of hyperuricemia, azotemia and metabolic derangements following dialysis initiation. Overall hospital mortality was 58.3%. Death in most patients was related to hyponatremia and hypoalbuminemia on admission. The serum sodium was found to have the best Youden index (0.86) and highest overall prediction accuracy (93%). Moreover, serum sodium and serum albumin for individual patients were significantly and positively correlated (r = 0.617, p = 0.032). This investigation confirms a grave prognosis for cancer patients with STLS inducing acute uric acid nephropathy. Hyponatremia and hypoalbuminemia on the first day of admission indicate poor prognosis in such patients.

  20. Supplementation of folic acid and vitamin B₁₂ reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke.

    Science.gov (United States)

    Xia, Xiao-Shuang; Li, Xin; Wang, Lin; Wang, Ji-Zuo; Ma, Jin-Ping; Wu, Cun-Jin

    2014-09-01

    Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3 days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500 μg twice daily) for 12 weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12 weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (psupplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12 weeks (psupplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke.

  1. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis.

    Science.gov (United States)

    Li, Wenchang; He, Bing; Dai, Wenbing; Zhang, Qiang; Liu, Yuling

    2014-06-01

    Conventional treatments of uveitis are not ideal because of the short period of therapeutic efficacy. In the present study, biodegradable polylactic-glycolic acid microspheres loaded with triamcinolone acetonide (TA) were prepared to achieve sustained drug release and their therapeutic efficacy was investigated on a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the solvent evaporation method and characterized for encapsulation efficiency, particle size, morphology and in vitro release. The therapeutic efficacy was studied on the rabbit experimental uveitis model based on scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination and histological examination. The TA-MS exhibited smooth and intact surfaces with an average diameter of 50.87 μm. The drug-loading coefficient and encapsulation efficiency were 15.2 ± 0.6 % and 91.24 ± 3.77 %, respectively. The drug release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The change in surface morphology also showed sustained drug release from TA-MS. TA-MS exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis compared to TA suspension, especially in regard to the inhibition of inflammation. The TA-MS had a longer-term therapeutic effect on intraocular inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The results suggested that TA-MS can be developed as a potential sustained-release system for the treatment of uveitis.

  2. Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats

    Directory of Open Access Journals (Sweden)

    Shim Eugene

    2011-10-01

    Full Text Available Abstract Background Dietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO, olive oil (OO, and beef tallow (BT on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity. Methods Male Sprague-Dawley rats were fed 15% (wt/wt CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg, samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity. Results Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets. Conclusions Dietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.

  3. Effect of the formulation parameters on the encapsulation efficiency and release behavior of p-aminobenzoic acid-loaded ethylcellulose microspheres

    Directory of Open Access Journals (Sweden)

    Mouffok Meryem

    2016-01-01

    Full Text Available In the current study, p-aminobenzoic acid-loaded ethylcellulose microspheres were prepared under various conditions by solvent evaporation method (o/w. This preparation was carried out with different p-aminobenzoic acid:ethylcellulose (PABA:EC ratios, stirring speed, surfactant nature and concentration in order to investigate their effect on encapsulation efficiency and drug release kinetics. Scanning Electron Microscopy (SEM studies showed spherical microspheres with a porous surface and different structures. The mean diameter of Sauter (d32 of these microparticles is in the range from 47 to 165 μm with PVA and from 793 to 870 μm with Tween 80 by adjusting process parameters. However, the encapsulation efficiency varied from 37.52 to 79.05 % suitable for the adjustment of a p-aminobenzoic acid with pro-longed release. Microspheres were characterized by FTIR, DSC and XRD. The release of cation of p-aminobenzoic acid was performed in simulated gastric medium at pH 1.2 and 37±0.5°C by UV-VIS analysis to estimate its content. The release data were best fitted to Higuchi model with high correlation coefficient (r² and the obtained values of n from Korsmeyer-Peppas showed that the drug release follows the Fickian diffusion mechanism.

  4. Mapping of critical loads of acidity for the Italian terrestrial ecosystems; Mappa dei carichi critici di acidita' totale riferita al territorio italiano

    Energy Technology Data Exchange (ETDEWEB)

    Bonanni, P.; Brini, S.; Delmonaco, G.; Liburdi, C.; Trocciola, A.; Vetrella, G. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente

    1999-07-01

    In this report the mapping of critical loads of acidity for the Italian terrestrial ecosystems is presented. The level 0 method (Stockholm Environment Institute) has been used to determine sensitivity to acid deposition; this semi-quantitative method has been modified to address some Italian characteristics. The sensitivity of the Italian soils to acidification is not particularly elevated: there are really only few small areas with poor tolerance to acid depositions in the north-east Italy, Alpine and Prealpine region. [Italian] Nel presente relazione vengono riportati i risultati della mappatura riferita ad ecosistemi terrestri del territorio italiano, dei carichi critici per l'acidita' totale. Il calcolo dei carichi e' stato eseguito sulla base della metodologia messa a punto dallo Stockholm Environment Institute con alcune modifiche per adattarlo meglio alle caratteristiche del territorio italiano. Si dimostra che la sensibilita' dei suoli italiani all'acidificazione non sia particolarmente elevata: sono state riscontrate infatti solo alcune aree, peraltro con superficie limitata, con una scarsa tolleranza alle deposizioni acide nelle zone del Nord Est, in zona alpina e prealpina.

  5. Propagated fixed-bed mixed-acid fermentation: effect of volatile solid loading rate and agitation at near-neutral pH.

    Science.gov (United States)

    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.

  6. Critical load of acid precipitations. Mapping of Italian regions; Mappa dei carichi critici di acidita' totale riferita al territorio italiano

    Energy Technology Data Exchange (ETDEWEB)

    Bonanni, P.; Brini, S.; Delmonaco, G.; Liburdi, R.; Trocciola, A.; Vetrella, G. [ENEA Centro Ricerche Casaccia, S. Maria di Galeria, RM (Italy). Dipt. Ambiente

    1999-07-01

    In this report the mapping of critical loads of acidity for the Italian terrestrial ecosystems is presented. The level O method (Stockholm Environment Institute) has been used to determine sensitivity to acid deposition; this semi-quantitative method has been modified to address some Italian characteristics. The results show that the sensitivity of the Italian soils to acidification is not particularly elevated: there are really only few small areas with poor tolerance to acid depositions. These areas are in the north-east of Italy, in Alpine and Prealpine region. [Italian] Nel rapporto vengono riportati i risultati della mappatura, riferita agli ecosistemi terrestri del territorio italiano, dei carichi critici per l'acidita' totale. Il calcolo dei carichi critici e' stato eseguito sulla base della metodologia messa a punto dallo Stokholm Environment Institute; a questo metodo semi-quantitativo sono state apportate alcune modifiche per meglio adattarlo alle caratteristiche del territorio italiano. Dall'analisi dei risultati ottenuti, si evince come la sensibilita' dei suoli italiani all'acidificazione non sia particolarmente elevata: sono state riscontrate infatti solo alcune aree, peraltro con superficie limitata, con una scarsa tolleranza alle deposizioni acide. Tali aree sono localizzate nell'Italia nord-orientale, in zona alpina e prealpina.

  7. Enteric-coated capsule containing β-galactosidase-loaded polylactic acid nanocapsules: enzyme stability and milk lactose hydrolysis under simulated gastrointestinal conditions.

