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Sample records for solvated l-arginine vasopressin

  1. Theoretical study about L-arginine complexes formation with thiotriazolin

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    L. I. Kucherenko

    2017-02-01

    Full Text Available Brain vascular diseases are one of the leading causes of morbidity, mortality and disability of population in the industrialized countries of the world. An important element of this problem’s solution is the creation of new highly effective and safe drugs, which would lead to mortality reduction, to increase in life expectancy and quality of life. Therefore it is interesting to create a new combined drug based on L-arginine and thiotriazolin. Purpose of the study: to consider the possible structure and energy characteristics of complexes formed by L-arginine, 3-methyl-1,2,4-triazolyl-5-thioacetate (MTTA and morpholine. Calculation method. The initial approximation to the complex geometry was obtained using molecular docking with the help of AutoDock Vina program. The obtained ternary complexes were pre-optimized by semi-empirical PM7 method with modeling the impact of the environment by COSMO method. The calculations were carried out using MOPAC2012 program. Then they were optimized by B97-D3/SVP + COSMO (Water dispersion-corrected DFT-D with geometrical spreading correction on insufficiency of gCP basis set. A more accurate calculation of the solvation energy was conducted by SMD. The calculations by density functional method were carried out using the ORCA 3.0.3 software. Energy complex formation in solution was calculated as the difference of the Gibbs free energy of the solvated complex and its individual components. Results. Quantum chemical calculations show, that thiotriazolin and L-arginine are able to form ternary complexes, where molecules are linked by multiple hydrogen bonds. The calculation data suggest, that studied complexes are thermodynamically unstable in solution. The energies of them are positive, but rather low despite charge gain of a number of intermolecular hydrogen bonds. Finding. Based on the results of the conducted quantum-chemical study of a three components system (MTTA, morpholine, and L-arginine it is possible

  2. Anti-aging effects of l-arginine

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    Mohamed Z. Gad

    2010-07-01

    Full Text Available l-Arginine is one of the most metabolically versatile amino acids. In addition to its role in the synthesis of nitric oxide, l-arginine serves as a precursor for the synthesis of polyamines, proline, glutamate, creatine, agmatine and urea. Several human and experimental animal studies have indicated that exogenous l-arginine intake has multiple beneficial pharmacological effects when taken in doses larger than normal dietary consumption. Such effects include reduction in the risk of vascular and heart diseases, reduction in erectile dysfunction, improvement in immune response and inhibition of gastric hyperacidity. This review summarises several positive studies and personal experiences of l-arginine. The demonstrated anti-aging benefits of l-arginine show greater potential than any pharmaceutical or nutraceutical agent ever previously discovered.

  3. L-arginine biosensors: A comprehensive review

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    Neelam Verma

    2017-12-01

    Full Text Available Arginine has been considered as the most potent nutraceutics discovered ever, due to its powerful healing property, and it's been known to scientists as the Miracle Molecule. Arginine detection in fermented food products is necessary because, high level of arginine in foods forms ethyl carbamate (EC during the fermentation process. Therefore, L-arginine detection in fermented food products is very important as a control measure for quality of fermented foods, food supplements and beverages including wine. In clinical analysis arginine detection is important due to their enormous inherent versatility in various metabolic pathways, topmost in the synthesis of Nitric oxide (NO and tumor growth. A number of methods are being used for arginine detection, but biosensors technique holds prime position due to rapid response, high sensitivity and high specificity. However, there are many problems still to be addressed, including selectivity, real time analysis and interference of urea presence in the sample. In the present review we aim to emphasize the significant role of arginine in human physiology and foods. A small attempt has been made to discuss the various techniques used for development of arginine biosensor and how these techniques affect their performance. The choice of transducers for arginine biosensor ranges from optical, pH sensing, ammonia gas sensing, ammonium ion-selective, conductometric and amperometric electrodes because ammonia is formed as a final product.

  4. Acellular matrix of bovine pericardium bound with L-arginine

    International Nuclear Information System (INIS)

    Kim, Hyo Joo; Bae, Jin Woo; Kim, Chun Ho; Lee, Jin Woo; Shin, Jung Woog; Park, Ki Dong

    2007-01-01

    Surface immobilization of bioactive molecules onto natural tissues has been interestingly studied for the development of new functional matrices for the replacement of lost or malfunctioning tissues. In this study, an acellular matrix of bovine pericardium (ABP) was chemically modified by the direct coupling of L-arginine after glutaraldehyde (GA) cross-linking. The effects of L-arginine coupling on durability and calcification were investigated and the biocompatibility was evaluated in vitro and in vivo. A four-step detergent and enzymatic extraction process has been utilized to remove cellular components from fresh bovine pericardium (BP). Microscopic observation confirmed that nearly all cellular constituents are removed. Thermal and mechanical properties showed that the durability of L-arginine-treated matrices increased as compared with control ABP and GA-treated ABP. Resistance to collagenase digestion revealed that modified matrices have greater resistance to enzyme digestion than control ABP and GA-treated ABP. The in vivo calcification study demonstrated much less calcium deposition on L-arginine-treated ABP than GA-treated one. In vitro cell viability results showed that ABP modified with L-arginine leads to a significant increase in attachment of human dermal fibroblasts. The obtained results attest to the usefulness of L-arginine-treated ABP matrices for cardiovascular bioprostheses

  5. Acellular matrix of bovine pericardium bound with L-arginine

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    Kim, Hyo Joo [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of); Bae, Jin Woo [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of); Kim, Chun Ho [Laboratory of Tissue Engineering, Korea Cancer Center Hospital, Seoul 139-240 (Korea, Republic of); Lee, Jin Woo [Department of Orthopaedic Surgery, College of Medicine, Yonsei University, Seoul 120-749 (Korea, Republic of); Shin, Jung Woog [Department of Biomedical Engineering, Inje University, Gimhae 621-749 (Korea, Republic of); Park, Ki Dong [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of)

    2007-09-15

    Surface immobilization of bioactive molecules onto natural tissues has been interestingly studied for the development of new functional matrices for the replacement of lost or malfunctioning tissues. In this study, an acellular matrix of bovine pericardium (ABP) was chemically modified by the direct coupling of L-arginine after glutaraldehyde (GA) cross-linking. The effects of L-arginine coupling on durability and calcification were investigated and the biocompatibility was evaluated in vitro and in vivo. A four-step detergent and enzymatic extraction process has been utilized to remove cellular components from fresh bovine pericardium (BP). Microscopic observation confirmed that nearly all cellular constituents are removed. Thermal and mechanical properties showed that the durability of L-arginine-treated matrices increased as compared with control ABP and GA-treated ABP. Resistance to collagenase digestion revealed that modified matrices have greater resistance to enzyme digestion than control ABP and GA-treated ABP. The in vivo calcification study demonstrated much less calcium deposition on L-arginine-treated ABP than GA-treated one. In vitro cell viability results showed that ABP modified with L-arginine leads to a significant increase in attachment of human dermal fibroblasts. The obtained results attest to the usefulness of L-arginine-treated ABP matrices for cardiovascular bioprostheses.

  6. Plasma glucagon responses to L-arginine in various diseases

    International Nuclear Information System (INIS)

    Morita, Nobuto; Hayakawa, Hiroyuki; Kawai, Kohzo; Noto, Yutaka; Ohno, Taro

    1978-01-01

    To clarify the mechanism of abnormal glucose metabolism in the secondary diabetes, we examined the dynamics of plasma glucagon levels in various diseases which may accompany glucose intolerance. Plasma glucagon responses to L-arginine were observed in 20 liver cirrhotics, 8 patients with chronic renal failure, 6 patients with chronic pancreatitis, 4 patients, with hyperthyroidism, 22 diabetics and 9 normal controls. Plasma glucagon levels were determined by the radioimmunoassay method of Unger using 125 I-glucagon and antiserum 30K which is specific for pancreatic glucagon. In the cirrhotics, the plasma glucagon responses to L-arginine were significantly higher than in normal controls. The patients whose BSP retention at 45 minutes were above 30% showed higher plasma glucagon responses than in the patients whose BSP retention at 45 minutes were below 30%, suggesting that the more severely the liver was damaged, the more the plasma glucagon levels were elevated. In the patients with chronic renal failure, the plasma glucagon responses to L-arginine were also significantly higher than in normal controls. These abnormal levels were not improved by a hemodialysis, although serum creatinine levels were fairly decreased. In the patients with chronic pancreatitis, the plasma glucagon responses to L-arginine were the same as those in normal controls. In the patients with hyperthyroidism the plasma glucagon responses to L-arginine seemed to be lower than normal controls. In the diabetics, the plasma glucagon responses to L-arginine were almost the same as in normal controls. However their glucagon levels seemed to be relatively high, considering the fact that diabetics had high blood glucose levels. (auth.)

  7. L-Arginine Supplementation and Metabolism in Asthma

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    Angela Linderholm

    2011-01-01

    Full Text Available L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with L-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of L-arginine (0.05 g/kg twice daily in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the L-arginine group had higher serum L-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 µmol/L, p < 0.05, ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 µmol/L serum, p < 0.05 and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 µmol/L serum, p < 0.05 on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with L-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study.

  8. [l-arginine efficiency in MELAS syndrome. A case report].

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    Moutaouakil, F; El Otmani, H; Fadel, H; Sefrioui, F; Slassi, I

    2009-05-01

    Mitochondrial encephalomyopathy lactic acidosis and stoke-like episodes (MELAS) is a rare neurodegenerative disease caused by mutations of mitochondrial DNA. We report the case of a 12-year-old child with MELAS syndrome who presented with recurrent migraine-like headache and sudden blindness suggesting stroke-like episodes. Furthermore, he developed progressive muscular impairment with bilateral hearing loss. Serum lactate and pyruvate levels were elevated and the muscle biopsy showed an aspect of red-ragged fibers with Gomori trichrome. Brain imaging showed calcifications of basal ganglia on the CT scan and a parieto-occipital high signal on diffusion-weighted MRI. A genetic analysis was not performed but the presence of hearing loss in the patient's mother was suggestive of maternal transmission. Stroke-like episodes in the form of migraine-like headache and blindness were the patient's major complaint and did not improve despite analgesic drugs. After oral administration of l-arginine at the dose of 0.4mg/kg per day, stroke-like symptoms totally and rapidly disappeared. The efficiency of l-arginine in stroke-like episodes was initially reported then confirmed in a controlled study. The pathophysiology of stoke-like episodes and the mechanisms underlying the action of l-arginine are discussed.

  9. L-Arginine Pathway in COPD Patients with Acute Exacerbation

    DEFF Research Database (Denmark)

    Ruzsics, Istvan; Nagy, Lajos; Keki, Sandor

    2016-01-01

    -performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects. RESULTS: Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p ....001, respectively). Oxygen content in capillaries correlated with serum ADMA concentration. However, the concentration of L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p

  10. Characterization of casein and poly-l-arginine multilayer films

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    Szyk-Warszyńska, Lilianna; Kilan, Katarzyna; Socha, Robert P.

    2014-06-01

    Thin films containing casein appear to be a promising material for coatings used in the medical area to promote biomineralization. alfa- and beta-casein and poly-L-arginine multilayer films were formed by the layer-by layer technique and their thickness and mass were analyzed by ellipsometry and quartz crystal microbalance with dissipation monitoring (QCM-D). We investigated the effect of the type of casein used for the film formation and of the polyethyleneimine anchoring layer on the thickness and mass of adsorbed films. The analysis of the mass of films during their post-treatment with the solutions of various ionic strength and pH provided the information concerning films stability, while the XPS elemental analysis confirmed binding of calcium ions by the casein embedded in the multilayers.

  11. Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

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    Sandqvist, Anna; Schneede, Jörn; Kylhammar, David; Henrohn, Dan; Lundgren, Jakob; Hedeland, Mikael; Bondesson, Ulf; Rådegran, Göran; Wikström, Gerhard

    2018-03-01

    Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p L-arginine than patients with LVSD (p L-Arginine correlated to 6 min walking distance (6MWD) (r s  = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s  = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

  12. Bioinformatic evaluation of L-arginine catabolic pathways in 24 cyanobacteria and transcriptional analysis of genes encoding enzymes of L-arginine catabolism in the cyanobacterium Synechocystis sp. PCC 6803

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    Pistorius Elfriede K

    2007-11-01

    Full Text Available Abstract Background So far very limited knowledge exists on L-arginine catabolism in cyanobacteria, although six major L-arginine-degrading pathways have been described for prokaryotes. Thus, we have performed a bioinformatic analysis of possible L-arginine-degrading pathways in cyanobacteria. Further, we chose Synechocystis sp. PCC 6803 for a more detailed bioinformatic analysis and for validation of the bioinformatic predictions on L-arginine catabolism with a transcript analysis. Results We have evaluated 24 cyanobacterial genomes of freshwater or marine strains for the presence of putative L-arginine-degrading enzymes. We identified an L-arginine decarboxylase pathway in all 24 strains. In addition, cyanobacteria have one or two further pathways representing either an arginase pathway or L-arginine deiminase pathway or an L-arginine oxidase/dehydrogenase pathway. An L-arginine amidinotransferase pathway as a major L-arginine-degrading pathway is not likely but can not be entirely excluded. A rather unusual finding was that the cyanobacterial L-arginine deiminases are substantially larger than the enzymes in non-photosynthetic bacteria and that they are membrane-bound. A more detailed bioinformatic analysis of Synechocystis sp. PCC 6803 revealed that three different L-arginine-degrading pathways may in principle be functional in this cyanobacterium. These are (i an L-arginine decarboxylase pathway, (ii an L-arginine deiminase pathway, and (iii an L-arginine oxidase/dehydrogenase pathway. A transcript analysis of cells grown either with nitrate or L-arginine as sole N-source and with an illumination of 50 μmol photons m-2 s-1 showed that the transcripts for the first enzyme(s of all three pathways were present, but that the transcript levels for the L-arginine deiminase and the L-arginine oxidase/dehydrogenase were substantially higher than that of the three isoenzymes of L-arginine decarboxylase. Conclusion The evaluation of 24

  13. L-arginine increases nitric oxide and attenuates pressor and heart ...

    African Journals Online (AJOL)

    olayemitoyin

    heart rate responses to change in posture in sickle cell anemia subjects. 1 .... the standing position and measurements made immediately. Arterial ... pressure was the difference between systolic and diastolic ... Table 3. Effect of L-Arginine Supplementation on Blood Pressure Parameters, Plasma L-Arginine and Nitric Oxide.

  14. Potentiality of application of the conductometric L-arginine biosensors for the real sample analysis

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    Jaffrezic-Renault N.

    2012-12-01

    Full Text Available Aim. To determine an influence of serum components on the L-arginine biosensor sensitivity and to formulate practical recommendations for its reliable analysis. Methods. The L-arginine biosensor comprised arginase and urease co-immobilized by cross-linking. Results. The biosensor specificity was investigated based on a series of representative studies (namely, through urea determination in the serum; inhibitory effect studies of mercury ions; high temperature treatment of sensors; studying the biosensor sensitivity to the serum treated by enzymes, and selectivity studies. It was found that the response of the biosensor to the serum injections was determined by high sensitivity of the L-arginine biosensor toward not only to L-arginine but also toward two other basic amino acids (L-lysine and L-histidine. Conclusions. A detailed procedure of optimization of the conductometric biosensor for L-arginine determination in blood serum has been proposed.

  15. L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

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    Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

    1997-01-21

    The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

  16. Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death.

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    Movafegh, Bahareh; Jalal, Razieh; Mohammadi, Zobeideh; Aldaghi, Seyyede Araste

    2018-04-11

    Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide-acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicin-induced cell death. Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24 h combined treatment of cells with doxorubicin (0.5 μM) and poly-L-arginine (1 μg ml-1) caused a small increase in doxorubicin-induced apoptosis and significant elevated necrosis in DU145 cells as compared to each agent alone. Conlusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferation-inducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.

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    Choe, Chi-un; Nabuurs, Christine; Stockebrand, Malte C; Neu, Axel; Nunes, Patricia; Morellini, Fabio; Sauter, Kathrin; Schillemeit, Stefan; Hermans-Borgmeyer, Irm; Marescau, Bart; Heerschap, Arend; Isbrandt, Dirk

    2013-01-01

    Phosphorylated creatine (Cr) serves as an energy buffer for ATP replenishment in organs with highly fluctuating energy demand. The central role of Cr in the brain and muscle is emphasized by severe neurometabolic disorders caused by Cr deficiency. Common symptoms of inborn errors of creatine synthesis or distribution include mental retardation and muscular weakness. Human mutations in l-arginine:glycine amidinotransferase (AGAT), the first enzyme of Cr synthesis, lead to severely reduced Cr and guanidinoacetate (GuA) levels. Here, we report the generation and metabolic characterization of AGAT-deficient mice that are devoid of Cr and its precursor GuA. AGAT-deficient mice exhibited decreased fat deposition, attenuated gluconeogenesis, reduced cholesterol levels and enhanced glucose tolerance. Furthermore, Cr deficiency completely protected from the development of metabolic syndrome caused by diet-induced obesity. Biochemical analyses revealed the chronic Cr-dependent activation of AMP-activated protein kinase (AMPK), which stimulates catabolic pathways in metabolically relevant tissues such as the brain, skeletal muscle, adipose tissue and liver, suggesting a mechanism underlying the metabolic phenotype. In summary, our results show marked metabolic effects of Cr deficiency via the chronic activation of AMPK in a first animal model of AGAT deficiency. In addition to insights into metabolic changes in Cr deficiency syndromes, our genetic model reveals a novel mechanism as a potential treatment option for obesity and type 2 diabetes mellitus.

  18. Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation.

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    Lundgren, Jakob; Sandqvist, Anna; Hedeland, Mikael; Bondesson, Ulf; Wikström, Gerhard; Rådegran, Göran

    2018-04-12

    Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered "normal" after HT.

  19. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

    2013-01-01

    Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet......-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...

  20. Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

    International Nuclear Information System (INIS)

    Sunatkari, A. L.; Talwatkar, S. S.; Tamgadge, Y. S.; Muley, G. G.

    2016-01-01

    We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

  1. Effects of dietary L-arginine on orthodontic tooth movement in rats

    African Journals Online (AJOL)

    Yomi

    2012-01-03

    Jan 3, 2012 ... arginine in drinking water six days before the insertion of springs to ... Key words: L-Arginine, dietary, orthodontic tooth movement, nitric oxide, root resorption, osteoclast, .... cAMP, interleukin 1-beta and neurotransmitters are.

  2. Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

    Energy Technology Data Exchange (ETDEWEB)

    Sunatkari, A. L., E-mail: ashok.sunatkari@rediffmail.com [Department of Physics, Siddhartha College of Arts, Science and Commerce, Fort, Mumbai-400001, India. Email: ashok.sunatkari@rediffmail.com (India); Talwatkar, S. S. [Department of Physics, N.G. Aacharya and D.K. Maratha College of Arts, Science and Commerce, Chembur, Mumbai-400071, India. Email: swarna-81@rediffmail.com (India); Tamgadge, Y. S. [Department of Physics, Mahatma Phule Arts, Commerce & S.R.C. Science College, Warud-444906, India. Email: ystamgadge@gmail.com (India); Muley, G. G., E-mail: gajananggm@yahoo.co.in [Department of Physics, Sant Gadge Baba Amravati University, Amravati-444602 India. Email: gajananggm@yahoo.co.in (India)

    2016-05-06

    We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

  3. Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

    Science.gov (United States)

    Flynn, K M; Kellihan, H B; Trepanier, L A

    2017-08-01

    To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Atropine and ODQ antagonize tetanic fade induced by L-arginine in cats

    Directory of Open Access Journals (Sweden)

    J.M. Cruciol-Souza

    1999-10-01

    Full Text Available Although it has been demonstrated that nitric oxide (NO released from sodium nitrite induces tetanic fade in the cat neuromuscular preparations, the effect of L-arginine on tetanic fade and its origin induced by NO have not been studied in these preparations. Furthermore, atropine reduces tetanic fade induced by several cholinergic and anticholinergic drugs in these preparations, whose mechanism is suggested to be mediated by the interaction of acetylcholine with inhibitory presynaptic muscarinic receptors. The present study was conducted in cats to determine the effects of L-arginine alone or after pretreatment with atropine or 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ on neuromuscular preparations indirectly stimulated at high frequency. Drugs were injected into the middle genicular artery. L-arginine (2 mg/kg and S-nitroso-N-acetylpenicillamine (SNAP; 16 µg/kg induced tetanic fade. The Nw-nitro-L-arginine (L-NOARG; 2 mg/kg alone did not produce any effect, but reduced the tetanic fade induced by L-arginine. D-arginine (2 mg/kg did not induce changes in tetanic fade. The tetanic fade induced by L-arginine or SNAP was reduced by previous injection of atropine (1.0 µg/kg or ODQ (15 µg/kg. ODQ alone did not change tetanic fade. The data suggest that the NO-synthase-GC pathway participates in the L-arginine-induced tetanic fade in cat neuromuscular preparations. The tetanic fade induced by L-arginine probably depends on the action of NO at the presynaptic level. NO may stimulate guanylate cyclase increasing acetylcholine release and thereby stimulating presynaptic muscarinic receptors.

  5. L-ARGININE PREVENTS METABOLIC EFFECTS OF HIGH GLUCOSE IN DIABETIC MICE

    OpenAIRE

    West, Matthew B.; Ramana, Kota V.; Kaiserova, Karin; Srivastava, Satish K.; Bhatnagar, Aruni

    2008-01-01

    We tested the hypothesis that activation of the polyol pathway and protein kinase C (PKC) during diabetes is due to loss of NO. Our results show that after 4 weeks of streptozotocin-induced diabetes, treatment with L-arginine restored NO levels and prevented tissue accumulation of sorbitol in mice, which was accompanied by an increase in glutathiolation of aldose reductase. L-arginine treatment decreased superoxide generation in the aorta, total PKC activity and PKC-βII phosphorylation in the...

  6. Kidney Mass Reduction Leads to l-Arginine Metabolism-Dependent Blood Pressure Increase in Mice.

    Science.gov (United States)

    Pillai, Samyuktha Muralidharan; Seebeck, Petra; Fingerhut, Ralph; Huang, Ji; Ming, Xiu-Fen; Yang, Zhihong; Verrey, François

    2018-02-25

    Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l-arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l-arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post-UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. l-citrulline, that is used in the kidney to produce l-arginine, was elevated post-UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with l-arginine and is a marker for renal failure. Interestingly, the UNX-induced blood pressure increase was prevented by supplementation of the diet with 5% of the l-arginine precursor, l-citrulline. Because l-arginine is metabolized in the kidney and other peripheral tissues by arginase-2, we tested whether the lack of this metabolic pathway also compensates for decreased l-arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase-2 knockout mice (Arg-2 -/- ) neither displayed an increase in asymmetric dimethylarginine and l-citrulline plasma levels nor a significant increase in blood pressure. UNX leads to a small increase in blood pressure that is prevented by l-citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on l-arginine metabolism. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the 'L-arginine paradox'

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Soyoung; Mohan, Srinidi [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States); Fung, Ho-Leung, E-mail: hlfung@buffalo.edu [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Our findings provide a possible solution to the 'L-arginine paradox'. Black-Right-Pointing-Pointer Extracellular L-arginine concentration is the major determinant of NO production. Black-Right-Pointing-Pointer Cellular L-arginine action is limited by cellular ARG transport, not the K{sub m} of NOS. Black-Right-Pointing-Pointer We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of {sup 15}N{sub 4}-ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, {sup 15}N{sub 4}-ARG, dimethylarginines, and L-citrulline by an LC-MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by{sup 15}N-nitrite or estimated {sup 15}N{sub 3}-citrulline concentrations when {sup 15}N{sub 4}-ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced {sup 15}N{sub 4}-ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by {sup 15}N-nitrite, total nitrite and {sup 15}N{sub 3}-citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside

  8. Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the “L-arginine paradox”

    International Nuclear Information System (INIS)

    Shin, Soyoung; Mohan, Srinidi; Fung, Ho-Leung

    2011-01-01

    Highlights: ► Our findings provide a possible solution to the “L-arginine paradox”. ► Extracellular L-arginine concentration is the major determinant of NO production. ► Cellular L-arginine action is limited by cellular ARG transport, not the K m of NOS. ► We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of 15 N 4 -ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, 15 N 4 -ARG, dimethylarginines, and L-citrulline by an LC–MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by 15 N-nitrite or estimated 15 N 3 -citrulline concentrations when 15 N 4 -ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced 15 N 4 -ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by 15 N-nitrite, total nitrite and 15 N 3 -citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside the cell, ARG can no longer gain access to the membrane-bound eNOS. These observations indicate that the “L-arginine paradox” should not consider intracellular ARG

  9. L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta.

    Science.gov (United States)

    Wong, Emily S W; Man, Ricky Y K; Ng, Kwok F J; Leung, Susan W S; Vanhoutte, Paul M

    2018-03-01

    The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. L-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of L-arginine in modulating the overall vascular response to dexmedetomidine. Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N-nitro-L-arginine methyl ester hydrochloride (L-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), L-arginine, (S)-(2-boronethyl)-L-cysteine hydrochloride (arginase inhibitor), N-hydroxy-L-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with L-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous L-arginine augmented the dexmedetomidine-induced contractions in the presence of L-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-L-cysteine hydrochloride (Emax 16 ± 4%) and N-hydroxy-L-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as L-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by L-arginine treatment in the presence of L-NAME (N = 4). These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of

  10. EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

    Science.gov (United States)

    Iacob, Andreea-Teodora; Drăgan, Maria; Constantin, Sandra; Lupaşcu, Florentina; Confederat, Luminiţa; Buron, F; Routier, S; Profire, Lenuţa

    2016-01-01

    L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

  11. Apple snack enriched with L-arginine using vacuum impregnation/ohmic heating technology.

    Science.gov (United States)

    Moreno, Jorge; Echeverria, Julian; Silva, Andrea; Escudero, Andrea; Petzold, Guillermo; Mella, Karla; Escudero, Carlos

    2017-07-01

    Modern life has created a high demand for functional food, and in this context, emerging technologies such as vacuum impregnation and ohmic heating have been applied to generate functional foods. The aim of this research was to enrich the content of the semi-essential amino acid L-arginine in apple cubes using vacuum impregnation, conventional heating, and ohmic heating. Additionally, combined vacuum impregnation/conventional heating and vacuum impregnation/ohmic heating treatments were evaluated. The above treatments were applied at 30, 40 and 50  ℃ and combined with air-drying at 40 ℃ in order to obtain an apple snack rich in L-arginine. Both the impregnation kinetics of L-arginine and sample color were evaluated. The impregnated samples created using vacuum impregnation/ohmic heating at 50 ℃ presented a high content of L-arginine, an effect attributed primarily to electropermeabilization. Overall, vacuum impregnation/ohmic heating treatment at 50 ℃, followed by drying at 40 ℃, was the best process for obtaining an apple snack rich in L-arginine.

  12. L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

    Science.gov (United States)

    Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2016-03-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

  13. Growth and dielectric, mechanical, thermal and etching studies of an organic nonlinear optical L-arginine trifluoroacetate (LATF) single crystal

    International Nuclear Information System (INIS)

    Arjunan, S.; Mohan Kumar, R.; Mohan, R.; Jayavel, R.

    2008-01-01

    L-arginine trifluoroacetate, an organic nonlinear optical material, has been synthesized from aqueous solution. Bulk single crystal of dimension 57 mm x 5 mm x 3 mm has been grown by temperature lowering technique. Powder X-ray diffraction studies confirmed the monoclinic structure of the grown L-arginine trifluoroacetate crystal. Linear optical property of the grown crystal has been studied by UV-vis spectrum. Dielectric response of the L-arginine trifluoroacetate crystal was analysed for different frequencies and temperatures in detail. Microhardness study on the sample reveals that the crystal possesses relatively higher hardness compared to many organic crystals. Thermal analyses confirmed that the L-arginine trifluoroacetate material is thermally stable upto 212 deg. C. The etching studies have been performed to assess the perfection of the L-arginine trifluoroacetate crystal. Kurtz powder second harmonic generation test confirms the nonlinear optical properties of the as-grown L-arginine trifluoroacetate crystal

  14. The second case of a young man with L-arginine-induced acute pancreatitis.

    Science.gov (United States)

    Binet, Quentin; Dufour, Inès; Agneessens, Emmanuel; Debongnie, Jean-Claude; Aouattah, Tarik; Covas, Angélique; Coche, Jean-Charles; De Koninck, Xavier

    2018-04-21

    Dietary supplementation of arginine has been used by numerous world-class athletes and professional bodybuilders over the past 30 years. L-Arginine indeed enhances muscular power and general performance via maintaining ATP level. However, L-arginine is also known to induce acute pancreatitis in murine models. We report the case of young man presenting with upper abdominal pain and increased serum lipase levels. Contrast-enhanced computed tomography confirms a mild acute pancreatitis. Common etiologies have been ruled out and toxicological anamnestic screening reveals the intake of protein powder. This is, to the best of our knowledge, the second case in human of arginine-induced acute pancreatitis. This case report suggests that every patient presenting with acute pancreatitis without obvious etiology should be evaluated for the intake of toxics other than alcohol, including L-arginine.

  15. Competitive metabolism of L-arginine: arginase as a therapeutic target in asthma☆

    Science.gov (United States)

    Bratt, Jennifer M.; Zeki, Amir A.; Last, Jerold A.; Kenyon, Nicholas J.

    2011-01-01

    Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential toxicity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics. PMID:23554705

  16. l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease

    DEFF Research Database (Denmark)

    Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

    2017-01-01

    Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease....

  17. Temporal Lob Epilepsi'sinde L-Arginine ve CaEDTA'nın Etkileri

    OpenAIRE

    NOYAN, Behzat

    2005-01-01

    Bu çalışmada, bir nitrik oksit (NO-) prekürsörü olan L-Arginine ve bir ekstrasellüler çinko şelatörü olan CaEDTA'nın pilokarpine HCl ile oluşturulan kısa süreli epileptik nöbet üzerine etkileri araştırıldı. Deney, nöbet kontrol (serum fizyolojik 10 µl, i.c.v., ve sonra 380 mg/kg pilokarpine HCl i.p.), L-Arginine (150 µg/10 µl, i.c.v.), CaEDTA (100 mM, 10 µl, i.c.v.), L-Arginine+CaEDTA olmak üzere 4 gruptan oluştu. Enjeksiyonlardan sonra iki saat boyunca nöbet davranışları gözlemlenen ...

  18. Deprivation of L-Arginine Induces Oxidative Stress Mediated Apoptosis in Leishmania donovani Promastigotes: Contribution of the Polyamine Pathway

    Science.gov (United States)

    Mandal, Abhishek; Das, Sushmita; Roy, Saptarshi; Ghosh, Ayan Kumar; Sardar, Abul Hasan; Verma, Sudha; Saini, Savita; Singh, Ruby; Abhishek, Kumar; Kumar, Ajay; Mandal, Chitra; Das, Pradeep

    2016-01-01

    The growth and survival of intracellular parasites depends on the availability of extracellular nutrients. Deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. To further understand the relationship, the mechanistic role of L-arginine in regulation of redox mediated survival of Leishmania donovani promastigotes was investigated. L-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferation and increase L-arginine uptake. Relative expression of enzymes, involved in L-arginine metabolism, which leads to polyamine and trypanothione biosynthesis, were downregulated causing decreased production of polyamines in L-arginine deprived parasites and cell death. The resultant increase in reactive oxygen species (ROS), due to L-arginine deprivation, correlated with increased NADP+/NADPH ratio, decreased superoxide dismutase (SOD) level, increased lipid peroxidation and reduced thiol content. A deficiency of L-arginine triggered phosphatidyl serine externalization, a change in mitochondrial membrane potential, release of intracellular calcium and cytochrome-c. This finally led to DNA damage in Leishmania promastigotes. In summary, the growth and survival of Leishmania depends on the availability of extracellular L-arginine. In its absence the parasite undergoes ROS mediated, caspase-independent apoptosis-like cell death. Therefore, L-arginine metabolism pathway could be a probable target for controlling the growth of Leishmania parasites and disease pathogenesis. PMID:26808657

  19. Supplementation with rumen-protected L-arginine-HCl increased fertility in sheep with synchronized estrus.

    Science.gov (United States)

    de Chávez, Julio Agustín Ruiz; Guzmán, Adrian; Zamora-Gutiérrez, Diana; Mendoza, Germán David; Melgoza, Luz María; Montes, Sergio; Rosales-Torres, Ana María

    2015-08-01

    The aim of the present study was to evaluate the effects of L-arginine-HCl supplementation on ovulation rate, fertility, prolificacy, and serum VEGF concentrations in ewes with synchronized oestrus. Thirty Suffolk ewes with a mean body weight of 45 ± 3 kg and a mean body condition score (BCS) of 2.4 ± 0.28 were synchronized for estrus presentation with a progestin-containing sponge (20 mg Chronogest® CR) for 9 days plus PGF2-α (Lutalyse; Pfizer, USA) on day 7 after the insertion of the sponge. The ewes were divided into two groups; i.e., a control group (n = 15) that was fed on the native pasture (basal diet) and an L-arginine-HCl group (n = 15) that received 7.8 g of rumen-protected L-arginine-HCl from day 5 of the sponge insertion until day 25 after mating plus the basal diet. The L-arginine-HCl was administered daily via an esophageal probe between days 5 and 9 of the synchronization protocol and every third day subsequently. Blood samples were drawn from the jugular vein every 6 days throughout the entire experimental period. The results revealed that the L-arginine-HCl supplementation increased fertility during the synchronized estrus (P = 0.05). However, no effects were observed on the final BCS (P = 0.78), estrus presentation (P = 0.33), multiple ovulations (P = 0.24), prolificacy (P = 0.63), or serum VEGF concentration. In conclusion, L-arginine-HCl supplementation during the period used in this study increased fertility in sheep with synchronized estrus possibly due to improved embryo-fetal survival during early pregnancy.

  20. L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

    Science.gov (United States)

    Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

    2009-02-01

    The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

  1. Developmental changes of l-arginine transport at the blood-brain barrier in rats.

    Science.gov (United States)

    Tachikawa, Masanori; Hirose, Shirou; Akanuma, Shin-Ichi; Matsuyama, Ryo; Hosoya, Ken-Ichi

    2018-05-01

    l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage. Kp, app of l-serine was also increased at the first postnatal week. In contrast, Kp, app of d-mannitol, a passively BBB-permeable molecule, did not change, indicating that increased transport of l-arginine and l-serine is not due to BBB immaturity. Double immunohistochemical staining of CAT1 and a marker protein, glucose transporter 1, revealed that CAT1 was localized on both luminal and abluminal membranes of brain capillary endothelial cells during the developmental and adult stages. A dramatic increase in CAT1 expression in the brain was seen at postnatal day 7 (P7) and day 14 (P14) and the expression subsequently decreased as the brain matured. In accordance with this, intense immunostaining of CAT1 was observed in brain capillaries at P7 and P14. These findings strongly support our hypothesis and suggest that the supply of blood-born l-arginine to the brain via CAT1 at the BBB plays a key role in meeting the elevated demand for l-arginine in postnatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Efficacy L-Arginine In Patients With Nonalcoholic Steatohepatitis Associated With Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Oleksandr Fediv

    2015-01-01

    Full Text Available Abstract Background and Purpose Recent research in the field of hematology indicate that among the many pathogenic mechanisms of development and progression of nonalcoholic steatohepatitis NASH which occurs on the background of the metabolic syndrome an important role is played by endothelial dysfunction and violations of haemocoagulation. The aim of this research was to study the effectiveness of L-arginine as it corrects endothelial dysfunction and disorders of homeostasis haemocoagulation link in patients with NASH associated with the metabolic syndrome. Subjects and Methods 128 patients with nonalcoholic steatohepatitis associated with metabolic syndrome were examined. Some patients 63 persons received standard treatment according to national guidelines. To another group 65 patients on the background of basic therapy L-arginine hydrochloride followed by transition to oral form of L-arginine aspartate was administered. Blood levels of stable nitrogen monoxide metabolites nitrites nitrates endothelin-1 and plasma recalcification time prothrombin time thrombin time activated partial thromboplastin time fibrinogen plasma level activity of antithrombin III and coagulation factor XIII potential activity of plasminogen plasma fibrinolytic blood activity were studied. Results Originally significantly increased levels of endothelin-1 decreased after the therapy in all studied groups but more noticeable changes in the group with L-arginine appointment were observed p0.05. In the studied groups normalization of stable nitrogen monoxide metabolites after treatment was also noticed. Significant p0.05 increase in all haemocoagulation time characteristics and activities of antithrombin-III and factor XIII was found. The positive effect of L-arginine on blood fibrinolytic activity was noted. Discussion and Conclusion Combined therapy of nonalcoholic steatohepatitis associated with metabolic syndrome with a differentiated degreeal L-arginine assignment by

  3. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

    Directory of Open Access Journals (Sweden)

    Amal Abdussalam Ali A. Hmaid

    2018-03-01

    Full Text Available Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C or cold (4 ± 1 °C and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis. Keywords: Cardiomyocyte, Cardiac hypertrophy, l-Arginine, l-NAME, Myocardium

  4. Thermal, FT–IR and SHG efficiency studies of L-arginine doped KDP ...

    Indian Academy of Sciences (India)

    TECS

    popular due to their applications in frequency converters, electro-optic switching and .... parameters of dehydration process of pure and L-arginine doped KDP crystals were ... action, R a gas constant, and a the heating rate in deg.C.min. –1.

  5. Erythrocytes L-arginine y+ transporter inhibition by N-ethylmaleimide in ice-bath.

    Science.gov (United States)

    Pinheiro da Costa, Bartira Ercília; de Almeida, Priscilla Barcellos; Conceição, Ioná Rosine; Antonello, Ivan Carlos Ferreira; d'Avila, Domingos O; Poli-de-Figueiredo, Carlos Eduardo

    2010-11-01

    Erythrocytes L: -arginine uptake is conveyed by y+ and y+L membrane transport systems. Pre-incubation with N-ethylmaleimide for 10 min at 37°C inhibits the y+ system. The aim of this study was to determine the ideal pre-incubation temperature in evaluating y+ and y+L systems. Cells were pre-incubated with or without N-ethylmaleimide for 10 min at 4°C and 37°C. L: -Arginine uptake was quantified by radioisotope and standard erythrocytes membrane flux methodology. Results demonstrate that erythrocytes L: -arginine content is depleted by pre-incubation at 37°C for 10 min, thus changing the V (max) measurement. The inhibitory effect of N-ethylmaleimide pre-incubation was temperature independent and already complete after 1 min of incubation. No significant difference in kinetic parameters was detected between cells pre-incubated at 37°C or 4°C, under zero-trans conditions. In conclusion, we suggest that measurement of erythrocytes L: -arginine uptake by y+ and y+L systems could be carried out without N-ethylmaleimide pre-incubation at 37°C.

  6. L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction

    NARCIS (Netherlands)

    Maarsingh, H.; Bossenga, B. E.; Bos, I. S. T.; Volders, H. H.; Zaagsma, J.; Meurs, H.

    Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low L-arginine concentrations.

  7. l-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy

    DEFF Research Database (Denmark)

    Szabo, P; Lantos, J; Nagy, L

    2016-01-01

    lactate levels were increased during reperfusion (p = .02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3 μmol/L [interquartile range 24.4-34.4 μmol/L] vs. 57.6 μmol/L [interquartile range...

  8. Growth and characterization of pure and doped NLO L-arginine ...

    Indian Academy of Sciences (India)

    Administrator

    NLO; SHG; solution growth; LAA. 1. Introduction. L-arginine phosphate monohydrate (LAP) was first repor- ted by Xu et al (1983) as a promising nonlinear optical. (NLO) material. LAP is nearly three times more nonlinear than KDP. Monaco et al (1987) reported the formation of. LAP and its chemical analogs from the strongly ...

  9. L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

    Science.gov (United States)

    L-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at th...

  10. L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m.

    Science.gov (United States)

    Mansoor, Jim K; Morrissey, Brian M; Walby, William F; Yoneda, Ken Y; Juarez, Maya; Kajekar, Radhika; Severinghaus, John W; Eldridge, Marlowe W; Schelegle, Edward S

    2005-01-01

    We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.

  11. L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats.

    Science.gov (United States)

    de Aguiar Picanço, Etiene; Lopes-Paulo, Francisco; Marques, Ruy G; Diestel, Cristina F; Caetano, Carlos Eduardo R; de Souza, Mônica Vieira Mano; Moscoso, Gabriela Mendes; Pazos, Helena Maria F

    2011-05-01

    Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.

  12. The effect of L-Arginine on the brain tissue of stressed rats

    Directory of Open Access Journals (Sweden)

    Batoul Ebadi

    2010-01-01

    Full Text Available Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

  13. The effect of L-Arginine on the brain tissue of stressed rats

    Directory of Open Access Journals (Sweden)

    Batoul Ebadi

    2010-01-01

    Full Text Available   Abstract  Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

  14. Effect of L-arginine on the growth of Plasmodium falciparum and immune modulation of host cells.

    Science.gov (United States)

    Awasthi, Vikky; Chauhan, Rubika; Chattopadhyay, Debprasad; Das, Jyoti

    2017-01-01

    Malaria is a life-threatening disease caused by Plasmodium parasites. The life-cycle of Plasmodium species involves several stages both in mosquito and the vertebrate host. In the erythrocytic stage, Plasmodium resides inside the red blood cells (RBCs), where it meets most of its nutritional requirement by degrad- ing host's haemoglobin. L-arginine is required for growth and division of cells. The present study was aimed to demonstrate the effect of supplementation of different concentrations of L-arginine and L-citrulline on the growth of parasite, and effect of the culture supernatant on the host's peripheral blood mononuclear cells (PBMCs). To examine the effect of supplementation of L-arginine and L-citrulline, Plasmodium falciparum (3D7 strain) was cultured in RPMI 1640, L-arginine deficient RPMI 1640, and in different concentrations of L-arginine, and L-citrulline supplemented in arginine deficient RPMI 1640 medium. To have a holistic view of in vivo cell activation, the PBMCs isolated from healthy human host were cultured in the supernatant collected from P. falciparum culture. Growth of the parasite was greatly enhanced in L-arginine supplemented media and was found to be concentration dependent. However, parasite growth was compromised in L-citrulline supplemented and L-arginine deficient media. The supernatant collected from L-arginine supplemented parasite media (sArg) showed increased FOXP3 and interleukin-10 (IL-10) expression as compared to the supernatant collected from L-citrulline supple- mented parasite media (sCit). The in vitro culture results showed, decreased parasite growth, and decreased expression of programmed cell death-1 (PD-1) (a coinhibitory molecule) and IL-10 in the L-citrulline supplemented media as compared to L-arginine supplemented media. Hence, it was concluded that L-citrulline supplementation would be a better alternative than L-arginine to inhibit the parasite growth.