    Science.gov (United States)

    He, Hongjun; Zhang, Xueting; Sheng, Yan

    2014-11-01

    In order to protect peroral β-galactosidase from being degraded and hydrolyse milk lactose efficiently in the environments of gastrointestinal tract, a double-capsule delivery system composed of enteric-coated capsule and polylactic acid (PLA) nanocapsules (NCs) was developed for encapsulation of β-galactosidase. β-galactosidase-loaded PLA NCs in the size range of 100-200 nm were prepared by a modified w1/o/w2 technique. During the encapsulation process, dichloromethane/ethyl acetate (1 : 1, v/v) as the solvent composition, high-pressure homogenisation (150 bar, 3 min) as the second emulsification method and polyvinyl alcohol or Poloxamer 188 as a stabiliser in the inner phase could efficiently improve the activity retention of β-galactosidase (>90%). Subsequently, the prepared NCs were freeze-dried and filled in a hydroxypropyl methylcellulose phthalate (HP55)-coated capsule. In vitro results revealed that the HP55-coated capsule remained intact in the simulated gastric fluid and efficiently protected the nested β-galactosidase from acidic denaturation. Under the simulated intestinal condition, the enteric coating dissolved rapidly and released the β-galactosidase-loaded PLA NCs, which exhibited greater stability against enzymatic degradation and higher hydrolysis ratio (∼100%) towards milk lactose than the free β-galactosidase. These results suggest that this double-capsule delivery system represents promising candidate for efficient lactose hydrolysis in the gastrointestinal tract.

  8. The Antidotal Effects of High-dosage γ-Aminobutyric Acid on Acute Tetramine Poisoning as Compared with Sodium Dimercaptopropane Sulfonate

    Institute of Scientific and Technical Information of China (English)

    SUN Peng; HAN Jiyuan; WENG Yuying

    2007-01-01

    To investigate the therapeutic effect of high-dosage γ-aminobutyric acid (GABA) on acute tetramine (TET) poisoning, 50 Kunming mice were divided into 5 groups at random and the antidotal effects of GABA or sodium dimercaptopropane sulfonate (Na-DMPS) on poisoned mice in different groups were observed in order to compare the therapeutic effects of high-dosage GABA with those of Na-DMPS. Slices of brain tissue of the poisoned mice were made to examine pathological changes of cells. The survival analysis was employed. Our results showed that both high-dosage GABA and Na-DMPS could obviously prolong the survival time, delay onset of convulsion and muscular twitch, and ameliorate the symptoms after acute tetramine poisoning in the mice.Better effects could be achieved with earlier use of high dosage GABA or Na-DMPS. There was no significant difference in prolonging the survival time between high-dose GABA and Na-DMPS used immediately after poisioning. It is concluded that high-dosage GABA can effectively antagonize acute toxicity of teramine in mice. And it is suggested that high-dosage GABA may be used as an excellent antidote for acute TET poisoning in clinical practice. The indications and correct dosage for clinical use awaits to be further studied.

  9. Partial liquid ventilation decreases tissue and serum tumor necrosis factor-α concentrations in acute lung injury model of immature piglet induced by oleic acid

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; FAN Xiang-ming; LI Xiao-feng; LI Zhi-qiang; WANG Qiang; SUN Li-zhong; LIU Ying-long

    2012-01-01

    Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-α in an immature piglet model of acute lung injury induced by oleic acid (OA).Methods Twelve Chinese immature piglets were induced acute lung injury by OA.The animals were randomly assigned to two groups of six animals,(1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group.Results Compared with MV group,the PLV group had better cardiopulmonary variables (P <0.05).These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen (PaO2),PaO2/inspired O2 fraction (FiO2) and partial pressure of arterial carbon dioxide (PaCO2).PLV reduced TNF-α levels both in plasma and tissue compared with MV group (P <0.05).Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.

  10. Acute Lethality of Inhaled Hydrogen Cyanide in the Laboratory Rat: Impact of Concentration x Time Profile and Evaluation of the Predictivity of Toxic Load Models

    Science.gov (United States)

    2013-05-03

    Naval Medical Research Unit Dayton Acute Lethality of Inhaled Hydrogen Cyanide in the Laboratory Rat : Impact of Concentration × Time Profile and...Cyanide in the Laboratory Rat : Impact of Concentration x Time Profile and Evaluation of the Predictivity of “Toxic Load” Models. 5a. Contract

  11. The effect of AZD2171- or sTRAIL/Apo2L-loaded polylactic-co-glycolic acid microspheres on a subcutaneous glioblastoma model.

    Science.gov (United States)

    Shivinsky, Anna; Bronshtein, Tomer; Haber, Tom; Machluf, Marcelle

    2015-08-01

    Studies with AZD2171-a new anti-angiogenic inhibitor of tyrosine kinases associated with VEGF signaling-have shown great promise for treating glioblastoma. Unfortunately, AZD2171 success is limited by low permeability through the blood-brain barrier. Due to AZD2171's short half-life and high toxicity, its local administration will require multiple intracranial procedures, making this approach clinically unfeasible. In this study, we investigated the potential of the highly hydrophobic AZD2171, released from modified polylactic-co-glycolic acid microspheres (PLGA-MS), to treat glioblastoma. To further demonstrate the versatile loading capacity of this system, the same PLGA formulation, which was found optimal for the loading and release of AZD2171, was tested with sTRAIL/Apo2L-a biologic drug that is very different than AZD2171 in its molecular weight, solubility, and charge. AZD2171 released from PLGA-MS was at least effective as the free drug in inhibiting endothelial growth and proliferation (in vitro), and, surprisingly, had a profound cytotoxic effect also towards in vitro cultured glioblastoma cell-lines (U87 and A172). Complete tumor inhibition was achieved following a single treatment with AZD2171-loaded PLGA-MS (6 (mg)/kg) administered locally adjacent to human U87 glioma tumors inoculated subcutaneously in nude mice. This improved effect, compared to other therapeutic approaches involving AZD2171, was shown to affect both tumor vasculature and the glioma cells. sTRAIL-loaded microspheres, administered at very low doses (0.3 (mg)/kg), led to 35 % inhibition of tumor growth in 2 weeks. Collectively, our results provide pre-clinical evidence for the potential of PLGA formulations of AZD2171 and sTRAIL to serve as an effective treatment for glioblastoma.

  12. Immobilization of salvianolic acid B-loaded chitosan microspheres distributed three-dimensionally and homogeneously on the porous surface of hydroxyapatite scaffolds.

    Science.gov (United States)

    Li, Jinyu; Wang, Qin; Zhi, Wei; Wang, Jianxin; Feng, Bo; Qu, Shuxin; Mu, Yandong; Weng, Jie

    2016-10-07

    Porous hydroxyapatite (HA) scaffolds combined with a drug delivery system have attracted much attention for bone tissue engineering. In this study, an easy and highly efficient method was developed to immobilize salvianolic acid B (Sal B)-loaded chitosan (CS) microspheres three dimensionally and homogeneously on the surface of HA scaffolds pre-coated with alginate. Porous HA scaffolds were prepared via a template-leaching process and CS microspheres (used as drug carriers) were fabricated by an emulsion method. To improve adhesion between the microspheres and HA scaffolds, alginate was used to pre-coat the porous surface of the HA scaffolds. Various concentrations of alginate were used to optimize the adhesion of Sal B-loaded CS microspheres to the scaffold surface. During the adherence process, coated HA scaffolds were immersed in an aqueous solution containing Sal B-loaded CS microspheres, followed by standing or shaking at 37 °C for a certain time. The results showed that the microspheres were solidly and homogeneously distributed on the porous surface of the alginate pre-coated HA scaffolds via electrostatic interactions. Few microspheres detached from the porous surface, even after the HA scaffolds with microspheres were treated by shaking in distilled water for as long as 7 d. Compared with the static condition, the distribution of Sal B-loaded CS microspheres on the porous surface of pre-coated HA scaffolds in the shaken condition was more homogeneous and almost unaggregated. Additionally, the compressive strength of the scaffolds coated with alginate was obviously improved. The optimal alginate coating concentration was 1% (i.e. the microstructure of the porous surfaces of the HA scaffolds was almost unchanged). The release profile of Sal B over a 30 d immersion found an initial burst release followed by a sustained release. The result of cell culture in vitro was that 1% alginate-coated scaffolds with Sal B-loaded CS microspheres obviously promoted cell

  13. Gambogic acid induces growth inhibition and differentiation via upregulation of p21waf1/cip1 expression in acute myeloid leukemia cells.

    Science.gov (United States)

    Chen, Yan; Hui, Hui; Li, Zheng; Wang, Hong-Mei; You, Qi-Dong; Lu, Na

    2014-10-01

    Gambogic acid (GA) is the major active ingredient of gamboges, a brownish to orange resin product from Garcinia hanburyi tree in Southeast Asia. This compound exhibits anti-cancer effect on solid tumors. In this study, we investigated the effects of GA on the growth and differentiation of acute myeloid leukemia cells by growth-inhibition detection, morphological changes observation, nitroblue tetrazolium reduction, and the expression of the relative cell-surface differentiation markers. The results showed that GA could inhibit cell growth and promote differentiation in U937 and HL-60 cells. In addition, GA upregulated the expression of p21waf1/cip1 in the two cell lines. Finally, downregulating the p21waf1/cip1 expression with small interfering RNA partially blocked GA-induced cell growth inhibition and differentiation. These results of this study revealed that GA may be used as one of the investigational drugs for acute myeloid leukemia.

  14. Positive correlation between uric acid and C-reactive protein serum level in healthy individuals and patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Emina Spahić

    2015-08-01

    Full Text Available Aim To assess serum levels and correlation between uric acid (UA and C-reactive protein (CRP in acute coronary syndrome (ACS and apparently healthy individuals. Methods The cross-sectional study included 116 examinees of age 44 to 83 years, distributed in two groups: 80 ACS patients including 40 with acute myocardial infarction (AMI, and 40 with unstable angina pectoris (UAP, and 36 apparently healthy (control group individuals. Patients with ACS were hospitalized at the Cardiology Clinic, Clinical Centre Sarajevo in the period October- December 2012. Laboratory analyses were conducted by standard methods. The accepted statistical significance level was p0.05. Conclusion The correlation between CRP and UA in the patients with ACS indicates the association of oxidative stress and inflammation intensity in damaged cardiomyocytes. Correlation between UA and CRP in apparently healthy individuals indicates a possible role of UA as a marker of low-grade inflammation and its potential in risk assessment in cardiovascular diseases.

  15. Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele­tal muscle of acute hepatic failure rats

    Directory of Open Access Journals (Sweden)

    Takei,Nobuyuki

    1985-02-01

    Full Text Available Branched chain amino acid (BCAA transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4 administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

  16. The interaction of equine lysozyme:oleic acid complexes with lipid membranes suggests a cargo off-loading mechanism

    DEFF Research Database (Denmark)

    Nielsen, Søren Bang; Wilhelm, Kristina; Vad, Brian

    2010-01-01

    extent when free oleic acid (OA) was added, but not when free OA was removed from ELOA by prior incubation with bovine serum albumin, emphasizing the role of OA in this process. NMR data indicated an equilibrium between free and bound OA, which shifts towards free OA as ELOA is progressively diluted...

  17. Development and optimization of N-Acetylcysteine-loaded poly (lactic-co-glycolic acid) nanoparticles by electrospray.

    Science.gov (United States)

    Karimi Zarchi, Ali Akbar; Abbasi, Shayan; Faramarzi, Mohammad Ali; Gilani, Kambiz; Ghazi-Khansari, Mahmoud; Amani, Amir

    2015-01-01

    N-Acetylcysteine (NAC) loaded PLGA nanoparticles were prepared by electrospray method. The influence of independent parameters such as concentration, flow rate and nozzle to collector distance was studied on particle size and size distribution of generated nanoparticles using a Box-Behnken experimental design. Smallest size was found to be obtained at minimum value for both flow rate and concentration of polymer, regardless of collecting distance value in the ranges studied. Additionally, the minimum value of size distribution was observed at lowest values of both concentration of polymer and collecting distance, regardless of flow rate value. In total, a sample with minimum size and polydispersity was predicted to have flow rate, polymer concentration and collecting distance values of 0.06(ml/h), 0.5(%w/w) and 9.28(cm), respectively. The experimentally prepared nanoparticles with lowest size and size distribution values, had a size of 122(nm) and size distribution of 24. Zeta potential, drug loading and encapsulation efficiency of optimized nanoparticles were -6.58, 5% and 54.5%, respectively.

  18. Serum Fatty Acids, Traditional Risk Factors, and Comorbidity as Related to Myocardial Injury in an Elderly Population with Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Kristian Laake

    2016-01-01

    Full Text Available Background. Epidemiological and randomized clinical trials indicate that marine polyunsaturated n-3 fatty acids (n-3 PUFAs may have cardioprotective effects. Aim. Evaluate the associations between serum fatty acid profile, traditional risk factors, the presence of cardiovascular diseases (CVD, and peak Troponin T (TnT levels in elderly patients with an acute myocardial infarction (AMI. Materials and Methods. Patients (n=299 consecutively included in the ongoing Omega-3 fatty acids in elderly patients with myocardial infarction (OMEMI trial were investigated. Peak TnT was registered during the hospital stay. Serum fatty acid analysis was performed 2–8 weeks later. Results. No significant correlations between peak TnT levels and any of the n-3 PUFAs were observed. However, patients with a history of atrial fibrillation had significantly lower docosahexaenoic acid levels than patients without. Significantly lower peak TnT levels were observed in patients with a history of hyperlipidemia, angina, MI, atrial fibrillation, intermittent claudication, and previous revascularization (all p<0.02. Conclusions. In an elderly population with AMI, no association between individual serum fatty acids and estimated myocardial infarct size could be demonstrated. However, a history of hyperlipidemia and the presence of CVD were associated with lower peak TnT levels, possibly because of treatment with cardioprotective medications.

  19. Identification and examination of a novel 9-bp insert/deletion polymorphism on porcine SFTPA1 exon 2 associated with acute lung injury using an oleic acid-acute lung injury model.

    Science.gov (United States)

    Zhang, Yuebo; Zhang, Longchao; Wang, Ligang; Qiao, Lijuan; Liang, Jing; Yan, Hua; Zhao, Kebin; Liu, Xin; Wang, Lixian

    2015-06-01

    The pulmonary surfactant-associated protein (SFTPA1, SP-A) gene has been studied as a candidate gene for lung disease resistance in humans and livestock. The objective of the present study was to identify polymorphisms of the porcine SFTPA1 gene coding region and its association with acute lung injury (ALI). Through DNA sequencing and the PCR-single-strand conformation polymorphism method, a novel 9-bp nucleotide insertion (+) or deletion (-) was detected on exon 2 of SFTPA1, which causes a change in three amino acids, namely, alanine (Ala), glycine (Gly) and proline (Pro). Individuals of three genotypes (-/-, +/- and +/+) were divided into equal groups from 60 Rongchang pigs that were genotyped. These pigs were selected for participation in the oleic acid (OA)-ALI model by 1-h and 3-h injections of OA, and there were equal numbers of pigs in the control and injection groups. The lung water content, a marker for acute lung injury, was measured in this study; there is a significant correlation between high lung water content and the presence of the 9-bp indel polymorphism (P polymorphism causing altered expression of the gene. The individuals with the -/- genotype showed lower lung water content than the +/+ genotype pigs, which suggests that polymorphism could be a potential marker for lung disease-resistant pig breeding and that pig can be a potential animal model for human lung disease resistance in future studies.

  20. A randomised placebo-controlled trial to differentiate the acute cognitive and mood effects of chlorogenic acid from decaffeinated coffee.