  15. The Effects of Pretreatment with Various Doses of L-Arginine on Cisplatin-Induced Nephropathy of Male Rats

    Directory of Open Access Journals (Sweden)

    B Rasoulian

    2016-09-01

    Full Text Available Introduction: Cisplatin is a widely used anti-cancer drug, which its application is limited by nephrotoxicity. In this study, the effect of pretreatment with different l-arginine doses on Cisplatin-induced renal functional injury was investigated. Methods: 63 male rats were divided into 7 groups: In groups 3, 4, 5 and 6, 60 min before the Cisplatin injection (5mg/kg; L-Arginine with doses of 50,100,200 or 400mg/kg was injected, respectively. In group7, normal saline was injected before Cisplatin administration. In groups 1 and 2, normal saline was injected instead of Cisplatin. In group 2, 60min before normal saline injection, 400mg/kg L-Arginine was administered and in group1, instead of L-arginine, normal saline was injected too. Injections were intraperitoneal. 72h after Cisplatin injection, blood sampling and plasma separation were done. Urine sample was collected 24 hours before blood sampling by metabolic cage. The mean of plasma urea and creatinine levels and creatinine clearance (ml/day.kg and fractional excretion of Na (FENa, % were compared among different groups as renal functional parameters. Results: In comparison to group 7, L-arginine injection in a dose of 400mg/kg led to significant amelioration of all parameters. 200 mg/kg L-arginine administration led to significant decrease in plasma urea level and FENa. 100mg/kg L-arginine caused significant improvement in fractional excretion of sodium. L-arginine injection with 50mg/kg dose, significantly ameliorate all renal function tests instead of creatinine clearance. Conclusion: Pretreatment with L-arginine administration with 400 or 50 mg/kg doses, respectively, had the highest effect on reducing Cisplatin-induced nephropathy. L-arginine injection with intermediate doses i.e. 200 or 100 mg/kg had less effect in reducing Cisplatin-induced nephropathy and it needs more investigations.

  16. The Histological Effects of L-arginine on Ventricular Myocardium in Iron Treated Male Rats

    Directory of Open Access Journals (Sweden)

    M Sofiabadi

    2012-05-01

    Full Text Available

    Background and Objectives: Iron overload is detrimental for the body and can create damage to different body tissues, such as myocardium by producing oxidative stress. Therefore, the antioxidant factors can neutralize iron induced damages. According to available reports, L-arginine as a precursor nitric oxide production has antioxidant effects. This study was carried out to evaluate the histological effects of iron overload on ventricular muscle and preventive role of L-arginine in male rats.
    Methods: In this experiment, 40 male rats with weight range of 300-250g were divided at random into five equal groups including:1- Control, 2- Iron (10mg/kg, ip, 3- Iron(10mg/kg, ip+L-arginine (1mg/ml, po, 4- Iron (50mg/kg, ip and 5- Iron (50mg/kg,ip+L-arginine(1mg/ml,po. After treatment (6 weeks, the animals were anesthetized and the samples of left apical ventricular myocardium were taken out and morphological studies were done following fixation with 10% formalin and H&E staining. Microscopic parameters under study were cell swelling, vessel dilatation and hypercongestion, cell necrosis and tissue deformity. The type and severity of damage to the tissue were also noted. Data were analyzed using chi-square statistical procedure, and Pvalue≤0.05 were considered to be significant. 
    Results: The data showed moderate changes in the ventricular myocardium of group 2 that was significant in comparison to the control group (P<0.05. The ventricular myocardium of group 3 showed low changes and wasn't significant in comparison to control group (P=0.84. The ventricular myocardium of the group 4 showed severe changes in comparison to the control group (P<0.01. The low change showed in the ventricular myocardium of group 5 that wasn't significant in comparison to the control group.

    Conclusion: This study showed

  17. Role of the L-citrulline/L-arginine cycle in iNANC nerve-mediated nitric oxide production and airway smooth muscle relaxation in allergic asthma

    NARCIS (Netherlands)

    Maarsingh, Ham; Leusink, John; Zaagsma, Johan; Meurs, Herman

    2006-01-01

    Nitric oxide synthase (NOS) converts L-arginine into nitric oxide (NO) and L-Citrulline. In NO-producing cells, L-citrulline can be recycled to L-arginine in a two-step reaction involving argininosuccinate synthase (ASS) and -lyase (ASL). In guinea pig trachea, L-arginine is a limiting factor in

  18. The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis

    DEFF Research Database (Denmark)

    Molnar, Tihamer; Pusch, Gabriella; Papp, Viktoria

    2014-01-01

    BACKGROUND: Endothelial dysfunction is associated with increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) resulting in a decreased production of nitric oxide, which regulates the vascular tone. METHODS: Patients with acute ischemic stroke (AIS, n = 55......) and asymptomatic significant carotid stenosis (AsCS, n = 44) were prospectively investigated. L-arginine, ADMA, SDMA, S100 B, and high-sensitivity C-reactive protein (hsCRP) were serially measured within 6 hours after the onset of stroke, at 24 and 72 poststroke hours. All markers were compared with healthy...... subjects (n = 45). The severity of AIS was daily assessed by National Institute of Health Stroke Scale scoring. RESULTS: Even within 6 hours after the onset of stroke, L-arginine, ADMA, and SDMA were significantly higher in patients with AIS compared with both AsCS and healthy subjects. S100 B reflecting...

  19. Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

    Science.gov (United States)

    Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

    2013-12-01

    Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

  20. Low dose vitamin C, vitamin E or L-arginine supplementation and ...

    African Journals Online (AJOL)

    The effect of chronic low-dose supplementation with vitamin C (300mg/day for 6 weeks in adults or 100mg/day for 6 weeks in children) or vitamin E (100 IU/day for 6 weeks in adults) or L-Arginine (1g/day for 6 weeks in adults) in ameliorating the pathophysiology and combating the deleterious effects of sickle cell disease in ...

  1. Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

    International Nuclear Information System (INIS)

    Cheng Wei; Oike, Masahiro; Hirakawa, Masakazu; Ohnaka, Keizo; Koyama, Tetsuya; Ito, Yushi

    2005-01-01

    The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca 2+ transients and cellular uptake of L-[ 3 H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[ 3 H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine

  2. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation.

    Science.gov (United States)

    Hmaid, Amal Abdussalam Ali A; Markelic, Milica; Otasevic, Vesna; Masovic, Sava; Jankovic, Aleksandra; Korac, Bato; Korac, Aleksandra

    2018-03-01

    Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N ω -nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.

  3. Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.

    Science.gov (United States)

    Escudero, Andrea; Petzold, Guillermo; Moreno, Jorge; Gonzalez, Marcelo; Junod, Julio; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

    2013-01-01

    Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  4. Exogenous L-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension

    DEFF Research Database (Denmark)

    Garcia, Vinicius P; Rocha, Helena N M; Silva, Gustavo M.

    2016-01-01

    Aims Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective L-arginine-NO pathway. Exogenous L-arginine improves endothelial function to prevent the onset of cardiovascular...... disease, but the mechanism by which this is accomplished remains unclear. We determined the effects of exogenous L-arginine infusion on vascular biomarkers in patients with hypertension. Main methods Venous blood samples were obtained from seven patients with hypertension (45 ± 5 yrs., HT group...... biomarkers between groups during the saline infusion (P > 0.05). Significance Exogenous L-arginine diminished metalloproteinase-2 and -9 activities and MMP-9/TIMP-1 ratio along with restoring the oxidative stress balance in patients with hypertension....

  5. Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Molnar, Tihamer; Pusch, Gabriella; Nagy, Lajos

    2016-01-01

    BACKGROUND: Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive...... and independent associations to outcome. METHODS: Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed...... as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month. RESULTS: Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most...

  6. The Effects Of L-Arginine And L-Name On Coronary Flow And Oxidative Stress In Isolated Rat Hearts

    Directory of Open Access Journals (Sweden)

    Sobot Tanja

    2015-12-01

    Full Text Available The aim of this experimental study was to assess the effects of the acute administration of L-arginine alone and in combination with L-NAME (a non-selective NO synthase inhibitor on the coronary flow and oxidative stress markers in isolated rat hearts. The experimental study was performed on hearts isolated from Wistar albino rats (n=12, male, 8 weeks old, body mass of 180-200 g. Retrograde perfusion of the isolated preparations was performed using a modified method according to the Langendorff technique with a gradual increase in the perfusion pressure (40–120 cmH2O. The following values were measured in the collected coronary effluents: coronary flow, released nitrites (NO production marker, superoxide anion radical and the index of lipid peroxidation (measured as thiobarbiturate reactive substances. The experimental protocol was performed under controlled conditions, followed by the administration of L-arginine alone (1 mmol and L-arginine (1 mmol + L-NAME (30 μmol. The results indicated that L-arginine did not significantly increase the coronary flow or the release of NO, TBARS and the superoxide anion radical. These effects were partially blocked by the joint administration of L-arginine + L-NAME, which indicated their competitive effect. Hence, the results of our study do not demonstrate significant effects of L-arginine administration on the coronary flow and oxidative stress markers in isolated rat hearts.

  7. Embryo Development and Post-Hatch Performances of Kampung Chicken by in Ovo Feeding of L-Arginine

    Directory of Open Access Journals (Sweden)

    M. Azhar

    2016-12-01

    Full Text Available The research was conducted to evaluate embryo development, post-hatch performances, and growth rate of kampung chicken treated in-ovo feeding of L-Arginine. A total of 135 kampung chicken fertile eggs (weight 42-43 g were used and divided into 5 treatment groups of three replications. They were placed in the semi-automatic incubator. The first group was without in-ovo feeding (negative control; the second group was in-ovo feeding of saline 0.9% (positive control; the 3, 4, and 5 groups were in-ovo feeding of 0.5, 1.0, and 1.5% L-Arginine, respectively. In-ovo feeding of L-Arginine were injected into albumen on day 10 of incubation period using automatic syringe in the narrow end side of egg by inserting needle through a small hole at 10 mm depth. After hatching, all day old chicks were placed in floor pens (1 x 0.5 x 0.5 m accordance with the previous egg groups. The results showed that in-ovo feeding of L-Arginine increased weight and circumference of the embryo, but did not affect the length of embryo. In-ovo feeding of L-Arginine resulted in a higher body weight gain and a lower feed conversion even though feed intake was not significantly different compared to the control groups. The growth rate performance up to 6 weeks rearing increased significantly by increasing L-Arginine administration to 1.0%. It can be concluded that embryo development and post-hatch performances of kampung chicken were markedly increased by in-ovo feeding of L-arginine.

  8. Unidirectional growth and characterization of L-arginine monohydrochloride monohydrate single crystals

    International Nuclear Information System (INIS)

    Sangeetha, K.; Babu, R. Ramesh; Bhagavannarayana, G.; Ramamurthi, K.

    2011-01-01

    Highlights: → L-Arginine monohydrochloride monohydrate (LAHCl) single crystal was grown successfully by unidirectional solution growth method for the first time. → High crystalline perfection was observed for UDS grown crystal compared to CS grown crystal. → The optical transparency and mechanical stability are high for UDS grown LAHCl single crystal. → Optical birefringence measurement on this material. → The piezoelectric resonance frequencies observation - first time observation on this material. - Abstract: L-Arginine monohydrochloride monohydrate (LAHCl) single crystals were grown successfully by conventional and unidirectional solution growth methods. The crystalline perfection of grown crystals was analyzed by high-resolution X-ray diffraction. The linear optical transmittance, mechanical stability of conventional and unidirectional grown LAHCl single crystals were analyzed and compared along (0 0 1) plane. The refractive index and birefringence of LAHCl single crystals were also measured using He-Ne laser source. From the dielectric studies, piezoelectric resonance frequencies were observed in kHz frequency range for both conventional and unidirectional grown LAHCl single crystals along (0 0 1) plane.

  9. Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation.

    Science.gov (United States)

    Xu, Meijuan; Qin, Jingru; Rao, Zhiming; You, Hengyi; Zhang, Xian; Yang, Taowei; Wang, Xiaoyuan; Xu, Zhenghong

    2016-01-19

    Corynebacterium crenatum SYPA 5 is the industrial strain for L-arginine production. Poly-β-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and L-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the L-arginine biosynthesis in C. crenatum SYPA 5. C. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of L-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L L-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key L-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9-3.0 times compared with the parent strain. Accumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time L-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular L-arginine

  10. Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

    Science.gov (United States)

    Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

    2017-02-01

    Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

  11. Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects

    Directory of Open Access Journals (Sweden)

    Beverly Giam

    2016-06-01

    Full Text Available Obesity related hypertension is a major risk factor for resistant hypertension. We do not completely understand the mechanism(s underlying the development of obesity related hypertension which hinders the development of novel treatment strategies for this condition. Data from experimental studies and small clinical trials indicate that transport of l-arginine, the substrate for nitric oxide (NO, and subsequent NO production are reduced in obesity induced hypertension. Reduced NO bioavailability can induce hypertension via multiple mechanisms. Mirmiran et al. recently analyzed data from a large population study and found that the association between dietary l-arginine and serum nitrate and nitrite was weakened in obese hypertensive subjects compared to obese normotensives. These data suggest that l-arginine dependent NO production is impaired in the former group compared to the latter which may represent a novel mechanism contributing to hypertension in the setting of obesity.

  12. L-arginine and L-NMMA for Assessing Cerebral Endothelial Dysfunction in Ischemic Cerebrovascular Disease: A Systematic Review

    DEFF Research Database (Denmark)

    Karlsson, William Kristian; Sørensen, Caspar Godthaab; Kruuse, Christina

    2017-01-01

    Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease....

  13. l-Arginine induces antioxidant response to prevent oxidative stress via stimulation of glutathione synthesis and activation of Nrf2 pathway.

    Science.gov (United States)

    Liang, Mingcai; Wang, Zhengxuan; Li, Hui; Cai, Liang; Pan, Jianghao; He, Hongjuan; Wu, Qiong; Tang, Yinzhao; Ma, Jiapei; Yang, Lin

    2018-05-01

    Arginine is a conditionally essential amino acid. To elucidate the influence of l-arginine on the activation of endogenous antioxidant defence, male Wistar rats were orally administered daily with l-arginine at different levels of 25, 50, 100 mg/100 g body weight. After 7 and 14 days feeding, the antioxidative capacities and glutathione (GSH) contents in the plasma and in the liver were uniformly enhanced with the increasing consumption of l-arginine, whereas the oxidative stress was effectively suppressed by l-arginine treatment. After 14 days feeding, the mRNA levels and protein expressions of Keap1 and Cul3 were gradually reduced by increasing l-arginine intake, resulting that the nuclear factor Nrf2 was activated. Upon activation of Nrf2, the expressions of antioxidant responsive element (ARE)-dependent genes and proteins (GCLC, GCLM, GS, GR, GST, GPx, CAT, SOD, NQO1, HO-1) were up-regulated by l-arginine feeding, indicating an upward trend in antioxidant capacity uniformly with the increasing consumption of l-arginine. The present study demonstrates that the supplementation of l-arginine stimulates GSH synthesis and activates Nrf2 pathway, leading to the up-regulation of ARE-driven antioxidant expressions via Nrf2-Keap1 pathway. Results suggest the availability of l-arginine is a critical factor to suppress oxidative stress and induce an endogenous antioxidant response. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.

    Science.gov (United States)

    Jankovic, Aleksandra; Ferreri, Carla; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Stancic, Ana; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2016-11-01

    Setting the correct ratio of superoxide anion (O 2 •- ) and nitric oxide ( • NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of • NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l  -1 ) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.

  15. Inhibition of nitric oxide synthesis by systemic N(G)-monomethyl-L-arginine administration in humans

    DEFF Research Database (Denmark)

    Frandsen, U; Bangsbo, J; Langberg, Henning

    2000-01-01

    (controls) and with prior N(G)-nitro-L-arginine methyl ester (L-NAME) infusion (4 mg/kg, intravenously). Samples from the interstitial fluid were obtained at rest, during exercise and after exercise with the microdialysis technique. Interstitial adenosine in controls increased (p0.05) to controls. The 6......-keto-prostaglandin F1alpha concentration in controls was 1.17+/-0.20 ng/ml at rest and increased (p0.05) in L-NAME. The interstitial K(+) concentration in controls increased (p......We examined whether the formation or the release of the vasodilators adenosine, prostacyclin (PGI(2)) and potassium (K(+)) increase in skeletal muscle interstitium in response to nitric oxide synthase (NOS) inhibition. Five subjects performed one-legged knee extensor exercise at 30 W without...

  16. L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Madsen, Andreas Nygaard; Smajilovic, Sanela

    2012-01-01

    L: -Arginine (L: -Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with L: -Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity....... However, the effects of L: -Arg on glucose homeostasis, body composition and energy metabolism remain unclear. In addition, no studies have, to our knowledge, examined whether L: -Arg has beneficial effects as a dietary supplement in the mouse model. In the present study, we investigated the effects of L...... groups. Glucose homeostasis experiments revealed a major effect of L: -Arg supplementation on glucose tolerance and insulin sensitivity, interestingly, independent of a parallel regulation in whole-body adiposity. Increased L: -Arg ingestion also raised energy expenditure; however, no concurrent effect...

  17. Effect of psychological stress on the L-arginine-nitric oxide pathway and semen quality

    Directory of Open Access Journals (Sweden)

    S. Eskiocak

    2006-05-01

    Full Text Available It has been reported that mental stress causes abnormality of spermiogram parameters. We investigated the effect of psychological stress on the L-arginine-nitric oxide (NO pathway. Semen samples were collected from 29 healthy fourth semester medical students just before (stress and 3 months after (non-stress the final examinations. Psychological stress was measured by the State Anxiety Inventory questionnaire. After standard semen analysis, arginase activity and NO concentration were measured spectrophotometrically in the seminal plasma. Measurements were made in duplicate. During the stress period, sperm concentration (41.28 ± 3.70 vs 77.62 ± 7.13 x 10(6/mL, rapid progressive motility of spermatozoa (8.79 ± 1.66 vs 20.86 ± 1.63% and seminal plasma arginase activity (0.12 ± 0.01 vs 0.22 ± 0.01 U/mL were significantly lower than in the non-stress situation, whereas seminal plasma NO (17.28 ± 0.56 vs 10.02 ± 0.49 µmol/L was higher compared to the non-stress period (P < 0.001 for all. During stress there was a negative correlation between NO concentration and sperm concentration, the percentage of rapid progressive motility and arginase activity (r = -0.622, P < 0.01; r = -0.425, P < 0.05 and r = -0.445, P < 0.05, respectively. These results indicate that psychological stress causes an increase of NO level and a decrease of arginase activity in the L-arginine-NO pathway. Furthermore, poor sperm quality may be due to excessive production of NO under psychological stress. In the light of these results, we suggest that the arginine-NO pathway, together with arginase and NO synthase, are involved in semen quality under stress conditions.

  18. Morphine hyposensitivity in streptozotocin-diabetic rats: Reversal by dietary l-arginine treatment.

    Science.gov (United States)

    Lotfipour, Shahrdad; Smith, Maree T

    2018-01-01

    Painful diabetic neuropathy (PDN) is a long-term complication of diabetes. Defining symptoms include mechanical allodynia (pain due to light pressure or touch) and morphine hyposensitivity. In our previous work using the streptozotocin (STZ)-diabetic rat model of PDN, morphine hyposensitivity developed in a temporal manner with efficacy abolished at 3 months post-STZ and maintained for 6 months post-STZ. As this time course mimicked that for the temporal development of hyposensitivity to the pain-relieving effects of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde) in STZ-diabetic rats, we hypothesized that progressive depletion of endogenous NO bioactivity may underpin the temporal loss of morphine sensitivity in STZ-diabetic rats. Furthermore, we hypothesized that replenishment of NO bioactivity may restore morphine sensitivity in these animals. Diabetes was induced in male Dark Agouti rats by intravenous injection of STZ (85 mg/kg). Diabetes was confirmed on day 7 if blood glucose concentrations were ≥15 mmol/L. Mechanical allodynia was fully developed in the bilateral hindpaws by 3 weeks of STZ-diabetes in rats and this was maintained for the study duration. Morphine hyposensitivity developed in a temporal manner with efficacy abolished by 3 months post-STZ. Administration of dietary l-arginine (NO precursor) at 1 g/d to STZ-diabetic rats according to a 15-week prevention protocol initiated at 9 weeks post-STZ prevented abolition of morphine efficacy. When given as an 8-week intervention protocol in rats where morphine efficacy was abolished, dietary l-arginine at 1 g/d progressively rescued morphine efficacy and potency. Our findings implicate NO depletion in the development of morphine hyposensitivity in STZ-diabetic rats. © 2017 John Wiley & Sons Australia, Ltd.

  19. Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L-Arginine

    Directory of Open Access Journals (Sweden)

    Sonia Alves Gouvea

    2014-01-01

    Full Text Available The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM, 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg, denervated normotensive (DN rats, denervated 2K1C (2K1C + DN rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP (from 106 ± 3 to 183 ± 5.8 mmHg, P<0.01, whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation.

  20. Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats

    Science.gov (United States)

    Nagahama, Kenji; Nishio, Hikaru; Yamato, Masanori; Takeuchi, Koji

    2012-01-01

    Summary Background Reflux esophagitis is caused mainly by excessive exposure of the mucosa to gastric contents. In the present study, we examined the effect of several amino acids on acid reflux esophagitis in rats. Material/Methods After 18 h of fasting, acid reflux esophagitis was induced by ligating both the pylorus and the transitional region between the forestomach and the corpus under ether anesthesia, and the animals were killed 4 h later. The severity of esophagitis was reduced by the oral administration of omeprazole, a proton pump inhibitor, or pepstatin, a specific pepsin inhibitor. Results The development of esophageal lesions was dose-dependently prevented by L-arginine and glycine, given intragastrically (i.g.) after the ligation, with complete inhibition obtained at 250 mg/kg and 750 mg/kg, respectively, and these effects were not influenced by the prior s.c. administration of indomethacin or L-NAME. By contrast, both L-alanine and L-glutamine given i.g. after the ligation aggravated these lesions in a dose-dependent manner. These amino acids had no effect on acid secretion but increased the pH of the gastric contents to 1.8~2.3 due to their buffering action. Conclusions The results confirmed an essential role for acid and pepsin in the pathogenesis of acid reflux esophagitis in the rat model and further suggested that various amino acids affect the severity of esophagitis in different ways, due to yet unidentified mechanisms; L-alanine and L-glutamine exert a deleterious effect on the esophagitis, while L-arginine and glycine are highly protective, independent of endogenous prostaglandins and nitric oxide. PMID:22207112

  1. [L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

    Science.gov (United States)

    Kopyl'chuk, G P; Buchkovskaia, I M

    2014-01-01

    The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

  2. l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis

    Directory of Open Access Journals (Sweden)

    Abhishek Mandal

    2017-07-01

    Full Text Available The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL, depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important

  3. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    Science.gov (United States)

    Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

    2017-01-01

    A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

  4. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Kuender D. Yang

    2017-04-01

    Full Text Available A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

  5. Solvation thermodynamics

    CERN Document Server

    Ben-Naim, Arieh

    1987-01-01

    This book deals with a subject that has been studied since the beginning of physical chemistry. Despite the thousands of articles and scores of books devoted to solvation thermodynamics, I feel that some fundamen­ tal and well-established concepts underlying the traditional approach to this subject are not satisfactory and need revision. The main reason for this need is that solvation thermodynamics has traditionally been treated in the context of classical (macroscopic) ther­ modynamics alone. However, solvation is inherently a molecular pro­ cess, dependent upon local rather than macroscopic properties of the system. Therefore, the starting point should be based on statistical mechanical methods. For many years it has been believed that certain thermodynamic quantities, such as the standard free energy (or enthalpy or entropy) of solution, may be used as measures of the corresponding functions of solvation of a given solute in a given solvent. I first challenged this notion in a paper published in 1978 b...

  6. L-Homoarginine and L-arginine are antagonistically related to blood pressure in an elderly population: the Hoorn study

    NARCIS (Netherlands)

    van der Zwan, L.P.; Davids, M.; Scheffer, P.G.; Dekker, J.M.; Stehouwer, C.D.A.; Teerlink, T.

    2013-01-01

    Objectives: Production of nitric oxide by the vascular endothelium is crucial for the maintenance of vascular tone, an important determinant of blood pressure. L-Arginine and its homolog L-homoarginine are competitive substrates of nitric oxide synthase (NOS), whereas asymmetric dimethylarginine

  7. Comparison of the effect of topical versus systemic L-arginine on wound healing in acute incisional diabetic rat model

    Directory of Open Access Journals (Sweden)

    Alireza Zandifar

    2015-01-01

    Full Text Available Background: Diabetes is associated with endothelial dysfunction and impaired wound healing. The amino acid L-arginine is the only substrate for nitric oxide (NO synthesis. The purpose of this study was to compare the topical versus systemic L-arginine treatment on total nitrite (NO x and vascular endothelial growth factor (VEGF concentrations in wound fluid and rate of wound healing in an acute incisional diabetic wound model. Materials and Methods: A total of 56 Sprague-Dawley rats were used of which 32 were rendered diabetic. Animals underwent a dorsal skin incision. Dm-sys-arg group (N = 8, diabetic and Norm-sys-arg group (N = 8, normoglycemic were gavaged with L-arginine. Dm-sys-control group (N = 8, diabetic and Norm-sys-control group (N = 8, normoglycemic were gavaged with water. Dm-top-arg group (N = 8, diabetic and norm-top-arg group (N = 8, normoglycemic received topical L-arginine gel. Dm-top-control group (N = 8, diabetic received gel vehicle. On the day 5 the amount of NO x in wound fluid was measured by Griess reaction. VEGF/total protein in wound fluids was also measured on day 5 using enzyme-linked immunosorbent assay. All wound tissue specimens were fixed and stained to be evaluated for rate of healing. Data were analyzed using SPSS software (version 18.0, Chicago, IL, USA through One-way analysis of variance test and Tukey′s post-hoc. Results: In dm-sys-arg group, the level of NO x on day 5 was significantly more than dm-top-arg group (P < 0.05. VEGF content in L-arginine treated groups were significantly more than controls (P < 0.05. Rate of diabetic wound healing in dm-sys-arg group was significantly more than dm-top-arg group. Conclusion: Systemic L-arginine is more efficient than topical L-arginine in wound healing. This process is mediated at least in part, by increasing VEGF and NO in the wound fluid.

  8. [Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris].

    Science.gov (United States)

    Sozykin, A V; Noeva, E A; Balakhonova, T V; Pogorelova, O A; Men'shikov, M Iu

    2000-01-01

    Examination of the action of donor NO (L-arginine) on platelet aggregation, endothelial function and exercise tolerance in patients with stable angina of effort (SAE). 42 patients with SAE (functional class I-II) and 10 healthy volunteers (control group) were assigned to two groups. 22 patients of group 1 were randomized to cross-over. They received cardiket (60 mg/day for 10 days or cardiket (60 mg/day) in combination with L-arginine (15 g/day for 10 days). 20 SAE patients of group 2 and control group received L-arginine (15 g/day for 10 days). In each group blood lipids were examined, and bicycle exercise test (BET) was performed. In addition, platelet aggregation and endothelial function were studied in group 2 and control group before and after the course of L-arginine. Compared to control group, endothelial function significantly improved in group 2 (from 5.0 +/- 2.9 to 7.8 +/- 4.1% vs 7.1 +/- 1.9 to 6.6 +/- 4.8%) (M +/- SD). BET duration increased in all the patients. After ADP addition in concentrations 1.5, 2.0, and 5.0 micromol/l platelet aggregation declined in 17 patients except 3 in whom the aggregation remained unchanged. Positive effect of L-arginine on endothelial function, exercise tolerance and platelet aggregation was observed in patients with stable angina of effort (functional class I-II). Therefore, arginine can be recommended as an adjuvant in the treatment of patients with ischemic heart disease.

  9. N-carbamylglutamate and L-arginine improved maternal and placental development in underfed ewes.

    Science.gov (United States)

    Zhang, Hao; Sun, Lingwei; Wang, Ziyu; Deng, Mingtian; Nie, Haitao; Zhang, Guomin; Ma, Tiewei; Wang, Feng

    2016-06-01

    The objectives of this study were to determine how dietary supplementation of N-carbamylglutamate (NCG) and rumen-protected L-arginine (RP-Arg) in nutrient-restricted pregnant Hu sheep would affect (1) maternal endocrine status; (2) maternal, fetal, and placental antioxidation capability; and (3) placental development. From day 35 to day 110 of gestation, 32 Hu ewes carrying twin fetuses were allocated randomly into four groups: 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations, 50% of NRC recommendations supplemented with 20g/day RP-Arg, and 50% of NRC recommendations supplemented with 5g/day NCG product. The results showed that in maternal and fetal plasma and placentomes, the activities of total antioxidant capacity and superoxide dismutase were increased (Pewes. The mRNA expression of vascular endothelial growth factor and Fms-like tyrosine kinase 1 was increased (Pewes than in 100% NRC ewes, and had no effect (P>0.05) in both NCG- and RP-Arg-treated underfed ewes. A supplement of RP-Arg and NCG reduced (Pewes. These results indicate that dietary supplementation of NCG and RP-Arg in underfed ewes could influence maternal endocrine status, improve the maternal-fetal-placental antioxidation capability, and promote fetal and placental development during early-to-late gestation. © 2016 Society for Reproduction and Fertility.

  10. Antagonism by hemoglobin of effects induced by L-arginine in neuromuscular preparations from rats

    Directory of Open Access Journals (Sweden)

    C.R. Ambiel

    2001-04-01

    Full Text Available Nitric oxide (NO-synthase is present in diaphragm, phrenic nerve and vascular smooth muscle. It has been shown that the NO precursor L-arginine (L-Arg at the presynaptic level increases the amplitude of muscular contraction (AMC and induces tetanic fade when the muscle is indirectly stimulated at low and high frequencies, respectively. However, the precursor in muscle reduces AMC and maximal tetanic fade when the preparations are stimulated directly. In the present study the importance of NO synthesized in different tissues for the L-Arg-induced neuromuscular effects was investigated. Hemoglobin (50 nM did not produce any neuromuscular effect, but antagonized the increase in AMC and tetanic fade induced by L-Arg (9.4 mM in rat phrenic nerve-diaphragm preparations. D-Arg (9.4 mM did not produce any effect when preparations were stimulated indirectly at low or high frequency. Hemoglobin did not inhibit the decrease of AMC or the reduction in maximal tetanic tension induced by L-Arg in preparations previously paralyzed with d-tubocurarine and directly stimulated. Since only the presynaptic effects induced by L-Arg were antagonized by hemoglobin, the present results suggest that NO synthesized in muscle acts on nerve and skeletal muscle. Nevertheless, NO produced in nerve and vascular smooth muscle does not seem to act on skeletal muscle.

  11. Antiviral and Virucidal Activities of N-Cocoyl-L-Arginine Ethyl Ester

    Directory of Open Access Journals (Sweden)

    Hisashi Yamasaki

    2011-01-01

    Full Text Available Various amino acid-derived compounds, for example, Nα-Cocoyl-L-arginine ethyl ester (CAE, alkyloxyhydroxylpropylarginine, arginine cocoate, and cocoyl glycine potassium salt (Amilite, were examined for their virucidal activities against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, influenza A virus (IAV, and poliovirus type 1 (PV-1 in comparison to benzalkonium chloride (BKC and sodium dodecylsulfate (SDS as a cationic and anionic control detergent and also to other commercially available disinfectants. While these amino acid-derived compounds were all effective against HSV-1 and HSV-2, CAE and Amilite were the most effective. These two compounds were, however, not as effective against IAV, another enveloped virus, as against HSV. Cytotoxicity of CAE was weak; at 0.012%, only 5% of the cells were killed under the conditions, in which 100% cells were killed by either SDS or BKC. In addition to these direct virucidal effects, CAE inhibited the virus growth in the HSV-1- or PV-1-infected cells even at 0.01%. These results suggest a potential application of CAE as a therapeutic or preventive medicine against HSV superficial infection at body surface.

  12. Evidence that L-Arginine inhibits glycation of human serum albumin (HSA) in vitro

    International Nuclear Information System (INIS)

    Servetnick, D.A.; Wiesenfeld, P.L.; Szepesi, B.

    1990-01-01

    Previous work by Brownlee has shown that glycation of bovine serum albumin can be reduced in the presence of aminoguanidine (AG). Presumably, the guanidinium group on AG interferes with further rearrangement of amadori products to advanced glycosylated end products (AGE). Since L-arginine (ARG) also contains a guanidinium group, its ability to inhibit the formation of AGE products was investigated. HSA was incubated at 37 degrees C in the presence or absence of glucose; with glucose and fructose; or with sugars in the presence or absence of ARG or AG. A tracer amount of U- 14 C-glucose was added to each tube containing sugars. Protein bound glucose was separated from unreacted glucose by gel filtration. Radioactivity, total protein, fluorescence, and glucose concentration were measured. Preliminary data show enhanced binding of 14 C-glucose to HSA with fructose at all time points. A 30-40% decrease in 14 C-glucose incorporation was observed when ARG or AG as present. ARG and AG were equally effective in inhibiting incorporation of 14 C-glucose. FPLC analysis is in progress to determine the type and degree of HSA crosslinking during the 2 week incubation period

  13. Formation and enzymatic degradation of poly-l-arginine/fucoidan multilayer films.

    Science.gov (United States)

    Webber, Jessie L; Benbow, Natalie L; Krasowska, Marta; Beattie, David A

    2017-11-01

    A polyelectrolyte multilayer (PEM) system based on biopolymers has been constructed and studied in its formation and enzymatic breakdown. The multilayer is composed of fucoidan (a proven antimicrobial/anti-inflammatory seaweed-based polysaccharide) and poly-l-arginine (a polypeptide that can be readily degraded with trypsin to yield arginine, a known NO donor), thus making the multilayer a potential dual action surface treatment for wound dressings. Studies on the formation of the multilayer revealed that the film built-up in the expected stepwise manner with consistent reversal of the zeta potential upon the adsorption of each subsequent polyion. The completed film (8 bilayers) was seen to have low hydration (30% water), as determined by H 2 O/D 2 O solvent replacement studies using the quartz crystal microbalance, with an adsorbed mass (without hydration water) of approx. 4.8μgcm -2 , as determined by quantitative attenuated total reflectance Fourier transform infrared (ATR FTIR) spectroscopy. The enzymatic breakdown of the film in response to exposure to trypsin was also investigated, and the film was seen to release both polymers over time, with a projected complete film removal period of approximately 24h. Critically, this information was determined using ATR FTIR spectroscopy experiments, which allowed unambiguous deconvolution of the removal rates of the two polyions, which is information that cannot be obtained from other methodologies used to study enzymatic breakdown of surface films. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Effects of L-arginine on anatomical and electrophysiological deterioration of the eye in a rodent model of nonarteritic ischemic optic neuropathy.

    Science.gov (United States)

    Chuman, Hideki; Maekubo, Tomoyuki; Osako, Takako; Ishiai, Michitaka; Kawano, Naoko; Nao-I, Nobuhisa

    2013-07-01

    The aims of this study were to clarify the effectiveness of L-arginine (1) for reducing the severity of anatomical changes in the eye and improving visual function in the acute stage of a rodent model of nonarteritic ischemic optic neuropathy (rNAION) and (2) in preventing those changes in anatomy and visual function. For the first aim, L-arginine was intravenously injected into rats 3 h after rNAION induction; for the second aim, rNAION was induced after the oral administration of L-arginine for 7 days. The inner retinal thickness was determined over time by optical coherence tomography, and the amplitude of the scotopic threshold response (STR) and the number of surviving retinal ganglion cells (RGCs) were measured. These data were compared with the baseline data from the control group. Both intravenous infusion of L-arginine after rNAION induction and oral pretreatment with L-arginine significantly decreased optic disc edema in the acute stage and thinning of the inner retina, reduced the decrease in STR amplitude, and reduced the decrease in the number of RGCs during rNAION. Based on these results, we conclude that L-arginine treatment is effective for reducing anatomical changes in the eye and improving visual function in the acute stage of rNAION and that pretreatment with L-arginine is an effective therapy to reduce the severity of the condition during recurrence in the other eye.

  15. Effect of Hydroxylamine Sulfate on Volumetric Behavior of Glycine, L-Alanine, and L-Arginine in Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Jie Chen

    2013-01-01

    Full Text Available The apparent molar volumes of glycine, L-alanine, and L-arginine in aqueous hydroxylamine sulfate solutions have been determined at T=298.15 K and atmospheric pressure. The standard partial molar volumes, V20, corresponding partial molar volumes of transfer, ΔtrV20, and hydration numbers, NH, have been calculated for these α-amino acids from the experimental data. The ΔtrV20 values are positive for glycine, L-alanine, and L-arginine and are all increased with the increase in the concentration of hydroxylamine ions. These parameters obtained from the volumetric data are interpreted in terms of various mixing effects between amino acids and hydroxylamine sulfate in aqueous solutions.

  16. Antioxidant Activity of Syringic Acid Prevents Oxidative Stress in l-arginine-Induced Acute Pancreatitis: An Experimental Study on Rats.

    Science.gov (United States)

    Cikman, Oztekin; Soylemez, Omer; Ozkan, Omer Faruk; Kiraz, Hasan Ali; Sayar, Ilyas; Ademoglu, Serkan; Taysi, Seyithan; Karaayvaz, Muammer

    2015-05-01

    The aim of this study was to investigate the possible protective role of antioxidant treatment with syringic acid (SA) on l-arginine-induced acute pancreatitis (AP) using biochemical and histopathologic approaches. A total of 30 rats were divided into 3 groups. The control group received normal saline intraperitoneally. The AP group was induced by 3.2 g/kg body weight l-arginine intraperitoneally, administered twice with an interval of 1 hour between administrations. The AP plus SA group, after having AP induced by 3.2 g/kg body weight l-arginine, was given SA (50 mg kg(-1)) in 2 parts within 24 hours. The rats were killed, and pancreatic tissue was removed and used in biochemical and histopathologic examinations. Compared with the control group, the mean pancreatic tissue total oxidant status level, oxidative stress index, and lipid hydroperoxide levels were significantly increased in the AP group, being 30.97 ± 7.13 (P < 0.05), 1.76 ± 0.34 (P < 0.0001), and 19.18 ± 4.91 (P < 0.01), respectively. However, mean total antioxidant status and sulfhydryl group levels were significantly decreased in the AP group compared with the control group, being 1.765 ± 0.21 (P < 0.0001) and 0.21 ± 0.04 (P < 0.0001), respectively. SA reduces oxidative stress markers and has antioxidant effects. It also augments antioxidant capacity in l-arginine-induced acute toxicity of pancreas in rats.

  17. The crucial role of L-arginine in macrophage activation: What you need to know about it

    Czech Academy of Sciences Publication Activity Database

    Pekarová, Michaela; Lojek, Antonín

    2015-01-01

    Roč. 137, SEP2015 (2015), s. 44-48 ISSN 0024-3205 R&D Projects: GA ČR GP13-40882P; GA MŠk(CZ) EE2.3.30.0030 Institutional support: RVO:68081707 Keywords : L-Arginine * Macrophage s * G-protein-coupled receptor Subject RIV: BO - Biophysics Impact factor: 2.685, year: 2015

  18. Bi-enzyme L-arginine-selective amperometric biosensor based on ammonium-sensing polyaniline-modified electrode.

    Science.gov (United States)

    Stasyuk, Nataliya; Smutok, Oleh; Gayda, Galina; Vus, Bohdan; Koval'chuk, Yevgen; Gonchar, Mykhailo

    2012-01-01

    A novel L-arginine-selective amperometric bi-enzyme biosensor based on recombinant human arginase I isolated from the gene-engineered strain of methylotrophic yeast Hansenula polymorpha and commercial urease is described. The biosensing layer was placed onto a polyaniline-Nafion composite platinum electrode and covered with a calcium alginate gel. The developed sensor revealed a good selectivity to L-arginine. The sensitivity of the biosensor was 110 ± 1.3 nA/(mM mm(2)) with the apparent Michaelis-Menten constant (K(M)(app)) derived from an L-arginine (L-Arg) calibration curve of 1.27 ± 0.29 mM. A linear concentration range was observed from 0.07 to 0.6mM, a limit of detection being 0.038 mM and a response time - 10s. The developed biosensor demonstrated good storage stability. A laboratory prototype of the proposed amperometric biosensor was applied to the samples of three commercial pharmaceuticals ("Tivortin", "Cytrarginine", "Aminoplazmal 10% E") for L-Arg testing. The obtained L-Arg-content values correlated well with those declared by producers. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Effect of L-arginine dietary supplementation on salivary urea concentration and pH in physically active individuals.

    Science.gov (United States)

    Vuletic, L; Spalj, S; Rogic, D; Ruzic, L; Alajbeg, I

    2013-12-01

    The aim of this study was to assess if the consumption of 3 g of a commercially available L-arginine dietary supplement causes a postabsorptive rise in urea concentration or pH of unstimulated saliva in a group of physically active individuals. Salivary urea and pH were determined for 117 participants in a randomized double-blinded placebo-controlled study. Samples were collected by 'spitting' method in fasting conditions. One hour prior to their second visit, participants consumed three tablets of L-arginine or placebo. Urea concentration was significantly lower at second measurement for both the study and control group. The magnitude of the change was not significant between the groups. pH was higher for both groups at second measurement, but only significant for the study group. The magnitude of the change was significant between the groups. Participants who intermittently ingested protein dietary supplements and those with a Body Mass Index (BMI) higher than 25 had significantly higher basal urea concentration. The results of this study did not confirm the hypothesis. Further studies are needed to determine the effects of different doses of L-arginine supplements on the biochemical composition of saliva and the influence of their long-term consumption on the risk of developing dental diseases. © 2013 Australian Dental Association.

  20. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    Science.gov (United States)

    Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

    2013-04-01

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-α, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  1. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Faddah, L. M.; Baky, Nayira A. Abdel [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia); Mohamed, Azza M., E-mail: azzamohamed99@yahoo.com [King Abdulaziz University, Biochemistry Department, Faculty of Science for Girls (Saudi Arabia); Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M. [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia)

    2013-04-15

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-{alpha}, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  2. Protective effect of L-carnitine and L-arginine against busulfan-induced oligospermia in adult rat.

    Science.gov (United States)

    Abd-Elrazek, A M; Ahmed-Farid, O A H

    2018-02-01

    Busulfan is an anticancer drug caused variety of adverse effects for patients with cancer. But it could cause damage to the male reproductive system as one of its adverse effects. This study aimed to investigate the protective effect of L-carnitine and L-arginine on semen quality, oxidative stress parameters and testes cell energy after busulfan treatment. Adult male rats were divided into four groups: control (Con), busulfan (Bus), busulfan plus L-arginine (Bus + L-arg) and busulfan plus L-carnitine (Bus + L-car). After 28 days, the semen was collected from the epididymis and the testes were assessed. Sperm count, motility and velocity were measured by CASA, and smears were prepared for assessment of sperm morphology. Serum and testes supernatants were separated for DNA metabolites, oxidative stress and cell energy parameters. Testes tissues also subjected for caspase-3. The results showed significant improvement in sperm morphology, motility, velocity and count in the groups treated with L-arginine and L-carnitine and accompanied with an increase in MDA, GSSG and ATP, reduction in GSH, AMP, ADP, NO and 8-OHDG also recorded. These results are supported by caspase-3. Administration of L-arg and L-car attenuated the cytotoxic effects of busulfan by improving semen parameters, reducing oxidative stress and maintaining cell energy. © 2017 Blackwell Verlag GmbH.

  3. L-arginine supplementation improves responses to injury and inflammation in dextran sulfate sodium colitis.

    Directory of Open Access Journals (Sweden)

    Lori A Coburn

    Full Text Available Inflammatory bowel disease (IBD, consisting of Crohn's disease and ulcerative colitis (UC, results in substantial morbidity and is difficult to treat. New strategies for adjunct therapies are needed. One candidate is the semi-essential amino acid, L-arginine (L-Arg, a complementary medicine purported to be an enhancer of immunity and vitality in the lay media. Using dextran sulfate sodium (DSS as a murine colonic injury and repair model with similarities to human UC, we assessed the effect of L-Arg, as DSS induced increases in colonic expression of the y(+ cationic amino acid transporter 2 (CAT2 and L-Arg uptake. L-Arg supplementation improved the clinical parameters of survival, body weight loss, and colon weight, and reduced colonic permeability and the number of myeloperoxidase-positive neutrophils in DSS colitis. Luminex-based multi-analyte profiling demonstrated that there was a marked reduction in proinflammatory cytokine and chemokine expression with L-Arg treatment. Genomic analysis by microarray demonstrated that DSS-treated mice supplemented with L-Arg clustered more closely with mice not exposed to DSS than to those receiving DSS alone, and revealed that multiple genes that were upregulated or downregulated with DSS alone exhibited normalization of expression with L-Arg supplementation. Additionally, L-Arg treatment of mice with DSS colitis resulted in increased ex vivo migration of colonic epithelial cells, suggestive of increased capacity for wound repair. Because CAT2 induction was sustained during L-Arg treatment and inducible nitric oxide (NO synthase (iNOS requires uptake of L-Arg for generation of NO, we tested the effect of L-Arg in iNOS(-/- mice and found that its benefits in DSS colitis were eliminated. These preclinical studies indicate that L-Arg supplementation could be a potential therapy for IBD, and that one mechanism of action may be functional enhancement of iNOS activity.

  4. L-Arginine Availability and Metabolism Is Altered in Ulcerative Colitis.

    Science.gov (United States)

    Coburn, Lori A; Horst, Sara N; Allaman, Margaret M; Brown, Caroline T; Williams, Christopher S; Hodges, Mallary E; Druce, Jennifer P; Beaulieu, Dawn B; Schwartz, David A; Wilson, Keith T

    2016-08-01

    L-arginine (L-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. L-Arg is actively transported into cells by means of cationic amino acid transporter (SLC7) proteins. We have linked L-Arg and arginase 1 activity to epithelial restitution. Our aim was to determine if L-Arg, related amino acids, and metabolic enzymes are altered in ulcerative colitis (UC). Serum and colonic tissues were prospectively collected from 38 control subjects and 137 UC patients. Dietary intake, histologic injury, and clinical disease activity were assessed. Amino acid levels were measured by high-performance liquid chromatography. Messenger RNA (mRNA) levels were measured by real-time PCR. Colon tissue samples from 12 Crohn's disease patients were obtained for comparison. Dietary intake of arginine and serum L-Arg levels were not different in UC patients versus control subjects. In active UC, tissue L-Arg was decreased, whereas L-citrulline (L-Cit) and the L-Cit/L-Arg ratio were increased. This pattern was also seen when paired involved (left) versus uninvolved (right) colon tissues in UC were assessed. In active UC, SLC7A2 and ARG1 mRNA levels were decreased, whereas ARG2 and NOS2 were increased. Similar alterations in mRNA expression occurred in tissues from Crohn's disease patients. In involved UC, SLC7A2 and ARG1 mRNA levels were decreased, and NOS2 and ARG2 increased, when compared with uninvolved tissues. Patients with UC exhibit diminished tissue L-Arg, likely attributable to decreased cellular uptake and increased consumption by NOS2. These findings combined with decreased ARG1 expression indicate a pattern of dysregulated L-Arg availability and metabolism in UC.

  5. Thirteen-week oral toxicity study of L-arginine in rats.

    Science.gov (United States)

    Tsubuku, Shoji; Hatayama, Kazuhisa; Mawatari, Kazunori; Smriga, Miro; Kimura, Takeshi

    2004-01-01

    The amino acid L-arginine (Arg) has been used extensively in dietary and pharmacological products. This study evaluated toxicological and behavioral effects of Arg produced by Ajinomoto Co. (Tokyo, Japan) during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w). A control group of rats received only a standard diet. All diets were administered ad libitum for 13 continuous weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week-long recovery, during which only a standard diet was provided. In male and female rats in each concentration group, treatment-related changes were not observed for clinical signs, body weights, diet consumption, ophthalmology, gross pathology, organ weight, or histopathology. An elevated level of plasma glucose was detected in some male rats (5.0%, w/w) during the analysis conducted in the fifth week of administration; however, the degree of the change was within the physiological range, and no changes were observed at the end of the administration period. In the same group, an increase in hemoglobin, together with a tendency toward an increase in the red blood cell counts, was found, but the change was considered toxicologically insignificant. The no-observed-adverse-effect level (NOAEL) for Arg was estimated at 5.0% (w/w) for both genders (males, 3.3 +/- 0.1 g/kg/day; females, 3.9 +/- 0.2 g/kg/day).

  6. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    International Nuclear Information System (INIS)

    Chen, Han; Sun, Yan Ping; Li, Yang; Liu, Wen Wu; Xiang, Hong Gang; Fan, Lie Ying; Sun, Qiang; Xu, Xin Yun; Cai, Jian Mei; Ruan, Can Ping; Su, Ning; Yan, Rong Lin; Sun, Xue Jun; Wang, Qiang

    2010-01-01

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-κB) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-κB activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-κB activation and to promote acinar cell proliferation.

  7. Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.

    Science.gov (United States)

    Scavella, Arnette; Leiva, Lily; Monjure, Hanh; Zea, Arnold H; Gardner, Renee V

    2010-08-01

    L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state. Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg. SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L-Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant. L-Arg levels in steady-state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups. (c) 2010 Wiley-Liss, Inc.

  8. N-hydroxylamine is not an intermediate in the conversion of L-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells.

    Science.gov (United States)

    Pou, S; Pou, W S; Rosen, G M; el-Fakahany, E E

    1991-01-01

    This study evaluates the role of N-hydroxylamine (NH2OH) in activating soluble guanylate cyclase in the mouse neuroblastoma clone N1E-115. It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine. NH2OH caused a time- and concentration-dependent increase in cyclic GMP formation in intact cells. This response was not dependent on Ca2+. In cytosol preparations the activation of guanylate cyclase by L-arginine was dose-dependent and required Ca2+ and NADPH. In contrast, NH2OH itself did not activate cytosolic guanylate cyclase but it inhibited the basal activity of this enzyme in a concentration-dependent manner. The formation of cyclic GMP in the cytosolic fractions in response to NH2OH required the addition of catalase and H2O2. On the other hand, catalase and/or H2O2 lead to a decrease in L-arginine-induced cyclic GMP formation. Furthermore, NH2OH inhibited L-arginine- and sodium nitroprusside-induced cyclic GMP formation in the cytosol. The inhibition of L-arginine-induced cyclic GMP formation in the cytosol by NH2OH was not reversed by the addition of superoxide dismutase. These data strongly suggest that NH2OH is not a putative intermediate in the metabolism of L-arginine to an activator of guanylate cyclase. PMID:1671745

  9. The Effect of L-arginine Supplementation on Blood Pressure in Patients with Type 2 Diabetes: A Double-Blind Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Sara Asadi

    2016-10-01

    Full Text Available Background: The prevalence of hypertension in patients with type 2 diabetes (T2D is approximately twice as much as healthy people. This study was designed to determine the effect of L-arginine supplementation on blood pressure in patients with T2D. Methods: In a double-blind randomized clinical trial, 75 T2D were randomly divided into three groups (3 g/d and 6g/d of L-arginine and placebo for 3 months. Height, weight, waist circumference, dietary intake, and blood pressure (BP were measured before and after intervention. Results: In patients who received 3g/d L-arginine, no significant difference was observed between BP before and after the intervention, however, subgroup analysis among patients with high BP showed significant reduction in systolic (P = 0.036 and diastolic BP (P = 0.027 after L-arginine supplementation. After 3 months of intervention, systolic and diastolic BP were significantly different compared to the baseline values and also with placebo value in patients receiving 6g/d of L-arginine (P < 0.05. Conclusions: The daily intake of 6g of L-arginine for 3 months in T2D may improve BP. Taking 3g/d of this supplement may help to improve BP only in patients with hypertension.

  10. Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung.

    Science.gov (United States)

    Grasemann, C; Herrmann, R; Starschinova, J; Gertsen, M; Palmert, M R; Grasemann, H

    2017-02-20

    Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice. We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring. Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring. These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring.

  11. Effect of rare-earth dopants on the growth and structural, optical, electrical and mechanical properties of L-arginine phosphate single crystals

    International Nuclear Information System (INIS)

    Arjunan, S.; Bhaskaran, A.; Kumar, R. Mohan; Mohan, R.; Jayavel, R.

    2010-01-01

    Research highlights: → Thorium, Lanthanum and Cerium rare-earth ions were doped with L-arginine phosphate material and the crystals were grown by slow evaporation technique. → The transparency of the rare-earth doped LAP crystals has enhanced compared to pure LAP. → The powder SHG measurements revealed that the SHG output of rare-earth doped LAP crystals increases considerably compared to that of LAP. → Vicker's hardness number of as-grown crystal of LAP is higher than that of rare-earth doped LAP crystals. - Abstract: Effect of Thorium, Lanthanum and Cerium rare-earth ions on the growth and properties of L-arginine phosphate single crystals has been reported. The incorporation of rare-earth dopants into the L-arginine phosphate crystals is confirmed by Inductively Coupled Plasma-Mass Spectroscopy analysis. The unit cell parameters for pure and rare-earth doped L-arginine phosphate crystals have been estimated by powder X-ray diffraction studies. UV-visible studies revealed the transmittance percentage and cut-off wavelengths of the grown crystals. Powder second harmonic generation measurement has been carried out for pure and doped L-arginine phosphate crystals. The dielectric behavior of the grown crystals was analyzed for different frequencies at room temperature. The mechanical properties have been determined for pure and the doped L-arginine phosphate crystals.

  12. Effect of rare-earth dopants on the growth and structural, optical, electrical and mechanical properties of L-arginine phosphate single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Arjunan, S., E-mail: arjunan_hce@yahoo.co.i [Department of Physics, Sri Ramachandra University, Porur, Chennai (India); Bhaskaran, A. [Department of Physics, Dr. Ambedkar Government College, Chennai (India); Kumar, R. Mohan; Mohan, R. [Department of Physics, Presidency College, Chennai (India); Jayavel, R. [Crystal Growth Centre, Anna University, Chennai (India)

    2010-09-17

    Research highlights: {yields} Thorium, Lanthanum and Cerium rare-earth ions were doped with L-arginine phosphate material and the crystals were grown by slow evaporation technique. {yields} The transparency of the rare-earth doped LAP crystals has enhanced compared to pure LAP. {yields} The powder SHG measurements revealed that the SHG output of rare-earth doped LAP crystals increases considerably compared to that of LAP. {yields} Vicker's hardness number of as-grown crystal of LAP is higher than that of rare-earth doped LAP crystals. - Abstract: Effect of Thorium, Lanthanum and Cerium rare-earth ions on the growth and properties of L-arginine phosphate single crystals has been reported. The incorporation of rare-earth dopants into the L-arginine phosphate crystals is confirmed by Inductively Coupled Plasma-Mass Spectroscopy analysis. The unit cell parameters for pure and rare-earth doped L-arginine phosphate crystals have been estimated by powder X-ray diffraction studies. UV-visible studies revealed the transmittance percentage and cut-off wavelengths of the grown crystals. Powder second harmonic generation measurement has been carried out for pure and doped L-arginine phosphate crystals. The dielectric behavior of the grown crystals was analyzed for different frequencies at room temperature. The mechanical properties have been determined for pure and the doped L-arginine phosphate crystals.

  13. Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

    Science.gov (United States)

    Reid, Ian A.

    1994-01-01

    Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

  14. The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factor-α therapy in inflammatory arthropathies. Associations with aortic stiffness.

    Science.gov (United States)

    Angel, Kristin; Provan, Sella Aarrestad; Mowinckel, Petter; Seljeflot, Ingebjørg; Kvien, Tore Kristian; Atar, Dan

    2012-11-01

    Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. Forty-eight patients who started with anti-TNF-α therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. Anti-TNF-α therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] μmol/L vs. 0.02 [0.07] μmol/L, P = 0.42, 12 months: 0.01 [0.08] μmol/L vs. 0.01 [0.09] μmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNF-α therapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT. Anti-TNF-α therapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    International Nuclear Information System (INIS)

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj; Selvam, Govindan Sadasivam

    2012-01-01

    Highlights: ► L-Arginine treatment reduced the metabolic disturbances in diabetic animals. ► Antioxidant marker proteins were found high in myocardium by L-arginine treatment. ► Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. ► L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. ► Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg −1 body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-κB. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be

  16. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India); Selvam, Govindan Sadasivam, E-mail: drselvamgsbiochem@rediffmail.com [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India)

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic

  17. Vasopressin and Vasopressin Antagonists in Heart Failure

    DEFF Research Database (Denmark)

    Vishram-Nielsen, Julie K; Gustafsson, Finn

    2017-01-01

    Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels...... by the V2 receptors in the renal collecting tubules. The optimal use of VRAs is yet to be determined, especially in patients with congestive HF. Although long-term effects on improvement in mortality have not been shown in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan...

  18. l-Arginine grafted alginate hydrogel beads: A novel pH-sensitive system for specific protein delivery

    Directory of Open Access Journals (Sweden)

    Mohamed S. Mohy Eldin

    2015-05-01

    Full Text Available Novel pH-sensitive hydrogels based on l-arginine grafted alginate (Arg-g-Alg hydrogel beads were synthesized and utilized as a new carrier for protein delivery (BSA in specific pH media. l-arginine was grafted onto the polysaccharide backbone of virgin alginate via amine functions. Evidences of grafting of alginate were extracted from FT-IR and thermal analysis, while the morphological structure of Arg-g-Alg hydrogel beads was investigated by SEM photographs. Factors affecting on the grafting process e.g. l-arginine concentration, reaction time, reaction temperature, reaction pH, and crosslinking conditions, have been studied. Whereas, grafting efficiency of each factor was evaluated. Grafting of alginate has improved both thermal and morphological properties of Arg-g-Alg hydrogel beads. The swelling behavior of Arg-g-Alg beads was determined as a function of pH and compared with virgin calcium alginate beads. The cumulative in vitro release profiles of BSA loaded beads were studied at different pHs for simulating the physiological environments of the gastrointestinal tract. The amount of BSA released from neat alginate beads at pH 2 was almost 15% after 5 h, while the Arg-g-Alg beads at the same conditions were clearly higher than 45%, then it increased to 90% at pH 7.2. Accordingly, grafting of alginate has improved its release profile behavior particularly in acidic media. The preliminary results clearly suggested that the Arg-g-Alg hydrogel may be a potential candidate for polymeric carrier for oral delivery of protein or drugs.

  19. Renal response to L-arginine in diabetic rats. A possible link between nitric oxide system and aquaporin-2.

    Directory of Open Access Journals (Sweden)

    María C Ortiz

    Full Text Available The aim of this study was to evaluate whether L-Arginine (L-Arg supplementation modifies nitric oxide (NO system and consequently aquaporin-2 (AQP2 expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression.

  20. Insulin-increased L-arginine transport requires A(2A adenosine receptors activation in human umbilical vein endothelium.

    Directory of Open Access Journals (Sweden)

    Enrique Guzmán-Gutiérrez

    Full Text Available Adenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1. This process involves the activation of A(2A adenosine receptors (A(2AAR in human umbilical vein endothelial cells (HUVECs. Insulin increases hCAT-1 activity and expression in HUVECs, and A(2AAR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A(2AAR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37°C in the absence or presence of nitrobenzylthioinosine (NBTI, 10 µmol/L, adenosine transport inhibitor and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR, and SLC7A1 (for hCAT-1 reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent K(m for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1(-1606 or pGL3-hCAT-1(-650 constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1(-1606, and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A(2AAR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes.

  1. Clinical effectiveness of exogenous L-arginine in patients with coronary heart disease after community-acquired pneumonia

    Directory of Open Access Journals (Sweden)

    T. O. Kulynych

    2017-02-01

    Full Text Available Coronary heart disease and community acquired pneumonia associated with a higher risk for morbidity and mortality. The optimization of treatment of comorbid pathology by medicines which modify endothelium functional state is important. Aim: to study effect of exogenous L-arginine on clinical course of disease, markers of systemic inflammation and endothelial dysfunction in patients with coronary heart disease (CHD and community-acquired pneumonia (CAP. Materials and methods. 60 patients with CHD and CAP (the median 72.50 years, range 66.00; 75.00 were included into the study. Patients were randomized in 2 groups: first – 30 patients with basic therapy combined with L-arginine; and second – 30 patients with basic therapy. hs-CRP, neopterin, РАРР-А, NT-proBNP were measured by ELISA-TEST before treatment and 1 month after. Clinical course was assessed during 1 year of follow-up. Results. In the first group the hospitalization rate due to CHD and heart failure decompensation was significantly rare. Biomarkers changes in the 1st group were significant: hs-CRP was significantly decreased by 57.14 % (in the 2nd group – by 28.57 %; neopterin – by 36.57 % (in the 2nd group – by 20.91 %; РАРР-А – by 35.71 % (in the 2nd group – by 4.76 %. There was revealed a significant decreasing of NT-proBNP levels in patients receiving L-arginine by comparing with basic therapy: with the I stage of heart failure (HF – by 50.97 % vs 21.82 %, with the II-A stage of HF – by 43.82 % vs 5.61 % (p < 0.05. After 1 month of therapy patients from the 1st group had significantly lower rates of neopterin – by 16.46 %, and NT-proBNP – by 40.92 % in the subgroup of patients with II-A stage of HF (p < 0.05 compared with patients who received only the basic therapy. Conclusions. Combination of exogenous L-arginine and basic therapy in patients with CHD and CAP was associated with benign clinical course and positive changes of endothelium functional

  2. Where do ions solvate?

    Indian Academy of Sciences (India)

    We study a simple model of ionic solvation inside a water cluster. The cluster is modeled as a spherical dielectric continuum. It is found that unpolarizable ions always prefer the bulk solvation. On the other hand, for polarizable ions, there exists a critical value of polarization above which surface solvation becomes ...

  3. A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(l-arginine)-based nanoparticles.

    Science.gov (United States)

    Kudo, Shinpei; Nagasaki, Yukio

    2015-11-10

    In the immune system, macrophages in tumor tissue generate nitric oxide (NO), producing versatile effects including apoptosis of tumor cells, because inducible NO synthase (iNOS) in the cytoplasm of a macrophage produces NO using l-arginine as a substrate. Here, we propose novel NO-triggered immune therapeutics based on our newly designed nanoparticle system. We designed a poly(ethylene glycol)-block-poly(l-arginine) (i.e., PEG-b-P(l-Arg)) block copolymer and prepared polyion complex micelles (PEG-b-P(l-Arg)/m) composed of PEG-b-P(l-Arg) and chondroitin sulfate for systemic anticancer immunotherapy. iNOS treatment of PEG-b-P(l-Arg) did not generate NO, but NO molecules were detected after trypsin pretreatment, indicating that hydrolysis of P(l-Arg) to monomeric arginine was taking place in vitro. RAW264.7 macrophages abundantly generated NO from the PEG-b-P(l-Arg)/m in comparison with control micelles; this finding is indicative of robustness of the proposed method. It is interesting to note that systemic administration of PEG-b-P(l-Arg)/m had no noticeable adverse effects and suppressed the tumor growth rate in C26 tumor-bearing mice in a dose-dependent manner. Our newly designed nanoparticle-assisted arginine delivery system seems to hold promise as an NO-mediated anticancer immunotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease.

    Science.gov (United States)

    Martens, Christopher R; Kuczmarski, James M; Kim, Jahyun; Guers, John J; Harris, M Brennan; Lennon-Edwards, Shannon; Edwards, David G

    2014-08-15

    Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[(3)H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine. Copyright © 2014 the American Physiological Society.

  5. Effects of L-arginine immobilization on the anticoagulant activity and hemolytic property of polyethylene terephthalate films

    International Nuclear Information System (INIS)

    Liu Yun; Yang Yun; Wu Feng

    2010-01-01

    Surface modification of polyethylene terephthalate (PET) films was performed with L-arginine (L-Arg) to gain an improved anticoagulant surface. The surface chemistry changes of modified films were characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The in vitro anticoagulant activities of the surface-modified PET films were evaluated by blood clotting test, hemolytic test, and the measurement of clotting time including plasma recalcification time (PRT), activated partial thromboplastin time (APTT), and prothrombin time (PT). The data of blood coagulation index (BCI) for L-arginine modified PET films (PET-Arg) was larger than that for PET at the same blood-sample contact time. The hemolysis ratio for PET-Arg was less than that for PET and within the accepted standard for biomaterials. The PRT and APTT for PET-Arg were significantly prolonged by 189 s and 25 s, respectively, compared to those for the unmodified PET. All results suggested that the currently described modification method could be a possible candidate to create antithrombogenic PET surfaces which would be useful for further medical applications.

  6. Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men

    Directory of Open Access Journals (Sweden)

    Wax Benjamin

    2012-04-01

    Full Text Available Abstract Background Dietary supplements containing L-arginine are marketed to improve exercise performance, but the efficacy of such supplements is not clear. Therefore, this study examined the efficacy of acute ingestion of L-arginine alpha-ketoglutarate (AAKG muscular strength and endurance in resistance trained and untrained men. Methods Eight resistance trained and eight untrained healthy males ingested either 3000mg of AAKG or a placebo 45 minutes prior to a resistance exercise protocol in a randomized, double-blind crossover design. One-repetition maximum (1RM on the standard barbell bench press and leg press were obtained. Upon determination of 1RM, subjects completed repetitions to failure at 60% 1RM on both the standard barbell bench press and leg press. Heart rate was measured pre and post exercise. One week later, subjects ingested the other supplement and performed the identical resistance exercise protocol. Results Our data showed statistical significant differences (p0.05 between supplementation conditions for either resistance trained or untrained men in the bench press or leg press exercises. Heart rate was similar at the end of the upper and lower body bouts of resistance exercise with AAKG vs. placebo. Conclusion The results from our study indicate that acute AAKG supplementation provides no ergogenic benefit on 1RM or TLV as measured by the standard barbell bench press and leg press, regardless of the subjects training status.

  7. Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men.

    Science.gov (United States)

    Wax, Benjamin; Kavazis, Andreas N; Webb, Heather E; Brown, Stanley P

    2012-04-17

    Dietary supplements containing L-arginine are marketed to improve exercise performance, but the efficacy of such supplements is not clear. Therefore, this study examined the efficacy of acute ingestion of L-arginine alpha-ketoglutarate (AAKG) muscular strength and endurance in resistance trained and untrained men. Eight resistance trained and eight untrained healthy males ingested either 3000mg of AAKG or a placebo 45 minutes prior to a resistance exercise protocol in a randomized, double-blind crossover design. One-repetition maximum (1RM) on the standard barbell bench press and leg press were obtained. Upon determination of 1RM, subjects completed repetitions to failure at 60% 1RM on both the standard barbell bench press and leg press. Heart rate was measured pre and post exercise. One week later, subjects ingested the other supplement and performed the identical resistance exercise protocol. Our data showed statistical significant differences (p0.05) between supplementation conditions for either resistance trained or untrained men in the bench press or leg press exercises. Heart rate was similar at the end of the upper and lower body bouts of resistance exercise with AAKG vs. placebo. The results from our study indicate that acute AAKG supplementation provides no ergogenic benefit on 1RM or TLV as measured by the standard barbell bench press and leg press, regardless of the subjects training status.

  8. L-arginine mediated renaturation enhances yield of human, α6 Type IV collagen non-collagenous domain from bacterial inclusion bodies.

    Science.gov (United States)

    Gunda, Venugopal; Boosani, Chandra Shekhar; Verma, Raj Kumar; Guda, Chittibabu; Sudhakar, Yakkanti Akul

    2012-10-01

    The anti-angiogenic, carboxy terminal non-collagenous domain (NC1) derived from human Collagen type IV alpha 6 chain, [α6(IV)NC1] or hexastatin, was earlier obtained using different recombinant methods of expression in bacterial systems. However, the effect of L-arginine mediated renaturation in enhancing the relative yields of this protein from bacterial inclusion bodies has not been evaluated. In the present study, direct stirring and on-column renaturation methods using L-arginine and different size exclusion chromatography matrices were applied for enhancing the solubility in purifying the recombinant α6(IV)NC1 from bacterial inclusion bodies. This methodology enabled purification of higher quantities of soluble protein from inclusion bodies, which inhibited endothelial cell proliferation, migration and tube formation. Thus, the scope for L-arginine mediated renaturation in obtaining higher yields of soluble, biologically active NC1 domain from bacterial inclusion bodies was evaluated.

  9. Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and L-arginine metabolism in mice.

    Science.gov (United States)

    Ito, Tatsuo; Kubo, Masayuki; Nagaoka, Kenjiro; Funakubo, Narumi; Setiawan, Heri; Takemoto, Kei; Eguchi, Eri; Fujikura, Yoshihisa; Ogino, Keiki

    2018-02-01

    Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in L-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as L-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of L-arginine bioavailability and NO 2 - were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas L-arginine levels were significantly reduced, and these changes were followed by reductions in NO 2 - levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with L-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma L-arginine and NO 2 - levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.

  10. Development of Isocratic RP-HPLC Method for Separation and Quantification of L-Citrulline and L-Arginine in Watermelons

    Directory of Open Access Journals (Sweden)

    Rasdin Ridwan

    2018-01-01

    Full Text Available Watermelons (Citrullus lanatus are known to have sufficient amino acid content. In this study, watermelons grown and consumed in Malaysia were investigated for their amino acid content, L-citrulline and L-arginine, by the isocratic RP-HPLC method. Flesh and rind watermelons were juiced, and freeze-dried samples were used for separation and quantification of L-citrulline and L-arginine. Three different mobile phases, 0.7% H3P04, 0.1% H3P04, and 0.7% H3P04 : ACN (90 : 10, were tested on two different columns using Zorbax Eclipse XDB-C18 and Gemini C18 with a flow rate of 0.5 mL/min and a detection wavelength at 195 nm. Efficient separation with reproducible resolution of L-citrulline and L-arginine was achieved using 0.1% H3P04 on the Gemini C18 column. The method was validated and good linearity of L-citrulline and L-arginine was obtained with R2 = 0.9956, y=0.1664x+2.4142 and R2=0.9912, y=0.4100x+3.4850, respectively. L-citrulline content showed the highest concentration in red watermelon of flesh and rind juice extract (43.81 mg/g and 45.02 mg/g, whereas L-arginine concentration was lower than L-citrulline, ranging from 3.39 to 11.14 mg/g. The isocratic RP-HPLC method with 0.1% H3P04 on the Gemini C18 column proved to be efficient for separation and quantification of L-citrulline and L-arginine in watermelons.

  11. Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

    Science.gov (United States)

    Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2017-06-25

    Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: L-glutamine inhibits the generation of L-arginine by cultured endothelial cells

    International Nuclear Information System (INIS)

    Sessa, W.C.; Hecker, M.; Mitchell, J.A.; Vane, J.R.

    1990-01-01

    The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium-derived factor from bovine aortic cultured endothelial cells was investigated. The intracellular concentration of L-arginine (L-Arg) in Arg-depleted endothelial cells was inversely related to the level of L-Gln. Removal of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM) but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg from L-citrulline (L-Cit), L-Cit-L-Phe, and N G -monomethyl-L-arginine. L-Gln also inhibited the conversion of L-[ 14 C]Cit to L-[ 14 C]Arg by Arg-depleted endothelial cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and non-cultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor

  13. The L-alpha-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in L-arginine-induced insulin release

    DEFF Research Database (Denmark)

    Smajilovic, Sanela; Clemmensen, Christoffer; Johansen, Lars Dan

    2013-01-01

    insulin secretion; therefore, the receptor has been hypothesized to have a role in regulating glucose metabolism. In this study, we demonstrate that GPRC6A is expressed in islets of Langerhans, but activation of the receptor by L-arginine did not stimulate insulin secretion. We also investigated central...... metabolic parameters in GPRC6A knockout mice compared with wildtype littermates and found no difference in glucose metabolism or body fat percentage when mice were administered a standard chow diet. In conclusion, our data do not support a role for GPRC6A in L-arginine-induced insulin release and glucose...

  14. Non linear optical studies on semiorganic single crystal: L-arginine 4-nitrophenalate 4-nitrophenol dihydrate (LAPP)

    Science.gov (United States)

    Mahadevan, M.; Sankar, P. K.; Vinitha, G.; Arivanandhan, M.; Ramachandran, K.; Anandan, P.

    2017-07-01

    L-arginine 4-nitrophenalate 4-nitrophenol dihydrate (LAPP) has been synthesized and grown by solution growth at room temperature using deionized water as a solvent. The various functional groups of the sample were identified by Fourier transform infra-red and Fourier transforms - Raman spectroscopic analyses. The Laser damage threshold of LAPP has been studied. Refractive index of LAPP single crystal was measured using Metricon prism coupler Instrument. The etching studies were carried out to study the quality of the grown crystals. The third order nonlinear optical properties of LAPP sample was analyzed by the Z-scan technique using 532 nm diode pumped CW Nd: YAG laser. The LAPP material exhibits negative optical nonlinearity. The results show that LAPP sample has potential applications in nonlinear optics and it can be exploited for optical limiting or switching.

  15. Protective effect of Mimosa pudica L. in an L-arginine model of acute necrotising pancreatitis in rats.

    Science.gov (United States)

    Kaur, Jagdeep; Sidhu, Shabir; Chopra, Kanwaljit; Khan, M U

    2016-07-01

    Mimosa pudica is used in traditional medicine for treating various disorders such as inflammatory conditions, diarrhoea, insomnia, alopecia, urogenital infections and wounds. The present study investigated the effect of M. pudica extract (MPE) on L-arginine-induced acute necrotising pancreatitis in rats. The ethanolic extract of M. pudica leaves was studied for the presence of quercetin and gallic acid using high-performance liquid chromatography. Four groups were employed-normal control rats, L-arginine control rats (two intraperitoneal [i.p.] injections of 2 g/kg at an interval of 1 h), MPE-treated rats (400 mg/kg orally) and melatonin-treated rats (positive control 10 mg/kg i.p.), which were further divided into subgroups according to time points (24 h, 3 days and 14 days). Serum amylase, lipase, tumour necrosis factor-α (TNF-α), pancreatic amylase, nucleic acid content, protein, transforming growth factor-β1 (TGF-β1), thiobarbituric reactive substances, glutathione, nitrite/nitrate, collagen content and histopathological examination were carried out. MPE significantly improved acute necrotising pancreatitis by modulating diagnostic markers of pancreatitis such as serum lipase and pancreatic amylase, inflammation (TNF-α), and oxidative and nitrosative stress. Moreover, MPE administration induced regenerative changes in the pancreas evidenced by increased levels of pancreatic proteins, nucleic acid content and histopathology report. In addition, MPE improved TGF-β1 and collagen levels thereby preventing fibrosis. The current investigation indicates the novel role of MPE in reducing the severity of acute necrotising pancreatitis by plausible mechanisms such as anti-inflammatory and anti-fibrotic activity and by promoting repair and regeneration of the pancreas.

  16. Population dynamics in vasopressin cells.

    Science.gov (United States)

    Leng, Gareth; Brown, Colin; Sabatier, Nancy; Scott, Victoria

    2008-01-01

    Most neurons sense and code change, and when presented with a constant stimulus they adapt, so as to be able to detect a fresh change. However, for some things it is important to know their absolute level; to encode such information, neurons must sustain their response to an unchanging stimulus while remaining able to respond to a change in that stimulus. One system that encodes the absolute level of a stimulus is the vasopressin system, which generates a hormonal signal that is proportional to plasma osmolality. Vasopressin cells sense plasma osmolality and secrete appropriate levels of vasopressin from the neurohypophysis as needed to control water excretion; this requires sustained secretion under basal conditions and the ability to increase (or decrease) secretion should plasma osmolality change. Here we explore the mechanisms that enable vasopressin cells to fulfill this function, and consider how coordination between the cells might distribute the secretory load across the population of vasopressin cells. 2008 S. Karger AG, Basel.

  17. Novel photoluminescence enzyme immunoassay based on supramolecular host-guest recognition using L-arginine/6-aza-2-thiothymine-stabilized gold nanocluster.

    Science.gov (United States)

    Wang, Youmei; Lu, Minghua; Tang, Dianping

    2018-06-30

    A new photoluminescence (PL) enzyme immunoassay was designed for sensitive detection of aflatoxin B 1 (AFB 1 ) via an innovative enzyme substrate, 6-aza-2-thiothymine-stabilized gold nanocluster (AAT-AuNC) with L-arginine. The enzyme substrate with strong PL intensity was formed through supramolecular host-guest assembly between guanidine group of L-arginine and AAT capped on the surface of AuNC. Upon arginase introduction, the captured L-arginine was hydrolyzed into ornithine and urea, thus resulting in the decreasing PL intensity. Based on this principle, a novel competitive-type immunoreaction was first carried out on AFB 1 -bovine serum albumin (AFB 1 -BSA) conjugate-coated microplate, using arginase-labeled anti-AFB 1 antibody as the competitor. Under the optimum conditions, the PL intensity increased with the increment of target AFB 1 , and allowed the detection of the analyte at concentrations as low as 3.2 pg mL -1 (ppt). Moreover, L-arginine-AAT-AuNC-based PL enzyme immunoassay afforded good reproducibility and acceptable specificity. In addition, the accuracy of this methodology, referring to commercial AFB 1 ELISA kit, was evaluated to analyze naturally contaminated or spiked peanut samples, giving well-matched results between two methods, thus representing a useful scheme for practical application in quantitative monitoring of mycotoxins in foodstuff. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Protective effect of chlorogenic acid on the inflammatory damage of pancreas and lung in mice with l-arginine-induced pancreatitis.

    Science.gov (United States)

    Ohkawara, Tatsuya; Takeda, Hiroshi; Nishihira, Jun

    2017-12-01

    Pancreatitis is characterized by inflammatory disease with severe tissue injury in pancreas, and the incidence of pancreatitis has been recently increasing. Although several treatments of acute pancreatitis have been developed, some patients have been resistant to current therapy. Chlorogenic acid (CGA) is one of the polyphenols, and is known to have an anti-inflammatory effect. In this study, we investigated the effects of CGA on experimental pancreatitis in mice. Pancreatitis was induced by twice injection of l-arginine (5g/kg body weight). Mice were intraperitoneally injected with CGA (20mg/kg or 40mg/kg) 1h before administration of l-arginine. Administration of 40mg/kg of CGA decreased the histological severity of pancreatitis and pancreatitis-associated lung injury. Moreover, administration of CGA inhibited the levels of pancreatic enzyme activity. Interestingly, CGA reduced the serum and pancreatic levels of macrophage migration inhibitory factor (MIF) in mice with l-arginine-induced pancreatitis. Our results suggest that CGA has an anti-inflammatory effect on l-arginine-induced pancreatitis and pancreatitis-associated lung injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Effect of l-arginine therapy on plasma NO/sub 2/ and NO/sub 3/ levels, and blood pressure in uremic rabbits

    International Nuclear Information System (INIS)

    Hanif, M.; Khemomal, A.

    2011-01-01

    Background: Normal kidney function is regulated by Nitric oxide (NO) and Superoxide (O/sub 2/-) in the body, and consequently controls blood pressure. Nitric Oxide promotes natriuresis and diuresis, and therefore results in reduction of blood pressure. The objective of this study was to determine the effect of L-arginine supplementation on blood pressure, urinary protein, nitrite and nitrate in addition to blood urea, serum creatinine and creatinine clearance in uremic rabbits. Methods: This study was carried out in the Department of Biochemistry Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. A total of 48 rabbits were included in the study. Twenty-four of the rabbits on surgical intervention were prepared as uremic and so became hypertensive as well. Two groups were uremic, one group was given L-arginine and the other was remained untreated. Systolic and diastolic blood pressure was measured on week 0, week 2, week 4, and week 6, while blood and urine was collected on week 0 and week 6. Results: On supplementation with L-arginine to uremic rabbits systolic and diastolic blood pressures were decreased significantly. Nitrite/nitrate and urinary protein were corrected to some extent while blood urea and serum creatinine were unaffected. Conclusion: L-arginine has a beneficial role as blood pressure lowering agent in uremic rabbits. It corrects NO/sub 2/NO/sub 3/ plasma level and proteinuria which is indicator of renal failure. (author)

  20. Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.

    Science.gov (United States)

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Gapsys, Vytautas; Ucurum, Zöhre; de Groot, Bert L; Fotiadis, Dimitrios

    2016-09-13

    Pathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-Å and 2.2-Å resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli.

  1. Structure of the C-terminal effector-binding domain of AhrC bound to its corepressor l-arginine

    International Nuclear Information System (INIS)

    Garnett, James A.; Baumberg, Simon; Stockley, Peter G.; Phillips, Simon E. V.

    2007-01-01

    The crystal structure of the C-terminal domain hexameric core of AhrC, with bound corepressor (l-arginine), has been solved at 1.95 Å resolution. Binding of l-arginine results in a rotation between the two trimers of the hexamer, leading to the activation of the DNA-binding state. The arginine repressor/activator protein (AhrC) from Bacillus subtilis belongs to a large family of multifunctional transcription factors that are involved in the regulation of bacterial arginine metabolism. AhrC interacts with operator sites in the promoters of arginine biosynthetic and catabolic operons, acting as a transcriptional repressor at biosynthetic sites and an activator of transcription at catabolic sites. AhrC is a hexamer of identical subunits, each having two domains. The C-terminal domains form the core of the protein and are involved in oligomerization and l-arginine binding. The N-terminal domains lie on the outside of the compact core and play a role in binding to 18 bp DNA operators called ARG boxes. The C-terminal domain of AhrC has been expressed, purified and characterized, and also crystallized as a hexamer with the bound corepressor l-arginine. Here, the crystal structure refined to 1.95 Å is presented

  2. New role for L-arginine in regulation of inducible nitric-oxide-synthase-derived superoxide anion production in Raw 264.7 macrophages

    Czech Academy of Sciences Publication Activity Database

    Pekarová, Michaela; Lojek, Antonín; Martíšková, Hana; Vašíček, Ondřej; Binó, Lucia; Klinke, A.; Lau, D.; Kuchta, R.; Kadlec, J.; Vrba, R.; Kubala, Lukáš

    2011-01-01

    Roč. 11, - (2011), s. 2443-2457 ISSN 1537-744X R&D Projects: GA ČR(CZ) GA524/08/1753 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : macrophage s * L-arginine * inducible nitric oxide synthase Subject RIV: BO - Biophysics Impact factor: 1.524, year: 2010

  3. Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.

    Science.gov (United States)

    Gangula, P R; Wimalawansa, S J; Yallampalli, C

    1997-04-01

    We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent. Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment

  4. Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ming Wei; Wei Yang; Li-Xia Liu; Wen-Xiu Qi

    2013-01-01

    Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity,learning and memory.In the present study,we assessed the effects of L-arginine and Nω-nitro-L-arginine methylester (L-NAME,a nitric oxide synthase inhibitor) on learning and memory.Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor),L-NAME,or 0.9% NaCI (control),once daily for seven consecutive days.Twelve hours after the last injection,they underwent an electric shock-paired Y maze test.Twenty-four hours later,the rats' memory of the safe illuminated arm was tested.After that,the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit,and immunohistochemistry and Western blots,respectively.We found that,compared to controls,L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion,and made fewer errors during the memory-testing session.In contrast,L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion,and made more errors during the memory-testing session.In parallel,NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.Similarly,α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus,as well as with learning and memory performance in the Y-maze.

  5. Combining glial cell line-derived neurotrophic factor gene delivery (AdGDNF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury.

    Science.gov (United States)

    Degeorge, M L; Marlowe, D; Werner, E; Soderstrom, K E; Stock, M; Mueller, A; Bohn, M C; Kozlowski, D A

    2011-07-27

    Our laboratory has previously demonstrated that viral administration of glial cell line-derived neurotrophic factor (AdGDNF), one week prior to a controlled cortical impact (CCI) over the forelimb sensorimotor cortex of the rat (FL-SMC) is neuroprotective, but does not significantly enhance recovery of sensorimotor function. One possible explanation for this discrepancy is that although protected, neurons may not have been functional due to enduring metabolic deficiencies. Additionally, metabolic events following TBI may interfere with expression of therapeutic proteins administered to the injured brain via gene therapy. The current study focused on enhancing the metabolic function of the brain by increasing cerebral blood flow (CBF) with l-arginine in conjunction with administration of AdGDNF immediately following CCI. An adenoviral vector harboring human GDNF was injected unilaterally into FL-SMC of the rat immediately following a unilateral CCI over the FL-SMC. Within 30min of the CCI and AdGDNF injections, some animals were injected with l-arginine (i.v.). Tests of forelimb function and asymmetry were administered for 4weeks post-injury. Animals were sacrificed and contusion size and GDNF protein expression measured. This study demonstrated that rats treated with AdGDNF and l-arginine post-CCI had a significantly smaller contusion than injured rats who did not receive any treatment, or injured rats treated with either AdGDNF or l-arginine alone. Nevertheless, no amelioration of behavioral deficits was seen. These findings suggest that AdGDNF alone following a CCI was not therapeutic and although combining it with l-arginine decreased contusion size, it did not enhance behavioral recovery. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. THE EFFECT OF L- ARGININE ON OXIDATIVE STRESS AND MICROALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE

    Directory of Open Access Journals (Sweden)

    L. P. Martynyuk

    2017-07-01

    Full Text Available Background. One of the severest complications of diabetes is diabetic kidney disease (DKD. Microalbuminuria (MAU is one of the first signals of DKD and an important pathogenetic mechanism of disease progression. With diabetes dramatically antioxidant properties worsen. Objective. The aim was to investigate the effect of L-arginine on oxidative stress parameters and microalbuminuria in type 2 diabetes mellitus and chronic kidney disease patients. Methods. Total of 57 patients with type 2 diabetes mellitus and chronic kidney disease and 30 healthy subjects (control group were included in the study. The patients were divided into 2 congruent groups. The 1-st group of patients (n=33, in addition to standard therapy, received L-arginine 4.2 g intravenously for 5 days, after that they took it 1,0 g orally three times a day during meals for 1 month. The second group of patients (n=24 received a standard therapy. The concentration of lipid peroxidation products was measured by a spectrophotometric method. The determination of MAU was carried out in morning portion of urine immunological semiquantitative using test strips. Results. Significant improvement in indexes of lipid peroxidation was observed in both groups after therapy (p˂0.01, but in patients treated with L-arginine it was more expressed (p˂0,01. The standard therapy did not significantly affect the level of MAU (p˃0,05. The patients treated with L-Arginine, showed a significant reduction in MAU (p˂0.01. Conclusions. The usage of L-arginine facilitates the correction of lipid peroxidation processes and reduces the severity of microalbuminuria in patients with diabetic kidney disease that slowing its progression.