    Directory of Open Access Journals (Sweden)

    David A Camfield

    Full Text Available In the current study, sixty healthy older adults aged 50 years or older, and who were light to moderate coffee drinkers, were administered 6g of a decaffeinated green coffee blend (NESCAFÉ Green Blend coffee; GB or 540mg pure chlorogenic acids (CGA or placebo in a double-blind acute cross-over design, with cognitive and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary outcome measure was accuracy in Rapid Visual Information Processing (RVIP. Secondary cognitive outcome measures included RVIP reaction time as well as Inspection time (IT, Jensen Box decision/reaction times, serial subtraction and N-Back working memory. Secondary mood measures included Bond-Lader and caffeine Research visual analogue scales (VAS. No significant treatment effects were found for the primary outcome measure, although significant effects were found amongst secondary measures. Overall, CGA in isolation was not found to significantly improve cognitive function relative to placebo whereas the GB was found to improve sustained attention as measured by the N-Back task in comparison to placebo overall (t=2.45,p=.05, as well as decision time on a 2-choice reaction time task (Jensen box in comparison to placebo at 40 minutes post-dose (t=2.45,p=.05. Similarly, GB was found to improve alertness on both the Bond-Lader at 120 minutes relative to CGA (t=2.86, p=0.02 and the caffeine Research VAS relative to CGA (t=3.09, p=0.009 and placebo (t=2.75,p=0.02 at 120 minutes post-dose. Both the GB and CGA were also found to significantly improve symptoms of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04 respectively, whilst there was a trend towards a reduction in jitteriness with GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and t=2.20,p=0.06 respectively. These findings suggest that the improvements in mood observed with GB, but not the improvements in cognitive function, are likely to some extent to be

  1. Effect of oleic acid-induced acute lung injury and conventional mechanical ventilation on renal function in piglets

    Institute of Scientific and Technical Information of China (English)

    LIU Ai-jun; LING Feng; LI Zhi-qiang; LI Xiao-feng; LIU Ying-long; DU Jie; HAN Ling

    2013-01-01

    Background Animal models that demonstrate changes of renal function in response to acute lung injury (ALl) and mechanical ventilation (MV) are few.The present study was performed to examine the effect of ALl induced by oleic acid (OA) in combination with conventional MV strategy on renal function in piglets.Methods Twelve Chinese mini-piglets were randomly divided into two groups:the OA group (n=6),animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALl induced by administration of OA,and the control group (n=6),animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of sterile saline.Results Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen,while no apparent histological abnormalities were observed in the control group.Although we observed an increase in the plasma concentrations of creatinine and urea after ALl,there was no significant difference compared with the control group.Plasma concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C increased (5.6±1.3) and (7.4±1.5) times in the OA group compared to baseline values,and were significantly higher than the values in the control group.OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters,while these parameters remained stable during the experiment in the control group.The plasma expression of TNF-α and IL-6 in the OA group were significantly higher than that in the control group.Compared with high expression in the lung and renal tissue in the OA group,TNF-α and IL-6 were too low to be detected in the lung and renal tissue in the control group.Conclusions OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury.The potential mechanisms involved a cytokine response of TNF-α and

  2. Combination of arsenicum trioxide and all trans retinoic acid in the treatment of relapsed acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    A. N. Sokolov

    2015-01-01

    Full Text Available From 2001 to 2013 eleven patients with relapsed acute promyelocytic leukemia (APL (median age – 30 years received arsenicum trioxide (ATO. ATO was administered as a 2nd line relapse therapy in 9 patients, as 1st line relapse therapy in 2 patients. ATO was administered in a dose of 0.1 mg/kg in 7 patients, 0.15 mg/kg – in 4 patients. The induction duration was 14 days in 3 patients, 24–35 days in 2 patients, 60 days in 6 patients. From the 1st day of ATO patients received 45 mg/m2 all trans retinoic acid (ATRA (1 patient – from day 29 of ATO therapy. Maintenance therapy ATO + ATRA (10–14 days courses, every four weeks patients were receiving during 10–15 months. 2 from 3 patients with molecular relapses achieved remission lasting 57 and 89 months after the 14-day ATO courses. 1 from 2 patients with bone marrow relapse achieved remission lasting 27 months after the 24–35-day ATO courses. 60-day courses were effective in 5 of 6 patients: in 4 of which remission are retained during 16, 19, 27, 57 months; 1 patient was relapsed after 12 months; 1 patient did not achieve molecular remission. 3 patients received allogeneic hematopoietic stem cell transplantation (alloHSCT, 2 of which alive in remission. 1 patient received autologous hematopoietic stem cell transplantation in the 2nd molecular remission (alive in remission. 4 patients died: 1 – in the 3rd relapse (duration of 2nd remission – 9 months, 1 – in remission from complications after alloHSCT, 1 – from APL progression, 1 – sudden death in 2nd remission lasting 72 months. ATO + ATRA for 60 days with supportive therapy are more effective than chemotherapy in the treatment of APL relapse. Interferon α + ATRA are inappropriate treatment of APL molecular and cytogenetic relapse. Using autologous HSCT in 2nd molecular remission will improve the results of APL relapse treatment.

  3. [Platelet aggregation upon acetylsalicylic acid and clopidogrel treatment and glycoprotein IIb/IIIa content in patients with acute coronary syndrome].

    Science.gov (United States)

    Khaspekova, S G; Ziuriaev, I T; Iakushkin, V V; Golubeva, N V; Ruda, M Ia; Mazurov, A V

    2011-01-01

    Interaction between aggregating activity of platelets and glycoprotein (GP) IIb/IIIa (fibrinogen receptor) content on their surface was investigated in patients with acute coronary syndrome (ACS). Eighty nine ACS patients were included into the study - 69 with and 20 without elevation of ST segment. Blood was collected within the first hour of admission to the clinic (1 day), and then at 3-5 and 8-12 days. All patients received standard antiaggregant therapy - acetylsalicylic acid - ASA (thromboxane A2 synthesis inhibitor) and clopidogrel (ADP receptor antagonist). Platelet aggregation was analyzed at the first time point when patients had already taken ASA but not clopidogrel, and then (3-5 and 8- 12 days) upon combined therapy with both preparations. Aggregation was induced by 5 and 20 uM ADP and measured by turbidimetric method. In comparison with the initial level (1 day, ASA) at days 3-5, i.e. after development of clopidogrel effect, platelet aggregation was decreased by 54 and 40% upon its stimulation with 5 and 20 uM ADP, and was not further changed at days 8-12. GP IIb/IIIa content on platelet surface was determined by binding of 125I-labelled monoclonal antibody CRC64. GP IIb/IIIa number varied from 31100 to 73000 per platelet with the mean level of 48500 +/- 8400 (mean +/- standard deviation). No differences were detected between mean GP IIb/IIIa number at 1, 3-5 and 8-12 days after ACS onset. Upon repeat GP IIb/IIIa measurement coefficient of variation was 6.1% demonstrating the stability of this parameter in each patient. Positive correlation between platelet aggregation and GP IIb/IIIa content was detected at the first day - correlation coefficients (r) 0.425 and 0.470 for 5 and 20 uM ADP (n=57, p0.05). These results indicates that variations of GP IIb/IIIa content affect platelet aggregating activity within first hours of ACS upon ASA treatment. However after saturation with clopidogrel this factor has no significant influence on platelet aggregation

  4. Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; ZHANG Yan-bo; LIU Dong-hai; LI Xiao-feng; LIU Ai-jun; FAN Xiang-ming; QIAO Chen-hui

    2013-01-01

    Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis,severe burns,and trauma.It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities,including effects on endothelial function and inflammation.A recent study has revealed that ANP exerts anti-inflammatory effects.In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALl) in rats.Methods Rats were randomly assigned to three groups (n=6 in each group).Rats in the control group received a 0.9% solution of NaCl (1 ml.kg1.h-1) by continuous intravenous infusion,after 30 minutes a 0.9% solution of NaCl (1 ml/kg) was injected intravenously,and then the 0.9% NaCl infusion was restarted.Rats in the ALl group received a 0.9% NaCl solution (1 ml·kg-1·h-1) intravenous infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the 0.9% NaCl infusion was restarted.Rats in the hANP-treated ALI group received a hANP (0.1μg·kg-1·min-1) infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the hANP infusion was restarted.The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels.Results Serum intedeukin (IL)-1β,IL-6,IL-10 and tumor necrosis factor (TNF) α were increased in the ALI group at six hours.The levels of all factors were significantly lower in the hANP treated rats (P <0.005).Similarly,levels of IL-1β,IL-6,IL-10 and TNF-α were higher in the lung tissue in the ALI group at six hours.hANP treatment significantly reduced the levels of these factors in the lungs (P <0.005).Histological examination revealed marked reduction in interstitial congestion,edema,and inflammation.Conclusion hANP can attenuate inflammation in an OA-induced lung injury in rat model.