  7. Dynamic Changes of Endothelium Derived Factors and Cyclic Nucleotides in Ascites Broilers and Control of L-arginine

    Institute of Scientific and Technical Information of China (English)

    HAN Bo; WANG Xiao-long

    2003-01-01

    A flock of AA breed chickens were reared in peterstme brood-vait chamber using high energypelleted feed, at 14 days of age, 400 birds were separated into 3 groups randomly as follows: 100 birds wereexposed to normal ambient temperature (20℃) as control group, 150 birds were exposed to low ambient tem-perature (11℃) in order to induce ascites as treatment Ⅰ group, another 100 birds were also exposed to lowambient temperature (11℃) and fed the diets containing 1% L-arginine for ascitic prophylactic treatment astreatment Ⅱ group. The blood samples were collected on 3, 4, 5, 6, 7 wk, respectively, to measure the con-tents of plasma endothelin (ET-1), angiotensin Ⅱ (Ang Ⅱ ) and cyclic adenosine monophosphate (cAMP) andcyclic guanosine monophosphate (cGMP). The results indicated that the contents of cAMP, cGMP, Ang Ⅱand the ratio of cAMP/cGMP in treatment Ⅰ and ascitic broilers were higher than that of correspondent con-trol group(P<0.01, P<0.05), ET-1 of preascitic broilers were higher than that of control group(P<0.05),while there were insignificant differences with later ascitic broilers, the contents of cAMP and cGMP in treat-ment Ⅱ were higher than treatment Ⅰ and control group(P<0.01, P<0.05), whereas, the ratio of cAMP/cGMP and the contents of Ang Ⅱ were gradually decreased than that of control group(P<0.05), the contentsof ET-1 were not changed. By further analysis, the increased plasma Ang Ⅱ at low ambient temperature condi-tion in broilers made endothelium cell secretion of increased ET-1, cAMP, cGMP and decreased NO. So lowtemperature accelarated ascites syndrome in broilers. Supplemented L-arginine can decrease ET-1, cAMP andcAMP/cGMP. It is concluded that cAMP mediated pulmonary hypertension syndrome in broilers.

  8. Venlafaxine prevents morphine antinociceptive tolerance: The role of neuroinflammation and the l-arginine-nitric oxide pathway.

    Science.gov (United States)

    Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam; Alboghobeish, Soheila; Amirgholami, Neda; Houshmand, Gholamreza; Cauli, Omar

    2018-05-01

    Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l-arginine hydrochloride (l-arg) or NO are involved in the effects rendered by VLF, animals were pre-treated with l-arg (200 mg/kg), or the NO synthesis inhibitors N(ω)-nitro-l-arginine methyl ester (L-NAME; 30 mg/kg) or aminoguanidine hydrochloride (AG; 100 mg/kg), along with VLF (40 mg/kg) for three days before receiving morphine for another three days. Nociception was assessed with a hot-plate test on the fourth day, and the concentration of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-10, brain-derived neurotrophic factor, NO, and oxidative stress factors such as total thiol, malondialdehyde content, and glutathione peroxidase (GPx) activity in the brain was also determined. Co-administration of VLF with morphine attenuated morphine-induced analgesic tolerance and prevented the upregulation of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), NO, and malondialdehyde in brains of mice with induced morphine tolerance; chronic VLF administration inhibited this decrease in brain-derived neurotrophic factor, total thiol, and GPx levels. Moreover, repeated administration of l-arg before receipt of VLF antagonized the effects induced by VLF, while L-NAME and AG potentiated these effects. VLF attenuates morphine-induced analgesic tolerance, at least partly because of its anti

  9. L-Arginine-Triggered Self-Assembly of CeO2 Nanosheaths on Palladium Nanoparticles in Water.

    Science.gov (United States)

    Wang, Xiao; Zhang, Yibo; Song, Shuyan; Yang, Xiangguang; Wang, Zhuo; Jin, Rongchao; Zhang, Hongjie

    2016-03-24

    Pd@CeO2 core-shell nanostructures with a tunable Pd core size, shape, and nanostructure as well as a tunable CeO2 sheath thickness were obtained by a biomolecule-assisted method. The synthetic process is simple and green, as it involves only the heating of a mixture of Ce(NO3 )3 , l-arginine, and preformed Pd seeds in water without additives. Importantly, the synthesis is free of thiol groups and halide ions, thus providing a possible solution to the problem of secondary pollution by Pd nanoparticles in the sheath-coating process. The Pd/CeO2 nanostructures can be composited well with γ-Al2 O3 to create a heterogeneous catalyst. In subsequent tests of catalytic NO reduction by CO, Pd@CeO2 /Al2 O3 samples based on Pd cubes (6, 10, and 18 nm), Pd octahedra (6 nm), and Pd cuboctahedra (9 nm) as well as a simply loaded Pd cube (6 nm)-CeO2 /Al2 O3 sample were used as catalysts to investigate the effects of the Pd core size and shape and the hybrid nanostructure on the catalytic performance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Investigations on nucleation, HRXRD, optical, piezoelectric, polarizability and Z-scan analysis of L-arginine maleate dihydrate single crystals

    Science.gov (United States)

    Sakthy Priya, S.; Alexandar, A.; Surendran, P.; Lakshmanan, A.; Rameshkumar, P.; Sagayaraj, P.

    2017-04-01

    An efficient organic nonlinear optical single crystal of L-arginine maleate dihydrate (LAMD) has been grown by slow evaporation solution technique (SEST) and slow cooling technique (SCT). The crystalline perfection of the crystal was examined using high-resolution X-ray diffractometry (HRXRD) analysis. Photoluminescence study confirmed the optical properties and defects level in the crystal lattice. Electromechanical behaviour was observed using piezoelectric co-efficient (d33) analysis. The photoconductivity analysis confirmed the negative photoconducting nature of the material. The dielectric constant and loss were measured as a function of frequency with varying temperature and vice-versa. The laser damage threshold (LDT) measurement was carried out using Nd:YAG Laser with a wavelength of 1064 nm (Focal length is 35 cm) and the obtained results showed that LDT value of the crystal is high compared to KDP crystal. The high laser damage threshold of the grown crystal makes it a potential candidate for second and higher order nonlinear optical device application. The third order nonlinear optical parameters of LAMD crystal is determined by open-aperture and closed-aperture studies using Z-scan technique. The third order linear and nonlinear optical parameters such as the nonlinear refractive index (n2), two photon absorption coefficient (β), Real part (Reχ3) and imaginary part (Imχ3) of third-order nonlinear optical susceptibility are calculated.

  11. Effect of reconstitution solvents and containers on kinetics and safety of cephradine neutralised with L-arginine

    International Nuclear Information System (INIS)

    Khan, A.U.; Iqbal, J.

    2015-01-01

    The effect of reconstitution solvents such as water, 0.5% metronidazole solution, 0.9% sodium chloride and 5% dextrose injections, have been investigated on the kinetics of degradation of cephradine neutralised with L-arginine contained in glass, polyvinylchloride (PVC) and polyethylene pthalate (PET) containers at 5, 15 and 30 degree C. The analytical method described in USP-31 for the analysis of cephradine injection was employed in this study and validation in respect of specificity, linearity, accuracy and precision was observed. The degradation of the compound showed first-order kinetics and the degradation rate constants Kobs were found in the range of 1.84-3.07 * 10/sup -3/h (r2= 0.990-0.999) at 5 degree C, 2.3-4.2 * 10/sup -3/h (r2= 0.993-0.999) at 15 degree C and 7.18-9.97 * 10/sup -3/h (r2= 0.998-0.999) at 30 degree C, respectively. Cephradine showed maximum stability in dextrose solution followed by water, sodium chloride and metronidazole injections, however, linear effect of containers on degradation rate could not be established. The extended degradation did not change the kinetics of the reaction. The abnormal toxicity/ safety test on mice for the admixtures in different containers at various temperatures showed no abnormal toxicity. (author)

  12. Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Masha, A; Manieri, C; Dinatale, S; Bruno, G A; Ghigo, E; Martina, V

    2009-12-01

    Nitric oxide (NO) plays a wide spectrum of biological actions including a positive role in oocyte maturation and ovulation. Free radicals levels have been shown elevated in polycystic ovary syndrome (PCOS) and therefore would be responsible for quenching NO that, in turn, would play a role in determining oligo- or amenorrhea connoting PCOS. Eight patients with PCOS displaying oligo-amenorrhea from at least 1 yr underwent a combined treatment with N-acetylcysteine (NAC) (1200 mg/die) plus L-arginine (ARG) (1600 mg/die) for 6 months. Menstrual function, glucose and insulin levels, and, in turn, homeostasis model assessment (HOMA) index were monitored. Menstrual function was at some extent restored as indicated by the number of uterine bleedings under treatment (3.00, 0.18-5.83 vs 0.00, 0.00-0.83; p<0.02). Also, a well-defined biphasic pattern in the basal body temperature suggested ovulatory cycles. The HOMA index decreased under treatment (2.12, 1.46-4.42 vs 3.48, 1.62-5.95; p<0.05). In conclusion, this preliminary, open study suggests that prolonged treatment with NAC+ARG might restore gonadal function in PCOS. This effect seems associated to an improvement in insulin sensitivity.

  13. Investigation on nonlinear optical and dielectric properties of L-arginine doped ZTC crystal to explore photonic device applications

    Directory of Open Access Journals (Sweden)

    Anis Mohd

    2016-09-01

    Full Text Available The present study is focused to explore the photonic device applications of L-arginine doped ZTC (LA-ZTC crystals using nonlinear optical (NLO and dielectric studies. The LA-ZTC crystals have been grown by slow evaporation solution technique. The chemical composition and surface of LA-ZTC crystal have been analyzed by means of energy dispersive spectroscopy (EDS and surface scanning electron microscopy (SEM techniques. The Vicker’s microhardness study has been carried out to determine the hardness, work hardening index, yield strength and elastic stiffness of LA-ZTC crystal. The enhanced SHG efficiency of LA-ZTC crystal has been ascertained using the Kurtz-Perry powder SHG test. The closed-and-open aperture Z-scan technique has been employed to confirm the third order nonlinear optical nature of LA-ZTC crystal. The Z-scan transmittance data has been utilized to calculate the superior cubic susceptibility, nonlinear refractive index, nonlinear absorption coefficient and figure of merit of LA-ZTC crystal. The behavior of dielectric constant and dielectric loss of LA-ZTC crystal at different temperatures has been investigated using the dielectric analysis.

  14. L-Arginine Increases Cytotoxicity in Irradiated Ehrlich Carcinoma Cell Line: Possible Potential Role of Nitric Oxide

    International Nuclear Information System (INIS)

    Noaman, E.

    2008-01-01

    Cancer cells possess nitric oxide syntheses (NOS) which metabolize L-Arginine (L-Arg) for producing nitric oxide (NO) The present study investigates the relations between NO and ionizing radiation in the Ehrlich ascites carcinoma (EAC) cell line. NOS activity was stimulated by exposure of cells to L-Arg just after irradiation. L-Arg (5 m M) supply led to an increase in ionizing radiation induced cytotoxicity (% of viability 18± 3 %) whereas, neither L-Arg itself nor ionizing irradiation caused cell death at the doses used in this study. Also, cells were treated either with L-Thio citrulline (L-Thio), an irreversible inhibitor of NOS or with exogenous superoxide dismutase (SOD) and catalase. L-Thio and SOD prevented L-Arg mediated deleterious effects on Irradiated cells, whereas catalase was ineffective. Intracellular antioxidant enzyme activity was also determined. Ionizing radiation + L-Arg stress altered the activity of catalase (66 % decrease) and glutathione peroxidase (83 % decrease). Our findings demonstrated that L-Arg induces increase the radiation-mediated deleterious effects in Ehrlich ascites carcinoma cells cytotoxicity and that the ratio NO/ O 2 plays a key role in these processes. NO could participate the deleterious effect of irradiation, in conjugation with others reactive oxygen species (ROS) produced during the oxidation of intracellular components by ionizing radiation (dose 6 Gy)

  15. Synergistic Effects of l-Arginine and Methyl Salicylate on Alleviating Postharvest Disease Caused by Botrysis cinerea in Tomato Fruit.

    Science.gov (United States)

    Zhang, Xinhua; Min, Dedong; Li, Fujun; Ji, Nana; Meng, Demei; Li, Ling

    2017-06-21

    The effects of l-arginine (Arg, 1 mM) and/or methyl salicylate (MeSA, 0.05 mM) treatment on gray mold caused by Botrytis cinerea in tomato fruit were studied. Results indicated that Arg or MeSA alleviated the incidence and severity of fruit disease caused by B. cinerea, and that both Arg and MeSA (Arg + MeSA) further inhibited the development of fruit decay. Treatment with Arg + MeSA not only enhanced the activities of superoxide dismutase, catalase, and peroxidase but also promoted the expression levels of pathogenesis-related protein 1 gene and the activities of defense-related enzymes of phenylalanine ammonia-lyase, polyphenol oxidase, β-1,3-glucanase, and chitinase during most of the storage periods, which were associated with lower disease incidence and disease index. In addition, the combined treatment elevated the levels of total phenolics, polyamines, especially putrescine, and nitric oxide. These observations suggest that treatment of fruit with Arg + MeSA is an effective and promising way to alleviate postharvest decays on a commercial scale.

  16. [Effect of L-arginine and the nitric oxide synthase blocker L-NNA on calcium capacity in rat liver mitochondria with differing resistance to hypoxia].

    Science.gov (United States)

    Kurhaliuk, N M; Ikkert, O V; Vovkanych, L S; Horyn', O V; Hal'kiv, M O; Hordiĭ, S K

    2001-01-01

    The effect of L-arginine and blockator of nitric oxide synthase L-NNA on processes of calcium mitochondrial capacity in liver with different resistance to hypoxia in the experiments with Wistar rats has been studied using the followrng substrates of energy support: succinic, alpha-ketoglutaric acids, alpha-ketolutarate and inhibitor succinatedehydrogenase malonate. As well we used substrates mixtures combination providing for activation of aminotransferase mechanism: glutamate and piruvate, glutamate and malate. It has been shown that L-arginine injection increases calcium mitochondrial capacity of low resistant rats using as substrates the succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of donors nitric oxide on this processes limit NO-synthase inhibitor L-NNA.

  17. The effects of L-arginine, D-arginine, L-name and methylene blue on channa striatus-induced peripheral antinociception in mice.

    Science.gov (United States)

    Zakaria, Zainul Amiruddin; Sulaiman, Mohd Rosian; Somchit, Muhammad Nazrul; Jais, Abdul Manan Mat; Ali, Daud Israf

    2005-08-03

    To determine the involvement of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway in aqueous supernatant of haruan (Channa striatus) fillet (ASH) antinociception using the acetic acid-induced abdominal constriction test. The ASH was prepared by soaking fresh haruan fillet in chloroform:methanol (CM) (2/1 (v/v)) for 72 h followed by evaporation of the upper layer supernatant to remove any solvent residues. The supernatant was then subjected to a freeze-drying process (48 h) followed by doses preparation. Subcutaneous (SC) administration of ASH alone (0.170, 0.426 and 1.704 mg/kg) exhibited a dose-dependent antinociception. On the other hand, 20 mg/kg (SC) of L-arginine and MB exhibited a significant nociception and antinociception, while D-arginine and L-NAME did not produce any effect at all. Pre-treatment with L-arginine was found to significantly reverse the three respective doses of ASH antinociception; pre-treatment with D-arginine did not produce any significant change in the ASH activity; pre-treatment with L-NAME only significantly increased the 0.170 and 0.426 mg/kg ASH antinociception; and pre-treatment with MB significantly enhanced the respective doses of ASH antinociception, respectively. Furthermore, co-treatment with L-NAME significantly enhanced the L-arginine reversal effect on 0.426 mg/kg ASH antinociception. In addition, MB significantly reversed the L-arginine nociception on 0.426 mg/kg ASH. These finding suggest ASH antinociception involves the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. The presence of NO was found to reverse ASH antinociceptive activity while blocking of cGMP system enhanced it.

  18. Analysis of L-citrulline and L-arginine in Ficus deltoidea leaf extracts by reverse phase high performance liquid chromatography

    Science.gov (United States)

    Shafaei, Armaghan; Aisha, Abdalrahim F. A.; Siddiqui, Mohammad Jamshed Ahmad; Ismail, Zhari

    2015-01-01

    Background: Ficus deltoidea (FD) is one of the native plants widely distributed in several countries in Southeast Asia. Previous studies have shown that FD leaf possess antinociceptive, wound healing and antioxidant properties. These beneficial effects have been attributed to the presence of primary and secondary metabolites such as polyphenols, amino acids and flavonoids. Objective: The aim was to develop a reverse phase high-performance liquid chromatography method with ultraviolet detection that involves precolumn derivatisation with O-phthaladehyde for simultaneous analysis of two amino acids L-citrulline and L-arginine in FD leaf extracts. Materials and Methods: An isocratic elution program consisting of methanol: acetonitrile: Water at 45:45:10 v/v (solvent A) and 0.1 M phosphate buffer pH 7.5 (solvent B) at A: B v/v ratio of 80:20 on Zorbax Eclipse C18 SB-Aq column (250 × 4.6 mm, 5 μm) were used. The flow rate was set at 1 ml/min and detection was carried out at 338 nm with 30 min separation time. Results: Good linearity for L-citrulline and L-arginine was obtained in the range 0.1-1000 μg/ml at R2 ≥ 0.998. The limit of detection and limit of quantification values for both L-citrulline and L-arginine were 1 and 5 μg/ml, respectively. The average of recoveries was in the range 94.94-101.95%, with relative standard deviation (%RSD) less than 3%. Intra- and inter-day precision was in the range 96.36-102.43% with RSD less than 2%. Conclusion: All validation parameters of the developed method indicate the method is reliable and efficient for simultaneous determination of L-citrulline and L-arginine for routine analysis of FD. PMID:25598632

  19. Control of utilization of L-arginine, L-ornithine, agmatine, and putrescine as nitrogen sources in Escherichia coli K-12.

    OpenAIRE

    Shaibe, E; Metzer, E; Halpern, Y S

    1985-01-01

    The regulation of the synthesis of the enzymes involved in the utilization of L-arginine, L-ornithine, agmatine, and putrescine as a sole nitrogen source in Escherichia coli K-12 was examined. The synthesis of agmatine ureohydrolase, putrescine aminotransferase, and pyrroline dehydrogenase is dually controlled by catabolite repression and nitrogen availability. Catabolite repression of agmatine ureohydrolase, but not that of putrescine aminotransferase or pyrroline dehydrogenase, is relieved ...

  20. Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?

    Directory of Open Access Journals (Sweden)

    Philippe Holzmuller

    2018-04-01

    Full Text Available Mononuclear phagocytes (monocytes, dendritic cells, and macrophages are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted–secreted (ES molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage’s inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the

  1. [State of mitochondrial respiration and calcium capacity in livers of rats with different resistance to hypoxia after injections of L-arginine].

    Science.gov (United States)

    Kurhaliuk, N M

    2001-01-01

    In experiments on rats with different resistance to hypoxia are investigated processes of mitochondrial respiration, oxidative phosphorylation and calcium capacity in liver under precursor nitric oxide L-arginine (600 mg/kg) and blockator nitric oxide synthase L-NNA (35 mg/kg) injections. We are used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate, 1 mM alpha-ketoglutarate and 2 mM malonic acid. Increasing of ADP-stimulation respiration states under exogenous L-arginine injection, decreasing efficacy of respiration processes (respiration control on Chance and ADP/O) under such substrates oxidation, testify to oxide energy support decreasing and reversing nitric oxide inhibit in such conditions. This will be used as mechanism cell regulation succinate dehydrogenase activity. It has shown that L-arginine injection increase calcium mitochondrial capacity low resistance to hypoxia rats using substrates of oxidation succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of nitric oxide precursor influence on this processes limit NO-synthase inhibitor L-NNA.

  2. The protective effect of NG-nitro-L-arginine methyl ester and insulin on nitric oxide inhibition and pathology in experimental diabetic rat liver

    International Nuclear Information System (INIS)

    Ozden, H.; Guven, G.; Tekin, N.; Akyuz, F.; Gurer, F.; Kucuk, F.; Ustuner, Mehmet C.; Yaylak, F.

    2009-01-01

    Objective was to determine on protective role of NG-nitro-L-arginine methyl ester (L-NAME) and insulin on the liver in streptoozotocin (STZ) induced diabetic rats. This study was performed in the Department of Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey in 2007. Forty male Wistar albino rats were divided into 5 groups. These were untreated, diabetic control, STZ+insulin, STZ+L-NAME and STZ+insulin+L-NAME induced groups. The STZ was intraperitonally injected into 3 groups and includes insulin, L-NAME and their joint administrations as protective agents. The blood glucose and nitric oxide (NO) levels were determined. The tissue samples were obtained at the end of the fourth week. The liver tissue distortions were evaluated using hematoxylin and eosin staining. The serum glucose level was significantly higher in diabetic control (p=0.000), than the untreated group. The focal pseudo lobular structures without vena centralis increased portal fibrillary necrosis and bile duct stenosis with voagulation necrosis of the peripheral hepatocytes were more observed in diabetic group than the protective agent groups. In addition, insulin and L-NAME lead to hepatocyte regeneration and minimal mononuclear cell infiltration was noted. NG-nitro-L-arginine methyl ester inhibits NO level in STZ+L-NAME induced group. NG-nitro-L-arginine methyl ester either alone or with insulin combination significantly attenuates the liver morphological disarrangements in STZ induced diabetic rats. (author)

  3. Effects of L- Arginine Supplementation on Antioxidant Status and Body Composition in Obese Patients with Pre-diabetes: A Randomized Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Siavash Fazelian

    2014-10-01

    Full Text Available Purpose: The aim of present study was to determine effects of L-Arginine supplementation on antioxidant status and body composition in obese patients with prediabetes. Methods: A double-blind randomized control trial was performed on 46 (24 men, 22 women obese patients with prediabetes. They were divided randomly into two groups. Patients in intervention (n = 23 and control group (n=23 received 3 gr/day L-arginine and placebo, respectively for 8 weeks. Anthropometric indices, dietary intake and biochemical measurements ((serum total antioxidant capacity (TAC, Glutathione Peroxidase (GPx and Superoxide Dismutase (SOD were performed at the baseline and after 8-week intervention. Results: The mean age and BMI of participants were 44.29±8.65 years old and 28.14±1.35 kg/m2, respectively. At the end of study, in both intervention and control group, percentage of carbohydrate decreased and %fat intake increased compared to the baseline (P0.05. Among measured biochemical factors, only serum TAC level showed significant differences at the end of study in the intervention group compared to the control group (pv<0.01. Conclusion: 3gr/day L-Arginine supplementation increased TAC level in obese patients with prediabetes.

  4. Blockade of the Naloxone-induced Aversion in Morphine-conditioned Wistar Rats by L-Arginine Intra-central Amygdala

    Directory of Open Access Journals (Sweden)

    Mahnaz Rahimpour

    2011-03-01

    Full Text Available AbstractObjective(sSingle injection of naloxone, a selective antagonist of morphine, prior to the drug conditioning testing was used to investigate on morphine dependence.Materials and MethodsConditioning to morphine (2.5-10 mg/kg, s.c. was established in adult male Wistar rats (weighing 200-250 g using an unbiased procedure. Nitric oxide agents were microinjected into the central amygdala prior to naloxone-paired place conditioning testing.ResultsThe results showed that morphine produced a significant dose-dependent place preference in animals. Naloxone (0.1-0.4 mg/kg, i.p. injections pre-testing of the response to morphine (7.5 mg/kg, s.c. caused a significant aversion at the higher doses (0.4 mg/kg, i.p.. This response was reversed by microinjection of L-arginine (0.3-3 µg/rat, intra-central amygdala prior to naloxone on the day of the testing. The response to L-arginine was blocked by pre-injection of NG-nitro-L-arginine methyl ester (L-NAME (intra-central amygdala.ConclusionA single injection of naloxone on the test day of morphine place conditioning may simply reveal the occurrence of morphine dependence in rats, and that the nitric oxide in the central amygdala most likely plays a key role in this phenomenon.

  5. l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.

    Science.gov (United States)

    Edvardson, Simon; Korman, Stanley H; Livne, Amir; Shaag, Avraham; Saada, Ann; Nalbandian, Ruppen; Allouche-Arnon, Hyla; Gomori, J Moshe; Katz-Brull, Rachel

    2010-01-01

    Creatine and creatine phosphate provide storage and transmission of phosphate-bound energy in muscle and brain. Of the three inborn errors of creatine metabolism causing brain creatine depletion, l-arginine:glycine amidinotransferase (AGAT) deficiency has been described in only two families. We describe clinical and biochemical features, magnetic resonance spectroscopy (MRS) findings and response to creatine supplementation in two siblings with a novel mutation in the AGAT-encoding GATM gene. The sister and brother were evaluated at age 12 and 18years, respectively, because of mild mental retardation, muscle weakness and low weight. Extensive work-up had previously yielded negative results. Electron microscopy of the muscle revealed tubular aggregates and the activity of respiratory chain complexes was decreased in the muscle. Urine organic acid concentrations normalized to urine creatinine concentration were all increased, suggesting a creatine metabolism disorder. Brain MRS was remarkable for absence of creatine. Urine guanidinoacetate levels by tandem mass spectrometry were low, suggesting AGAT deficiency. GATM sequencing revealed a homozygous single nucleotide insertion 1111_1112insA, producing a frame-shift at Met-371 and premature termination at codon 376. Eleven months after commencing treatment with oral creatine monohydrate 100mg/kg/day, repeat MRI/MRS showed significantly increased brain creatine in the sister and a slight increase in the older brother. The parents' impression of improved strength and stamina was substantiated by increased post-treatment versus pre-treatment scores in the Vineland Adaptive Behavior Scale, straight-arm raising and timed up-and-go tests. Similarly, there was an apparent improvement in cognitive function, with significantly increased IQ-scores in the sister and marginal improvement in the brother. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Effects of L-Arginine supplementation on semen quality, testosterone concentration and testes histological parameters of Ross 308 breeder roosters

    Directory of Open Access Journals (Sweden)

    Ahangar M

    2017-03-01

    Full Text Available Objective: To assess the effects of dietary L-Arginine (L-Arg supplementation on testes histological parameters and semen quality of male broiler breeder. Methods: Twenty male broiler breeders at 37 wk of age were distributed in a completely randomized design with 4 treatments and 5 replicates each. The treatments consisted of 4 dietary levels of L-Arg (0.00, 1.35, 2.33 and 3.22 g/kg of the diet and fed to birds for 8 wk. At the end of the experiment semen samples were collected by abdominal massage to determination of semen quality. The blood samples were used to determination of serum testosterone concentration at the end of the experiment. Furthermore, testes from each rooster were used to evaluation of their weights and histological parameters. Results: The results of the experiment showed that dietary L-Arg at 2.33 g/kg improved testes weight, semen volume and sperm forward motility in roosters (P<0.05. Besides, serum concentration of testosterone was increased in roosters fed 2.33 g/kg L-Arg (P<0.05. The results of testes histology indicated that seminiferous tubules lumen diameter, leydig cells, spermatides and sperm cells counts were greater in birds received 3.22 g/kg dietary L-Arg (P<0.05. However, the birds fed diet supplemented with 2.33 g/kg L-Arg had greater seminiferous tubules diameter, sertoli and spermatogonia cell counts than other groups (P<0.05. Conclusion: According to the results of this experiment, it is concluded that dietary L-Arg had positive effects on reproductive traits in roosters.

  7. Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction.

    Science.gov (United States)

    Stühlinger, Markus C; Stanger, Olaf

    2005-02-01

    (e)ine concentrations could be supplementation with L-arginine to reverse the detrimental effects of ADMA.

  8. The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats.

    Science.gov (United States)

    Sadek, A S; Khattab, R T

    2017-01-01

    Acute pancreatitis (AP) is an inflammatory disease that has an increasing incidence worldwide. AP is associated with high morbidity and mortality rates ranging 15-40% in its severe form. Oxidative stress plays an important role in pancreatic acinar cell injury in case of AP. Melatonin (Mel) is proven to have both antioxidant and anti-inflammatory effects. The aim of the work was to investigate the protective role of Mel against L-arginine (L-arg)-induced AP in adult male albino rats. Thirty-six adult male albino rats were used in this study. Animals were divided into four groups; Control group (Group A; n = 6), Mel group (Group B; n = 6), L-arg group (Group C; n = 12) receiving two doses of L-arg injection with 1 h interval in-between, and L-arg+Mel group (Group D; n = 12) receiving Mel 1 h after each L-arg injection. 24 h after the second L-arg injection, the serum levels of amylase (AM), lipase (LP), interleukin-6 (IL-6) and tumour necrotic factor-alpha (TNF-α) were determined. Then, pancreatic specimens were processed for histological and immunohistochemical staining with vascular endothelial growth factor (VEGF) and the area percentage of VEGF and collagen content were measured by digital image analysis. Microscopic examination revealed that animals received L-arg only (Group C) showed loss of the pancreatic lobular architecture with marked fibrosis, acinar degeneration, inflammatory reaction and marked oedema with vascular congestion. Also, L-arg-induced AP caused a significant elevation of the serum levels of AM, LP, IL-6. All these histo-pathological and serological parameters were markedly improved by Mel administration. Melatonin exhibits strong therapeutic effects in the course of AP. Hence, the use of Mel as adjuvant treatment in AP is recommended.

  9. Common Hepatic Branch of Vagus Nerve-Dependent Expression of Immediate Early Genes in the Mouse Brain by Intraportal L-Arginine: Comparison with Cholecystokinin-8

    Directory of Open Access Journals (Sweden)

    Daisuke Yamada

    2017-06-01

    Full Text Available Information from the peripheral organs is thought to be transmitted to the brain by humoral factors and neurons such as afferent vagal or spinal nerves. The common hepatic branch of the vagus (CHBV is one of the main vagus nerve branches, and consists of heterogeneous neuronal fibers that innervate multiple peripheral organs such as the bile duct, portal vein, paraganglia, and gastroduodenal tract. Although, previous studies suggested that the CHBV has a pivotal role in transmitting information on the status of the liver to the brain, the details of its central projections remain unknown. The purpose of the present study was to investigate the brain regions activated by the CHBV. For this purpose, we injected L-arginine or anorexia-associated peptide cholecystokinin-8 (CCK, which are known to increase CHBV electrical activity, into the portal vein of transgenic Arc-dVenus mice expressing the fluorescent protein Venus under control of the activity-regulated cytoskeleton-associated protein (Arc promotor. The brain slices were prepared from these mice and the number of Venus positive cells in the slices was counted. After that, c-Fos expression in these slices was analyzed by immunohistochemistry using the avidin-biotin-peroxidase complex method. Intraportal administration of L-arginine increased the number of Venus positive or c-Fos positive cells in the insular cortex. This action of L-arginine was not observed in CHBV-vagotomized Arc-dVenus mice. In contrast, intraportal administration of CCK did not increase the number of c-Fos positive or Venus positive cells in the insular cortex. Intraportal CCK induced c-Fos expression in the dorsomedial hypothalamus, while intraportal L-arginine did not. This action of CCK was abolished by CHBV vagotomy. Intraportal L-arginine reduced, while intraportal CCK increased, the number of c-Fos positive cells in the nucleus tractus solitarii in a CHBV-dependent manner. The present results suggest that the CHBV

  10. L-Arginine

    Science.gov (United States)

    ... elderly (senile dementia), erectile dysfunction (ED), altitude sickness, nitrate tolerance, diabetes, diabetic nerve pain, kidney toxicity from cyclosporine, kidney disease, tuberculosis, critical illness, head and neck cancer, obesity, ovary disease (polycystic ovary syndrome), pressure ulcers, ...

  11. How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

    Science.gov (United States)

    Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

    2018-05-01

    The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

  12. Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Alizadeh, Mohammad; Safaeiyan, Abdolrasoul; Ostadrahimi, Alireza; Estakhri, Rassul; Daneghian, Sevana; Ghaffari, Aida; Gargari, Bahram Pourghassem

    2012-01-01

    We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 μg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NO(x)), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NO(x). HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NO(x) and TG. Copyright © 2012 S. Karger AG, Basel.

  13. How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

    Science.gov (United States)

    Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

    2017-12-01

    The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

  14. Oral administration of L-arginine in patients with angina or following myocardial infarction may be protective by increasing plasma superoxide dismutase and total thiols with reduction in serum cholesterol and xanthine oxidase

    Science.gov (United States)

    Tripathi, Pratima; Chandra, M

    2009-01-01

    Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA) and acute myocardial infarction (MI)]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days) resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD) and increase in the levels of total thiols (T-SH) and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO). These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes. PMID:20716909

  15. Oral Administration of L-Arginine in Patients With Angina or Following Myocardial Infarction May Be Protective By Increasing Plasma Superoxide Dismutase and Total Thiols With Reduction in Serum Cholesterol and Xanthine Oxidase

    Directory of Open Access Journals (Sweden)

    Pratima Tripathi

    2009-01-01

    Full Text Available Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA and acute myocardial infarction (MI]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD and increase in the levels of total thiols (T-SH and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO. These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes.

  16. A radioimmunoassay for vasopressin

    International Nuclear Information System (INIS)

    Glaenzer, K.

    1989-01-01

    Described are the development and RIA experimental clinical use of determination for an antidiuretic hormone, 8-arginine vasopressin. The lower limits of detection for this RIA were 0.3 pg/ml in the plasma and 0.6 pg/ml in the urine. For purposes of reference, plasma AVP levels were determined in 50 normal volunteers and found to average 1.2 ± 0.6 pg/ml in females and 1.7 ± 0.7 pg/ml in males. The average AVP excretion with the urine ws 73 ± 43 ng/day. AVP levels determined in urine and plasma samples from patients showing diabetes insipidus centralis or healthy subjects that had not been offered any drink for 24 hours provided evidence in confirmation of supposed physiological interactions. The plasma AVP concentrations of subjects, in which the osmotic processes were impaired by the effects of contrast media used for X-ray examinations, proved to be far above the maximum antidiuretic concentrations and were also very likely to be within the effective range for cardiovascular influences. A series of further examinations was to throw some light on the question whether dramatic surges in ADH during and after surgical replacement of the mitral valve would be accompagnied by the occurrence of a hypoosmolar syndrome. Other examinations were to give insights into the particular role of AVP in the regulation of blood pressure. The last series of examinations had the aim to elucidate the interactions between the angiotensin-renin system and AVP secretion, which were studied in healthy volunteers using the tilting table test both before and during suppression of angiotensin II formation by captopril. There was no conclusive evidence from these examinations that angiotensin II mediates the stimulation of plasma AVP under the conditions of passive orthostatism. (orig./MG) With 24 figs., 8 tabs [de

  17. A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test.

    Science.gov (United States)

    Gigliucci, Valentina; Buckley, Kathleen Niamh; Nunan, John; O'Shea, Karen; Harkin, Andrew

    2010-02-01

    The present study determined regional serotonin (5-HT) synthesis and metabolism changes associated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NA) and the influence of 5-HT receptor blockade in the antidepressant-like actions of L-NA in the forced swimming test (FST). Regional effects of L-NA (5,10 and 20mg/kg i.p.) on tryptophan hydroxylase (TPH) activity, the rate limiting enzyme for 5-HT synthesis, were determined by measuring accumulation of the transient intermediate 5-hydoxytryptophan (5-HTP) following in vivo administration of the amino acid decarboxylase inhibitor, NSD 1015 (100mg/kg). L-NA (5-20mg/kg) dose dependently increased 5-HTP accumulation, particularly in the amygdaloid cortex, following exposure to the FST. L-NA also provoked an increase in regional brain 5-HIAA concentrations and in the 5-HIAA:5-HT metabolism ratio. Co-treatment with NSD-1015 failed to consistently modify the antidepressant-like effects of L-NA in the FST. Sub-active doses of L-NA (1mg/kg) and the 5-HT re-uptake inhibitor fluoxetine (2.5mg/kg) acted synergistically to increase swimming in the test. Co-treatment with the non-selective 5-HT receptor antagonist metergoline (1, 2 and 4mg/kg), attenuated the L-NA (20mg/kg)-induced reduction in immobility and increase in swimming behaviours. Metergoline alone however provoked an increase in immobility and reduction in swimming behaviours in the test. A similar response was obtained following co-treatment with the preferential 5-HT(2A) receptor antagonist ketanserin (5mg/kg) and the 5-HT(2C) receptor antagonist RO-430440 (5mg/kg). Co-treatment with the 5-HT(1A) receptor antagonist WAY 100635 (0.3mg/kg) or the 5-HT(1B) receptor antagonist GR 127935 (4mg/kg) failed to influence the antidepressant-like activity of L-NA. Taken together these data provide further support for a role for 5-HT in the antidepressant-like properties of NOS inhibitors. Copyright 2009 Elsevier Inc. All rights reserved.

  18. Exogenous L-Arginine Attenuates the Effects of Angiotensin II on Renal Hemodynamics and the Pressure Natriuresis-Diuresis Relationship

    Science.gov (United States)

    Das, Satarupa; Mattson, David L.

    2014-01-01

    SUMMARY Administration of exogenous L-Arginine (L-Arg) attenuates Angiotensin II (AngII)-mediated hypertension and kidney disease in rats. The present study assessed renal hemodynamics and pressure-diuresis-natriuresis in anesthetized rats infused with vehicle, AngII (20 ng/kg/min, iv) or AngII + L-Arg (300 µg/kg/min, iv). Increasing renal perfusion pressure (RPP) from approximately 100 to 140 mmHg resulted in a 9–10 fold increase in urine flow and sodium excretion rate in control animals. In comparison, AngII infusion significantly reduced renal blood flow (RBF) and glomerular filtration rate (GFR) by 40–42% and blunted the pressure-dependent increase in urine flow and sodium excretion rate by 54–58% at elevated RPP. Supplementation of L-Arg reversed the vasoconstrictor effects of AngII and restored pressure-dependent diuresis to levels not significantly different from control rats. Experiments in isolated aortic rings were performed to assess L-Arg effects on the vasculature. Dose-dependent contraction to AngII (10−10M to 10−7M) was observed with a maximal force equal to 27±3% of the response to 10−5M phenylephrine. Contraction to 10−7M AngII was blunted by 75±3% with 10−4M L-Arg. The influence of L-Arg to blunt AngII mediated contraction was eliminated by endothelial denudation or incubation with nitric oxide synthase inhibitors. Moreover, the addition of 10−3M cationic or neutral amino acids, which compete with L-Arg for cellular uptake, blocked the effect of L-Arg. Anionic amino acids did not influence the effects of L-Arg on AngII-mediated contraction. These studies indicate that L-Arg blunts AngII-mediated vascular contraction by an endothelial- and NOS-dependent mechanism involving cellular uptake of L-Arg. PMID:24472006

  19. Biochemical enrichment and biophysical characterization of a taste receptor for L-arginine from the catfish, Ictalurus puntatus

    Directory of Open Access Journals (Sweden)

    Spielman Andrew I

    2004-07-01

    Full Text Available Abstract Background The channel catfish, Ictalurus punctatus, is invested with a high density of cutaneous taste receptors, particularly on the barbel appendages. Many of these receptors are sensitive to selected amino acids, one of these being a receptor for L-arginine (L-Arg. Previous neurophysiological and biophysical studies suggested that this taste receptor is coupled directly to a cation channel and behaves as a ligand-gated ion channel receptor (LGICR. Earlier studies demonstrated that two lectins, Ricinus communis agglutinin I (RCA-I and Phaseolus vulgaris Erythroagglutinin (PHA-E, inhibited the binding of L-Arg to its presumed receptor sites, and that PHA-E inhibited the L-Arg-stimulated ion conductance of barbel membranes reconstituted into lipid bilayers. Results Both PHA-E and RCA-I almost exclusively labeled an 82–84 kDa protein band of an SDS-PAGE of solubilized barbel taste epithelial membranes. Further, both rhodamine-conjugated RCA-I and polyclonal antibodies raised to the 82–84 kDa electroeluted peptides labeled the apical region of catfish taste buds. Because of the specificity shown by RCA-I, lectin affinity was chosen as the first of a three-step procedure designed to enrich the presumed LGICR for L-Arg. Purified and CHAPS-solubilized taste epithelial membrane proteins were subjected successively to (1, lectin (RCA-I affinity; (2, gel filtration (Sephacryl S-300HR; and (3, ion exchange chromatography. All fractions from each chromatography step were evaluated for L-Arg-induced ion channel activity by reconstituting each fraction into a lipid bilayer. Active fractions demonstrated L-Arg-induced channel activity that was inhibited by D-arginine (D-Arg with kinetics nearly identical to those reported earlier for L-Arg-stimulated ion channels of native barbel membranes reconstituted into lipid bilayers. After the final enrichment step, SDS-PAGE of the active ion channel protein fraction revealed a single band at 82–84 k

  20. Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats Efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensas

    Directory of Open Access Journals (Sweden)

    José Ricardo Sousa Ayres de Moura

    2006-08-01

    Full Text Available PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR. METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1. Pregnancy was confirmed by sperm-positive vaginal smear (Day 0. Wistar-EPM-1 rats served as counterpart control (C-1. SHR rats were randomized in 4 groups (n=10: Group Control 2, non-treated rats; Group L-Arginine treated with L-arginine 2%; Group Alpha-methyldopa treated with Alpha-methyldopa 33mg/Kg; Group L-Arginine+Alpha-methyldopa treated with L-arginine 2%+Alpha-methyldopa 33mg/Kg. L-arginine 2% solution was offered ad libitum in drinking water and Alpha-methyldopa was administered by gavage twice a day during the length of pregnancy (20 days. Blood pressure was measured by tailcuff plethysmography on days 0 and 20. Body weight was measured on days 0, 10 and 20. Results were expressed as mean ± SD (Standard Deviation. One-Way ANOVA/Tukey (or Kruskal-Wallis/Dunn, as appropriate was used for group comparisons. Statistical significance was accepted as pOBJETIVO: Avaliar os efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensivas (SHR. MÉTODOS: 30 SHR e 10 Wistar-EPM-1 ratas virgens foram utilizadas no estudo. Antes da distribuição, as fêmeas foram acasaladas com machos da mesma linhagem (3:1; a prenhez foi confirmada pela presença de espermatozóides no esfregaço vaginal. As ratas Wistar-EPM-1 foram utilizadas como controles. As ratas SHR foram aleatoriamente distribuídas em 4 grupos (n=10: Grupo Controle-2, não-tratado; Grupo L-Arginina, tratado com L-arginina; Grupo Alfa-metildopa, tratado com alfa-metildopa; Grupo L-Arginina+Alfa-metildopa, tratado com arginina+Alfa-metildopa. L-arginina (2% foi oferecida ad libitum na água de beber e a Alfa-metildopa (33 mg/Kg foi administrada por gavagem, duas vezes ao dia, durante toda a

  1. Inhibition of the L-arginine-nitric oxide pathway mediates the antidepressant effects of ketamine in rats in the forced swimming test.

    Science.gov (United States)

    Zhang, Guang-Fen; Wang, Nan; Shi, Jin-Yun; Xu, Shi-Xia; Li, Xiao-Min; Ji, Mu-Huo; Zuo, Zhi-Yi; Zhou, Zhi-Qiang; Yang, Jian-Jun

    2013-09-01

    Converging evidence shows that the acute administration of a sub-anaesthetic dose ketamine produces fast-acting and robust antidepressant properties in patients suffering from major depressive disorder. However, the underlying mechanisms have not been fully elucidated. The present study aimed to investigate the role of the L-arginine-nitric oxide pathway in the antidepressant effects of ketamine in rats performing the forced swimming test (FST). Ketamine (10 mg/kg) significantly decreased immobility times in the FST and the activities of total nitric oxide synthases (T-NOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in the rat hippocampus. Interestingly, the plasma activities of T-NOS, iNOS, and eNOS increased after administration of ketamine. Furthermore, the activities of neuronal NOS (nNOS) did not change significantly in either the hippocampus or plasma after ketamine administration. The antidepressant effects of ketamine were prevented by pre-treatment with l-arginine (750 mg/kg). Pre-treatment with the NOS inhibitor L-NG-nitroarginine methyl ester at a sub-antidepressant dose of 50 mg/kg and ketamine at a sub-antidepressant dose of 3 mg/kg reduced immobility time in the FST compared to treatment with either drug alone. None of the drugs affected crossing and rearing scores in the open field test. These results suggest that the L-arginine-nitric oxide pathway is involved in the antidepressant effects of ketamine observed in rats in the FST and this involvement is characterised by the inhibition of brain T-NOS, iNOS, and eNOS activities. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Metabolically induced heteroplasmy shifting and L-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS

    Science.gov (United States)

    Desquiret-Dumas, Valerie; Gueguen, Naig; Barth, Magalie; Chevrollier, Arnaud; Hancock, Saege; Wallace, Douglas C; Amati-Bonneau, Patrizia; Henrion, Daniel; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent

    2012-01-01

    The m.3243A>G variant in the mitochondrial tRNALeu (UUR) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of L-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of L-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and L-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID:22306605

  3. Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

    Directory of Open Access Journals (Sweden)

    C.H. Santuzzi

    2015-01-01

    Full Text Available Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK and L-arginine treatment both alone and in combination on blood pressure (BP, and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C hypertension, 2K1C+ALSK (ALSK, 2K1C+L-arginine (L-arg, and 2K1C+ALSK+L-arginine (ALSK+L-arg treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

  4. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome.

    Directory of Open Access Journals (Sweden)

    Lance H Rodan

    Full Text Available To study the effects of L-arginine (L-Arg on total body aerobic capacity and muscle metabolism as assessed by (31Phosphorus Magnetic Resonance Spectroscopy ((31P-MRS in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes syndrome.We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR in MTTL1 gene with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine.At baseline (no L-Arg, MELAS had lower serum Arg (p = 0.001. On 3(1P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr (p = 0.05, decreased ATP (p = 0.018, and decreased intracellular Mg(2+ (p = 0.0002 when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1 increase in mean % maximum work at anaerobic threshold (AT (2 increase in % maximum heart rate at AT (3 small increase in VO(2peak. On (31P-MRS the following mean trends were noted: (1 A blunted decrease in pH after exercise (less acidosis (2 increase in Pi/PCr ratio (ADP suggesting increased work capacity (3 a faster half time of PCr recovery (marker of mitochondrial activity following 5 minutes of moderate intensity exercise (4 increase in torque.These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study.Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects.ClinicalTrials.gov NCT01603446.

  5. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.

    Science.gov (United States)

    Rodan, Lance H; Wells, Greg D; Banks, Laura; Thompson, Sara; Schneiderman, Jane E; Tein, Ingrid

    2015-01-01

    To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. ClinicalTrials.gov NCT01603446.

  6. Modeling of Reactive Blue 19 azo dye removal from colored textile wastewater using L-arginine-functionalized Fe{sub 3}O{sub 4} nanoparticles: Optimization, reusability, kinetic and equilibrium studies

    Energy Technology Data Exchange (ETDEWEB)

    Dalvand, Arash; Nabizadeh, Ramin [Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Reza Ganjali, Mohammad [Center of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, Tehran (Iran, Islamic Republic of); Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Khoobi, Mehdi [Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176 (Iran, Islamic Republic of); Nazmara, Shahrokh [Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Hossein Mahvi, Amir, E-mail: ahmahvi@yahoo.com [Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Center for Solid Waste Research, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); National Institute of Health Research, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-04-15

    This study aimed to investigate the removal of Reactive Blue 19 from colored wastewater using Fe{sub 3}O{sub 4} magnetic nanoparticles modified with L-arginine (Fe{sub 3}O{sub 4}@L-arginine). In order to investigate the effect of independent variables on dye removal and determining the optimum condition, the Box–Behnken Design (BBD) under Response Surface Methodology (RSM) was employed. Fe{sub 3}O{sub 4}@L-arginine nanoparticles were synthesized and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and vibrating sample magnetometer. Applying Fe{sub 3}O{sub 4}@L-arginine nanoparticles for dye removal showed that; by increasing adsorbent dose and decreasing pH, dye concentration, and ionic strength dye removal has been increased. In the optimum condition, Fe{sub 3}O{sub 4}@L-arginine nanoparticles were able to remove dye as high as 96.34% at an initial dye concentration of 50 mg/L, adsorbent dose of 0.74 g/L, and pH 3. The findings indicated that dye removal followed pseudo-second-order kinetic (R{sup 2}=0.999) and Freundlich isotherm (R{sup 2}=0.989). Based on the obtained results, as an efficient and reusable adsorbent, Fe{sub 3}O{sub 4}@L-arginine nanoparticles can be successfully applied for dye removal from colored wastewater. - Highlights: • The Fe{sub 3}O{sub 4}@L-arginine removed RB 19 azo dye from wastewater efficiently. • BBD under RSM was used to analyze and optimize the adsorption process. • pH was the most influential parameter in dye removal.

  7. [Experimental and computation studies of polar solvation

    International Nuclear Information System (INIS)

    1990-01-01

    This report from the Pennsylvania State University contains seven sections: (1) radiative rate effects in solvatlvatochromic probes; (2) intramolecular charge transfer reactions; (3) Solvation dynamics in low temperature alcohols; (4) Ionic solvation dynamics; (5) solvation and proton-transfer dynamics in 7-azaindole; (6) computer simulations of solvation dynamics; (7) solvation in supercritical fluids. 20 refs., 11 figs

  8. Interfacial electrostatics of poly(vinylamine hydrochloride), poly(diallyldimethylammonium chloride), poly-l-lysine, and poly-l-arginine interacting with lipid bilayers.

    Science.gov (United States)

    McGeachy, A C; Dalchand, N; Caudill, E R; Li, T; Doğangün, M; Olenick, L L; Chang, H; Pedersen, J A; Geiger, F M

    2018-04-25

    Charge densities of cationic polymers adsorbed to lipid bilayers are estimated from second harmonic generation (SHG) spectroscopy and quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. The systems surveyed included poly(vinylamine hydrochloride) (PVAm), poly(diallyldimethylammonium chloride) (PDADMAC), poly-l-lysine (PLL), and poly-l-arginine (PLR), as well as polyalcohol controls. Upon accounting for the number of positive charges associated with each polyelectrolyte, the binding constants and apparent free energies of adsorption as estimated from SHG data are comparable despite differences in molecular masses and molecular structure, with ΔGads values of -61 ± 2, -58 ± 2, -57 ± 1, -52 ± 2, -52 ± 1 kJ mol-1 for PDADMAC400, PDADMAC100, PVAm, PLL, and PLR, respectively. Moreover, we find charge densities for polymer adlayers of approximately 0.3 C m-2 for poly(diallyldimethylammonium chloride) while those of poly(vinylamine) hydrochloride, poly-l-lysine, and poly-l-arginine are approximately 0.2 C m-2. Time-dependent studies indicate that polycation adsorption to supported lipid bilayers is only partially reversible for most of the polymers explored. Poly(diallyldimethylammonium chloride) does not demonstrate reversible binding even over long timescales (>8 hours).

  9. Comparison of the effects of NG-nitro-L-arginine and indomethacin on the hypercapnic cerebral blood flow increase in rats

    DEFF Research Database (Denmark)

    Wang, Qian; Pelligrino, D A; Paulson, O B

    1994-01-01

    The effects of NG-nitro-L-arginine (NOLAG), an inhibitor of nitric oxide synthase (NOS), and of indomethacin, an inhibitor of cyclooxygenase, on the rise in cerebral blood flow (CBF) accompanying increasing levels of hypercapnia (paCO2 = 40-135 mmHg) were studied in anesthetized rats. CBF...... with additional step increase in paCO2. Intracarotid infusion of 7.5 mg/kg NOLAG significantly attenuated the CO2-elicited CBF increase by about 45-65% at paCO2 values below 115 mmHg. Beyond this level, there was a lesser inhibition of about 27-35%. 30 mg/kg NOLAG had essentially the same effect as 7.5 mg....../kg NOLAG. 50 mg/kg NOLAG, given intraperitoneally (i.p.) twice daily for 4 days, also caused an attenuated CBF response to CO2, but the inhibitory effect was significantly less than with acute NOLAG administration in the paCO2 range of 61-90 mmHg. Infusion of L-arginine, 1 g/kg/h, prevented the effect of 7...

  10. L-Arginine modified multi-walled carbon nanotube/sulfonated poly(ether ether ketone) nanocomposite films for biomedical applications

    Science.gov (United States)

    Kaya, Hatice; Bulut, Osman; Kamali, Ali Reza; Ege, Duygu

    2018-06-01

    Favorable implant-tissue interactions are crucial to achieve successful osseointegration of the implants. Poly(ether ether ketone) (PEEK) is an interesting alternative to titanium in orthopedics because of its low cost, high biocompatibility and comparable mechanical properties with cancellous bone. Despite these advantages; however, the untreated surface of PEEK fails to osseointegrate due to its bioinert and hydrophobic behavior. This paper deals with the surface modification of PEEK with a novel method. For this, PEEK was first treated with concentrated sulfuric acid to prepare sulfonated PEEK (SPEEK) films using a solvent casting method. Then, 1 and 2 wt% multi-walled carbon nanotube was incorporated into SPEEK to form nanocomposite films. The samples were characterized with Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy. After successful preparation of the nanocomposite films, L-arginine was covalently conjugated on the nanocomposite films to further improve their surface properties. Subsequently, the samples were characterized using X-ray Photoemission Spectroscopy (XPS), water contact angle measurements and Atomic Force Microscopy (AFM) and Dynamic Mechanical Thermal Analysis (DMTA). Finally, cell culture studies were carried out by using Alamar Blue assay to evaluate the biocompatibility of the films. The results obtained indicate the successful preparation of L-arginine-conjugated MWCNT/SPEEK nanocomposite films. The modified surface shows potential to improve implants' mechanical and biological performances.

  11. Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliação do pré-tratamento com Nw-nitro-L-arginine methyl ester (L-NAME The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME

    Directory of Open Access Journals (Sweden)

    Edgard Ferro Collares

    2006-09-01

    Full Text Available RACIONAL: Há evidências de que o óxido nítrico participa do mecanismo de retardo do esvaziamento gástrico determinado pelo lipopolissacarídio bacteriano. OBJETIVO: Avaliar o efeito do pré-tratamento com Nw-nitro-L-arginine methyl ester, um inibidor competitivo das óxido nítrico-sintetases, sobre o fenômeno. MATERIAL E MÉTODOS: Utilizaram-se ratos, Wistar, machos, SPF ("specific-pathogen free", adultos, adaptados às condições do laboratório, que após 24 horas de jejum alimentar foram pré-tratados endovenosamente com veículo (salina ou Nw-nitro-L-arginine methyl ester nas doses de 0,5, 1, 2,5 e 5 mg/kg. No tratamento, administrou-se endovenosamente veículo (salina ou lipopolissacarídio (50 µg/kg. O intervalo entre o pré-tratamento e o tratamento foi de 10 minutos, e entre este e a avaliação do esvaziamento gástrico foi de 60 minutos. O esvaziamento gástrico foi avaliado indiretamente através da determinação da retenção gástrica da solução salina marcada com fenol vermelho 10 minutos após administração por via orogástrica. RESULTADOS: Entre os animais pré-tratados com veículo, o tratamento com lipopolissacarídio determinou elevação significativa da retenção gástrica (média = 57% em relação aos tratados com veículo (38,1%. O pré-tratamento com as diferentes doses de Nw-nitro-L-arginine methyl ester não modificou a retenção gástrica nos animais controles do tratamento. O pré-tratamento com Nw-nitro-L-arginine methyl ester com a dose de 1 mg/kg determinou redução discreta, mas significativa, na retenção gástrica (52% nos animais tratados com lipopolissacarídio, em relação ao observado naqueles com pré-tratamento e tratamento com veículo (35,9%. Nos animais pré-tratados com 2,5 e 5 mg/kg de Nw-nitro-L-arginine methyl ester e tratados com lipopolissacarídio, houve aumento significante da retenção gástrica (74,7% e 80,5%, respectivamente em relação aos seus controles pr

  12. Interfacial solvation thermodynamics

    International Nuclear Information System (INIS)

    Ben-Amotz, Dor

    2016-01-01

    Previous studies have reached conflicting conclusions regarding the interplay of cavity formation, polarizability, desolvation, and surface capillary waves in driving the interfacial adsorptions of ions and molecules at air–water interfaces. Here we revisit these questions by combining exact potential distribution results with linear response theory and other physically motivated approximations. The results highlight both exact and approximate compensation relations pertaining to direct (solute–solvent) and indirect (solvent–solvent) contributions to adsorption thermodynamics, of relevance to solvation at air–water interfaces, as well as a broader class of processes linked to the mean force potential between ions, molecules, nanoparticles, proteins, and biological assemblies. (paper)

  13. Comparison of Three Sample Preparation Procedures for the Quantification of L-Arginine, Asymmetric Dimethylarginine, and Symmetric Dimethylarginine in Human Plasma Using HPLC-FLD

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie Voigt; Lykkesfeldt, Jens

    2018-01-01

    Increased asymmetric dimethylarginine (ADMA) in human plasma has been associated with reduced generation of nitric oxide, leading to atherosclerotic diseases. ADMA may therefore be an important biomarker for cardiovascular disease. In the present study, three sample preparation techniques were co...... sample preparation of human plasma samples before HPLC-FLD in providing important information regarding elevated ADMA concentrations.......Increased asymmetric dimethylarginine (ADMA) in human plasma has been associated with reduced generation of nitric oxide, leading to atherosclerotic diseases. ADMA may therefore be an important biomarker for cardiovascular disease. In the present study, three sample preparation techniques were...... compared regarding the quantification of L-arginine and ADMA in human plasma: (A) protein precipitation (PP) based on aqueous trichloroacetic acid (TCA), (B) PP using a mixture of ammonia and acetonitrile, and (C) solid-phase extraction (SPE). The samples were analysed by using high-performance liquid...

  14. Comparison of Three Sample Preparation Procedures for the Quantification of L-Arginine, Asymmetric Dimethylarginine, and Symmetric Dimethylarginine in Human Plasma Using HPLC-FLD

    Science.gov (United States)

    Schou-Pedersen, Anne Marie Voigt

    2018-01-01

    Increased asymmetric dimethylarginine (ADMA) in human plasma has been associated with reduced generation of nitric oxide, leading to atherosclerotic diseases. ADMA may therefore be an important biomarker for cardiovascular disease. In the present study, three sample preparation techniques were compared regarding the quantification of L-arginine and ADMA in human plasma: (A) protein precipitation (PP) based on aqueous trichloroacetic acid (TCA), (B) PP using a mixture of ammonia and acetonitrile, and (C) solid-phase extraction (SPE). The samples were analysed by using high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The analytical performance of (A) was comparable with that of (C), demonstrating recoveries of >90%, coefficient of variations (CVs, %) of 0.994), precision (sample preparation of human plasma samples before HPLC-FLD in providing important information regarding elevated ADMA concentrations. PMID:29484214

  15. Time-dependent alterations in serum NO concentration after oral administration of L-arginine, L-NAME, and allopurinol in intestinal ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Amalia E Yanni

    2008-04-01

    Full Text Available Amalia E Yanni1, Eleutherios Margaritis2, Nikolaos Liarakos2, Alkisti Pantopoulou2, Maria Poulakou2, Maria Kostakis2, Despoina Perrea2, Alkis Kostakis31Department of Science of Dietetics and Nutrition, Harokopio University of Athens, Athens, Greece, 2Laboratory of Experimental Surgery and Surgical Research, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, 32nd Department of Propedeutic Surgery, School of Medicine, National and Kapodistrian University of Athens, Athens, GreeceObjective: To study the effect of oral administration of a nitric oxide (NO donor L-arginine (L-Arg, a NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME and an inhibitor of xanthine oxidase, allopurinol (Allo, on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R in rats.Methods: Male Wistar rats received per os L-Arg (800 mg/kg or L-NAME (50 mg/kg or Allo (100 mg/kg 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (L-Arg(IR1, L-NAME(IR1 and Allo(IR1 respectively or 1 hr occlusion followed by 8 hrs of reperfusion (L-Arg(IR8, L-NAME(IR8 and Allo(IR8 respectively. There was one group underwent 1 hr occlusion (I, a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1, a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8 and a last group that served as control (C. Serum NO concentration and catalase activity were measured.Results: After 1 hr of reperfusion serum NO concentration was elevated in IR1 and L-Arg(IR1 groups compared with group C but not in L-NAME(IR1 and Allo(IR1 group. Catalase activity was enhanced in L-NAME(IR1 group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, L-Arg(IR8, L-NAME(IR8 and Allo(IR8 compared with control while catalase activity did not show significant difference in any group.Conclusions: The results of the

  16. A novel method for the functionalization of aminoacids L-glycine, L-glutamic acid and L-arginine on maghemite/magnetite nanoparticles

    Science.gov (United States)

    Bruno, A. J.; Correa, J. R.; Peláez-Abellán, E.; Urones-Garrote, E.

    2018-06-01

    Nanoparticles of maghemite/magnetite functionalized with L-glycine, L-glutamic acid and L-arginine were synthesized by a novel method. The novel procedure consists in an alternative of that reported by Massart for the precipitation of magnetite in which the aminoacid is added in the carboxylate form. The amounts of aminoacid in the initial molar concentrations were 35%, 45% and 65% with respect to the ferrophase. The obtained nanoparticles were characterized by several techniques: X-ray diffraction (XRD), Fourier transform IR spectroscopy (FT-IR), transmission electron microscopy (TEM), Electron energy-loss spectroscopy (EELS) and magnetometry. The IR spectroscopy confirmed that the selected aminoacids were functionalized on the surface of iron oxide. XRD and EELS confirm that iron oxide consists of a maghemite-magnetite intermediate phase with an average particle size about 6 nm, which was measured by transmission electron microscopy. The superparamagnetic character of the nanoparticles was evaluated by magnetometry.

  17. Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study.

    Directory of Open Access Journals (Sweden)

    Patricia Hafner

    Full Text Available Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d and metformin (2 x 250 mg/d for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients.ClinicalTrials.gov NCT02516085.

  18. On the synthesis of tailored biomimetic hydroxyapatite nanoplates through a bioinspired approach in the presence of collagen or chitosan and L-arginine

    Energy Technology Data Exchange (ETDEWEB)

    Tsetsekou, A., E-mail: athtse@metal.ntua.gr; Brasinika, D.; Vaou, V.; Chatzitheodoridis, E.

    2014-10-01

    Controlling the structure of hydroxyapatite nanocrystals is vital for acquiring a consistent product. In an effort to synthesize crystals mimicking the morphology of natural bone's apatite, a bioinspired process was developed based on the use of a natural biomacromolecule, collagen or chitosan, in conjunction with L-arginine to direct the formation of hydroxyapatite from H{sub 3}PO{sub 4} and Ca(OH){sub 2}. Different cases were investigated by employing various concentrations of the precursors and two molar ratios of Ca/P 1/1 and 10/6. The reaction was carried out at basic pH conditions and at biomimetic temperature (40 °C). The resulting aqueous suspensions were characterized in terms of their rheological behavior, whereas the derived powders were fully evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis and Raman spectroscopy. The analysis showed that in all cases, the only phase detected was hydroxyapatite of a plate-like morphology very similar to that of natural apatite. The homogeneity of the morphology and the crystal size distribution depend on the precursors' final concentration with the mean size ranging from 5 nm up to 20 nm. The powder that demonstrated the best characteristics in terms of homogeneity was that produced in the presence of collagen for molar ratio of Ca/P 1/1. - Highlights: • Hydroxyapatite nanoplates similar to those of bone's apatite were developed. • A novel approach simulating the biomineralization environment was developed. • L-Arginine was combined with collagen or chitosan to direct HAp nucleation. • Depending on reaction conditions a very homogeneous nanostructure is attained.

  19. On the synthesis of tailored biomimetic hydroxyapatite nanoplates through a bioinspired approach in the presence of collagen or chitosan and L-arginine

    International Nuclear Information System (INIS)

    Tsetsekou, A.; Brasinika, D.; Vaou, V.; Chatzitheodoridis, E.

    2014-01-01

    Controlling the structure of hydroxyapatite nanocrystals is vital for acquiring a consistent product. In an effort to synthesize crystals mimicking the morphology of natural bone's apatite, a bioinspired process was developed based on the use of a natural biomacromolecule, collagen or chitosan, in conjunction with L-arginine to direct the formation of hydroxyapatite from H 3 PO 4 and Ca(OH) 2 . Different cases were investigated by employing various concentrations of the precursors and two molar ratios of Ca/P 1/1 and 10/6. The reaction was carried out at basic pH conditions and at biomimetic temperature (40 °C). The resulting aqueous suspensions were characterized in terms of their rheological behavior, whereas the derived powders were fully evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis and Raman spectroscopy. The analysis showed that in all cases, the only phase detected was hydroxyapatite of a plate-like morphology very similar to that of natural apatite. The homogeneity of the morphology and the crystal size distribution depend on the precursors' final concentration with the mean size ranging from 5 nm up to 20 nm. The powder that demonstrated the best characteristics in terms of homogeneity was that produced in the presence of collagen for molar ratio of Ca/P 1/1. - Highlights: • Hydroxyapatite nanoplates similar to those of bone's apatite were developed. • A novel approach simulating the biomineralization environment was developed. • L-Arginine was combined with collagen or chitosan to direct HAp nucleation. • Depending on reaction conditions a very homogeneous nanostructure is attained

  20. Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study.

    Science.gov (United States)

    Hafner, Patricia; Bonati, Ulrike; Erne, Beat; Schmid, Maurice; Rubino, Daniela; Pohlman, Urs; Peters, Thomas; Rutz, Erich; Frank, Stephan; Neuhaus, Cornelia; Deuster, Stefanie; Gloor, Monika; Bieri, Oliver; Fischmann, Arne; Sinnreich, Michael; Gueven, Nuri; Fischer, Dirk

    2016-01-01

    Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients. ClinicalTrials.gov NCT02516085.

  1. Heterologous radioimmunoassay for arginine vasopressin

    International Nuclear Information System (INIS)

    Shimamoto, K.; Murase, T.; Yamaji, T.

    1976-01-01

    A sensitive and specific radioimmunoassay for arginine vasopressin (AVP) was developed utilizing the antisera against lysine vasopressin (LVP) in combination with a labeled AVP. The assay employs an acetone extraction procedure and detects as little as 0.8 pg. per millimeter of AVP in human plasma. In normal subjects, the mean (+- S.D.) plasma concentration of AVP was 4.9 +- 1.2 pg. per milliliter after fluid deprivation and 1.2 +- 0.4 pg. per milliliter after water loading. Plasma AVP levels correlated significantly with plasma osmolalities. In four patients with diabetes insipidus, plasma AVP concentrations ranged from less than 0.8 to 1.2 pg. per milliliter, whereas six patients with the syndrome of inappropriate ADH secretion showed plasma levels of AVP which correspond to those of the dehydrated state in normal subjects or greater, although plasma osmolalities were low in all cases. It was concluded that the present radioimmunoassay method for AVP provides a useful way of assessing neurohypophyseal function in man

  2. Effects of acute and chronic stress on the L-arginine nitric oxide pathway in black and white South Africans: the sympathetic activity and ambulatory blood pressure in Africans study.

    Science.gov (United States)

    Reimann, Manja; Hamer, Mark; Malan, Nicolaas T; Schlaich, Markus P; Lambert, Gavin W; Ziemssen, Tjalf; Boeger, Rainer H; Malan, Leoné

    2013-10-01

    This study investigated the impact of stress on effectors of the L-arginine/nitric oxide (NO) system including the endogenous inhibitor asymmetric dimethylarginine (ADMA). Black (n = 168) and white (n = 206) South African teachers were exposed to a mental and a physical stressor for 1 minute, respectively. Serum samples for determination of l-arginine, NO metabolites, ADMA, and symmetric dimethylarginine (SDMA) were obtained at rest and during stress exposure. Perception of task stressfulness was assessed on a 7-point Likert scale, and psychological distress was estimated by the General Health Questionnaire. Black South Africans exhibited higher resting levels of NO metabolites (adjusted mean [standard error of the mean] = 11.3 [1.3] versus 3.9 [1.1] μmol/l, p stress were evident for NO metabolites (blacks versus whites: 5.94 [1.55] versus -0.74 [1.25] μmol/l, p = .004) and SDMA (blacks versus whites: -0.02 [0.01] versus 0.02 [0.01] μmol/l, p = .004). Ethnicity-by-psychological distress interaction for stress responses was found for l-arginine/ADMA ratio (p = .027). The l-arginine/NO system is affected by psychosocial distress with higher susceptibility in black South Africans. This interaction may contribute to the higher cardiovascular disease risk in black South Africans.

  3. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters

    Directory of Open Access Journals (Sweden)

    Hüseyin Ilgü

    2018-03-01

    Full Text Available The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg, agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5, an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  4. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.

    Science.gov (United States)

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

    2018-03-20

    The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures ( T m s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting T m s indicated stabilization of AdiC variants upon ligand binding, in which T m s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  5. The radioimmunological determination of vasopressin in urine

    International Nuclear Information System (INIS)

    Horn, M.J. van der.

    1981-01-01

    This thesis describes the development of a radioimmunoassay (RIA) for antidiuretic hormone (ADH) or vasopressin, which can be used for the quantitative measurement of the urinary excretion of the hormone in man during physiological and pathological conditions. The final RIA method, using approximately 5 pg 125 I-AVP diluted (1 : 50,000) antiserum 121 and charcoal-dextran separation of the antibody-bound and free fractions, is found to be specific for vasopressin and closely related substances; the sensitivity is 9 pg. The validity is demonstrated and the results of measurements of vasopressin excretion in urine from 39 normal subjects, including 4 children are presented. (Auth.)

  6. Intracellular acidification reduces l-arginine transport via system y+L but not via system y+/CATs and nitric oxide synthase activity in human umbilical vein endothelial cells.

    Science.gov (United States)

    Ramírez, Marco A; Morales, Jorge; Cornejo, Marcelo; Blanco, Elias H; Mancilla-Sierpe, Edgardo; Toledo, Fernando; Beltrán, Ana R; Sobrevia, Luis

    2018-04-01

    l-Arginine is taken up via the cationic amino acid transporters (system y + /CATs) and system y + L in human umbilical vein endothelial cells (HUVECs). l-Arginine is the substrate for endothelial NO synthase (eNOS) which is activated by intracellular alkalization, but nothing is known regarding modulation of system y + /CATs and system y + L activity, and eNOS activity by the pHi in HUVECs. We studied whether an acidic pHi modulates l-arginine transport and eNOS activity in HUVECs. Cells loaded with a pH-sensitive probe were subjected to 0.1-20 mmol/L NH 4 Cl pulse assay to generate pHi 7.13-6.55. Before pHi started to recover, l-arginine transport (0-20 or 0-1000 μmol/L, 10 s, 37 °C) in the absence or presence of 200 μmol/L N-ethylmaleimide (NEM) (system y + /CATs inhibitor) or 2 mmol/L l-leucine (systemy + L substrate) was measured. Protein abundance for eNOS and serine 1177 or threonine 495 phosphorylated eNOS was determined. The results show that intracellular acidification reduced system y + L but not system y + /CATs mediated l-arginine maximal transport capacity due to reduced maximal velocity. Acidic pHi reduced NO synthesis and eNOS serine 1177 phosphorylation. Thus, system y + L activity is downregulated by an acidic pHi, a phenomenon that may result in reduced NO synthesis in HUVECs. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Dietary L-arginine supplement alleviates hepatic heat stress and improves feed conversion ratio of Pekin ducks exposed to high environmental temperature.

    Science.gov (United States)

    Zhu, W; Jiang, W; Wu, L Y

    2014-12-01

    The current intensive indoor production system of commercial Pekin ducks never allows adequate water for swimming or wetting. Therefore, heat stress is a key factor affecting health and growth of ducks in the hot regions and season. Experiment 1 was conducted to study whether heat stress was deleterious to certain organs of ducks. Forty-one-day-old mixed-sex Pekin ducks were randomly allocated to four electrically heated battery brooders comprised of 10 ducks each. Ducks were suddenly exposed to 37 °C ambient temperature for 3 h and then slaughtered, in one brooder at 21 days and in another brooder at 49 days of age. The results showed that body weight and weight of immune organs, particularly liver markedly decreased in acute heat stress ducks compared with the control. Experiment 2 was carried out to investigate the influences of dietary L-arginine (Arg) supplement on weight and compositions of certain lymphoid organs, and growth performance in Pekin ducks, under daily cyclic hot temperature environment. A total of 151-day-old mixed-sex Pekin ducks were randomly divided into one negative control and two treatment groups, fed experimental diets supplemented with 0, 5, and 10 g L-Arginine (L-Arg)/kg to the basal diet respectively. Ducks were exposed to cyclic high temperature simulating natural summer season. The results showed that the addition of L-Arg improves feed conversion ratio (FCR) during a period of 7-week trial, as well as increases hepatic weight relative to body weight at 21 days, while decreases the hepatic water content at 49 days of age. This study indicated that the liver was more sensitive to acute heat stress, and the hepatic relative weight and chemical composition could be regulated by dietary L-Arg supplementation in Pekin ducks being reared at high ambient temperature. These beneficial effects of Arg on liver might be a cause of improved FCR. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  8. A novel sensor based on electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode for determination of fluoroquinolones

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Fenfen [School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); Gu, Shuqing [Department of Chemistry, Shanghai University, Shanghai 200444 (China); School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); Ding, Yaping, E-mail: wdingyp@sina.com [Department of Chemistry, Shanghai University, Shanghai 200444 (China); School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); Zhang, Zhen [School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); School of Chemistry and Chemical Engineering, Linyi University, 18 TongDa Road, Linyi 276005 (China); Li, Li [Department of Chemistry, Shanghai University, Shanghai 200444 (China)

    2013-04-03

    Graphical abstract: The inner cavities of β-CD could restrain fluoroquinolones to form stable host–guest inclusion complexes, and the guanidyl group of L-arg could enable L-arg to form electrostatic interactions with negatively charged groups -COO{sup −} of fluoroquinolones. Highlights: ► Electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode. ► The electrooxidation and reaction of FQs on the modified CPE were surmised. ► The sensor is used to detect ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. ► Determine FQs drugs in pharmaceutical formulations and human serum samples. ► It showed high stability, repeatability, reproducibility, good sensitivity. -- Abstract: An electrochemical sensor for fluoroquinolones (FQs) based on polymerization of β-cyclodextrin (β-CD) and L-arginine (L-arg) modified carbon paste electrode (CPE) (P-β-CD-L-arg/CPE) was built for the first time. Synergistic effect of L-arg and β-CD was used to construct this sensor for quantification of these important antibiotics. Scanning electron microscope (SEM) image shows that polymer of β-CD and L-arg has been successfully modified on electrode. Electrochemical impedance spectroscopy (EIS) and cyclic voltammograms (CV) further indicate that polymer of β-CD and L-arg efficiently decreased the charge transfer resistance value of electrode and improved the electron transfer kinetic between analyte and electrode. Under the optimized conditions, this modified electrode was utilized to determine the concentrations of ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. The differential pulse voltammogram (DPV) exhibits the oxidation peak currents were linearly proportional to their concentration in the range of 0.05–100 μM for ciprofloxacin, 0.1–100 μM for ofloxacin, 0.1–40 μM for norfloxacin and 0.06–100 μM for gatifloxacin, respectively. This method was also successfully used to detect the concentrations of each drug in

  9. A novel sensor based on electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode for determination of fluoroquinolones

    International Nuclear Information System (INIS)

    Zhang, Fenfen; Gu, Shuqing; Ding, Yaping; Zhang, Zhen; Li, Li

    2013-01-01

    Graphical abstract: The inner cavities of β-CD could restrain fluoroquinolones to form stable host–guest inclusion complexes, and the guanidyl group of L-arg could enable L-arg to form electrostatic interactions with negatively charged groups -COO − of fluoroquinolones. Highlights: ► Electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode. ► The electrooxidation and reaction of FQs on the modified CPE were surmised. ► The sensor is used to detect ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. ► Determine FQs drugs in pharmaceutical formulations and human serum samples. ► It showed high stability, repeatability, reproducibility, good sensitivity. -- Abstract: An electrochemical sensor for fluoroquinolones (FQs) based on polymerization of β-cyclodextrin (β-CD) and L-arginine (L-arg) modified carbon paste electrode (CPE) (P-β-CD-L-arg/CPE) was built for the first time. Synergistic effect of L-arg and β-CD was used to construct this sensor for quantification of these important antibiotics. Scanning electron microscope (SEM) image shows that polymer of β-CD and L-arg has been successfully modified on electrode. Electrochemical impedance spectroscopy (EIS) and cyclic voltammograms (CV) further indicate that polymer of β-CD and L-arg efficiently decreased the charge transfer resistance value of electrode and improved the electron transfer kinetic between analyte and electrode. Under the optimized conditions, this modified electrode was utilized to determine the concentrations of ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. The differential pulse voltammogram (DPV) exhibits the oxidation peak currents were linearly proportional to their concentration in the range of 0.05–100 μM for ciprofloxacin, 0.1–100 μM for ofloxacin, 0.1–40 μM for norfloxacin and 0.06–100 μM for gatifloxacin, respectively. This method was also successfully used to detect the concentrations of each drug in pharmaceutical

  10. Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

    Science.gov (United States)

    Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

    2017-05-17

    The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

  11. Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension

    DEFF Research Database (Denmark)

    Wang, Qian; Paulson, O B; Lassen, N A

    1992-01-01

    The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia......, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 +/- 10 to 78 +/- 6, 64 +/- 5, and 52 +/- 5 ml 100 g-1 min-1, respectively. This effect lasted for at least 2 h. Raising PaCO2 from a control level of 40...... to 68 mm Hg increased CBF to 230 +/- 27 ml 100 g-1 min-1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 +/- 0.6%/mm Hg PaCO2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood...

  12. Reversal effect of intra-central amygdala microinjection of L-arginine on place aversion induced by naloxone in morphine conditioned rats.

    Science.gov (United States)

    Karimi, Sara; Karami, Manizheh; Sahraei, Hedayat; Rahimpour, Mahnaz

    2011-01-01

    Role of nitric oxide (NO) on expression of morphine conditioning using a solely classic task has been proposed previously. In this work, the involvement of NO on the expression of opioid-induced conditioning in the task paired with an injection of naloxone was investigated. Conditioning was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Naloxone (0.05-0.4 mg/kg, i.p.), a selective antagonist of mu-opioid receptor, was administered once prior to morphine response testing. NO agents were administered directly into the central amygdala (CeA) prior to naloxone injection pre-testing. Morphine (2.5-10 mg/kg, s.c.) produced a significant dose-dependent place preference in experimental animals. When naloxone (0.05-0.4 mg/kg, i.p.) was injected before testing of morphine (5 mg/kg, s.c.) response, the antagonist induced a significant aversion. This response was reversed due to injection of L-arginine (0.3-3 microg/rat), intra-CeA prior to naloxone administration. However, pre-injection of L-NAME (intra-CeA), an inhibitor of NO production, blocked this effect. The finding may reflect that NO in the nucleus participates in morphine plus naloxone interaction.

  13. Effect of Oral Supplementation of L-arginine on Sexual Function in Men with Type 2 Diabetes: A Double-blind Clinical Trial

    Directory of Open Access Journals (Sweden)

    Hassan Mozaffari-Khosravi

    2017-02-01

    of the intervention. Total testosterone concentrations were measured too. Results: The total mean score of sexual function parameters significantly increased only in AG than PG (43.2 ± 6.2 vs. 39.4 ± 4.0, P = 0.003. Against PG, the mean of all parameters significantly improved in AG after intervention. Only the mean score of erectile function in AG had a significant increase compared to PG. Mean of other sexual activity scores between the two groups had no significant differences. The mean of testosterone concentration had a significant increase in both groups after the intervention, but the mean of changes was significantly higher in AG than in PG (1.91 μg/L vs. 0.53 μg/L, P = 0.004. Conclusions: The present trial showed that daily consumption of 5 g L-arginine for four weeks in T2D men with mild-to-moderate sexual dysfunction improved various parameters such as erectile function, sexual satisfaction, sexual desire, pleasure from sexual intercourse, and testosterone level.

  14. Synthesis of the arginine labelled by {sup 15}N on the amidine group; Synthese de l'arginine marquee par {sup 15}N dans le groupe amidine

    Energy Technology Data Exchange (ETDEWEB)

    Pichat, L; Clement, J [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

    1955-07-01

    For some biologic studies, it was necessarily to have (+) arginine marked by nitrogen 15 in the amidine group. This report describes the synthesis of the labelled arginine. The first step is the synthesis of the methyl-isourated hydro-chlorate, the intermediate reactive, from the ClNH{sub 4} isotope. The arginine is obtained from the ornithine which we previously blocked the amino group as cupric complex. The mean yield in arginine reaches 30%, based on the ammonium chloride uses. (M.B.) [French] Pour certaines etudes biologiques, il etait indispensable de disposer de (+) arginine marquee par l'azote 15 dans le groupement amidine. Ce rapport decrit la synthese de l'ariginine marquee. La premiere etape est la synthese du chlorhydrate de methylisouree, intermediaire reactif, a partir du ClNH{sub 4} isotopique. L'obtention de l'arginine est obtenue a partir de l'ornithine dont on a prealablement bloque le groupe amino sous forme de complexe cuivrique. Le rendement global moyen en arginine atteint 30 %, base sur le chlorure d'ammonium utilise. (M.B.)

  15. Acute L-arginine supplementation has no effect on cardiovascular or thermoregulatory responses to rest, exercise, and recovery in the heat.

    Science.gov (United States)

    Tyler, Christopher J; Coffey, Thomas R M; Hodges, Gary J

    2016-02-01

    To investigate the effect of acute L-arginine (L-ARG) supplementation on cardiovascular and thermoregulatory responses to rest, exercise, and recovery in the heat. Eight healthy men (age 27 ± 6 years; stature 176 ± 6 cm; body mass 76 ± 4 kg; maximal power output 237 ± 39 W) participated in a double-blind, crossover study, attending the laboratory for two experimental trials. On each occasion, participants consumed 500 ml of a black currant-flavoured cordial beverage 30 min before completing a 90 min experiment in the heat (35 °C and 50% rh). The experiment consisted of 30 min of seated rest, followed by 30 min submaximal cycling (60% maximal power output) and 30 min passive seated recovery. On one visit the drink contained 10 g of dissolved L-ARG while on the other visit it did not. L-ARG supplementation increased plasma L-ARG concentrations (peak +223 ± 80% after 60 min of the 90 min experiment); however, supplementation had no effect on rectal temperature, mean skin temperature, heart rate, arterial pressure, forearm skin vascular conductance, oxygen consumption or sweat loss at rest, during exercise, or during recovery in the heat (p > 0.05). Acute ingestion of 10 g L-ARG supplementation failed to elicit any changes in the cardiovascular or thermoregulatory responses to active or passive heat exposure in young, healthy males.

  16. Highly sensitive and simultaneous electrochemical determination of 2-aminophenol and 4-aminophenol based on poly(l-arginine)-β-cyclodextrin/carbon nanotubes@graphene nanoribbons modified electrode.

    Science.gov (United States)

    Yi, Yinhui; Zhu, Gangbing; Wu, Xiangyang; Wang, Kun

    2016-03-15

    Owing to the similar characteristics and physiochemical property of 2-aminophenol (2-AP) and 4-aminophenol (4-AP), the highly sensitive simultaneous electrochemical determination of 2- and 4-AP is a great challenge. In this paper, by electropolymerizing β-cyclodextrin (β-CD) and l-arginine (l-Arg) on the surface of carbon nanotubes@graphene nanoribbons (CNTs@GNRs) core-shell heterostructure, a P-β-CD-l-Arg/CNTs@GNRs nanohybrid modified electrode was prepared successfully, and it could exhibit the synergetic effects of β-CD (high host-guest recognition and enrichment ability), l-Arg (excellent electrocatalytic activity) and CNTs@GNRs (prominent electrochemical properties and large surface area), the P-β-CD-l-Arg/CNTs@GNRs modified electrode was used in the electrochemical determination of 2- and 4-AP, the results demonstrated that the highly sensitive and simultaneous determination of 2- and 4-AP is successfully achieved and the modified electrode has a linear response range of 25.0-1300.0 nM for both 2- and 4-AP, and the detection limits of 2- and 4-AP obtained in this work are 6.2 and 3.5 nM, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.

    Science.gov (United States)

    Jaggumantri, Sravan; Dunbar, Mary; Edgar, Vanessa; Mignone, Cristina; Newlove, Theresa; Elango, Rajavel; Collet, Jean Paul; Sargent, Michael; Stockler-Ipsiroglu, Sylvia; van Karnebeek, Clara D M

    2015-10-01

    Creatine transporter (SLC6A8) deficiency is an X-linked inborn error of metabolism characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual developmental disability. A third of patients are amenable to treatment with high-dose oral creatine, glycine, and L-arginine supplementation. Given the limited treatment response, we initiated an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine to further enhance intracerebral creatine synthesis. Significant and reproducible issues with sleep and behavior were noted in both male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl methionine and did not come for any follow-up. A safe and tolerable dose (17 mg/kg/day) was identified in the other patient. On magnetic resonance spectroscopy, this 8-year-old male did not show an increase in intracerebral creatine. However, significant improvement in speech/language skills, muscle mass were observed as well as in personal outcomes as defined by the family in activities related to communication and decision making. Further research is needed to assess the potential of S-adenosyl methionine as an adjunctive therapy for creatine transporter deficiency patients and to define the optimal dose. Our study also illustrates the importance of pathophysiology-based treatment, individualized outcome assessment, and patient/family participation in rare diseases research. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Inclusion complexes of cefuroxime axetil with β-cyclodextrin: Physicochemical characterization, molecular modeling and effect of l-arginine on complexation

    Directory of Open Access Journals (Sweden)

    Sarika Sapte

    2016-10-01

    Full Text Available The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil (CFA, were prepared with β-cyclodextrin (βCD with or without addition of l-arginine (ARG to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency (CE of βCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL (linear type of solubility curve in presence and absence of ARG, the CE and association constant (Ks of βCD towards CFA were significantly promoted in presence of ARG, justifying its use as a ternary component. The solid systems of CFA with βCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning calorimetry (DSC, X-ray powder diffractometry (XRPD, scanning electron microscopy (SEM, and saturation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA inside βCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation with βCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclusion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA via βCD complexation.

  19. The effect of hypocaloric diet enriched in legumes with or without L- arginine and selenium on anthropometric measures in central obese women

    Directory of Open Access Journals (Sweden)

    Mohammad Alizadeh

    2010-01-01

    Full Text Available Background: Identifying new ways to decrease adiposity will be very valuable for health. The aim of this study was to find out whether L- Arginine (Arg and selenium alone or together can increase the effect of hypocaloric diet enriched in legumes (HDEL on anthropometric measures in healthy obese women. Methods: This randomized, double- blind, placebo- controlled trial was undertaken in 84 healthy premenopausal women with central obesity. After 2 weeks of run- in on an isocaloric diet, participants were randomly considered to eat HDEL, Arg (5 g/d and HDEL, selenium (200 μg/d and HDEL or Arg, selenium and HDEL for 6 weeks. The following variables were assessed before intervention and 3 and 6 weeks after it: weight, waist circumference, hip circumference, waist to hip ratio (WHR, body mass index (BMI, and fasting nitrite/nitrate (NOx concentrations. Other variables (arm, thigh, calf and breast circumferences, subscapular, triceps, biceps and suprailiac skinfold thicknesses, sum of skinfold thicknesses (SSF, body density (D and estimated percent of body fat (EPF were assessed before and after intervention. Results: HDEL showed a significant effect in reduction of waist, hip, arm, thigh, calf and breast circumferences, triceps, biceps, subscapular and suprailiac skinfold thicknesses, WHR, SSF, D and EPF. HDEL + Arg + selenium significantly reduced suprailiac skinfold thicknesses; and there was no significant effect of HDEL, Arg, selenium and Arg plus selenium on weight, BMI and fasting NOx . Conclusions: The study indicates that HDEL + Arg + selenium reduce suprailiac skinfold thicknesses which represents the abdominal obesity reduction.