  5. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions

    Institute of Scientific and Technical Information of China (English)

    Li Zhu; Zhong Cheng Yang; Ao Li; De Chang Cheng

    2000-01-01

    AIM To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS A rat model with 30% TBSA fullthickness burn injury was employed and the gastric acid production, together with gastric mucosal blood flow (GMBF) and energy charge ( EC ) were measured serially within 48h postburn.RESULTS The gastric acid production in the acute shock period was markedly inhibited after severe burn injury. At the 3rd h postburn, the gastric juice volume, total acidity and acid output were already significantly decreased (P<0.01), and reached the lowest point,0.63mL/L ± 0.20mL/L, 10.81mmol/L ±2.58mmol/L and 2.23 mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24 h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore,taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment.

  6. Effect of immunologic reactions on rat intestinal epithelium. Correlation of increased permeability to chromium 51-labeled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis

    Energy Technology Data Exchange (ETDEWEB)

    Ramage, J.K.; Stanisz, A.; Scicchitano, R.; Hunt, R.H.; Perdue, M.H.

    1988-06-01

    In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens.

  7. In vitro study on arsenic sulfide (realgar)-induced apoptosis of retinoic acid susceptible or resistant acute promyelocytic leukemia cell lines

    Institute of Scientific and Technical Information of China (English)

    CHEN Si-yu; LIU Shan-xi; LI Xin-min

    2002-01-01

    Objective: To further understand the possible mechanisms of arsenic sulfide (realgar) in the treatment of acute promyelocytic leukemia (APL). Methods: All-trans retinoic acid (ATRA)-susceptible APL cell line (NB4 cells) and ATRA-resistant APL cell line (MR2 subclone) were used as models in vitro. At various times after incubated with various concentrations of realgar, NB4 and MR2 cells were observed by cell viability, cell proliferation and cell morphology; cell cycle and the expression of Annexin V were assayed by flow cytometry. Results: Cell viability and proliferation of NB4 and MR2 cells were inhibited after the treatment,to some extent, in a dose and time dependent manner. 177-711 μg/L of realgar treated NB4 and MR2 cell presented morphologically some features of apoptotic cells such as intact cell membrane, chromatin condensation and nuclear fragmentation, apoptosis body could be found by electron microscopy as well. Sub-G1 ceils andcell cycle arrest were observed by flow cytometry. The proportion of Annexin V -FITC+/PI cells, which represent apoptotic cells, was up-regulated. Conclusion: Realgar could induce apoptosis of acute promyelocytic leukemia cell despite its susceptibility to retinoic acid in the way that may be different from retinoic acid.

  8. Novel lansoprazole-loaded nanoparticles for the treatment of gastric acid secretion-related ulcers: in vitro and in vivo pharmacokinetic pharmacodynamic evaluation.

    Science.gov (United States)

    Alai, Milind; Lin, Wen Jen

    2014-05-01

    The objective of this study is to combine nanoparticle design and enteric coating technique to sustain the delivery of an acid-labile drug, lansoprazole (LPZ), in the treatment of acid reflux disorders. Lansoprazole-loaded Eudragit® RS100 nanoparticles (ERSNP-LPZ) as well as poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGANP-LPZ) were prepared using a solvent evaporation/extraction method. The effects of nanoparticle charge and permeation enhancers on lansoprazole uptake was assessed in Caco-2 cells. The confocal microscopic images revealed the successful localization of nanoparticles in the cytoplasm of Caco-2 cells. The cellular uptake of positively charged Eudragit nanoparticles was significantly higher than that of negatively charged PLGA nanoparticles, which were enhanced by sodium caprate via the transcellular pathway. Both types of nanoparticles exhibited sustained drug release behavior in vitro. The oral administration of enteric-coated capsules filled with nanoparticles sustained and prolonged the LPZ concentration up to 24 h in ulcer-induced Wistar rats, and 92.4% and 89.2% of gastric ulcers healed after a 7-day treatment with either EC-ERSNP1010-Na caprate or EC-PLGANP1005-Na caprate, respectively.

  9. Enhanced proton conductivity of Nafion hybrid membrane under different humidities by incorporating metal-organic frameworks with high phytic acid loading.

    Science.gov (United States)

    Li, Zhen; He, Guangwei; Zhang, Bei; Cao, Ying; Wu, Hong; Jiang, Zhongyi; Tiantian, Zhou

    2014-06-25

    In this study, phytic acid (myo-inositol hexaphosphonic acid) was first immobilized by MIL101 via vacuum-assisted impregnation method. The obtained phytic@MIL101 was then utilized as a novel filler to incorporate into Nafion to fabricate hybrid proton exchange membrane for application in PEMFC under different relative humidities (RHs), especially under low RHs. High loading and uniform dispersion of phytic acid in MIL 101(Cr) were achieved as demonstrated by ICP, FT-IR, XPS, and EDS-mapping. The phytic@MIL101 was dispersed homogeneously in the Nafion matrix when the filler content was less than 12%. Hybrid membranes were evaluated by proton conductivity, mechanical property, thermal stability, and so forth. Remarkably, the Nafion/phytic@MIL hybrid membranes showed high proton conductivity at different RHs, especially under low RHs, which was up to 0.0608 S cm(-1) and 7.63 × 10(-4) S cm(-1) at 57.4% RH and 10.5% RH (2.8 and 11.0 times higher than that of pristine membrane), respectively. Moreover, the mechanical property of Nafion/phtic@MIL hybrid membranes was substantially enhanced and the thermal stability of membranes was well preserved.

  10. Multi-scale strategy to eradicate Pseudomonas aeruginosa on surfaces using solid lipid nanoparticles loaded with free fatty acids

    Science.gov (United States)

    Taylor, Erik N.; Kummer, Kim M.; Dyondi, Deepti; Webster, Thomas J.; Banerjee, Rinti

    2013-12-01

    Infections are both frequent and costly in hospitals around the world, leading to longer hospital stays, overuse of antibiotics, and excessive costs to the healthcare system. Moreover, antibiotic resistant organisms, such as Pseudomonas aeruginosa are increasing in frequency, leading to 1.7 million infections per year in USA hospitals, and 99 000 deaths, both due to the evolution of antibiotic resistance and the formation of biofilms on medical devices. In particular, respiratory infections are costly, deadly to 4.5 million persons per year worldwide, and can spread to the lungs through the placement of endotracheal tubing. In this study, towards a reduction in infections, solid lipid nanoparticles were formulated from free fatty acids, or natural lipophilic constituents found in tissues of the body. A strategy was developed to target infections by producing coatings made of non-toxic chemistries lauric acid and oleic acid delivered by core-shell solid lipid nanoparticles that act against bacteria by multiple mechanisms at the nanoscale, including disruption of bacteria leading to DNA release, and reducing the adhesion of dead bacteria to ~1%. This is the first such study to explore an anti-infection surface relying on these multi-tier strategies at the nanoscale.