  20. L-Arginine Enhances Protein Synthesis by Phosphorylating mTOR (Thr 2446 in a Nitric Oxide-Dependent Manner in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Ruxia Wang

    2018-01-01

    Full Text Available Muscle atrophy may arise from many factors such as inactivity, malnutrition, and inflammation. In the present study, we investigated the stimulatory effect of nitric oxide (NO on muscle protein synthesis. Primarily, C2C12 cells were supplied with extra L-arginine (L-Arg in the culture media. L-Arg supplementation increased the activity of inducible nitric oxide synthase (iNOS, the rate of protein synthesis, and the phosphorylation of mTOR (Thr 2446 and p70S6K (Thr 389. L-NAME, an NOS inhibitor, decreased NO concentrations within cells and abolished the stimulatory effect of L-Arg on protein synthesis and the phosphorylation of mTOR and p70S6K. In contrast, SNP (sodium nitroprusside, an NO donor, increased NO concentrations, enhanced protein synthesis, and upregulated mTOR and p70S6K phosphorylation, regardless of L-NAME treatment. Blocking mTOR with rapamycin abolished the stimulatory effect of both L-Arg and SNP on protein synthesis and p70S6K phosphorylation. These results indicate that L-Arg stimulates protein synthesis via the activation of the mTOR (Thr 2446/p70S6K signaling pathway in an NO-dependent manner.

  1. On the synthesis of tailored biomimetic hydroxyapatite nanoplates through a bioinspired approach in the presence of collagen or chitosan and L-arginine.

    Science.gov (United States)

    Tsetsekou, A; Brasinika, D; Vaou, V; Chatzitheodoridis, E

    2014-10-01

    Controlling the structure of hydroxyapatite nanocrystals is vital for acquiring a consistent product. In an effort to synthesize crystals mimicking the morphology of natural bone's apatite, a bioinspired process was developed based on the use of a natural biomacromolecule, collagen or chitosan, in conjunction with l-arginine to direct the formation of hydroxyapatite from H3PO4 and Ca(OH)2. Different cases were investigated by employing various concentrations of the precursors and two molar ratios of Ca/P 1/1 and 10/6. The reaction was carried out at basic pH conditions and at biomimetic temperature (40°C). The resulting aqueous suspensions were characterized in terms of their rheological behavior, whereas the derived powders were fully evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis and Raman spectroscopy. The analysis showed that in all cases, the only phase detected was hydroxyapatite of a plate-like morphology very similar to that of natural apatite. The homogeneity of the morphology and the crystal size distribution depend on the precursors' final concentration with the mean size ranging from 5 nm up to 20 nm. The powder that demonstrated the best characteristics in terms of homogeneity was that produced in the presence of collagen for molar ratio of Ca/P 1/1. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Synthesis, characterization and anti-microbial activity of pure, Cu2+ and Cd2+ doped organic NLO l-arginine trifluoroacetate single crystals

    Science.gov (United States)

    Prasanyaa, T.; Haris, M.; Jayaramakrishnan, V.; Amgalan, M.; Mathivanan, V.

    2013-10-01

    Optically transparent Cu2+ and Cd2+ doped l-arginine trifluoroacetate (LATF) single crystals were grown from its aqueous solution using the slow solvent evaporation technique. The grown crystals were characterized by powder x-ray diffraction to confirm the monoclinic crystal structure. The percentage of transmittance measured using the ultraviolet-visible-near infrared spectrophotometer was found to be more than 80% for doped crystals. The functional group analysis of the grown crystals has been made by Fourier transform infrared spectroscopy. Thermogravimetric/differential thermal analysis was performed for the grown crystals. An atomic absorption study was carried out to determine the presence of Cu2+ and Cd2+. The hardness of the grown crystals was assessed and the results show a significant variation in the hardness value between the pure and doped LATF crystals. The second harmonic generation measurements show that Cu2+ doped LATF is 2.8 times greater and Cd2+ doped is 2.6 times greater than KDP. The anti-bacterial and anti-fungal activities of the title compound were performed using the disc diffusion method against standard bacteria Escherichia coli, Xanthomonas oryzae and against the fungus Aspergillus niger and Aspergillus flavus.

  3. Synthesis, characterization and anti-microbial activity of pure, Cu2+ and Cd2+ doped organic NLO l-arginine trifluoroacetate single crystals

    International Nuclear Information System (INIS)

    Prasanyaa, T; Haris, M; Amgalan, M; Mathivanan, V; Jayaramakrishnan, V

    2013-01-01

    Optically transparent Cu 2+ and Cd 2+ doped l-arginine trifluoroacetate (LATF) single crystals were grown from its aqueous solution using the slow solvent evaporation technique. The grown crystals were characterized by powder x-ray diffraction to confirm the monoclinic crystal structure. The percentage of transmittance measured using the ultraviolet–visible–near infrared spectrophotometer was found to be more than 80% for doped crystals. The functional group analysis of the grown crystals has been made by Fourier transform infrared spectroscopy. Thermogravimetric/differential thermal analysis was performed for the grown crystals. An atomic absorption study was carried out to determine the presence of Cu 2+ and Cd 2+ . The hardness of the grown crystals was assessed and the results show a significant variation in the hardness value between the pure and doped LATF crystals. The second harmonic generation measurements show that Cu 2+ doped LATF is 2.8 times greater and Cd 2+ doped is 2.6 times greater than KDP. The anti-bacterial and anti-fungal activities of the title compound were performed using the disc diffusion method against standard bacteria Escherichia coli, Xanthomonas oryzae and against the fungus Aspergillus niger and Aspergillus flavus. (paper)

  4. INF-β1b therapy modulates L-arginine and nitric oxide metabolism in patients with relapse remittent multiple sclerosis.

    Science.gov (United States)

    Stojanovic, Ivana; Vojinovic, Slobodan; Ljubisavljevic, Srdjan; Pavlovic, Radmila; Basic, Jelena; Pavlovic, Dusica; Ilic, Andjelka; Cvetkovic, Tatjana; Stukalov, Maja

    2012-12-15

    The scope of this study is the examination of NO(2)+NO(3), 3-nitrotyrosine (3-NT), S-nitrosothiols (RSNO), arginase activity and asymmetric (ADMA) and symmetric (SDMA) dimethyl-L-arginine concentrations in plasma of MS patients during interferon-β1b therapy. The study population included 15 (12 women, 3 men) untreated MS patients and 12 (10 women, 2 men) interferon-β1b treated MS patients with clinically definite relapsing MS (McDonalds criteria) for at least 1 year and a baseline EDSS score of 1.0 to 3.5 inclusive. Patients were treated with 250 μg IU interferon-β1b s.c. every second day during 30 months. The disease course was evaluated using correlations between baseline EDSS score and relapse rates in both groups. During interferon-β1b treatment, EDSS scores in treated patients were decreased compared to untreated ones - after 18 and 30 months (p<0.05). In interferon-β1b treated MS patients, NO(2)+NO(3), 3-NT and RSNO plasma concentrations were significantly lower (p<0.05), while arginase activity, ADMA and SDMA levels were significantly increased (p<0.05) during the therapy, compared to the baseline levels in treated patients. The investigated parameters may be the new biomarkers, providing information for the therapeutic approach and valuable in clinical monitoring. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Solvation in supercritical water

    International Nuclear Information System (INIS)

    Cochran, H.D.; Cummings, P.T.; Karaborni, S.

    1991-01-01

    The aim of this work is to determine the solvation structure in supercritical water composed with that in ambient water and in simple supercritical solvents. Molecular dynamics studies have been undertaken of systems that model ionic sodium and chloride, atomic argon, and molecular methanol in supercritical aqueous solutions using the simple point charge model of Berendsen for water. Because of the strong interactions between water and ions, ionic solutes are strongly attractive in supercritical water, forming large clusters of water molecules around each ion. Methanol is found to be a weakly-attractive solute in supercritical water. The cluster of excess water molecules surrounding a dissolved ion or polar molecule in supercritical aqueous solutions is comparable to the solvent clusters surrounding attractive solutes in simple supercritical fluids. Likewise, the deficit of water molecules surrounding a dissolved argon atom in supercritical aqueous solutions is comparable to that surrounding repulsive solutes in simple supercritical fluids. The number of hydrogen bonds per water molecule in supercritical water was found to be about one third the number in ambient water. The number of hydrogen bonds per water molecule surrounding a central particle in supercritical water was only mildly affected by the identify of the central particle--atom, molecule, or ion. These results should be helpful in developing a qualitative understanding of important processes that occur in supercritical water. 29 refs., 6 figs

  6. Comparison of ex vivo stability of copeptin and vasopressin

    NARCIS (Netherlands)

    Heida, Judith E; Boesten, Lianne S M; Ettema, Esmée M; Muller Kobold, Anneke C.; Franssen, Casper F M; Gansevoort, Ron T; Zittema, Debbie

    BACKGROUND: Copeptin, part of the vasopressin precursor, is increasingly used as marker for vasopressin and is claimed to have better ex vivo stability. However, no study has directly compared the ex vivo stability of copeptin and vasopressin. METHODS: Blood of ten healthy volunteers was collected

  7. Theories of the solvated electron

    International Nuclear Information System (INIS)

    Kestner, N.R.

    1987-01-01

    In this chapter the authors address only the final state of the electron, that is, the solvated state, which, if no chemical reaction would occur, is a stable entity with well-defined characteristics. Except for some metal-ammonia solutions, and possible a few other cases, such stable species, in reality, exist but a short time (often as short as microseconds). Nevertheless, this chapter only deals with this final time-independent,'' completely solvated,'' equilibrium species. The last statement is added to indicate that the solvent around the electron has also come to thermal equilibrium with the field of the charge

  8. Effects of a supplement combining Pycnogenol® and l-arginine aspartate on lower urinary dysfunction compared with saw palmetto extract.

    Science.gov (United States)

    Yagi, Hiroshi; Sato, Ryo; Nishio, Kojiro; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

    2017-01-01

    Lower urinary tract symptoms (LUTS) and sexual dysfunction (SDys) are common problems that affect quality of life (QOL) in elderly men. In addition to prescribed drugs, many over-the-counter medications including supplements are used to treat QOL diseases. Phosphodiesterase inhibitors are reported to be effective for both LUTS and SDys by increasing nitric oxide levels. French maritime pine bark extract Pycnogenol ® , which is a potent nitric oxide donor, is reported to be effective for SDys. However, no reports have been published on whether it ameliorates LUTS. Open-labeled, randomized study. The effects of two supplements, Nokogiriyashi EX ® containing 160 mg saw palmetto (SP) extract per tablet and Edicare ® containing 10 mg of Pycnogenol ® , 115 mg of l-arginine and 92 mg of aspartate (PAA) per tablet on International Prostate Symptom Score (IPSS), IPSS-QOL, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), urinary 8-OHdG and uroflowmetry (UFM) of total 40 men with LUTS and SDys were examined. 19 subjects were instructed to take two tablets of SP, on the other 20 were on four tablets of PAA for 16 weeks. IPSS and IPSS-QOL showed statistically significant improvements in both groups. OABSS and IIEF5 were significantly improved in the PAA group. Conversely, ICIQ-SF, 8-OHdG and UFM did not change in either group. PAA might be an effective therapeutic alternative for elderly patients with LUTS and SDys.

  9. Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.

    Science.gov (United States)

    Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

    2016-09-10

    The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy. Results of phase-solubility studies indicated that addition of arginine enhanced the RameβCD complexing and solubilizing power of about 3.0 and 4.5 times, respectively, in comparison with the binary complex (both at pH≈6.8). The effect of arginine was not simply additive, but synergistic, being the ternary system solubility higher than the sum of those of the respective drug-CD and drug-arginine binary systems. Solid equimolar ternary systems were prepared by physical mixing, co-grinding, coevaporation and kneading techniques, to explore the effect of the preparation method on the physicochemical properties of the final products. The ternary co-ground product exhibited a dramatic increase in both drug dissolution efficiency and percent dissolved at 60min, whose values (83.6 and 97.1, respectively) were about 3 times higher than the sum of those given by the respective drug-CD and drug-aminoacid binary systems. Therefore, the ternary co-ground system with arginine and RameβCD appears as a very valuable product for the development of new more effective delivery systems of oxaprozin, with improved safety and bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue.

    Directory of Open Access Journals (Sweden)

    Ying Lu

    Full Text Available We previously showed that L-arginine (Arg accumulates in colorectal cancer tissues. The aim of this study was to investigate the mechanism by which Arg accumulates and determine its biological significance. The concentration of Arg and Citrulline (Cit in sera and tumor tissues from colorectal cancer (CRC patients was analyzed by high-performance liquid chromatography (HPLC. The expression of Arg transporters was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR and immunohistochemical analysis of tissue microarray. We also transfected the colon cancer cell line HCT-116 with siRNA specific for the Arg transporter CAT-1 and measured the induction of apoptosis by flow cytometry and cell proliferation by MTT assay. Consistent with our previous results, serum Arg and Cit concentrations in colorectal cancer patients were significantly lower than those in normal volunteers, while Arg and Cit concentrations in colorectal cancer tissues were significantly higher than in matched adjacent normal colon tissues. Quantitative RT-PCR showed that the CAT-1 gene was highly overexpressed in 70.5% of colorectal cancer tissue samples relative to adjacent normal colon tissues in all 122 patients with colorectal cancer. Immunohistochemical analysis of tissue microarray confirmed that the expression of CAT-1 was higher in all 25 colorectal cancer tissues tested. CAT-1 siRNA significantly induced apoptosis of HCT-116 cells and subsequently inhibited cell growth by 20-50%. Our findings indicate that accumulation of L-Arg and Cit and cell growth in colorectal cancer tissues is associated with over-expression of the Arg transporter gene CAT-1. Our results may be useful for the development of molecular diagnostic tools and targeted therapy for colorectal cancer.

  11. Diagnostic significance of nitrates and nitrites and L-arginine, in development of hepatorenal syndrome in patients with end stage alcoholic liver cirrhosis.

    Science.gov (United States)

    Nickovic, Vanja; Kocic, Gordana; Bjelakovic, Goran; Pavlovic, Radmila; Stojanovic, Ivana; Katanic, Radoslav; Stojanovic, Svetlana; Djindjic, Boris

    2013-01-01

    Hepatorenal syndrome (HRS) represents a complication of the end-stage liver cirrhosis. The aim of the present study was to analyze concentrations of nitrates and nitrites (NO2 + NO3) and L-arginine in patients with liver cirrhosis and HRS as a possible predictive marker for the development of HRS. The research was performed in a group of 28 patients with cirrhosis and HRS, a group of 22 patients suffering from cirrhosis without HRS and a control group comprised of 42 healthy voluntary blood donors. In patients with end-stage alcoholic liver cirrhosis, with HRS, the concentrations of NO2 + NO3 increased and correlated with the degree of cirrhosis progression, compared to patients without HRS and significantly higher compared to the control group. The level of NO2 + NO3 was in a positive correlation with the degree of liver damage de Ritis coefficient (HRS = 0.72; cirrhosis: = 0.55; control = -0.10). Significant positive correlation was found between NO2 + NO3 concentration and inflammatory marker C-reactive protein (HRSC = 0.75; cirrhosis = 0.70, control = -0.25). The correlation between NO2 + NO3 concentration and creatinine concentration in patients with HRS was significantly higher compared to patients without HRS (HRS = 0.82; cirrhosis = 0.32; control = -0.25). By using binary regression analysis, on the basis of clinical criteria of HRS diagnosis, the strongest independent positive predictor for HRS development was NO2 + NO3, associated with 45.02 times higher incidence of HRS, compared to arginine (12.7 times higher incidence), creatinine (13.1 times higher incidence), and AST/ALT ratio (10.55 higher incidence of HRS). Since the determination of NO2 + NO3 represents a reliable and easily applicable method, it may be used as an early predictive marker for HRS development.

  12. The effect of hypocaloric diet enriched in legumes with or without L-arginine and selenium on anthropometric measures in central obese women

    Science.gov (United States)

    Alizadeh, Mohammad; Daneghian, Sevana; Ghaffari, Aida; Ostadrahimi, Alireza; Safaeiyan, Abdolrasoul; Estakhri, Rassul; Gargari, Bahram Pourghasem

    2010-01-01

    BACKGROUND: Identifying new ways to decrease adiposity will be very valuable for health. The aim of this study was to find out whether L-Arginine (Arg) and selenium alone or together can increase the effect of hypocaloric diet enriched in legumes (HDEL) on anthropometric measures in healthy obese women. METHODS: This randomized, double-blind, placebo-controlled trial was undertaken in 84 healthy premenopausal women with central obesity. After 2 weeks of run-in on an isocaloric diet, participants were randomly considered to eat HDEL, Arg (5 g/d) and HDEL, selenium (200 µg/d) and HDEL or Arg, selenium and HDEL for 6 weeks. The following variables were assessed before intervention and 3 and 6 weeks after it: weight, waist circumference, hip circumference, waist to hip ratio (WHR), body mass index (BMI), and fasting nitrite/nitrate (NOx) concentrations. Other variables (arm, thigh, calf and breast circumferences, subscapular, triceps, biceps and suprailiac skinfold thicknesses, sum of skinfold thicknesses (SSF), body density (D) and estimated percent of body fat (EPF)) were assessed before and after intervention. RESULTS: HDEL showed a significant effect in reduction of waist, hip, arm, thigh, calf and breast circumferences, triceps, biceps, subscapular and suprailiac skinfold thicknesses, WHR, SSF, D and EPF. HDEL + Arg + selenium significantly reduced suprailiac skinfold thicknesses; and there was no significant effect of HDEL, Arg, selenium and Arg plus selenium on weight, BMI and fasting NOx. CONCLUSIONS: The study indicates that HDEL + Arg + selenium reduce suprailiac skinfold thicknesses which represents the abdominal obesity reduction. PMID:21526106

  13. Effects of Nitric Oxide Production Inhibitor Named, NG-Nitro-L-Arginine Methyl Ester (L-NAME, on Rat Mesenchymal Stem Cells Differentiation

    Directory of Open Access Journals (Sweden)

    E Arfaei

    2010-04-01

    Full Text Available Introduction & Objectives: Recently, the findings of some studies have shown that, nitric oxide (NO probably has an important role in differentiation of mesenchymal stem cells to osteoblasts. The aim of the present investigation was to study the effects of nitric oxide production inhibitor named, NG-nitro-L-arginine methyl ester (L-NAME, on rat mesenchymal stem cells differentiation to osteoblasts in vitro. Materials & Methods: This was an experimental study conducted at Hamedan University of Medical Sciences in 2009, in which rat bone marrow stem cells were isolated in an aseptic condition and cultured in vitro. After third passage, the cells were cultured in osteogenic differentiation medium. To study the effects of L-NAME on osteogenic differentiation, the L-NAME was added to the culture medium at a concentration of 125, 250, and 500 μM in some culture plates. During the culture procedure, the media were replaced with fresh ones, with a three days interval. After 28 days of culturing the mineralized matrix was stained using Alizarian red staining method. The gathered data were analyzed by SPSS software version 12 using one way ANOVA. Results: The findings of this study showed that in the presence of L-NAME, differentiation of bone marrow mesenchymal stem cells to osteoblasts was disordered and matrix mineralization significantly decreased in a dose dependent manner. Conclusion: This study revealed that, inhibition of nitric oxide production using L-NAME can prevent the differentiation of rat bone marrow mesenchymal stem cells to osteoblast. The results imply that NO is an important constituent in differentiation of mesenchymal stem cell to osteoblasts.

  14. Cardiovascular action of insulin in health and disease: focus in endothelial L-arginine transport and cardiac voltage-dependent potassium channels.

    Directory of Open Access Journals (Sweden)

    Sebastián eDubó

    2016-03-01

    Full Text Available The impairment of insulin signaling on diabetes mellitus has been related to cardiovascular dysfunction, heart failure and sudden death. In human endothelium, cationic amino acid transporter 1 (hCAT-1 is related to the synthesis of nitric oxide (NO. Insulin has a vascular effect in endothelial cells through a signaling pathway that involved increases of hCAT-1 expression and L-arginine transport. This mechanism is disrupted in diabetes, a phenomenon potentiated by excessive accumulation of reactive oxygen species (ROS, which contributes to lower availability of NO and endothelial dysfunction. On the other hand, the electrical remodeling in cardiomyocytes is considered a key factor in heart failure progression associated to diabetes mellitus, generating a challenge to understand the specific role of insulin and the pathways involved in cardiac function. Studies on isolated mammalian cardiomyocytes have shown a prolongated action potential in ventricular repolarization phase that produces a long QT interval. The long QT generated is well explained by attenuation in the repolarizing potassium currents in cardiac ventricles. The impaired insulin signaling causes specific changes in these currents, such a decrease amplitude of the transient outward K+ (Ito and the ultra-rapid delayed rectifier (IKur currents where, together, a reduction of mRNA and protein expression levels of α-subunits (Ito, fast; Kv 4.2 and IKs; Kv 1.5 or β-subunits (KChIP2 and MiRP of K+ channels involved in these currents in a MAPK mediated pathway process have been described. These results support the hypothesis that the lack of insulin signaling can produce an abnormal repolarization in cardiomyocytes. Furthermore, the arrhythmogenic potential due to reduced Ito current can contribute to an increase in the incidence of sudden death in heart failure. This review aims to show, based on pathophysiological models, the regulatory function that would have insulin in vascular

  15. Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes.

    Science.gov (United States)

    Martina, Valentino; Masha, Andi; Gigliardi, Valentina Ramella; Brocato, Loredana; Manzato, Enzo; Berchio, Arrigo; Massarenti, Paola; Settanni, Fabio; Della Casa, Lara; Bergamini, Stefania; Iannone, Anna

    2008-05-01

    Reactive oxygen and nitric oxide (NO) have recently been considered to be involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we tested the effects of l-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing NO bioavailability by reducing free radical formation. A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that randomly received either an oral supplementation of placebo or NAC + ARG for 6 months. The NAC + ARG treatment caused a reduction of both systolic (P < 0.05) and diastolic (P < 0.05) mean arterial blood pressure, total cholesterol (P < 0.01), LDL cholesterol (P < 0.005), oxidized LDL (P < 0.05), high-sensitive C-reactive protein (P < 0.05), intracellular adhesion molecule (P < 0.05), vascular cell adhesion molecule (P < 0.01), nitrotyrosine (P < 0.01), fibrinogen (P < 0.01), and plasminogen activator inhibitor-1 (P < 0.05), and an improvement of the intima-media thickness during endothelial postischemic vasodilation (P < 0.02). HDL cholesterol increased (P < 0.05). No changes in other parameters studied were observed. NAC + ARG administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of oxidative stress and increase of NO production. Our study's results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients.

  16. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.

    Directory of Open Access Journals (Sweden)

    Niwanthi W Rajapakse

    Full Text Available Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1 can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13 and CAT1 overexpressing mice (CAT+; n=13 were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p. on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%. The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001, but was similar in obese and lean CAT+ (P = 0.65. In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001. Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001, but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%, but greater in obese CAT+ (37 ± 2%, when compared to respective lean WT (31 ± 3% and lean CAT+ controls (27 ± 2%; P ≤ 0.02. We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.

  17. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.

    Science.gov (United States)

    Rajapakse, Niwanthi W; Karim, Florian; Evans, Roger G; Kaye, David M; Head, Geoffrey A

    2015-01-01

    Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ≤ 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.

  18. Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

    Science.gov (United States)

    Ostadhadi, Sattar; Khan, Muhammad Imran; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Jazaeri, Farahnaz; Zolfaghari, Samira; Dehpour, Ahmad-Reza

    2016-04-01

    Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specific NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Abnormal myocardial energy-production state in mitochondrial cardiomyopathy and acute response to L-arginine infusion. C-11 acetate kinetics revealed by positron emission tomography

    International Nuclear Information System (INIS)

    Arakawa, Kenichiro; Kudo, Takashi; Ikawa, Masamichi

    2010-01-01

    Cardiomyopathy is a life-threatening condition in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (known as MELAS). However, no effective therapy has been available until now. In the present study cardiac energetics and acute effects of L-arginine (Arg) were evaluated in MELAS patients. The 6 patients with MELAS (M-group) and 6 volunteers (C-group) underwent dynamic C-11 acetate positron emission tomography (PET) imaging. Tricarboxylic acid (TCA)-cycle metabolic rate (k mono ), myocardial efficiency (double product (DP)/k mono ), and myocardial blood flow (MBF) were determined before and after L-Arg administration. Baseline k mono showed a lower value in the M-group than in the C-group (0.051±0.013 vs 0.070±0.019 min -1 , P=0.055). On the other hand, baseline DP/k mono was significantly greater in the M-group (1.69±5.9 vs 0.95±1.2 x 10 5 , P=0.004). After L-Arg administration, 4 patients showed significant elevation of k mono . No relationship was observed between the distribution of k mono elevation and the increase in MBF. The TCA cycle metabolic rate is markedly suppressed in MELAS patients, indicating a shift in energy production to the anaerobic pathway, leading to a paradoxical increase in myocardial efficiency. L-Arg can enhance TCA-cycle metabolism, regardless of its vasodilatation effect, and can be used as a treatment for patients with mitochondrial cardiomyopathy. (author)

  20. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

    Science.gov (United States)

    Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

    2016-11-01

    Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. We examined whether maternal melatonin or N-acetylcysteine therapy can prevent N G -nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to N G -nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. Pregnant Sprague-Dawley rats were assigned to 4 groups: control, N G -nitro-L-arginine-methyl ester, N G -nitro-L-arginine-methyl ester +melatonin, and N G -nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received N G -nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. N G -nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against N G -nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by N G -nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the N G -nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway

  1. Vasopressin and the Neurogenetics of Parental Care.

    Science.gov (United States)

    Snyder-Mackler, Noah; Tung, Jenny

    2017-07-05

    Making robust connections between genetic variation, neurophysiology, and social behavior remains a challenge. A study by Bendesky et al. (2017) tackles this challenge by dissecting the genetic architecture of parental care in deer mice to discover an important contribution of vasopressin signaling to the evolution of nest building. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Continuous vasopressin replacement in diabetes insipidus.

    OpenAIRE

    Ralston, C; Butt, W

    1990-01-01

    Five children who developed diabetes insipidus as a manifestation of severe brain injury received continuous intravenous treatment with a solution containing both aqueous vasopressin and appropriate crystalloid replacement. Polyuria, hypernatraemia, and decreased urine osmolalities were safely corrected in all patients within eight to 28 hours.

  3. Vasopressin in perioperative management of congenital ...

    African Journals Online (AJOL)

    Perioperative care of infants with diaphragmatic hernias can be a challenge because of pulmonary hypertension and systemic hypotension. The objective of this study was to report the usefulness of vasopressin infusion in improving pulmonary and systemic haemodynamics in an infant with congenital diaphragmatic hernia.

  4. REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

    Science.gov (United States)

    Jiang, Jiaye; Gan, Zhongyuan; Li, Yuan; Zhao, Wenqi; Li, Hanqing; Zheng, Jian-Pu; Ke, Yan

    2017-01-01

    Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

  5. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

    Science.gov (United States)

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  6. The effects of bupivacaine, L-nitro-L-arginine-methyl ester, and phenylephrine on cardiovascular adaptations to asphyxia in the preterm fetal lamb.

    Science.gov (United States)

    Santos, A C; Yun, E M; Bobby, P D; Noble, G; Arthur, G R; Finster, M

    1997-12-01

    The preterm fetal lamb that is exposed to clinically relevant plasma concentrations of lidocaine loses its cardiovascular adaptations to asphyxia, and its condition deteriorates further. Nitric oxide (NO) is an important regulator of vascular tone, and local anesthetics are known to inhibit endothelium-dependent vasodilation. The purpose of the present study was to determine whether the adverse effects of lidocaine noted in the preterm fetal lamb also occur with bupivacaine and whether the inhibition of NO results in effects similar to those of bupivacaine. Thirty-two chronically prepared pregnant sheep were studied at 117-119 days' gestation. Maternal and fetal blood pressure, heart rate, and acid-base state were evaluated. Fetal organ blood flows were determined using 15-microM diameter dye-labeled microspheres. After a control period, mild to moderate asphyxia (fetal PaO2 15 mm Hg) was induced by partial umbilical cord occlusion and maintained throughout the experiment. Ewes in Group I (n = 13) were given a two-step intravenous infusion of bupivacaine for 180 min. Fetuses in Group II (n = 12) received an intravenous injection of L-nitro-L-arginine-methyl ester (L-NAME) (25 mg/kg), and measurements were taken 10 and 30 min after the injection. A third group (Group III) of fetuses (n = 7) were given an intravenous infusion of phenylephrine to mimic the blood pressure increases noted in L-NAME-treated fetuses. At 90 min of stable asphyxia, there was a significant decrease in fetal PaO2 and pHa and an increase in PaCO2 and mean arterial blood pressure. There was also an increase in blood flow to the adrenals, myocardium, and cerebral cortex, whereas blood flow to the placenta decreased. Administration of bupivacaine during asphyxia did not affect the changes in mean arterial blood pressure and acid-base state but did abolish the increases in blood flows to the myocardium and cerebral cortex. Injection of L-NAME to the asphyxiated fetus resulted in an increase in

  7. Bilateral inferior petrosal sinus sampling using vasopressin

    Directory of Open Access Journals (Sweden)

    Narendra Kotwal

    2016-01-01

    Full Text Available Context: Anatomical localization of pituitary adenoma can be challenging in adrenocorticotropic hormone (ACTH-dependent Cushing's syndrome, and bilateral inferior petrosal sinus sampling (BIPSS is considered gold standard in this regard. Stimulation using corticotrophin-releasing hormone (CRH improves the sensitivity of BIPSS, however, same is not easily available in India. Therefore, we undertook this study of BIPPS using vasopressin as agent for stimulation owing to its ability to stimulate V3 receptors present on corticotrophs. Aims: To study the tumor localization and lateralization in difficult to localize cases of ACTH-dependent Cushing's syndrome by bilateral inferior petrosal sinus sampling using vasopressin for corticotroph stimulation. Settings and Design: Prospective observational study. Subjects and Methods: Six patients (5 females meeting inclusion criteria underwent BIPSS using vasopressin for stimulation. Results: All six patients had nonsuppressible overnight and low dose dexamethasone suppression test with elevated plasma ACTH levels suggestive of ACTH-dependent Cushing's syndrome. High dose dexamethasone suppression test showed suppressible cortisol in two cases, and microadenoma was seen in two patients on magnetic resonance imaging pituitary. Contrast enhanced computed tomography of the abdomen showed left adrenal hyperplasia in one case and anterior mediastinal mass with bilateral adrenal hyperplasia another. Using BIPSS four patients were classified as having Cushing's disease that was confirmed histopathologically following surgery. Of the remaining two, one had primary pigmented nodular adrenocortical disease, and another had thymic carcinoid with ectopic ACTH production as the cause of Cushing's syndrome. No serious adverse events were noted. Conclusions: Vasopressin may be used instead of CRH and desmopressin for stimulation in BIPSS.

  8. La(III) sorption studies on poly(dibenzo-18-crown-6) for the sequential separation of La(III), Th(IV) and U(VI) in L-arginine

    International Nuclear Information System (INIS)

    Sabale, Sandip; Nikam, Gurunath; Mohite, B.S.

    2010-01-01

    Poly(dibenzo-18-crown-6) is used as a stationary phase to study the sorption behavior of La(III) in L-arginine medium. The quantitative adsorption of La(III) was found at 1 x 10 -4 to 1 x 10 -6 M L-arginine. 1.0-8.0 M HCl, 0.5-8.0 M HBr and HClO 4 were found to be an efficient eluents for La(III). The capacity of crown polymer for La(III) was found to be 1.37±0.01 mmol/g. The tolerance limit of various cations and anions for La(III) was determined. La(III) was quantitatively separated from other metal ions in binary as well as multicomponent mixtures. The study was extended to sequential separation of La(III), U(VI) and Th(IV). The good separation yields were obtained and have good reproducibility (±2%). The method incorporates the determination of La(III) in real sample. The method is simple, rapid and selective. (author)

  9. Updated Abraham solvation parameters for polychlorinated biphenyls

    NARCIS (Netherlands)

    van Noort, P.C.M.; Haftka, J.J.H.; Parsons, J.R.

    2010-01-01

    This study shows that the recently published polychlorinated biphenyl (PCB) Abraham solvation parameters predict PCB air−n-hexadecane and n-octanol−water partition coefficients very poorly, especially for highly ortho-chlorinated congeners. Therefore, an updated set of PCB solvation parameters was

  10. Updated Abraham solvation parameters for polychlorinated biphenyls

    NARCIS (Netherlands)

    Noort, van P.C.M.; Haftka, J.J.H.; Parsons, J.R.

    2010-01-01

    This study shows that the recently published polychlorinated biphenyl (PCB) Abraham solvation parameters predict PCB air-n-hexadecane and n-octanol-water partition coefficients very poorly, especially for highly ortho-chlorinated congeners. Therefore, an updated set of PCB solvation parameters was

  11. Solvates of silico-12-molybdic acid with alcohols

    International Nuclear Information System (INIS)

    Punchuk, I.N.; Chuvaev, V.F.

    1984-01-01

    With the aim of investigating interaction processes of solid heteropolyacids and organic compounds, solvates are prepared. Solvates are products of adding gaseous methanol, ethanol and isopropanol to silico-12-molybdic acid. The compounds are studied by IR and PMR spectroscopy methods. Possible models for solvate structure are considered, as well as their connection with solvate properties and thermal decomposition

  12. 1 SUPPLEMENTARY INFORMATION Nonpolar Solvation Dynamics ...

    Indian Academy of Sciences (India)

    IITP

    . S. NP. ( t. ) ( )t. SNeqm. NP. (a). (b). Figure S2. (a) Nonequilibrium solvation response functions calculated after averaging over different number of nonequilibrium trajectories. The response function converges after averaging over more than ...

  13. Pancreatite aguda experimental induzida pela L-arginina: avaliação histológica e bioquímica Experimental acute pancreatitis induced by L-arginine: a histological and biochemical evaluation

    Directory of Open Access Journals (Sweden)

    Odery Ramos Jr.

    2005-03-01

    induzida pela L-arginina induz a necrose pancreática, apresentando evolução auto-limitada com regeneração do pâncreas em 2 semanas.BACKGROUND: Excessive doses of basic amino acids such as L-arginine are able to injure the pancreas of rats. AIM: To describe and evaluate the biochemical and histological characteristics of acute pancreatitis in rats induced by L-arginine during the installation, development and repair stages of the pancreatic inflammatory process. MATERIAL AND METHODS - The study group consisted of 105 male Wistar rats. The rats in the experimental group (n = 70 received 500 mg/100 g of corporal weight L-arginine injection intraperitoneally. In the control group (n = 35, isotonic saline solution was injected. Ten rats in the experiment group and five in the control group were analyzed after 6, 12, 24, 48, and 72 hours, on the 7th and 14th days. During those times, blood samples were collected for laboratory testing and samples from the pancreas were collected for an optical microscopy analysis. RESULTS: From 12 to 24 hours after the injection of L-arginine, the amylase serum levels raised to their peak values when compared to the rats in the control group, decreasing gradually, reaching an equal level after the 48th hour and being significantly lower after 72 hours and 7 days. The enzymatic activity returned to its basal level after 14 days. The amylase values were normal in all the times evaluated in the control group. In optical microscopy, after the injection of L-arginine, a pancreatic architecture histologically preserved was observed after 6 hours, evidencing an important interstitial edema in 24 hours. After 48 hours, the acinar architecture was partially destroyed with focal cellular necrosis, reaching its maximum severity after 72 hours. On the 7th, the tissue necrosis and the edema had diminished, and the regeneration of the acinar architecture initiated. The pancreatic structural reconstruction could be observed after 14 days. Pancreatic

  14. Solvated electron structure in glassy matrices

    International Nuclear Information System (INIS)

    Kevan, L.

    1981-01-01

    Current knowledge of the detailed geometrical structure of solvated electrons in aqueous and organic media is summarized. The geometry of solvated electrons in glassy methanol, ethanol, and 2-methyltetrahydrofuran is discussed. Advanced electron magnetic resonance methods and development of new methods of analysis of electron spin echo modulation patterns, second moment line shapes, and forbidden photon spin-flip transitions for paramagnetic species in these disordered systems are discussed. 66 references are cited

  15. Sensitive radioimmunoassay for plasma arginine vasopressin

    International Nuclear Information System (INIS)

    Thibonnier, M.; Soto, M.E.; Corvol, P.; Milliez, P.; Marchetti, J.; Menard, J.

    1980-01-01

    Using an ion exchange resin, a sensitive radioimmunoassay for plasma arginine vasopressin (AVP) was developed. This assay was characterized by the absence of blank values, an excellent recovery rate, great sensitivity (0.1 pg of AVP was significantly detected) and reproducibility. In 8 normal men, plasma AVP after overnight dehydration was 1.57+-0.17 pg/ml, and dropped to 0.58+-0.11 pg/ml after 20 ml/kg oral water loading. Significant correlations between plasma AVP levels and plasma or urinary osmolality confirm the validity of this assay. In complete pituitary diabetes insipidus (n=4) plasma AVP was undetectable whereas it was frankly increased in Schwartz-Bartter syndrome (3 to 33 pg/ml, n=8) [fr

  16. Biomolecular electrostatics and solvation: a computational perspective.

    Science.gov (United States)

    Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G; Schnieders, Michael J; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A

    2012-11-01

    An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

  17. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  18. Radioimmunological detection of vasopressin in urine extracts

    International Nuclear Information System (INIS)

    Buengner, R.

    1983-01-01

    After initial measures had been taken to ensure that ion exchange chromatography would yield a sufficiently high recovery of labelled and non-labelled hormone as well as to eliminate all intervening factors it was possible to use the described extraction procedure in connection with the RIA introduced by Freisenhausen et al. At the clinical level, the technique was employed to assess the post-operative release of AVP (argenine vasopressin) in 24-hour urine samples obtained from patients subjected to hypophysectomy. In a total of 10 patients, where hypophysectomy had been performed for different clinical reasons, the AVP values were seen to be significantly decreased for the first three hours after surgical intervention. They recovered slightly during the following three hours to remain at an average level of 2 pg / 400 μl urine. The extraction procedure described can be used to determine levels of AVP approaching the limit of detection - either due to large volumes of urine or very low concentrations of AVP. (orig./MG) [de

  19. Radioimmunoassay of arginine vasopressin in human plasma

    International Nuclear Information System (INIS)

    Uhlich, E.; Weber, P.; Groeschel-Stewart, U.; Roeschlau, T.; Wuerzburg Univ.

    1975-01-01

    Antibodies for the radioimmunoassay of arginine vasopressin (AVP) described here were produced in rabbits using synthetic AVP coupled to rabbit γ-globulin with carbodiimide. In three out of six rabbits, significant antibody titres were obtained. Using the best antisera produced, 40% of labelled AVP was bound at a final dilution of 1 : 50,000. After iodination of synthetic AVP with 125 I using the chloramin-T method, a gel filtration on Sephadex G-25 was performed to purify the iodinated AVP. For separation of antibody bound and free hormone, a second antibody precipitation was used. There was no crossreactivity with oxytocin. AVP was extracted from plasma after ammoniumsulfate precipitation of the proteins by adsorption to Florisil. The recovery of AVP added to plasma in amounts of 5-25 pg/ml was 60 +- 15% (n = 6). The minimum amount of AVP detectable was 1 pg per ml plasma. The plasma level in normal adults under standard conditions was 3.4 +- 2.2 pg/ml. This is in agreement with data recently published by other researchers. The applicability and reproducibility was further tested in measurements of samples taken hourly during the entire day under water diuresis and after hormonal stimulation of AVP. (orig.) [de

  20. L-Arginine ethylester enhances in vitro amplification of PrP(Sc) in macaques with atypical L-type bovine spongiform encephalopathy and enables presymptomatic detection of PrP(Sc) in the bodily fluids.

    Science.gov (United States)

    Murayama, Y; Ono, F; Shimozaki, N; Shibata, H

    2016-02-12

    Protease-resistant, misfolded isoforms (PrP(Sc)) of a normal cellular prion protein (PrP(C)) in the bodily fluids, including blood, urine, and saliva, are expected to be useful diagnostic markers of prion diseases, and nonhuman primate models are suited for performing valid diagnostic tests for human Creutzfeldt-Jakob disease (CJD). We developed an effective amplification method for PrP(Sc) derived from macaques infected with the atypical L-type bovine spongiform encephalopathy (L-BSE) prion by using mouse brain homogenate as a substrate in the presence of polyanions and L-arginine ethylester. This method was highly sensitive and detected PrP(Sc) in infected brain homogenate diluted up to 10(10) by sequential amplification. This method in combination with PrP(Sc) precipitation by sodium phosphotungstic acid is capable of amplifying very small amounts of PrP(Sc) contained in the cerebrospinal fluid (CSF), saliva, urine, and plasma of macaques that have been intracerebrally inoculated with the L-BSE prion. Furthermore, PrP(Sc) was detectable in the saliva or urine samples as well as CSF samples obtained at the preclinical phases of the disease. Thus, our novel method may be useful for furthering the understanding of bodily fluid leakage of PrP(Sc) in nonhuman primate models. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Vasopressin in chronic kidney disease, in particular ADPKD : Causal factor or innocent bystander?

    NARCIS (Netherlands)

    Zittema, Debbie

    2016-01-01

    Vasopressin is an important hormone for water regulation of the body. When dehydration occurs, vasopressin secretion leads to water reabsorption in the kidney to prevent water loss. However, vasopressin seems to have deleterious effects on the kidney as well. In autosomal dominant polycystic kidney

  2. Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.

    2011-01-01

    The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of

  3. Solvated protein-DNA docking using HADDOCK

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marc van; Visscher, Koen M.; Kastritis, Panagiotis L.; Bonvin, Alexandre M. J. J., E-mail: a.m.j.j.bonvin@uu.nl [Utrecht University, Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry (Netherlands)

    2013-05-15

    Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein-DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein-DNA complexes containing crystallographically-determined water molecules at their interfaces. Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases. Solvated docking leads to an overall improvement in the quality of the generated protein-DNA models for cases with limited conformational change of the partners upon complex formation. The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints. As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein-DNA complexes.

  4. Solvated protein–DNA docking using HADDOCK

    International Nuclear Information System (INIS)

    Dijk, Marc van; Visscher, Koen M.; Kastritis, Panagiotis L.; Bonvin, Alexandre M. J. J.

    2013-01-01

    Interfacial water molecules play an important role in many aspects of protein–DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein–DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein–DNA complexes containing crystallographically-determined water molecules at their interfaces. Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases. Solvated docking leads to an overall improvement in the quality of the generated protein–DNA models for cases with limited conformational change of the partners upon complex formation. The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints. As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein–DNA complexes.

  5. Solvated protein-DNA docking using HADDOCK

    NARCIS (Netherlands)

    van Dijk, Marc; Visscher, Koen M; Bonvin, Alexandre M.J.J; Kastritis, Panagiotis L.

    2013-01-01

    Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the

  6. Partial solvation parameters and LSER molecular descriptors

    International Nuclear Information System (INIS)

    Panayiotou, Costas

    2012-01-01

    Graphical abstract: The one-to-one correspondence of LSER molecular descriptors and partial solvation parameters (PSPs) for propionic acid. Highlights: ► Quantum-mechanics based development of a new QSPR predictive method. ► One-to-one correspondence of partial solvation parameters and LSER molecular descriptors. ► Development of alternative routes for the determination of partial solvation parameters and solubility parameters. ► Expansion and enhancement of solubility parameter approach. - Abstract: The partial solvation parameters (PSP) have been defined recently, on the basis of the insight derived from modern quantum chemical calculations, in an effort to overcome some of the inherent restrictions of the original definition of solubility parameter and expand its range of applications. The present work continues along these lines and introduces two new solvation parameters, the van der Waals and the polarity/refractivity ones, which may replace both of the former dispersion and polar PSPs. Thus, one may use either the former scheme of PSPs (dispersion, polar, acidic, and basic) or, equivalently, the new scheme (van der Waals, polarity/refractivity, acidic, basic). The new definitions are made in a simple and straightforward manner and, thus, the strength and appeal of the widely accepted concept of solubility parameter is preserved. The inter-relations of the various PSPs are critically discussed and their values are tabulated for a variety of common substances. The advantage of the new scheme of PSPs is the bridge that makes with the corresponding Abraham’s LSER descriptors. With this bridge, one may exchange information between PSPs, LSER experimental scales, and quantum mechanics calculations such as via the COSMO-RS theory. The proposed scheme is a predictive one and it is applicable to, both, homo-solvated and hetero-solvated compounds. The new scheme is tested for the calculation of activity coefficients at infinite dilution, for octanol

  7. Advanced dielectric continuum model of preferential solvation

    Science.gov (United States)

    Basilevsky, Mikhail; Odinokov, Alexey; Nikitina, Ekaterina; Grigoriev, Fedor; Petrov, Nikolai; Alfimov, Mikhail

    2009-01-01

    A continuum model for solvation effects in binary solvent mixtures is formulated in terms of the density functional theory. The presence of two variables, namely, the dimensionless solvent composition y and the dimensionless total solvent density z, is an essential feature of binary systems. Their coupling, hidden in the structure of the local dielectric permittivity function, is postulated at the phenomenological level. Local equilibrium conditions are derived by a variation in the free energy functional expressed in terms of the composition and density variables. They appear as a pair of coupled equations defining y and z as spatial distributions. We consider the simplest spherically symmetric case of the Born-type ion immersed in the benzene/dimethylsulfoxide (DMSO) solvent mixture. The profiles of y(R ) and z(R ) along the radius R, which measures the distance from the ion center, are found in molecular dynamics (MD) simulations. It is shown that for a given solute ion z(R ) does not depend significantly on the composition variable y. A simplified solution is then obtained by inserting z(R ), found in the MD simulation for the pure DMSO, in the single equation which defines y(R ). In this way composition dependences of the main solvation effects are investigated. The local density augmentation appears as a peak of z(R ) at the ion boundary. It is responsible for the fine solvation effects missing when the ordinary solvation theories, in which z =1, are applied. These phenomena, studied for negative ions, reproduce consistently the simulation results. For positive ions the simulation shows that z ≫1 (z =5-6 at the maximum of the z peak), which means that an extremely dense solvation shell is formed. In such a situation the continuum description fails to be valid within a consistent parametrization.

  8. Immunohistochemical evaluation of vasopressin expression in breast fibrocystic disease and ductal carcinoma in situ (DCIS).

    Science.gov (United States)

    North, William G; Wells, Wendy; Fay, Michael J; Mathew, Rennie S; Donnelly, Edward M; Memoli, Vincent A

    2003-01-01

    We previously found that expression of the vasopressin gene is a common feature of human breast cancer. In the present study we first examined 21 different cases of benign fibrocystic breast disease for vasopressin expression using immunohistochemistry and antibodies directed against vasopressin (anti-VP) and against vasopressin-associated glycopeptide (anti-VAG). All cases examined were negative for vasopressin gene expression using these antibodies. Alternatively, we examined 16 cases of breast ductal carcinoma in situ (DCIS) using the second of these antibodies (anti-VAG), and all of these cases were positive for vasopressin gene expression. Our results suggest that products of vasopressin gene expression are not markers of cellular proliferation in the breast, and might rather represent an early part of the carcinogenic process in this tissue.

  9. Neonatal oxytocin and vasopressin manipulation alter social behavior during the juvenile period in Mongolian gerbils.

    Science.gov (United States)

    Taylor, Jack H; Cavanaugh, Jon; French, Jeffrey A

    2017-07-01

    Oxytocin and vasopressin are important modulators of a wide variety of social behaviors, and increasing evidence is showing that these neuropeptides are important organizational effectors of later-life behavior as well. We treated day-old gerbil pups with oxytocin, vasopressin, an oxytocin receptor antagonist, a vasopressin V1a receptor antagonist, or saline control, and then measured received parental responsiveness during the early postnatal period and juvenile social behavior during weaning. Neonatal vasopressin treatment enhanced sociality in males, but not females, at both developmental time points. When pups were individually placed outside the nest, parents were more responsive to male pups treated with vasopressin compared with littermates, and vasopressin treated male pups exhibited increased play with littermates as juveniles. These results show that vasopressin during very early life can enhance social interactions throughout early development. © 2017 Wiley Periodicals, Inc.

  10. Probing the interaction of human serum albumin with vitamin B2 (riboflavin) and L-Arginine (L-Arg) using multi-spectroscopic, molecular modeling and zeta potential techniques

    Energy Technology Data Exchange (ETDEWEB)

    Memarpoor-Yazdi, Mina [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Mahaki, Hanie, E-mail: hanieh.mahaki@gmail.com [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of)

    2013-04-15

    This study was designed to examine the interaction of Riboflavin (RB) and L-Arginine (L-Arg) with human serum albumin (HSA) using different spectroscopic, zeta potential and molecular modeling techniques under imitated physiological conditions. The resonance light scattering (RLS) method determined the critical aggregation concentration of RB on HSA in the presence and absence of L-Arg which confirmed the zeta potential results. The binding constants (K{sub a}) of HSA–RB were 2.5×10{sup 4} and 9.7×10{sup 3} M{sup −1}, respectively in binary and ternary system at the excitation wavelength of 280 nm, also were 7.5×10{sup 3} and 7.3×10{sup 3}, respectively in binary and ternary system at the excitation wavelength of 295 nm. Fluorescence spectroscopy demonstrated that in the presence of L-Arg, the binding constant of HSA–RB was increased. Static quenching was confirmed to results in the fluorescence quenching and FRET. The binding distances between HSA and RB in two- and three-component systems were estimated by the Forster theory which revealed that nonradiative energy transfer from HSA to RB occurred with a high probability. The effect of RB on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy and circular dichroism (CD) in both systems. Docking studies demonstrated a reduction in the binding affinity between RB and HSA in the presence of L-Arg. -- Highlights: ► We studied the interaction of riboflavin with HSA in presence and absence of L-Arg. ► Molecular modeling and zeta-potential used to describe competitive interaction. ► We compared the binding mechanism of riboflavin (RB) to HSA in both systems. ► We determined critical aggregation concentration of RB on HSA in both systems. ► The binding site of RB on HSA in both systems has been determined.

  11. Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.

    Science.gov (United States)

    Jin, Li; Lin, Ming Quan; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Sun, Simei; Kee, Hae Jin; Jeong, Myung Ho

    2017-07-01

    Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

  12. Application of a Salt Coformer in a Co-Amorphous Drug System Dramatically Enhances the Glass Transition Temperature: A Case Study of the Ternary System Carbamazepine, Citric Acid, and l-Arginine.

    Science.gov (United States)

    Ueda, Hiroshi; Wu, Wenqi; Löbmann, Korbinian; Grohganz, Holger; Müllertz, Anette; Rades, Thomas

    2018-04-13

    The use of co-amorphous systems containing a combination of low molecular weight drugs and excipients is a relatively new technology in the pharmaceutical field to improve the solubility of poorly water-soluble drugs. However, some co-amorphous systems show a lower glass transition temperature ( T g ) than many of their polymeric solid dispersion counterparts. In this study, we aimed at designing a stable co-amorphous system with an elevated T g . Carbamazepine (CBM) and citric acid (CA) were employed as the model drug and the coformer, respectively. co-amorphous CBM-CA at a 1:1 molar ratio was formed by ball milling, but a transition from the glassy to the supercooled melt state was observed under ambient conditions, due to the relatively low T g of 38.8 °C of the co-amorphous system and moisture absorption. To improve the T g of the coformer, salt formation of a combination of l-arginine (ARG) with CA was studied. First, ball milling of CA-ARG at molar ratios of 1:1, 1:2, and 1:3 forming co-amorphous systems was performed and led to a dramatic enhancement of the T g , depending on the CA-ARG ratio. Salt formation between CA and ARG was observed by infrared spectroscopy. Next, ball milling of CBM-CA-ARG at molar ratios of 1:1:1, 1:1:2, and 1:1:3 resulted in co-amorphous blends, which had a single T g at 77.8, 105.3, and 127.8 °C, respectively. These ternary co-amorphous samples remained in a solid amorphous form for 2 months at 40 °C. From these results, it can be concluded that blending of the salt coformer with a drug is a promising strategy to design stable co-amorphous formulations.

  13. Probing the interaction of human serum albumin with vitamin B2 (riboflavin) and L-Arginine (L-Arg) using multi-spectroscopic, molecular modeling and zeta potential techniques

    International Nuclear Information System (INIS)

    Memarpoor-Yazdi, Mina; Mahaki, Hanie

    2013-01-01

    This study was designed to examine the interaction of Riboflavin (RB) and L-Arginine (L-Arg) with human serum albumin (HSA) using different spectroscopic, zeta potential and molecular modeling techniques under imitated physiological conditions. The resonance light scattering (RLS) method determined the critical aggregation concentration of RB on HSA in the presence and absence of L-Arg which confirmed the zeta potential results. The binding constants (K a ) of HSA–RB were 2.5×10 4 and 9.7×10 3 M −1 , respectively in binary and ternary system at the excitation wavelength of 280 nm, also were 7.5×10 3 and 7.3×10 3 , respectively in binary and ternary system at the excitation wavelength of 295 nm. Fluorescence spectroscopy demonstrated that in the presence of L-Arg, the binding constant of HSA–RB was increased. Static quenching was confirmed to results in the fluorescence quenching and FRET. The binding distances between HSA and RB in two- and three-component systems were estimated by the Forster theory which revealed that nonradiative energy transfer from HSA to RB occurred with a high probability. The effect of RB on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy and circular dichroism (CD) in both systems. Docking studies demonstrated a reduction in the binding affinity between RB and HSA in the presence of L-Arg. -- Highlights: ► We studied the interaction of riboflavin with HSA in presence and absence of L-Arg. ► Molecular modeling and zeta-potential used to describe competitive interaction. ► We compared the binding mechanism of riboflavin (RB) to HSA in both systems. ► We determined critical aggregation concentration of RB on HSA in both systems. ► The binding site of RB on HSA in both systems has been determined

  14. Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), L-arginine, and L-lysine.

    Science.gov (United States)

    Baier, Shawn; Johannsen, Darcy; Abumrad, Naji; Rathmacher, John A; Nissen, Steven; Flakoll, Paul

    2009-01-01

    A major contributing factor to the loss of mobility in elderly people is the gradual and continuous loss of lean body mass. To determine whether supplementation of an amino acid cocktail daily for 1 year could improve the age-associated changes in protein turnover and lean body mass in elderly people. Elderly (76+/-1.6 years) women (n=39) and men (n=38) were recruited for a double-blinded controlled study. Study participants were randomly assigned to either an isonitrogenous control-supplement (n=37) or a treatment-supplement (HMB/Arg/Lys) consisting of beta-hydroxy-beta-methylbutyrate, L-arginine, and L-lysine (n=40) for the 1-year study. Lean tissue mass was measured using both bioelectrical-impedance analysis (BIA) and dual energy x-ray absorptiometry (DXA). Rates of whole-body protein turnover were estimated using primed/intermittent oral doses of 15N-glycine. In subjects taking the HMB/Arg/Lys supplement, lean tissue increased over the year of study while in the control group, lean tissue did not change. Compared with control, HMB/Arg/Lys increased body cell mass (BIA) by 1.6% (P=.002) and lean mass (DXA) by 1.2% (P=.05). The rates of protein turnover were significantly increased 8% and 12% in the HMB/Arg/Lys-supplemented group while rates of protein turnover decreased 11% and 9% in the control-supplemented subjects (P<.01), at 3 and 12 months, respectively. Consumption of a simple amino acid-related cocktail increased protein turnover and lean tissue in elderly individuals in a year-long study.

  15. Protective effects on vascular endothelial cell in N'-nitro-L-arginine (L-NNA)-induced hypertensive rats from the combination of effective components of Uncaria rhynchophylla and Semen Raphani.

    Science.gov (United States)

    Li, Yunlun; Yang, Wenqing; Zhu, Qingjun; Yang, Jinguo; Wang, Zhen

    2015-08-01

    Endothelial dysfunction is closely associated with hypertension. Protection of vascular endothelial cell is the key to prevention and treatment of hypertension. Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid, isolated from traditional Chinese medicine Uncaria rbyncbopbylla and Semen Raphani respectively, exhibit properties of anti-hypertension and protection of blood vessels. In the present study, we observed the protective effect of the combined use of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid to the vascular endothelial cell in N'-nitro-L-arginine-induced hypertensive rats and investigate the preliminary mechanism. Blood pressure was detected by non-invasive rats tail method to observe the anti-hypertension effect of drugs. Scanning electron microscopy was used to observe the integrity or shedding state of vascular endothelial cell. The amount of circulating endothelial cells and CD54 and CD62P expression on circulating endothelial cells were tested to evaluate the endothelium function. In this study, we found that the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility can effectively lower the blood pressure, improve the structural integrity of vascular endothelium, and significantly reduce the number of circulating endothelial cells. Furthermore, the mean fluorescence intensity of CD54 and CD62P expressed showed decrease after the intervention of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility. In conclusion, the combination of effective components of the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid demonstrated good antihypertension effect and vascular endothelium protective effect. The preliminary mechanism of the protective effect may attribute to relieve the overall low-grade inflammation.

  16. Analogies and surprising differences between recombinant nitric oxide synthase-like proteins from Staphylococcus aureus and Bacillus anthracis in their interactions with l-arginine analogs and iron ligands.

    Science.gov (United States)

    Salard, Isabelle; Mercey, Emilie; Rekka, Eleni; Boucher, Jean-Luc; Nioche, Pierre; Mikula, Ivan; Martasek, Pavel; Raman, C S; Mansuy, Daniel

    2006-12-01

    Genome sequencing has recently shown the presence of genes coding for NO-synthase (NOS)-like proteins in bacteria. The roles of these proteins remain unclear. The interactions of a series of l-arginine (l-arg) analogs and iron ligands with two recombinant NOS-like proteins from Staphylococcus aureus (saNOS) and Bacillus anthracis (baNOS) have been studied by UV-visible spectroscopy. SaNOS and baNOS in their ferric native state, as well as their complexes with l-arg analogs and with various ligands, exhibit spectral characteristics highly similar to the corresponding complexes of heme-thiolate proteins such as cytochromes P450 and NOSs. However, saNOS greatly differs from baNOS at the level of three main properties: (i) native saNOS mainly exists under an hexacoordinated low-spin ferric state whereas native baNOS is mainly high-spin, (ii) the addition of tetrahydrobiopterin (H4B) or H4B analogs leads to an increase of the affinity of l-arg for saNOS but not for baNOS, and (iii) saNOS Fe(II), contrary to baNOS, binds relatively bulky ligands such as nitrosoalkanes and tert-butylisocyanide. Thus, saNOS exhibits properties very similar to those of the oxygenase domain of inducible NOS (iNOS(oxy)) not containing H4B, as expected for a NOSoxy-like protein that does not contain H4B. By contrast, the properties of baNOS which look like those of H4B-containing iNOS(oxy) are unexpected for a NOS-like protein not containing H4B. The origin of these surprising properties of baNOS remains to be determined.

  17. Relaxation dynamics following transition of solvated electrons

    International Nuclear Information System (INIS)

    Barnett, R.B.; Landman, U.; Nitzan, A.

    1989-01-01

    Relaxation dynamics following an electronic transition of an excess solvated electron in clusters and in bulk water is studied using an adiabatic simulation method. In this method the solvent evolves classically and the electron is constrained to a specified state. The coupling between the solvent and the excess electron is evaluated via the quantum expectation value of the electron--water molecule interaction potential. The relaxation following excitation (or deexcitation) is characterized by two time scales: (i) a very fast (/similar to/20--30 fs) one associated with molecular rotations in the first solvation shell about the electron, and (ii) a slower stage (/similar to/200 fs), which is of the order of the longitudinal dielectric relaxation time. The fast relaxation stage exhibits an isotope effect. The spectroscopical consequences of the relaxation dynamics are discussed

  18. Generalized Born Models of Macromolecular Solvation Effects

    Science.gov (United States)

    Bashford, Donald; Case, David A.

    2000-10-01

    It would often be useful in computer simulations to use a simple description of solvation effects, instead of explicitly representing the individual solvent molecules. Continuum dielectric models often work well in describing the thermodynamic aspects of aqueous solvation, and approximations to such models that avoid the need to solve the Poisson equation are attractive because of their computational efficiency. Here we give an overview of one such approximation, the generalized Born model, which is simple and fast enough to be used for molecular dynamics simulations of proteins and nucleic acids. We discuss its strengths and weaknesses, both for its fidelity to the underlying continuum model and for its ability to replace explicit consideration of solvent molecules in macromolecular simulations. We focus particularly on versions of the generalized Born model that have a pair-wise analytical form, and therefore fit most naturally into conventional molecular mechanics calculations.

  19. Human platelet vasopressin receptor identification by direct ultraviolet photoaffinity labeling

    International Nuclear Information System (INIS)

    Thibonnier, M.

    1987-01-01

    Tritiated vasopressin ([ 3 H]AVP) was directly crosslinked to its human platelet receptor by using an ultraviolet irradiation procedure. After preincubation with [ 3 H]AVP, the hydrodynamic parameters of the hormone-receptor complexes solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate were derived from Sephacryl S-300 superfine gel filtration and from sucrose density gradient ultracentrifugation experiments. The following values were obtained: Stoke's radius = 5.48 +/- 0.1 nm, apparent sedimentation coefficient = 5.55 +/- 0.1 S, and calculated molecular weight = 132,000. On sodium dodecyl sulfate-8% polyacrylamide slab gel electrophoresis under reducing conditions, [ 3 H]AVP preferentially and specifically labeled a 125,000-dalton protein. The labeling of this protein was suppressed by addition of excess cold vasopressin, whereas angiotensin II did not inhibit incorporation of tritiated vasopressin in this protein. These results suggest that direct UV-photoaffinity labelling with [ 3 H]AVP is a suitable tool for the purification of the human platelet vasopressin receptor

  20. Testosterone supplementation restores vasopressin innervation in the senescent rat brain

    NARCIS (Netherlands)

    Goudsmit, E.; Fliers, E.; Swaab, D. F.

    1988-01-01

    The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the

  1. Medial Amygdala and Aggressive Behavior : Interaction Between Testosterone and Vasopressin

    NARCIS (Netherlands)

    Koolhaas, J.M.; Roozendaal, B.; Boorsma, F.; Van Den Brink, T.H.C.

    1990-01-01

    This paper considers the functional significance of the testosterone-dependent vasopressinergic neurons of the medial amygdala (Ame) in intermale aggressive behavior of rats. Local microinfusion of vasopressin into the medial amygdala causes an increase in offensive behavior both in gonadally intact

  2. Vasopressin – Emerging Importance in Sepsis | Skowno | Southern ...

    African Journals Online (AJOL)

    Southern African Journal of Anaesthesia and Analgesia. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2003) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Vasopressin – Emerging ...

  3. Lysine-vasopressin analogues with glycoconjugates in position 8

    Czech Academy of Sciences Publication Activity Database

    Marcinkowska, A.; Borovičková, Lenka; Slaninová, Jiřina; Grzonka, Z.

    2006-01-01

    Roč. 80, č. 5 (2006), s. 759-766 ISSN 0137- 5083 Institutional research plan: CEZ:AV0Z40550506 Keywords : glycoconjugates * glycopeptides * lysine-vasopressin analogues Subject RIV: CC - Organic Chemistry Impact factor: 0.491, year: 2006

  4. Theory of optical spectra of solvated electrons

    International Nuclear Information System (INIS)

    Kestner, N.R.

    1975-01-01

    During the last few years better theoretical models of solvated electron have been developed. These models allow one to calculate a priori the observable properties of the trapped electron. One of the most important and most widely determined properties is the optical spectrum. In this paper we consider the predictions of the theories not only as to the band maximum but line shape and width. In addition we will review how the theories predict these will depend on the solvent, pressure, temperature, and solvent density. In all cases extensive comparisons will be made with experimental work. In addition four new areas will be explored and recent results will be presented. These concern electrons in dense polar gases, the time development of the solvated electron spectrum, solvated electrons in mixed solvents, and photoelectron emission spectra (PEE) as it relates to higher excited states. This paper will review all recent theoretical calculations and present a critical review of the present status and future developments which are anticipated. The best theories are quite successful in predicting trends, and qualitative agreement concerning band maximum. The theory is still weak in predicting line shape and line width

  5. Preferential solvation: dividing surface vs excess numbers.

    Science.gov (United States)

    Shimizu, Seishi; Matubayasi, Nobuyuki

    2014-04-10

    How do osmolytes affect the conformation and configuration of supramolecular assembly, such as ion channel opening and actin polymerization? The key to the answer lies in the excess solvation numbers of water and osmolyte molecules; these numbers are determinable solely from experimental data, as guaranteed by the phase rule, as we show through the exact solution theory of Kirkwood and Buff (KB). The osmotic stress technique (OST), in contrast, purposes to yield alternative hydration numbers through the use of the dividing surface borrowed from the adsorption theory. However, we show (i) OST is equivalent, when it becomes exact, to the crowding effect in which the osmolyte exclusion dominates over hydration; (ii) crowding is not the universal driving force of the osmolyte effect (e.g., actin polymerization); (iii) the dividing surface for solvation is useful only for crowding, unlike in the adsorption theory which necessitates its use due to the phase rule. KB thus clarifies the true meaning and limitations of the older perspectives on preferential solvation (such as solvent binding models, crowding, and OST), and enables excess number determination without any further assumptions.

  6. Preferential Solvation of an Asymmetric Redox Molecule

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kee Sung; Rajput, Nav Nidhi; Vijayakumar, M.; Wei, Xiaoliang; Wang, Wei; Hu, Jian Z.; Persson, Kristin A.; Mueller, Karl T.

    2016-12-15

    The fundamental correlations between inter-molecular interactions, solvation structure and functionality of electrolytes are in many cases unknown, particularly for multi-component liquid systems. In this work, we explore such correlations by investigating the complex interplay between solubility and solvation structure for the electrolyte system comprising N-(ferrocenylmethyl)-N,N-dimethyl-N-ethylammonium bistrifluoromethylsulfonimide (Fc1N112-TFSI) dissolved in a ternary carbonate solvent mixture using combined NMR relaxation and computational analyses. Probing the evolution of the solvent-solvent, ion-solvent and ion-ion interactions with an increase in solute concentration provides a molecular level understanding of the solubility limit of the Fc1N112-TFSI system. An increase in solute con-centration leads to pronounced Fc1N112-TFSI contact-ion pair formation by diminishing solvent-solvent and ion-solvent type interactions. At the solubility limit, the precipitation of solute is initiated through agglomeration of contact-ion pairs due to overlapping solvation shells.

  7. Experimental cardiac arrest treatment with adrenaline, vasopressin, or placebo.

    Science.gov (United States)

    Palácio, Manoel Ângelo Gomes; Paiva, Edison Ferreira de; Azevedo, Luciano Cesar Pontes de; Timerman, Ari

    2013-12-01

    The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p < 0.001). Vasopressin effect remained at 15-20 mmHg after three doses versus zero with adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate.

  8. The vasopressin deficient Brattleboro rats: A natural knockout model used in the search for CNS effects of vasopressin

    NARCIS (Netherlands)

    Bohus, B; de Wied, David; Urban, I.J.A.; Burbach, J.P.H.; De Wied, D.

    1999-01-01

    Behavioral neuroscience is using mon and more gene knockout techniques to produce animals with a specific deletion. These studies have their precedent in nature. A mutation may result in a limited genetic defect, as seen in the vasopressin (VP) deficiency in the Brattleboro rat. The mutation is in a

  9. Extrahypothalamic vasopressin and oxytocin in the human brain; presence of vasopressin cells in the bed nucleus of the stria terminalis

    NARCIS (Netherlands)

    Fliers, E.; Guldenaar, S. E.; van de Wal, N.; Swaab, D. F.

    1986-01-01

    In the present study, the distribution of extrahypothalamic vasopressin (VP) and oxytocin (OXT) in the human brain was investigated by means of immunocytochemistry. In the septum verum, few VP fibers were found in the nucleus septalis lateralis and medialis (NSL and NSM), and in the bed nucleus of

  10. Conductometric determination of solvation numbers of alkali metal cations

    International Nuclear Information System (INIS)

    Fialkov, Yu.Ya.; Gorbachev, V.Yu.; Chumak, V.L.

    1997-01-01

    Theories describing the interrelation of ion mobility with their effective radii in solutions are considered. Possibility of using these theories for determination the solvation numbers n s of some ions is estimated. According to conductometric data values of n s are calculated for alkali metal ions in propylene carbonate. The data obtained are compared with solvation numbers determined with the use of entropies of ions solvation. Change of n s values within temperature range 273.15-323.15 K is considered. Using literature data the effect of crystallographic radii of cations and medium permittivity on the the values of solvation numbers of cations are analyzed. (author)

  11. Induction of hypertension blunts baroreflex inhibition of vasopressin neurons in the rat.

    Science.gov (United States)

    Han, Su Young; Bouwer, Gregory T; Seymour, Alexander J; Korpal, Aaron K; Schwenke, Daryl O; Brown, Colin H

    2015-11-01

    Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the α1-adrenoreceptor agonist, phenylephrine (2.5 μg/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8)

    NARCIS (Netherlands)

    Gispen, W.H.; Chepkova, A.N.; French, P.; Wied, D. de; Ontskul, A.H.; Ramakers, G.M.J.; Skrebitski, V.G.; Urban, I.J.A.

    1995-01-01

    Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into

  13. Vasopressin and Oxytocin Reduce Food Sharing Behavior in Male, but Not Female Marmosets in Family Groups

    Directory of Open Access Journals (Sweden)

    Jack H. Taylor

    2017-07-01

    Full Text Available Oxytocin (OT is critical for lactation and maternal care, but OT and the related nonapeptide vasopressin are important for caregiving behaviors in fathers and alloparents as well. This experiment tested the effects of vasopressin and OT on food sharing in marmoset families. We treated caregivers (parents, siblings with intranasal vasopressin, OT, or saline, and then paired them with the youngest marmoset in the family. Caregivers were given preferred food, and then observed for food sharing and aggressive behavior with young marmosets. OT reduced food sharing from male alloparents to youngest siblings, and fathers that received vasopressin refused to share food with their youngest offspring more often than when treated with OT. Vasopressin increased aggressive vocalizations directed toward potential food recipients in all classes of caregivers. These results indicate that vasopressin and OT do not always enhance prosocial behavior: modulation of food sharing depends on both sex and parental status.

  14. Nonpolar solvation dynamics for a nonpolar solute in room ...

    Indian Academy of Sciences (India)

    Sandipa Indra

    2018-01-30

    Jan 30, 2018 ... Keywords. Solvation dynamics; nonpolar solvation; ionic liquid; molecular dynamics; linear response theory. 1. ... J. Chem. Sci. (2018) 130:3 spectrum of the excited probe molecule for imida- .... Therefore, the solute and the RTIL ions interact only ... interval of 30 ps from a long equilibrium trajectory of dura-.

  15. Abacavir methanol 2.5-solvate

    Directory of Open Access Journals (Sweden)

    Phuong-Truc T. Pham

    2009-08-01

    Full Text Available The structure of abacavir (systematic name: {(1S,4R-4-[2-amino-6-(cyclopropylamino-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol, C14H18N6O·2.5CH3OH, consists of hydrogen-bonded ribbons which are further held together by additional hydrogen bonds involving the hydroxyl group and two N atoms on an adjacent purine. The asymmetric unit also contains 2.5 molecules of methanol solvate which were grossly disordered and were excluded using SQUEEZE subroutine in PLATON [Spek, (2009. Acta Cryst. D65, 148–155].

  16. Rotation and solvation of ammonium ion

    International Nuclear Information System (INIS)

    Perrin, C.L.; Gipe, R.K.

    1987-01-01

    From nitrogen-15 spin-lattice relaxation times and nuclear Overhauser enhancements, the rotational correlations time tau/sub c/ for 15 NH 4 + was determined in s series of solvents. Values of tau/sub c/ range from 0.46 to 20 picoseconds. The solvent dependent of tau/sub c/ cannot be explained in terms of solvent polarity, molecular dipole moment, solvent basicity, solvent dielectric relaxation, or solvent viscosity. The rapid rotation and the variation with solvent can be accounted for by a model that involves hydrogen bonding of an NH proton to more than one solvent molecule in a disordered solvation environment. 25 references, 1 table

  17. Radioimmunoassay of arginine vasopressin (AVP) and clinical application

    International Nuclear Information System (INIS)

    Wagner, H.; Haeberle, M.; Franz, H.E.; Maier, V.

    1977-01-01

    The low circulating levels of vasopressin required an initial extraction procedure. The extraction method itself presented problems with the specificity and the reproducibility of the extracted hormone from serum. The presented paper describes the developement of a radioimmunoassay without an extraction procedure. The AVP was coupled with rabbit-albumin by gluteraldehyde condensation for the immunization of rabbits. Synthetic AVP was iodinated by the method of GREENWOOD and HUNTER (1963) and purified by the addition of Dowex. The antibody cannot differentiate between lysine- and arginine-, ornithine-, glycerine - vasopressin and oxytocin. 1 - 24 ACTH and gastrin did not crosscreact. Normal subjects were found to have 5.7 +- 4.4/uU/ml after a dehydration period of 12 hours. Subjects suffering from psychogenic polydipsia showed normal levels, however, different forms of stress yielded higher levels in normal subjects. In patients suffering from liver cirrhosis the values normalized when ascites was under control. (orig.) [de

  18. Effects of vasopressin on the isolated perfused human collecting tubule.

    Science.gov (United States)

    Yanagawa, N; Trizna, W; Bar-Khayim, Y; Fine, L G

    1981-05-01

    Cortical collecting tubules (CCT) were dissected from the surviving normal tissue of human kidneys removed at operation for either carcinoma or calculus. These CCT's were perfused in vitro shortly after the nephrectomy was performed. Transtubular potential differences in different tubules varied from +3.2 to -2.0 mV and were reduced towards zero by lowering the temperature or by adding ouabain to the bath. In the absence of vasopressin, tubules were essentially impermeable to water with extremely low net water fluxes even in the presence of a transtubular osmotic gradient. Addition of vasopressin to the bath caused the transtubular osmotic water permeability coefficient to increase to values of 125, 175, and 155 X 10(-4) cm/sec in three tubules thus studied. These results demonstrate close similarities between the human CCT and the more extensively studied rabbit CCT.

  19. Osmosensation in vasopressin neurons: changing actin density to optimize function.

    Science.gov (United States)

    Prager-Khoutorsky, Masha; Bourque, Charles W

    2010-02-01

    The proportional relation between circulating vasopressin concentration and plasma osmolality is fundamental for body fluid homeostasis. Although changes in the sensitivity of this relation are associated with pathophysiological conditions, central mechanisms modulating osmoregulatory gain are unknown. Here, we review recent data that sheds important light on this process. The cell autonomous osmosensitivity of vasopressin neurons depends on cation channels comprising a variant of the transient receptor potential vanilloid 1 (TRPV1) channel. Hyperosmotic activation is mediated by a mechanical process where sensitivity increases in proportion with actin filament density. Moreover, angiotensin II amplifies osmotic activation by a rapid stimulation of actin polymerization, suggesting that neurotransmitter-induced changes in cytoskeletal organization in osmosensory neurons can mediate central changes in osmoregulatory gain. (c) 2009 Elsevier Ltd. All rights reserved.

  20. Experimental Cardiac Arrest Treatment with Adrenaline, Vasopressin, or Placebo

    Science.gov (United States)

    Palácio, Manoel Ângelo Gomes; de Paiva, Edison Ferreira; de Azevedo, Luciano Cesar Pontes; Timerman, Ari

    2013-01-01

    Background The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. Objectives To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). Methods A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Results Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). Conclusion The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate. PMID:24173134

  1. Diabetes insipidus: celebrating a century of vasopressin therapy.

    Science.gov (United States)

    Qureshi, Sana; Galiveeti, Sneha; Bichet, Daniel G; Roth, Jesse

    2014-12-01

    Diabetes mellitus, widely known to the ancients for polyuria and glycosuria, budded off diabetes insipidus (DI) about 200 years ago, based on the glucose-free polyuria that characterized a subset of patients. In the late 19th century, clinicians identified the posterior pituitary as the site of pathology, and pharmacologists found multiple bioactivities there. Early in the 20th century, the amelioration of the polyuria with extracts of the posterior pituitary inaugurated a new era in therapy and advanced the hypothesis that DI was due to a hormone deficiency. Decades later, a subset of patients with polyuria unresponsive to therapy were recognized, leading to the distinction between central DI and nephrogenic DI, an early example of a hormone-resistant condition. Recognition that the posterior pituitary had 2 hormones was followed by du Vigneaud's Nobel Prize winning isolation, sequencing, and chemical synthesis of oxytocin and vasopressin. The pure hormones accelerated the development of bioassays and immunoassays that confirmed the hormone deficiency in vasopressin-sensitive DI and abundant levels of hormone in patients with the nephrogenic disorder. With both forms of the disease, acquired and inborn defects were recognized. Emerging concepts of receptors and of genetic analysis led to the recognition of patients with mutations in the genes for 1) arginine vasopressin (AVP), 2) the AVP receptor 2 (AVPR2), and 3) the aquaporin 2 water channel (AQP2). We recount here the multiple skeins of clinical and laboratory research that intersected frequently over the centuries since the first recognition of DI.

  2. Solvation of hydrocarbons in aqueous-organic mixtures

    International Nuclear Information System (INIS)

    Sedov, I.A.; Magsumov, T.I.; Solomonov, B.N.

    2016-01-01

    Highlights: • Thermodynamic functions of solvation in mixtures of water with acetone and acetonitrile are measured at T = 298.15 K. • Solvation of n-octane and toluene in aqueous-organic mixtures is studied. • When increasing water content, Gibbs free energies grow up steadily, while enthalpies have a maximum. • Hydrocarbons are preferentially solvated with organic cosolvent even in mixtures with rather high water content. • Acetonitrile suppresses the hydrophobic effect less than acetone. - Abstract: We study the solvation of two hydrocarbons, n-octane and toluene, in binary mixtures of water with organic cosolvents. Two polar aprotic cosolvents that are miscible with water in any proportions, acetonitrile and acetone, were considered. We determine the magnitudes of thermodynamic functions of dissolution and solvation at T = 298.15 K in the mixtures with various compositions. Solution calorimetry was used to measure the enthalpies of solution, and GC headspace analysis was applied to obtain limiting activity coefficients of solutes in the studied systems. For the first time, the enthalpies of solution of alkane in the mixtures with high water content were measured directly. We observed well-pronounced maxima of the dependencies of enthalpies of solvation from the composition of solvent and no maxima for the Gibbs free energies of solvation. Two factors are concluded to be important to explain the observed tendencies: high energy cost of reorganization of binary solvent upon insertion of solute molecules and preferential surrounding of hydrocarbons with the molecules of organic cosolvent. Enthalpy-entropy compensation leads to a steady growth of the Gibbs free energies with increasing water content. On the other hand, consideration of the plots of the Gibbs free energy against enthalpy of solvation clearly shows that the solvation properties are changed dramatically after addition of a rather small amount of organic cosolvents. It is shown that they

  3. Solvation of lithium ion in dimethoxyethane and propylene carbonate

    Science.gov (United States)

    Chaban, Vitaly

    2015-07-01

    Solvation of the lithium ion (Li+) in dimethoxyethane (DME) and propylene carbonate (PC) is of scientific significance and urgency in the context of lithium-ion batteries. I report PM7-MD simulations on the composition of Li+ solvation shells (SH) in a few DME/PC mixtures. The equimolar mixture features preferential solvation by PC, in agreement with classical MD studies. However, one DME molecule is always present in the first SH, supplementing the cage formed by five PC molecules. As PC molecules get removed, DME gradually substitutes vacant places. In the PC-poor mixtures, an entire SH is populated by five DME molecules.

  4. Vasopressin and angiotensin II stimulate oxygen uptake in the perfused rat hindlimb

    DEFF Research Database (Denmark)

    Colquhoun, E Q; Hettiarachchi, M; Ye, J M

    1988-01-01

    Vasopressin and angiotensin II markedly stimulated oxygen uptake in the perfused rat hindlimb. The increase due to each agent approached 70% of the basal rate, and was greater than that produced by a maximal concentration of norepinephrine. Half-maximal stimulation occurred at 60 pM vasopressin, 0...

  5. Radioimmunoassay of [8-D-arginine] deamino-vasopressin (dDAVP)

    International Nuclear Information System (INIS)

    Slaninova, J.; Barth, T.

    1978-01-01

    Specific antibodies to [8-D-arginine] deamino-vasopressin (dDAVP) were prepared by immunizing pigs with the conjugate of [8-D-arginine] vasopressin (DVAP) and rabbit immunoglobulin. The specificity of the antibodies was studied by comparing their cross-reactivity with 20 analogues of neurohypophysial hormones. The sensitivity of the developed radioimmunoassay was 30 pg/ml. (authors)

  6. Mechanisms involved in dual vasopressin/apelin neuron dysfunction during aging.

    Directory of Open Access Journals (Sweden)

    Julie Sauvant

    Full Text Available Normal aging is associated with vasopressin neuron adaptation, but little is known about its effects on the release of apelin, an aquaretic peptide colocalized with vasopressin. We found that plasma vasopressin concentrations were higher and plasma apelin concentrations lower in aged rats than in younger adults. The response of AVP/apelin neurons to osmotic challenge was impaired in aged rats. The overactivity of vasopressin neurons was sustained partly by the increased expression of Transient receptor potential vanilloid2 (Trpv2, because central Trpv blocker injection reversed the age-induced increase in plasma vasopressin concentration without modifying plasma apelin concentration. The morphofunctional plasticity of the supraoptic nucleus neuron-astrocyte network normally observed during chronic dehydration in adults appeared to be impaired in aged rats as well. IL-6 overproduction by astrocytes and low-grade microglial neuroinflammation may contribute to the modification of neuronal functioning during aging. Indeed, central treatment with antibodies against IL-6 decreased plasma vasopressin levels and increased plasma apelin concentration toward the values observed in younger adults. Conversely, minocycline treatment (inhibiting microglial metabolism did not affect plasma vasopressin concentration, but increased plasma apelin concentration toward control values for younger adults. This study is the first to demonstrate dual vasopressin/apelin adaptation mediated by inflammatory molecules and neuronal Trpv2, during aging.

  7. Radioimmunoassay measurement of plasma oxytocin and vasopressin in cows during machine milking

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R; Wehowsky, G; Schulz, J; Schulze, H; Bothur, D [Forschungsinstitut fuer Koerperkultur und Sport, Leipzig (German Democratic Republic); Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Tierproduktion und Veterinaermedizin)

    1982-07-01

    The response of plasma oxytocin and vasopressin to machine milking in cows was studied by radioimmunoassay. Depending on the method of machine milking used, plasma oxytocin increased to a greater or lesser degree after teat cup application. Plasma vasopressin was not affected by the milking procedures.

  8. Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression.

    NARCIS (Netherlands)

    van Londen, L.; Goekoop, J.G.; Kerkhof, G.A.; Zwindeman, K.H.; Wiegant, V.M.; de Wied, D.

    2001-01-01

    Earlier work has shown that plasma vasopressin levels of depressed patients were higher than those of healthy controls. The aim of the present study was to determine whether plasma vasopressin levels were correlated to parameters of the circadian rhythm. 41 patients with major depression (aged 22-77

  9. Dehydration-induced modulation of κ-opioid inhibition of vasopressin neurone activity

    Science.gov (United States)

    Scott, Victoria; Bishop, Valerie R; Leng, Gareth; Brown, Colin H

    2009-01-01

    Dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland to reduce water loss in the urine. Vasopressin secretion is determined by action potential firing in vasopressin neurones, which can exhibit continuous, phasic (alternating periods of activity and silence), or irregular activity. Autocrine κ-opioid inhibition contributes to the generation of activity patterning of vasopressin neurones under basal conditions and so we used in vivo extracellular single unit recording to test the hypothesis that changes in autocrine κ-opioid inhibition drive changes in activity patterning of vasopressin neurones during dehydration. Dehydration increased the firing rate of rat vasopressin neurones displaying continuous activity (from 7.1 ± 0.5 to 9.0 ± 0.6 spikes s−1) and phasic activity (from 4.2 ± 0.7 to 7.8 ± 0.9 spikes s−1), but not those displaying irregular activity. The dehydration-induced increase in phasic activity was via an increase in intraburst firing rate. The selective κ-opioid receptor antagonist nor-binaltorphimine increased the firing rate of phasic neurones in non-dehydrated rats (from 3.4 ± 0.8 to 5.3 ± 0.6 spikes s−1) and dehydrated rats (from 6.4 ± 0.5 to 9.1 ± 1.2 spikes s−1), indicating that κ-opioid feedback inhibition of phasic bursts is maintained during dehydration. In a separate series of experiments, prodynorphin mRNA expression was increased in vasopressin neurones of hyperosmotic rats, compared to hypo-osmotic rats. Hence, it appears that dynorphin expression in vasopressin neurones undergoes dynamic changes in proportion to the required secretion of vasopressin so that, even under stimulated conditions, autocrine feedback inhibition of vasopressin neurones prevents over-excitation. PMID:19822541

  10. Zero-point energy effects in anion solvation shells.

    Science.gov (United States)

    Habershon, Scott

    2014-05-21

    By comparing classical and quantum-mechanical (path-integral-based) molecular simulations of solvated halide anions X(-) [X = F, Cl, Br and I], we identify an ion-specific quantum contribution to anion-water hydrogen-bond dynamics; this effect has not been identified in previous simulation studies. For anions such as fluoride, which strongly bind water molecules in the first solvation shell, quantum simulations exhibit hydrogen-bond dynamics nearly 40% faster than the corresponding classical results, whereas those anions which form a weakly bound solvation shell, such as iodide, exhibit a quantum effect of around 10%. This observation can be rationalized by considering the different zero-point energy (ZPE) of the water vibrational modes in the first solvation shell; for strongly binding anions, the ZPE of bound water molecules is larger, giving rise to faster dynamics in quantum simulations. These results are consistent with experimental investigations of anion-bound water vibrational and reorientational motion.

  11. Proton solvation and proton transfer in chemical and electrochemical processes

    International Nuclear Information System (INIS)

    Lengyel, S.; Conway, B.E.