  11. Fabrication and in vitro release behavior of a novel antibacterial coating containing halogenated furanone-loaded poly(L-lactic acid nanoparticles on microarc-oxidized titanium

    Directory of Open Access Journals (Sweden)

    Cheng YC

    2012-11-01

    Full Text Available Yicheng Cheng,1 Jiang Wu,1 Bo Gao,1 Xianghui Zhao,2 Junyan Yao,3 Shenglin Mei,1 Liang Zhang,4 Huifang Ren1 1Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, 2Institute of Neuroscience, School of Basic Medicine, Fourth Military Medical University, 3Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, 4Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, ChinaYicheng Cheng and Jiang Wu contributed equally to this workBackground: 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

  12. Effects of Rebixiao Granules(热痹消颗粒剂) on Blood Uric Acid in Patients with Repeatedly Attacking Acute Gouty Arthritis

    Institute of Scientific and Technical Information of China (English)

    JI Wei; ZHU Xuan-xuan; TAN Wen-feng; LU Yan

    2005-01-01

    Objective:To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therapeutic mechanism. Methods: Ninety repeatedly attacking acute gouty arthritis patients were divided into the treated group (n= 60) and control group (n = 30). The treated group was treated with RBXG, and the control group was treated with Futalin tablets (diclofenac sodium). The baseline treatment including good rest, Iow purine diet, sufficient water drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine 600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage to establish the animal models. Results: The clinical effective rate of the treated group was 95.0% and that of the control 90.0 %. Good therapeutic effects were won, insignificant difference (P>0.05)was shown between the two groups. However, the cure rate of the treated group was 26.7% while that of the control group was 10.0%, with significant difference (P<0.01) shown between them. The treated group had its blood uric acid lowered, which was significantly different (P<0.05) from that of the control group. The animal experiment indicated that all the three groups treated with different dosages of RBXG, as well as the Ash bark and Smilax glabra rhizome groups had their blood uric acid content reduced in the hyperuricemic mice. Conclusion: RBXG has a quicker initiation and better treatment effects than sole anti-inflammatory and analgesic agents on the treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic or adverse reactions and therefore good for long-term administration and likely to be a safe TCM preparation to control the symptoms and reduce the onsets of repeatedly attacking of acute gouty arthritis. The animal experiment shows that both the compound preparation and part of the single ingredients in the

  13. Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects

    OpenAIRE

    Lee, Sang-rok; Schriefer, JohnHenry M; Trint A. Gunnels; Harvey, Innocence C; Bloomer, Richard J

    2013-01-01

    Background Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist—possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. Methods Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, ca...

  14. A Complicated Case of Acute Promyelocytic Leukemia in the Second Trimester of Pregnancy Successfully Treated with All-trans-Retinoic Acid.

    Science.gov (United States)

    Agarwal, Kanika; Patel, Megha; Agarwal, Vandana

    2015-01-01

    A 40-year-old female at 26-week gestation was diagnosed with acute promyelocytic leukemia (APL) after an abnormal prenatal lab workup showed pancytopenia. She was treated with all-trans-retinoic acid (ATRA), idarubicin, and dexamethasone. After day one of treatment, she developed differentiation syndrome, which was treated with dexamethasone. At 30-week gestation, she had preterm premature rupture of membranes and delivered by cesarean section because of the fetus' breech presentation. Despite ATRA's potential for teratogenicity, a viable infant was born without apparent anomalies. Postpartum, she underwent consolidation treatment with ATRA and arsenic trioxide (ATO). The patient continued ATRA therapy after delivery and is currently in remission.

  15. [Successful treatment of acute promyelocytic leukemia in a pregnant patient with all-trans retinoic acid and chemotherapy resulting in a safe delivery].

    Science.gov (United States)

    Itoh, Mitsuru; Takao, Sumiko; Yago, Kazuhiro; Shimada, Hideto

    2003-06-01

    A 32-year-old woman at 21 gestational weeks was admitted because of leukocytosis with DIC. She was diagnosed as having acute promyelocytic leukemia and treated with all-trans retinoic acid (70 mg/body) in combination with daunorubicin and cytosine arabinoside. She achieved complete remission, and continuously received a second treatment with daunorubicin and cytosine arabinoside. Cesarean section was performed, and a live male infant was born in the 30th week of pregnancy. The mother and baby have progressed excellently to date. In a such case, the choice of treatment and time of birth should be considered depending on the individual situation.

  16. Preparation of folic acid-conjugated, doxorubicin-loaded, magnetic bovine serum albumin nanospheres and their antitumor effects in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Yang R

    2014-09-01

    Full Text Available Rui Yang,1 YanLi An,2 FengQin Miao,1 MengFei Li,1 PeiDang Liu,1 QiuSha Tang1 1School of Medicine, Southeast University, 2Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing, Jiangsu Province, People’s Republic of China Background: This study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored. Methods: FA-DOX-BSA MNPs comprising encapsulated magnetic iron oxide nanoparticles were prepared using a desolvation cross-linking method. Activated folic acid (N-hydroxysuccinimide ester of folic acid was conjugated to the surface of albumin nanospheres via amino groups.Results: Folic acid was successfully expressed on the surface of the nanospheres. Electron microscopy revealed that the FA-DOX-BSA MNPs were nearly spherical and uniform in size, with an average diameter of 180 nm. The nanomaterial could deliver doxorubicin at clinically relevant doses with an entrapment efficiency of 80%. An increasing temperature test revealed that incorporation of magnetic iron oxide into nanospheres could achieve a satisfactory heat treatment temperature at a significantly lower dose when placed in a high-frequency alternating magnetic field. FA-DOX-BSA MNPs showed greater inhibition of tumors than in the absence of folic acid in vitro and in vivo. Compared with chemotherapy alone, hyperthermia combined with chemotherapy was more effective against tumor cells.Conclusion: Folic acid-conjugated bovine serum albumin nanospheres composed of mixed

  17. Incidence of secondary neoplasms in patients with acute promyelocytic leukemia treated with all-trans retinoic acid plus chemotherapy or with all-trans retinoic acid plus arsenic trioxide.

    Science.gov (United States)

    Eghtedar, Alireza; Rodriguez, Ildefonso; Kantarjian, Hagop; O'Brien, Susan; Daver, Naval; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Kadia, Tapan; Pierce, Sherry; Cortes, Jorge; Ravandi, Farhad

    2015-05-01

    The incidence and pattern of secondary neoplasms in patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA)-containing regimens is not well described. We compared 160 patients with APL treated with ATRA plus idarubicin (n = 54) or ATRA plus arsenic trioxide (ATO) (n = 106) for the incidence of secondary cancers per unit time of follow-up. Median follow-up times for the two cohorts were 136 and 29 months, respectively. Nine patients developed secondary cancers in the chemotherapy group. These included two breast cancers, three myelodysplastic syndromes/acute myeloid leukemia, one vulvar cancer, one prostate cancer, one colon cancer and one soft tissue sarcoma. A melanoma and one pancreatic cancer developed in the ATO group. We conclude that treatment of patients with APL using the non-chemotherapy regimen of ATRA plus ATO is not associated with a higher incidence of secondary cancers (p = 0.29) adjusted for unit time of exposure.

  18. Effectiveness of Losartan-Loaded Hyaluronic Acid (HA) Micelles for the Reduction of Advanced Hepatic Fibrosis in C3H/HeN Mice Model.

    Science.gov (United States)

    Thomas, Reju George; Moon, Myeong Ju; Kim, Jo Heon; Lee, Jae Hyuk; Jeong, Yong Yeon

    2015-01-01

    Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis.

  19. Pig α1-Acid Glycoprotein: Characterization and First Description in Any Species as a Negative Acute Phase Protein

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Miller, Ingrid; Sørensen, Nanna Skall;

    2013-01-01

    concentrations of pig AGP were in the range of 1-3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2-5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative...... acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase...

  20. Assessment of zinc loading in an acid rock drainage alpine catchment using a tracer-injection and synoptic-sampling study

    Science.gov (United States)

    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

  1. Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma.

    Science.gov (United States)

    Chiang, B; Kim, Y C; Doty, A C; Grossniklaus, H E; Schwendeman, S P; Prausnitz, M R

    2016-04-28

    Although effective drugs that lower intraocular pressure (IOP) in the management of glaucoma exist, their efficacy is limited by poor patient adherence to the prescribed eye drop regimen. To replace the need for eye drops, in this study we tested the hypothesis that IOP can be reduced for one month after a single targeted injection using a microneedle for administration of a glaucoma medication (i.e., brimonidine) formulated for sustained release in the supraciliary space of the eye adjacent to the drug's site of action at the ciliary body. To test this hypothesis, brimonidine-loaded microspheres were formulated using poly(lactic acid) (PLA) to release brimonidine at a constant rate for 35 days and microneedles were designed to penetrate through the sclera, without penetrating into the choroid/retina, in order to target injection into the supraciliary space. A single administration of these microspheres using a hollow microneedle was performed in the eye of New Zealand White rabbits and was found to reduce IOP initially by 6 mmHg and then by progressively smaller amounts for more than one month. All administrations were well tolerated without significant adverse events, although histological examination showed a foreign-body reaction to the microspheres. This study demonstrates, for the first time, that the highly-targeted delivery of brimonidine-loaded microspheres into the supraciliary space using a microneedle is able to reduce IOP for one month as an alternative to daily eye drops.

  2. Development of disulfiram-loaded poly(lactic-co-glycolic acid) wafers for the localised treatment of glioblastoma multiforme: a comparison of manufacturing techniques.

    Science.gov (United States)

    Zembko, Iwona; Ahmed, Iram; Farooq, Aneesa; Dail, Jagdeep; Tawari, Patrica; Wang, Weiguang; Mcconville, Christopher

    2015-03-01

    Glioblastoma multiforme (GBM) is the most common primary malignant brain tumour in adults with a very poor prognosis. This paper describes the development of disulfiram (DSF)-loaded biodegradable wafers manufactured using three standard techniques: compression, solvent casting and heat compression moulding. The paper demonstrates that neither technique has an adverse effect on the stability of the DSF within the wafers. However, the solvent casting technique results in an interaction between the poly(lactic-co-glycolic acid) (PLGA) and the DSF. The physical state of the DSF within the wafers was dependent on the manufacturing technique, with the DSF in the wafers manufactured by compression or solvent casting retaining between 40% and 98% crystallinity, whereas the DSF in the wafers manufactured using heat compression moulding was completely amorphous. Release of DSF from the wafers is dependent on the degradation of the PLGA, the manufacturing technique used, and the DSF loading. DSF in the compressed and heat compression moulded wafers had a similar cytotoxicity against a GBM cell line compared with the unprocessed DSF control. However, the cytotoxicity of the DSF in the solvent-casted wafers was significantly lower than the unprocessed DSF.

  3. Nanostructured poly (lactic acid) electrospun fiber with high loadings of TiO2 nanoparticles: Insights into bactericidal activity and cell viability.

    Science.gov (United States)

    Toniatto, T V; Rodrigues, B V M; Marsi, T C O; Ricci, R; Marciano, F R; Webster, T J; Lobo, A O

    2017-02-01

    Researchers have been looking for modifying surfaces of polymeric biomaterials approved by FDA to obtain nanofeatures and bactericidal properties. If modified, it would be very interesting because the antibiotic administration could be reduced and, therefore, the bacterial resistance. Here, we report the electrospinning of poly (lactic acid) (PLA) with high loadings of titanium dioxide nanoparticles (TiO2, 1-5wt%) and their bactericidal properties. TiO2 nanoparticles have been recognized for a long time for their antibacterial, low cost and self-cleaning properties. However, their ability to reduce bacteria functions when used in polymers has not been well studied to date. In this context, we aimed here to generate nanostructured PLA electrospun fiber-TiO2 nanoparticle composites for further evaluation of their bactericidal activity and cell viability. TEM and SEM micrographs revealed the successful electrospinning of PLA/TiO2 and the generation of polymer-TiO2 nanostructures. When increasing the TiO2 concentration, we observed a proportional increase in the nanoparticle density along the fiber and surface. The nanostructured PLA/TiO2 nanofibers showed no mammalian cell toxicity and, most importantly, possessed bactericidal activity with higher TiO2 loads. Such results suggest that the present PLA electrospun fiber-TiO2 nanoparticle composites should be further studied for a wide range of biomedical applications.

  4. Valine, a Branched-Chain Amino Acid, Reduced HCV Viral Load and Led to Eradication of HCV by Interferon Therapy in a Decompensated Cirrhotic Patient

    Directory of Open Access Journals (Sweden)

    Takumi Kawaguchi

    2012-10-01

    Full Text Available A decreased serum level of branched-chain amino acid (BCAA is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV load has never been reported. Here, we first describe a case of HCV-related advanced liver cirrhosis that was treated by an oral valine agent. The administration of valine resulted in an improvement of fatigue and a reduction in hepatic fibrosis indexes as well as serum α-fetoprotein level. Furthermore, a marked reduction in HCV RNA levels was seen after valine treatment. The patient was then treated by interferon β, resulting in the successful eradication of chronic HCV infection. Thus, valine may be involved in the reduction of HCV viral load and could support a sustained virologic response to interferon therapy.

  5. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

    Directory of Open Access Journals (Sweden)

    Wang QS

    2015-11-01

    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  6. Hyaluronic acid-coated bovine serum albumin nanoparticles loaded with brucine as selective nanovectors for intra-articular injection

    Directory of Open Access Journals (Sweden)

    Chen Z

    2013-10-01

    Full Text Available Zhipeng Chen,* Juan Chen,* Li Wu, Weidong Li, Jun Chen, Haibo Cheng, Jinhuo Pan, Baochang CaiDepartment of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China*These authors contributed equally to this workObjective: To evaluate the potential of hyaluronic acid (HA-coated bovine serum albumin nanoparticles (BSANPs as a novel chondrocyte-targeting drug-delivery nanomedicine.Methods: The HA-BSANPs were characterized by dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction. Fluorescence imaging was used to visualize the distribution of nanoparticles after intra-articular injection. The chondrocyte-targeting efficiency and cellular uptake mechanism of HA-BSANPs were investigated using endocytic inhibitors.Results: HA-BSANPs were successfully prepared with HA coating the surface and amorphous drug in the core. Compared with BSANPs, HA-BSANPs exhibited improved uptake by chondrocytes through a receptor-mediated active uptake mechanism. The endocytosis process of BSANPs and HA-BSANPs involved clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis. No apparent thickening or hyperplasia of the synovium was observed in either BSANPs or HA-BSANPs. The HA-BSANPs could reside in the articular cavity of rats for more than 14 days, which was significantly longer than BSANPs.Conclusion: HA-BSANPs are a promising carrier for articular-related diseases due to elongated articular residence and improved chondrocytic accumulation.Keywords: chondrocyte, intra-articular injection, hyaluronic acid, BSA, nanoparticles

  7. TA1 oncofetal rat liver cDNA and putative amino acid permease: temporal correlation with c-myc during acute CCl4 liver injury and variation of RNA levels in response to amino acids in hepatocyte cultures.

    Science.gov (United States)

    Shultz, V D; Campbell, W; Karr, S; Hixson, D C; Thompson, N L

    1999-01-01

    TA1 is a rat liver oncofetal cDNA and a member of an emerging family of evolutionarily conserved molecules with homology to amino acid transporters and permeases. The aim of these studies was to characterize the regulation and role of TA1 in acute rat liver injury by examining its relation to regeneration and metabolic stress. Following a single dose of CCl4, TA1 message was expressed 3-48 h. The major 3.3-kb TA1 transcript correlated temporally with c-myc expression. A novel 2.9-kb TA1 transcript was expressed more variably 24-48 h. TA1 protein was restricted to hepatocytes in G0 and G1 phases of the cell cycle. Relative to CCl4, a much smaller increase in TA1 was noted after partial hepatectomy and TA1 preceded the peak of c-myc expression. In vitro TA1 was not induced in hepatocytes by EGF or the acute-phase cytokines IL-6 and TNF-alpha, but was found to be modulated in response to amino acid availability. TA1 expression increased in media without arginine and glutamine and was repressed by total amino acid levels 5-fold over basal MEM. Together, these results contrast with the constitutive expression observed in transformed cells and suggest an adaptive role for TA1 during liver injury.

  8. Caffeic Acid Phenethyl Ester Loaded PLGA Nanoparticles: Effect of Various Process Parameters on Reaction Yield, Encapsulation Efficiency, and Particle Size

    Directory of Open Access Journals (Sweden)

    Serap Derman

    2015-01-01

    Full Text Available CAPE loaded PLGA nanoparticles were prepared using the oil in water (o/w single emulsion solvent evaporation methods. Five different processing parameters including initial CAPE amount, initial PLGA amount, PVA concentration in aqueous phase, PVA volume, and solvent type were screened systematically to improve encapsulation of hydrophobic CAPE molecule, simultaneously minimize particle size, and raise the reaction yield. Obtained results showed that the encapsulation efficiency of the nanoparticles significantly increased with the increase of the initial CAPE amount (p<0.05 and particle size (p<0.05. Furthermore, the particle size is significantly influenced by initial polymer amount (p<0.05 and surfactant concentration (p<0.05. By the optimization of process parameters, the nanoparticles produced 70±6% reaction yield, 89±3% encapsulation efficiency, -34.4±2.5 mV zeta potential, and 163±2 nm particle size with low polydispersity index 0.119±0.002. The particle size and surface morphology of optimized nanoparticles were studied and analyses showed that the nanoparticles have uniform size distribution, smooth surface, and spherical shape. Lyophilized nanoparticles with different CAPE and PLGA concentration in formulation were examined for in vitro release at physiological pH. Interestingly, the optimized nanoparticles showed a high (83.08% and sustained CAPE release (lasting for 16 days compared to nonoptimized nanoparticle.

  9. Impacts of acute imipramine treatment on plasma and brain amino acid metabolism in mice given graded levels of dietary chicken protein.

    Science.gov (United States)

    Nagasawa, Mao; Murakami, Tatsuro; Tomonaga, Shozo; Sato, Mikako; Takahata, Yoshihisa; Morimatsu, Fumiki; Furuse, Mitsuhiro

    2012-12-01

    Several studies have shown a relationship between depression and animal protein intake. To evaluate whether the difference of dietary chicken protein levels induces an antidepressant-like effect and potentiates acute antidepressant effects, three levels of dietary chicken protein were used as the representative animal protein with imipramine used as the antidepressant. In addition, the effects of dietary chicken protein on brain metabolism were evaluated. Open field test (OFT) and forced swimming test (FST) were conducted on the 27th and 28th days, respectively. OFT and FST were not influenced by both imipramine and dietary protein levels. However, characteristic effects of imipramine treatment on brain monoamine metabolism were observed in the cerebral cortex and hypothalamus. In addition, dietary protein significantly increased taurine and L-ornithine levels even though these amino acids were not contained in the diets. In conclusion, the metabolism of several amino acids in the plasma and brain were altered by dietary chicken protein.

  10. Core-shell hybrid liposomal vesicles loaded with panax notoginsenoside: preparation, characterization and protective effects on global cerebral ischemia/reperfusion injury and acute myocardial ischemia in rats

    OpenAIRE

    Zhang J.; Han XZ; Li X.; Luo Y; Zhao HP; Yang M.; Ni B; Liao ZG

    2012-01-01

    Jing Zhang,1,* Xizhen Han,1,* Xiang Li,2 Yun Luo,1 Haiping Zhao,1 Ming Yang,1 Bin Ni,1 Zhenggen Liao11Key Laboratory of Modern Preparation of TCM, Ministry of Education, 2National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China*These authors contributed equally to this workPurpose: Novel panax notoginsenoside-loaded core-shell hybrid liposomal vesicles (PNS-HLV)...

  11. Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves de Albuquerque

    2012-01-01

    Full Text Available Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs can be toxic to cells. Increased blood concentration of oleic acid (OLA and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets.

  12. Combined laboratory and epidemiological study of the effect of load on the excretion of Beta aminoisobutyric acid

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, W.R.; Fischbein, A.; Sharma, O.K.S.

    1987-01-01

    Beta Aminoisobutyric Acid (BAIB) is the end product of the catabolism of thymine. BAIB is actively secreted and is a common component of human urine. Since lead has not been reported to degrade DNA we were surprised to find elevated amounts of BAIB in the urine of workers who had lead poisoning. To further study this phenomenon a group of 26 males engaged in demolition work which exposed them to lead was compared to a control group of 40 male hospital workers with regard to BAIB excretion. The exposed workers excreted an average of 19.26 nmoles of BAIB per ..mu..mole creatinine. The value for the control group was 6.02. In order to determine the effect of lead on BAIB excretion under controlled conditions, the authors exposed marmosets to different doses of lead and monitored the lead poisoning via the blood level of zinc protoporphyrin. They found a strong correlation between exposure to lead and excretion of BAIB.

  13. Association of serum uric acid level with mortality and morbidity of patients with acute ST-elevation myocardial infarction

    Directory of Open Access Journals (Sweden)

    Reza Hajizadeh

    2016-06-01

    Conclusion: In the current study, high serum UA level in patients with acute myocardial infarction (MI was not associated with higher in-hospital or midterm mortality, but it was associated with lower LVEF, higher Killip class, elevated cTnI, creatinine, triglyceride, and higher AF.

  14. Does acute led (Pb) contamination influence membrane fatty acid composition and freeze tolerance in intertidal blue mussels in arctic Greenland?

    DEFF Research Database (Denmark)

    Thyrring, Jakob; Juhl, Bodil Klein; Holmstrup, Martin;

    2015-01-01

    In their natural habitats, organisms are exposed to multiple stressors. Heavy metal contamination stresses the cell membrane due to increased peroxidation of lipids. Likewise, sub-zero air temperatures potentially reduce membrane functionality in ectothermal animals. We tested if acute lead (Pb...... tolerance and does not induce membrane damage in terms of persistent lipid peroxidation....

  15. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    Directory of Open Access Journals (Sweden)

    Chu QC

    2016-01-01

    Full Text Available Qiuchen Chu,1,* Hong Xu,2,* Meng Gao,1 Xin Guan,1 Hongyan Liu,1 Sa Deng,1 Xiaokui Huo,1 Kexin Liu,1 Yan Tian,1 Xiaochi Ma1 1College of Pharmacy, 2College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer remains a major problem around the world. Resibufogenin (RBG is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison, which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid (PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN, and RBG/coumarin-6-loaded PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS, and 5-fluorouracil solution (used as the negative controls, as assayed using flow cytometry. LD50 (median lethal dose values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in

  16. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    Science.gov (United States)

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  17. Pharmacokinetics, biodistribution and in vivo efficacy of cisplatin loaded poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) complex nanoparticles for tumor therapy.

    Science.gov (United States)

    Yu, Haiyang; Tang, Zhaohui; Zhang, Dawei; Song, Wantong; Zhang, Ying; Yang, Yan; Ahmad, Zaheer; Chen, Xuesi

    2015-05-10

    Platinum-based polymeric nano-drugs, especially cisplatin-loaded polymeric nanoparticles (CDDP-NPs), have been extensively exploited for the treatment of solid tumors. However, it is still unclear what role the processing procedure and the properties of the polymeric carrier materials may play in influencing the plasma pharmacokinetics, biodistribution and in vivo efficacy of CDDP-NPs. In this study, a series of poly(l-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-mPEG) copolymers were synthesized for the preparation of CDDP-loaded PLG-g-mPEG (CDDP/PLG-g-mPEG) nanoparticles. All of the parameters, including PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length, ultrafiltration purification and cisplatin loading content, were found to have a significant influence on the plasma pharmacokinetics of the CDDP/PLG-g-mPEG nanoparticles. The blood circulation time of the nanoparticles was prolonged with increases in PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length and CDDP loading content. The use of ultrafiltration purification could prolong the blood circulation time of the nanoparticles as well. Experiments to measure the pharmacokinetics and biodistribution demonstrated that the selected CDDP/PLG-g-mPEG nanoparticles, NP10, had a long blood circulation time and could achieve selective and significant accumulation in Lewis lung carcinoma (LLC) tumors. The platinum plasma concentrations in the LLC tumor-bearing mice receiving NP10 remained up to 46-fold higher than that of mice receiving equivalent doses of free CDDP. In addition, the plasma area under the concentration time curve (AUC) of NP10 was 31-fold higher than that of free CDDP in 48h. The platinum concentration ratio of NP10 to free CDDP in tumors reached a