    1983-01-01

    This chapter examines the proton solvation and characterization of the H 3 O + ion, proton transfer in chemical ionization processes in solution, continuous proton transfer in conductance processes, and proton transfer in electrode processes. Topics considered include the condition of the proton in solution, the molecular structure of the H 3 O + ion, thermodynamics of proton solvation, overall hydration energy of the proton, hydration of H 3 O + , deuteron solvation, partial molal entropy and volume and the entropy of proton hydration, proton solvation in alcoholic solutions, analogies to electrons in semiconductors, continuous proton transfer in conductance, definition and phenomenology of the unusual mobility of the proton in solution, solvent structure changes in relation to anomalous proton mobility, the kinetics of the proton-transfer event, theories of abnormal proton conductance, and the general theory of the contribution of transfer reactions to overall transport processes

  12. Sexual arousal and rhythmic synchronization: A possible effect of vasopressin

    DEFF Research Database (Denmark)

    Miani, Alessandro

    2016-01-01

    Music is ubiquitous. Yet, its biological relevance is still an ongoing debate. Supporting the view that music had an ancestral role in courtship displays, a pilot study presented here provides preliminary evidence on the link between music and sexual selection. The underlying hypothesis is based...... by vasopressin and its genes. Hence, to test this hypothesis, a rhythmic synchronization task was employed here on one male subject during sexual arousal. Results revealed a significant effect of sexual arousal on rhythm synchronization. This is the first report that empirically supports the hypothesis...

  13. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Siggaard, C; Herlin, Troels

    2000-01-01

    as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron...... of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe...

  14. Ultrafast transient-absorption of the solvated electron in water

    International Nuclear Information System (INIS)

    Kimura, Y.; Alfano, J.C.; Walhout, P.K.; Barbara, P.F.

    1994-01-01

    Ultrafast near infrared (NIR)-pump/variable wavelength probe transient-absorption spectroscopy has been performed on the aqueous solvated electron. The photodynamics of the solvated electron excited to its p-state are qualitatively similar to previous measurements of the dynamics of photoinjected electrons at high energy. This result confirms the previous interpretation of photoinjected electron dynamics as having a rate-limiting bottleneck at low energies presumably involving the p-state

  15. Estimation of abraham solvation equation coefficients for hydrogen bond formation from abraham solvation parameters for solute activity and basicity

    NARCIS (Netherlands)

    Noort, van P.C.M.

    2013-01-01

    Abraham solvation equations find widespread use in environmental chemistry and pharmaco-chemistry. The coefficients in these equations, which are solvent (system) descriptors, are usually determined by fitting experimental data. To simplify the determination of these coefficients in Abraham

  16. Effects of arginine vasopressin on musical working memory.

    Science.gov (United States)

    Granot, Roni Y; Uzefovsky, Florina; Bogopolsky, Helena; Ebstein, Richard P

    2013-01-01

    Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP) and musical working memory (WM). The current study set out to test the influence of intranasal administration (INA) of AVP on musical as compared to verbal WM using a double blind crossover (AVP-placebo) design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo) in a second session, 1 week apart. In each session subjects completed the tonal subtest from Gordon's "Musical Aptitude Profile," the interval subtest from the "Montreal Battery for Evaluation of Amusias (MBEA)," and the forward and backward digit span tests. Scores in the digit span tests were not influenced by AVP. In contrast, in the music tests there was an AVP effect. In the MBEA test, scores for the group receiving placebo in the first session (PV) were higher than for the group receiving vasopressin in the first session (VP) (p music test these scores were significantly correlated with memory scores. Together the results reflect a complex interaction between AVP, musical memory, arousal, and contextual effects such as session, and base levels of memory. The results are interpreted in light of music's universal use as a means to modulate arousal on the one hand, and AVP's influence on mood, arousal, and social interactions on the other.

  17. Water-enhanced solvation of organics

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jane H. [Univ. of California, Berkeley, CA (United States)

    1993-07-01

    Water-enhanced solvation (WES) was explored for Lewis acid solutes in Lewis base organic solvents, to develop cheap extract regeneration processes. WES for solid solutes was determined from ratios of solubilities of solutes in water-sat. and low-water solvent; both were determined from solid-liquid equilibrium. Vapor-headspace analysis was used to determine solute activity coefficients as function of organic phase water concentration. WES magnitudes of volatile solutes were normalized, set equal to slope of log γs vs xw/xs curve. From graph shape Δ(log γs) represents relative change in solute activity coefficient. Solutes investigated by vapor-headspace analysis were acetic acid, propionic acid, ethanol, 1,2-propylene glycol, 2,3-butylene glycol. Monocarboxylic acids had largest decrease in activity coefficient with water addition followed by glycols and alcohols. Propionic acid in cyclohexanone showed greatest water-enhancement Δ(log γacid)/Δ(xw/xacid) = -0.25. In methylcyclohexanone, the decrease of the activity coefficient of propionic acid was -0.19. Activity coefficient of propionic acid in methylcyclohexanone stopped decreasing once the water reached a 2:1 water to acid mole ratio, implying a stoichiometric relation between water, ketone, and acid. Except for 2,3-butanediol, activity coefficients of the solutes studied decreased monotonically with water content. Activity coefficient curves of ethanol, 1,2-propanediol and 2,3-butanediol did not level off at large water/solute mole ratio. Solutes investigated by solid-liquid equilibrium were citric acid, gallic acid, phenol, xylenols, 2-naphthol. Saturation concentration of citric acid in anhydrous butyl acetate increased from 0.0009 to 0.087 mol/L after 1.3 % (g/g) water co-dissolved into organic phase. Effect of water-enhanced solvation for citric acid is very large but very small for phenol and its derivatives.

  18. Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

    Science.gov (United States)

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2016-11-01

    Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

    International Nuclear Information System (INIS)

    Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P.

    1990-01-01

    The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of [35S]cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of [35S]cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, [35S]cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes

  20. Cluster expansion of the solvation free energy difference: Systematic improvements in the solvation of single ions

    Science.gov (United States)

    Pliego, Josefredo R.

    2017-07-01

    The cluster expansion method has been used in the imperfect gas theory for several decades. This paper proposes a cluster expansion of the solvation free energy difference. This difference, which results from a change in the solute-solvent potential energy, can be written as the logarithm of a finite series. Similar to the Mayer function, the terms in the series are related to configurational integrals, which makes the integrand relevant only for configurations of the solvent molecules close to the solute. In addition, the terms involve interaction of solute with one, two, and so on solvent molecules. The approach could be used for hybrid quantum mechanical and molecular mechanics methods or mixed cluster-continuum approximation. A simple form of the theory was applied for prediction of pKa in methanol; the results indicated that three explicit methanol molecules and the dielectric continuum lead to a root of mean squared error (RMSE) of only 1.3 pKa units, whereas the pure continuum solvation model based on density method leads to a RMSE of 6.6 pKa units.

  1. Order and correlation contributions to the entropy of hydrophobic solvation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Maoyuan; Besford, Quinn Alexander; Mulvaney, Thomas; Gray-Weale, Angus, E-mail: gusgw@gusgw.net [School of Chemistry, The University of Melbourne, Victoria 3010 (Australia)

    2015-03-21

    The entropy of hydrophobic solvation has been explained as the result of ordered solvation structures, of hydrogen bonds, of the small size of the water molecule, of dispersion forces, and of solvent density fluctuations. We report a new approach to the calculation of the entropy of hydrophobic solvation, along with tests of and comparisons to several other methods. The methods are assessed in the light of the available thermodynamic and spectroscopic information on the effects of temperature on hydrophobic solvation. Five model hydrophobes in SPC/E water give benchmark solvation entropies via Widom’s test-particle insertion method, and other methods and models are tested against these particle-insertion results. Entropies associated with distributions of tetrahedral order, of electric field, and of solvent dipole orientations are examined. We find these contributions are small compared to the benchmark particle-insertion entropy. Competitive with or better than other theories in accuracy, but with no free parameters, is the new estimate of the entropy contributed by correlations between dipole moments. Dipole correlations account for most of the hydrophobic solvation entropy for all models studied and capture the distinctive temperature dependence seen in thermodynamic and spectroscopic experiments. Entropies based on pair and many-body correlations in number density approach the correct magnitudes but fail to describe temperature and size dependences, respectively. Hydrogen-bond definitions and free energies that best reproduce entropies from simulations are reported, but it is difficult to choose one hydrogen bond model that fits a variety of experiments. The use of information theory, scaled-particle theory, and related methods is discussed briefly. Our results provide a test of the Frank-Evans hypothesis that the negative solvation entropy is due to structured water near the solute, complement the spectroscopic detection of that solvation structure by

  2. Alterações Bioquímicas Produzidas pela Suplementação com L-Arginina em Ratos Induzidos à Obesidade e Submetidos a Treinamento Físico/Biochemical Changes Produced by Supplementation with L-Arginine in Induced Obesity Mice and Subjected to Physical Training

    Directory of Open Access Journals (Sweden)

    Alexandre Veraldi Rossettini

    2012-09-01

    Full Text Available Objetivo: analisar as alterações bioquímicas produzidas pela suplementação com L-Arginina (L-arg em ratos induzidos à obesidade e submetidos a treinamento físico. Materiais e Métodos: foram utilizados 35 ratos Wistar adultos machos induzidos à obesidade e divididos em 03 grupos: Controle: água destilada, L-arginina T1: 100mg/kg, L-arginina T2: 500mg/Kg, testados individualmente, submetidos à natação forçada. Após 60 dias, foram eutanasiados e amostras de tecidos foram coletadas para análise bioquímica. Resultados: não se encontrou alterações bioquímicas para ureia, creatinina, colesterol total, HDLc e proteínas totais, mas houve alterações significativas (p < 0,05 em todas as comparações no teste t de Student e ANOVA para triglicérides, albumina e glicemia. Conclusão: a L-arg não é nefrotóxica, nem hepatotóxica, mas causou hiperglicemia e hipertrigliceridemia em ratos. No entanto, as dosagens foram realizadas num momento fixo do experimento, quando o GH (hormônio do crescimento poderia estar agindo, interferindo nos resultados, uma vez que os processos metabólicos e fisiológicos são dinâmicos. Além disso, a L-arg pode ser benéfica na cicatrização de feridas de pele e músculo, uma vez que aumenta a albumina circulante. Objetive: To analyze the biochemical changes produced by L-arginine supplementation in rats induced to obesity and subjected to physical training. Materials and Methods: A total of 35 adult male Wistar rats induced to obesity and divided into 03 groups: Control - distilled water, L-arginine - 100mg/kg (T1, L-arginine - 500mg/Kg (T2, were tested individually and submitted to forced swimming. After 60 days they were euthanized and the tissue samples were collected for biochemical analysis. Results: biochemical changes were not found for urea, creatinine, total cholesterol, HDL cholesterol and total protein, but significant changes (p <0.05 were found in all comparisons of the Student t test

  3. Standard electrode potential, Tafel equation, and the solvation thermodynamics.

    Science.gov (United States)

    Matyushov, Dmitry V

    2009-06-21

    Equilibrium in the electronic subsystem across the solution-metal interface is considered to connect the standard electrode potential to the statistics of localized electronic states in solution. We argue that a correct derivation of the Nernst equation for the electrode potential requires a careful separation of the relevant time scales. An equation for the standard metal potential is derived linking it to the thermodynamics of solvation. The Anderson-Newns model for electronic delocalization between the solution and the electrode is combined with a bilinear model of solute-solvent coupling introducing nonlinear solvation into the theory of heterogeneous electron transfer. We therefore are capable of addressing the question of how nonlinear solvation affects electrochemical observables. The transfer coefficient of electrode kinetics is shown to be equal to the derivative of the free energy, or generalized force, required to shift the unoccupied electronic level in the bulk. The transfer coefficient thus directly quantifies the extent of nonlinear solvation of the redox couple. The current model allows the transfer coefficient to deviate from the value of 0.5 of the linear solvation models at zero electrode overpotential. The electrode current curves become asymmetric in respect to the change in the sign of the electrode overpotential.

  4. Solvation structures of lithium halides in methanol–water mixtures

    International Nuclear Information System (INIS)

    Sarkar, Atanu; Dixit, Mayank Kumar; Tembe, B.L.

    2015-01-01

    Highlights: • Potentials of mean force for Li + -halides are calculated in methanol–water mixtures. • Stable CIP for x methanol = 1.0 becomes unstable at and below x methanol = 0.75. • The Li + ion is preferentially solvated by methanol molecules. • The halide ions are preferentially solvated by water molecules. - Abstract: The potentials of mean force (PMFs) for the ion pairs, Li + −Cl − , Li + −Br − and Li + −I − have been calculated in five methanol–water compositions. The results obtained are verified by trailing the trajectories and calculating the ion pair distance residence times. Local structures around the ions are studied using the radial distribution functions, density profiles, orientational correlation functions, running coordination numbers and excess coordination numbers. The major change in PMF is observed as the methanol mole fraction (x methanol ) is changed from 1.0 to 0.75. The stable contact ion pair occurring for x methanol = 1.0 becomes unstable at and below x methanol = 0.75. The preferential solvation data show that the halide ions are always preferentially solvated by water molecules. Although the lithium ion is preferentially solvated by methanol molecules, there is significant affinity towards water molecules as well

  5. Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

    International Nuclear Information System (INIS)

    Wagner, H.; Maier, V.; Franz, H.W.; Ulm Univ.; Ulm Univ.

    1977-01-01

    A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 μU/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 μU/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control. (orig.) [de

  6. A non-equilibrium 24-hour vasopressin radioimmunoassay: development and basal levels in the rat brain

    International Nuclear Information System (INIS)

    Brinton, R.E.; Deshmukh, P.P.; Chen, A.; Davis, T.P.; Hsiao, S.; Yamamura, H.I.

    1983-01-01

    In this paper the authors report a highly-sensitive non-equilibrium RIA which can be performed within 24 h. To demonstrate the sensitivity of this RIA, brain regions from rat were examined for vasopressin content. (Auth.)

  7. Vasopressin Gene-Related Products in the Management of Breast Cancer

    National Research Council Canada - National Science Library

    North, William

    1999-01-01

    ...), and this information coupled with an absence of vasopressin gene-related products from fibrocystic disease potentially provides us with a new screening test for distinguishing both breast cancer...

  8. Oxytocin and vasopressin neural networks: Implications for social behavioral diversity and translational neuroscience.

    Science.gov (United States)

    Johnson, Zachary V; Young, Larry J

    2017-05-01

    Oxytocin- and vasopressin-related systems are present in invertebrate and vertebrate bilaterian animals, including humans, and exhibit conserved neuroanatomical and functional properties. In vertebrates, these systems innervate conserved neural networks that regulate social learning and behavior, including conspecific recognition, social attachment, and parental behavior. Individual and species-level variation in central organization of oxytocin and vasopressin systems has been linked to individual and species variation in social learning and behavior. In humans, genetic polymorphisms in the genes encoding oxytocin and vasopressin peptides and/or their respective target receptors have been associated with individual variation in social recognition, social attachment phenotypes, parental behavior, and psychiatric phenotypes such as autism. Here we describe both conserved and variable features of central oxytocin and vasopressin systems in the context of social behavioral diversity, with a particular focus on neural networks that modulate social learning, behavior, and salience of sociosensory stimuli during species-typical social contexts. Published by Elsevier Ltd.

  9. Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, H; Maier, V; Franz, H W [Ulm Univ. (Germany, F.R.). Abt. Endokrinologie und Stoffwechsel; Ulm Univ. (Germany, F.R.). Zentrum fuer Innere Medizin und Kinderheilkunde; Ulm Univ. (Germany, F.R.). Sektion Nephrologie)

    1977-05-01

    A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 ..mu..U/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 ..mu..U/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control.

  10. Radioimmunoassay for human plasma 8-arginine-vasopressin

    International Nuclear Information System (INIS)

    Conte-Devolx, B.; Rougon-Rapuzzi, G.; Millet, Y.

    1977-01-01

    A radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormone (ADH) level as low as 0.8pg/ml, was developed. The average plasma level of AVP after overnight water restriction was found to be 14.3pg/ml (sd=4.4pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion: in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated [fr

  11. Radioimmunoassay for human plasma 8-arginine-vasopressin

    Energy Technology Data Exchange (ETDEWEB)

    Conte-Devolx, B [Hopital de la Conception, 13 - Marseille (France); Rougon-Rapuzzi, G [Centre National de la Recherche Scientifique, 13 - Marseille (France); Millet, Y [Aix-Marseille-2 Univ., 13 - Marseille (France)

    1977-01-01

    A radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormone (ADH) level as low as 0.8pg/ml, was developed. The average plasma level of AVP after overnight water restriction was found to be 14.3pg/ml (sd=4.4pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion: in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated.

  12. Endocrine Disruption of Vasopressin Systems and Related Behaviors

    Directory of Open Access Journals (Sweden)

    Heather B. Patisaul

    2017-06-01

    Full Text Available Endocrine disrupting chemicals (EDCs are chemicals that interfere with the organizational or activational effects of hormones. Although the vast majority of the EDC literature focuses on steroid hormone signaling related impacts, growing evidence from a myriad of species reveals that the nonapeptide hormones vasopressin (AVP and oxytocin (OT may also be EDC targets. EDCs shown to alter pathways and behaviors coordinated by AVP and/or OT include the plastics component bisphenol A (BPA, the soy phytoestrogen genistein (GEN, and various flame retardants. Many effects are sex specific and likely involve action at nuclear estrogen receptors. Effects include the elimination or reversal of well-characterized sexually dimorphic aspects of the AVP system, including innervation of the lateral septum and other brain regions critical for social and other non-reproductive behaviors. Disruption of magnocellular AVP function has also been reported in rats, suggesting possible effects on hemodynamics and cardiovascular function.

  13. Reliability of basal plasma vasopressin concentrations in healthy male adults.

    Science.gov (United States)

    Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

    2017-10-01

    The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important and interrelated roles in modulating mammalian social behaviour. While the OT system has received considerable research attention for its potential to treat psychiatric symptoms, comparatively little is known about the role of the AVP system in human social behaviour. To better understand the intraindividual stability of basal AVP, the present study assessed the reproducibility of basal plasma AVP concentrations. Basal plasma AVP was assessed at four sampling points separated by 8 days, on average, in 16 healthy adult males. Only one out of six comparisons revealed strong evidence for reproducibility of basal AVP concentrations (visit 2 vs. visit 4: r=0.8, p0.1). The concordance correlation coefficient [0.15, 95% CI (-0.55, 0.73)] also revealed poor overall reproducibility. Poor reliability of basal AVP concentrations suggests future work covarying AVP with trait markers should proceed with careful consideration of intraindividual fluctuations.

  14. The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience.

    Science.gov (United States)

    Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R

    2017-06-01

    The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic

  15. Effects of Arginine Vasopressin on musical short-term memory

    Directory of Open Access Journals (Sweden)

    Roni Y. Granot

    2013-10-01

    Full Text Available Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP and musical working memory (WM. The current study set out to test the influence of intranasal administration (INA of AVP on musical as compared to verbal WM using a double blind crossover (AVP – placebo design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo in a second session, one week apart. In each session subjects completed the tonal subtest from Gordon's Musical Aptitude Profile, the interval subtest from the Montreal Battery for Evaluation of Amusias (MBEA, and the forward and backward digit span tests. Scores in the digit span tests were not influenced by AVP. In contrast, in the music tests there was an AVP effect. In the MBEA test, scores for the group receiving placebo in the first session (PV were higher than for the group receiving vasopressin in the first session (VP (p < .05 with no main Session effect nor Group * Session interaction. In the Gordon test there was a main Session effect (p < .05 with scores higher in the second as compared to the first session, a marginal main Group effect (p = .093 and a marginal Group X Session interaction (p = 0.88. In addition we found that the group that received AVP in the first session scored higher on scales indicative of happiness, and alertness on the Positive and Negative Affect Scale, (PANAS. Only in this group and only in the music test these scores were significantly correlated with memory scores. Together the results reflect a complex interaction between AVP, musical memory, arousal, and contextual effects such as session, and base levels of memory. The results are interpreted in light of music's universal use as a means to modulate arousal on the one hand, and AVP's influence on mood, arousal, and social interactions on the other.

  16. Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice.

    Science.gov (United States)

    Song 宋志林, Zhilin; Roncal-Jimenez, Carlos A; Lanaspa-Garcia, Miguel A; Oppelt, Sarah A; Kuwabara, Masanari; Jensen, Thomas; Milagres, Tamara; Andres-Hernando, Ana; Ishimoto, Takuji; Garcia, Gabriela E; Johnson, Ginger; MacLean, Paul S; Sanchez-Lozada, Laura-Gabriela; Tolan, Dean R; Johnson, Richard J

    2017-02-01

    Fructose stimulates vasopressin in humans and can be generated endogenously by activation of the polyol pathway with hyperosmolarity. We hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration. Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired. This study increases our understanding of the

  17. Protein synthesis inhibitors attenuate water flow in vasopressin-stimulated toad urinary bladder

    International Nuclear Information System (INIS)

    Hoch, B.S.; Ast, M.B.; Fusco, M.J.; Jacoby, M.; Levine, S.D.

    1988-01-01

    Vasopressin stimulates the introduction of aggregated particles, which may represent pathways for water flow, into the luminal membrane of toad urinary bladder. It is not known whether water transport pathways are degraded on removal from membrane or whether they are recycled. The authors examined the effect of the protein synthesis inhibitors cycloheximide and puromycin using repeated 30-min cycles of vasopressin followed by washout of vasopressin, all in the presence of an osmotic gradient, a protocol that maximizes aggregate turnover. High dose cycloheximide inhibited flow immediately. Low dose cycloheximide did not affect initial flow. In the absence of vasopressin, inhibition did not develop. Despite the inhibition of flow in vasopressin-treated tissues, the cAMP-dependent protein kinase ratio was elevated in cycloheximide-treated tissues, suggesting modulation at a distal site in the stimulatory cascade. [ 14 C]urea permeability was not inhibited by cycloheximide. Puromycin also inhibited water flow by the fourth challenge with vasopressin. The data suggest that protein synthesis inhibitors attenuate flow at a site that is distal to cAMP-dependent protein kinase. However, the reversal of inhibition in MIX-treated tissues suggests that the water pathway can be fully manifested given suitable stimulation. They conclude that either large stores of the transport system are available or that the transport system is extensively recycled on retrieval from the membrane

  18. Vasopressin facilitates excitatory transmission in slices of the rat dorso-lateral septum.

    Science.gov (United States)

    Van den Hooff, P; Urban, I J

    1990-01-01

    The effect of vasopressin on neurons of the rat dorso-lateral septum (DLS) was studied in brain slices with intracellular microelectrodes. Two out of 13 neurons showed a small depolarization, spontaneous activity, and increased input resistances following a 15 min exposure to 10(-6) to 10(-8) M vasopressin (VP). These membrane effects disappeared completely within 3-5 min after the application. The remaining DLS neurons treated with these vasopressin concentrations showed an increase in glutamate-mediated excitatory postsynaptic potentials (EPSPs), evoked by stimulation of the fimbria fibers. As little as 10(-12) MVP increased these EPSPs markedly in nearly 80% of the cells studied. This increase in most of the cells disappeared within 15 min after the application period, whereas the increase in EPSPs induced by 10(-10) M VP outlasted the peptide application period for more than 30 min. Neither the blockade of GABA-ergic synaptic inhibition nor the pre-treatment of the neurons with d(CH2)5-Tyr(Me)-arginine vasopressin or 2-amino-5-phosphonovaleric acid (2-APV), antagonists for the V1 type of vasopressin receptor and NMDA receptors, respectively, interfered with the EPSPs potentiating effect of the peptide. It is concluded that a type of vasopressin receptor other then the V1 type is involved in the long-lasting potentiation of the primarily non-NMDA receptor mediated transmission in DLS neurons.

  19. Changes in social functioning and circulating oxytocin and vasopressin following the migration to a new country.

    Science.gov (United States)

    Gouin, Jean-Philippe; Pournajafi-Nazarloo, Hossein; Carter, C Sue

    2015-02-01

    Prior studies have reported associations between plasma oxytocin and vasopressin and markers of social functioning. However, because most human studies have used cross-sectional designs, it is unclear whether plasma oxytocin and vasopressin influences social functioning or whether social functioning modulates the production and peripheral release of these peptides. In order to address this question, we followed individuals who experienced major changes in social functioning subsequent to the migration to a new country. In this study, 59 new international students were recruited shortly after arrival in the host country and reassessed 2 and 5 months later. At each assessment participants provided information on their current social functioning and blood samples for oxytocin and vasopressin analysis. Results indicated that changes in social functioning were not related to changes in plasma oxytocin. Instead, baseline oxytocin predicted changes in social relationship satisfaction, social support, and loneliness over time. In contrast, plasma vasopressin changed as a function of social integration. Baseline vasopressin was not related to changes in social functioning over time. These results emphasize the different roles of plasma oxytocin and vasopressin in responses to changes in social functioning in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man

    Science.gov (United States)

    Convertino, V. A.; Keil, L. C.; Bernauer, E. M.; Greenleaf, J. E.

    1981-01-01

    The influence of work intensity on plasma volume, osmolality, vasopressin and renin activity and the interrelationships between these responses are investigated. Plasma volume, renin activity and osmotic, sodium and arginine vasopressin concentrations were measured in venous blood samples taken from 15 healthy male subjects before and after six minutes of bicycle ergometer exercise at 100, 175 and 225 W. Plasma volume is found to decrease significantly with increasing work intensity, while increases in Na(+) concentration, osmolality and vasopressin are only observed to be significant when the work intensity exceeds 40% maximal aerobic capacity and plasma resin activity increased linearly at all work levels. In addition, significant correlations are observed between plasma volume and osmolality and sodium changes, and between vasopressin and osmolality and sodium content changes. Data thus support the hypotheses that (1) vasopressin may be the primary controlling endocrine for fluid and electrolyte levels following exercise; (2) an exercise intensity greater than 40% maximal aerobic capacity is required to stimulate vasopressin release through changes in plasma osmolality; and (3) the stimulation of the renin-angiotensin system is a more general stress response.

  1. Effect of the addition of vasopressin or vasopressin plus nitroglycerin to epinephrine on arterial blood pressure during cardiopulmonary resuscitation in humans.

    Science.gov (United States)

    Ducros, Laurent; Vicaut, Eric; Soleil, Christian; Le Guen, Morgan; Gueye, Papa; Poussant, Thomas; Mebazaa, Alexandre; Payen, Didier; Plaisance, Patrick

    2011-11-01

    Infusion of a vasopressor during cardiopulmonary resuscitation (CPR) in humans increases end decompression (diastolic) arterial blood pressure, and consequently increases vital organ perfusion pressure and survival. Several vasoactive drugs have been tested alone or in combination, but their hemodynamic effects have not been investigated clinically in humans. We tested the hypothesis that epinephrine (1 mg) co-administered with vasopressin (40 IU) ± nitroglycerin (300 μg) results in higher diastolic blood pressure than epinephrine alone. A prospective, randomized, double-blinded controlled trial in the prehospital setting. The study included 48 patients with witnessed cardiac arrest. Patients received either epinephrine alone (E alone) or epinephrine plus vasopressin (E+V) or epinephrine plus vasopressin plus nitroglycerin (E+V+N). A femoral arterial catheter was inserted for arterial pressure measurement. The primary end point was diastolic blood pressure during CPR, 15 min after the first drug administration (T = 15 min). After exclusions, a total of 44 patients were enrolled. Diastolic blood pressures (mm Hg) at T = 15 min were not statistically different between groups (median [interquartile range]: 20 [10], 15 [6], and 15 [13] for E alone, E+V, and E+V+N, respectively. The rate of return of spontaneous circulation was 63% (n = 10) in the epinephrine group, 43% (n = 6) in the epinephrine plus vasopressin group, and 36% (n = 5) in the triple therapy group (NS). Addition of vasopressin or vasopressin plus nitroglycerin to epinephrine did not increase perfusion blood pressure compared to epinephrine alone in humans in cardiac arrest, suggesting the absence of benefit in using these drug combination(s). Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Difference rule-a new thermodynamic principle: prediction of standard thermodynamic data for inorganic solvates.

    Science.gov (United States)

    Jenkins, H Donald Brooke; Glasser, Leslie

    2004-12-08

    We present a quite general thermodynamic "difference" rule, derived from thermochemical first principles, quantifying the difference between the standard thermodynamic properties, P, of a solid n-solvate (or n-hydrate), n-S, containing n molecules of solvate, S (water or other) and the corresponding solid parent (unsolvated) salt: [P[n-solvate] - P[parent

  3. Water Evaporation and Conformational Changes from Partially Solvated Ubiquitin

    Directory of Open Access Journals (Sweden)

    Saravana Prakash Thirumuruganandham

    2010-01-01

    Full Text Available Using molecular dynamics simulation, we study the evaporation of water molecules off partially solvated ubiquitin. The evaporation and cooling rates are determined for a molecule at the initial temperature of 300 K. The cooling rate is found to be around 3 K/ns, and decreases with water temperature in the course of the evaporation. The conformation changes are monitored by studying a variety of intermediate partially solvated ubiquitin structures. We find that ubiquitin shrinks with decreasing hydration shell and exposes more of its hydrophilic surface area to the surrounding.

  4. Dipole moments of molecules solvated in helium nanodroplets

    International Nuclear Information System (INIS)

    Stiles, Paul L.; Nauta, Klaas; Miller, Roger E.

    2003-01-01

    Stark spectra are reported for hydrogen cyanide and cyanoacetylene solvated in helium nanodroplets. The goal of this study is to understand the influence of the helium solvent on measurements of the permanent electric dipole moment of a molecule. We find that the dipole moments of the helium solvated molecules, calculated assuming the electric field is the same as in vacuum, are slightly smaller than the well-known gas-phase dipole moments of HCN and HCCCN. A simple elliptical cavity model quantitatively accounts for this difference, which arises from the dipole-induced polarization of the helium

  5. Differential geometry based solvation model II: Lagrangian formulation.

    Science.gov (United States)

    Chen, Zhan; Baker, Nathan A; Wei, G W

    2011-12-01

    Solvation is an elementary process in nature and is of paramount importance to more sophisticated chemical, biological and biomolecular processes. The understanding of solvation is an essential prerequisite for the quantitative description and analysis of biomolecular systems. This work presents a Lagrangian formulation of our differential geometry based solvation models. The Lagrangian representation of biomolecular surfaces has a few utilities/advantages. First, it provides an essential basis for biomolecular visualization, surface electrostatic potential map and visual perception of biomolecules. Additionally, it is consistent with the conventional setting of implicit solvent theories and thus, many existing theoretical algorithms and computational software packages can be directly employed. Finally, the Lagrangian representation does not need to resort to artificially enlarged van der Waals radii as often required by the Eulerian representation in solvation analysis. The main goal of the present work is to analyze the connection, similarity and difference between the Eulerian and Lagrangian formalisms of the solvation model. Such analysis is important to the understanding of the differential geometry based solvation model. The present model extends the scaled particle theory of nonpolar solvation model with a solvent-solute interaction potential. The nonpolar solvation model is completed with a Poisson-Boltzmann (PB) theory based polar solvation model. The differential geometry theory of surfaces is employed to provide a natural description of solvent-solute interfaces. The optimization of the total free energy functional, which encompasses the polar and nonpolar contributions, leads to coupled potential driven geometric flow and PB equations. Due to the development of singularities and nonsmooth manifolds in the Lagrangian representation, the resulting potential-driven geometric flow equation is embedded into the Eulerian representation for the purpose of

  6. Thermodynamics of solvation and solvophobic effect in formamide

    International Nuclear Information System (INIS)

    Sedov, I.A.; Stolov, M.A.; Solomonov, B.N.

    2013-01-01

    Highlights: • Enthalpies of solution of apolar organic compounds in formamide were measured. • Gibbs free energies of solution were experimentally determined. • Influence of the solvophobic effect on solvation thermodynamics was studied. • Thermodynamic features of solutions in formamide resemble those of aqueous solutions. -- Abstract: Using semi-adiabatic calorimetry, we measured the enthalpies of solution for various low-polar compounds including alkanes, aromatic hydrocarbons and their halogenated derivatives in formamide at temperature of 298 K. For the same compounds, the values of limiting activity coefficients in formamide were determined using GC headspace analysis at 298 K, and Gibbs free energies of solution and solvation were calculated. Based on these data and the available literature values of the Gibbs free energy of solvation in formamide for a number of other low-polar solutes, a study of the solvophobic effect in this solvent is performed, and its resemblance to the hydrophobic effect in aqueous solutions is demonstrated. It is shown that the contribution of the solvophobic effect into the solvation Gibbs free energy in formamide is much higher than that in aliphatic alcohols, but lower than that in water. Like in water, the magnitude of this contribution for different solutes linearly increases with the solute molecular volume. Solvophobic effect also significantly affects the enthalpies of dissolution in formamide, causing them to be more negative in the case of alkanes and more positive in the case of arenes

  7. Isotope effect in enthalpy of solvation of the lithium ion

    International Nuclear Information System (INIS)

    Krestov, G.A.; Egorov, G.I.; Korolev, V.P.

    1989-01-01

    At 298.15 K, the authors determined the standard enthalpies of solution for 6 LiCl and 7 LiCl in water, heavy water, dimethylsulfoxide (DMSO) and aqueous solutions of DMSO. The authors have established that solvation of 6 Li + is differentiated in water and DMSO to a greater degree than for 7 Li +

  8. The solvation of carbohydrates in dimethylsulfoxide and water

    International Nuclear Information System (INIS)

    Berger, S.; Diaz, M.D.; Horwat, Ch.

    1999-01-01

    The solvation of sucrose and other carbohydrates in DMSO and water is probed by intermolecular NOE measurements. The NOE effects are interpreted in terms of specific binding of the solvent to certain sites of the molecules. It is shown that DMSO attaches to specific sites of the sucrose molecule, whereas for water such a clear differentiation cannot be proven. (author)

  9. Microscopic picture of the aqueous solvation of glutamic acid

    NARCIS (Netherlands)

    Leenders, E.J.M.; Bolhuis, P.G.; Meijer, E.J.

    2008-01-01

    We present molecular dynamics simulations of glutamic acid and glutamate solvated in water, using both density functional theory (DFT) and the Gromos96 force field. We focus on the microscopic aspects of the solvation−particularly on the hydrogen bond structures and dynamics−and investigate the

  10. On the coupling between molecular diffusion and solvation shell exchange

    DEFF Research Database (Denmark)

    Møller, Klaus Braagaard; Rey, Rossend; Masia, Marco

    2005-01-01

    The connection between diffusion and solvent exchanges between first and second solvation shells is studied by means of molecular dynamics simulations and analytic calculations, with detailed illustrations for water exchange for the Li+ and Na+ ions, and for liquid argon. First, two methods...

  11. Comparison between implicit and hybrid solvation methods for the ...

    Indian Academy of Sciences (India)

    Administrator

    Both implicit solvation method (dielectric polarizable continuum model, DPCM) and hybrid ... the free energy change (ΔGsol) as per the PCM ... Here the gas phase change is written as ΔGg = ΔEelec + ..... bution to the field of electrochemistry.

  12. Polarizability and Aqueous Solvation of the Sulfate Dianion

    Czech Academy of Sciences Publication Activity Database

    Jungwirth, Pavel; Curtis, J. E.; Tobias, D. J.

    2003-01-01

    Roč. 367, - (2003), s. 704-710 ISSN 0009-2614 R&D Projects: GA MŠk LN00A032 Institutional research plan: CEZ:AV0Z4040901 Keywords : polarizability * aqueous solvation * dianion Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.438, year: 2003

  13. Vasopressin and nitroglycerin decrease portal and hepatic venous pressure and hepato-splanchnic blood flow.

    Science.gov (United States)

    Wisén, E; Svennerholm, K; Bown, L S; Houltz, E; Rizell, M; Lundin, S; Ricksten, S-E

    2018-03-26

    Various methods are used to reduce venous blood pressure in the hepato-splanchnic circulation, and hence minimise blood loss during liver surgery. Previous studies show that combination of vasopressin and nitroglycerin reduces portal pressure and flow in patients with portal hypertension, and in this study we investigated this combination in patients with normal portal pressure. In all, 13 patients were studied. Measurements were made twice to confirm baseline (C1 and BL), during vasopressin infusion 4.8 U/h (V), and during vasopressin infusion combined with nitroglycerin infusion (V + N). Portal venous pressure (PVP), hepatic venous pressure (HVP), central haemodynamics and arterial and venous blood gases were obtained at each measuring point, and portal (splanchnic) and hepato-splanchnic blood flow changes were calculated. Vasopressin alone did not affect PVP, whereas HVP increased slightly. In combination with nitroglycerin, PVP decreased from 10.1 ± 1.6 to 8.9 ± 1.3 mmHg (P HVP decreased from 7.9 ± 1.9 to 6.2 ± 1.3 mmHg (P = 0.001). Vasopressin reduced portal blood flow by 47 ± 19% and hepatic venous flow by 11 ± 18%, respectively. Addition of nitroglycerin further reduced portal- and hepatic flow by 55 ± 13% and 30 ± 13%, respectively. Vasopressin alone had minor effects on central haemodynamics, whereas addition of nitroglycerin reduced cardiac index (3.2 ± 0.7 to 2.7 ± 0.5; P < 0.0001). The arterial-portal vein lactate gradient was unaffected. The combination of vasopressin and nitroglycerin decreases portal pressure and hepato-splanchnic blood flow, and could be a potential treatment to reduce bleeding in liver resection surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. Ionic Liquids: Radiation Chemistry, Solvation Dynamics and Reactivity Patterns

    International Nuclear Information System (INIS)

    Wishart, J.F.

    2011-01-01

    Ionic liquids (ILs) are a rapidly expanding family of condensed-phase media with important applications in energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs generally have low volatilities and are combustion-resistant, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of primary radiation chemistry, charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of reactions and product distributions. We study these issues by characterization of primary radiolysis products and measurements of their yields and reactivity, quantification of electron solvation dynamics and scavenging of electrons in different states of solvation. From this knowledge we wish to learn how to predict radiolytic mechanisms and control them or mitigate their effects on the properties of materials used in nuclear fuel processing, for example, and to apply IL radiation chemistry to answer questions about general chemical reactivity in ionic liquids that will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that the slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increase the importance of pre-solvated electron reactivity and consequently alter product distributions and subsequent chemistry. This difference from conventional solvents has profound effects on predicting and controlling radiolytic yields

  15. Plasma arginine vasopressin response to water load during labour

    International Nuclear Information System (INIS)

    Singhi, Sunit; Parshad, Omkar

    1985-01-01

    To find out whether plasma vasopressin (Psub(AVP)) response to a water load during pregnancy is inappropriately high, as had been speculated, we measured Psub(AVP)by radioimmunoassay in 30 women at the time of delivery. Ten women had received infusion of aqueous glucose solution during labour for hydration (GW group); another ten received infusion of glucose solution as a vehicle for oxytocin (IOT group), and ten women did not receive any intrapartum intravenous fluid therapy (controls). Serum sodium and osmolality were also determined in all the subjects. Psub(AVP) levels were significantly lower in GW (0.70 +- 0.4 pg/ml) and OT groups (0.7 +- 0.6 pg/ml) (P<0.05). Significant negative correlation was seen between the amount of glucose solution infused and levels of Psub(AVP) (r = -0.66; P<0.01), while a significant positive correlation was seen between Psub(AVP) and serum sodium (r = 0.61; P<0.01). These findings suggest that during labour, the physiological relationship between serum osmolality and Psub(AVP) in intact, and the infusion of a water load in the form of aqueous glucose solution is attended by an expected lowering of Psub(AVP). We infer that inappropriate ADH response is not the cause of water retention and hyponatremia often seen in women receiving aqueous glucose solution during labor. (author)

  16. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

    DEFF Research Database (Denmark)

    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...... the swim stress-induced OT response. CONCLUSION: 5-HT(2A), 5-HT(2C) and possibly 5-HT(3) and 5-HT(4) receptors, but not 5-HT(1A) receptors, are involved in the restraint stress-induced AVP secretion. 5-HT does not seem to be involved in the dehydration- or hemorrhage-induced AVP response. The restraint...... stress-induced OT response seems to be mediated via 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors. The dehydration and hemorrhage-induced OT responses are at least mediated by the 5-HT(2A) and 5-HT(2C) receptors. The 5-HT(3) and 5-HT(4) receptors are not involved in stress-induced OT secretion....

  17. Plasma arginine vasopressin response to water load during labour

    Energy Technology Data Exchange (ETDEWEB)

    Singhi, S. (West Indies Univ., Mona (Jamaica). Dept. of Child Health); Parshad, O. (West Indies Univ., Mona (Jamaica). Dept. of Physiology)

    1985-02-01

    To find out whether plasma vasopressin (Psub(AVP)) response to a water load during pregnancy is inappropriately high, as had been speculated, we measured Psub(AVP)by radioimmunoassay in 30 women at the time of delivery. Ten women had received infusion of aqueous glucose solution during labour for hydration (GW group); another ten received infusion of glucose solution as a vehicle for oxytocin (IOT group), and ten women did not receive any intrapartum intravenous fluid therapy (controls). Serum sodium and osmolality were also determined in all the subjects. Psub(AVP) levels were significantly lower in GW (0.70 +- 0.4 pg/ml) and OT groups (0.7 +- 0.6 pg/ml) (P < 0.05). Significant negative correlation was seen between the amount of glucose solution infused and levels of Psub(AVP) (r = -0.66; P < 0.01), while a significant positive correlation was seen between Psub(AVP) and serum sodium (r = 0.61; P < 0.01). These findings suggest that during labour, the physiological relationship between serum osmolality and Psub(AVP) in intact, and the infusion of a water load in the form of aqueous glucose solution is attended by an expected lowering of Psub(AVP). We infer that inappropriate ADH response is not the cause of water retention and hyponatremia often seen in women receiving aqueous glucose solution during labor.

  18. Cerebral glucose utilization after vasopressin barrel rotation or bicuculline seizures

    International Nuclear Information System (INIS)

    Wurpel, J.; Dundore, R.; Bryan, R.; Keil, L.; Severs, W.B.

    1986-01-01

    Intraventricular (ivt) arginine vasopressin (AVP) causes a violent motor behavior termed barrel rotation (BR). AVP-BR is affected by visual/vestibular sensory input and may be related to other CNS motor disorders (seizures). Local cerebral glucose utilization (LCGU) was compared in SD rats during AVP-BR and bicuculline (BIC) seizures. Three groups were used: saline-ivt; AVP-ivt 0.5 μg; BIC-5.5 mg/kg,sc. 14 C-glucose (40 μCI iv) was injected 15 sec. after ivt-saline or AVP or onset of BIC seizures. Rats were decapitated 10 min. after 14 C-glucose. Brains were removed and dissected into 19 regions which were digested and glucose uptake quantified by liquid scintillation counting. LCGU was significantly increased in all CNS areas during BIC seizures vs controls (21-92%; p < 0.05 ANOVA). LCGU exhibits variable (upward arrow, downward arrow) changes in discrete areas during AVP-BR (p < .05). Glucose uptake increased in: cortex-olfactory (21%), sensory (9%), motor (8%) cerebellum-rt (13%) and 1t (17%) hemispheres, vermis (6%); pyramidal tract (6%); mesencephalon (5%); and pons (8%). Two areas decreased LCGU during AVP-BR: auditory cortex (-8%) and hippocampus (-11%). AVP-BR exhibits distinct changes in LCGU vs BIC seizures

  19. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors.

    Science.gov (United States)

    Song, Zhilin; Levin, Barry E; Stevens, Wanida; Sladek, Celia D

    2014-04-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation.

  20. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

    Science.gov (United States)

    Song, Zhilin; Levin, Barry E.; Stevens, Wanida

    2014-01-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca2+]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating KATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and “metabolic” sensors to participate in appetite regulation. PMID:24477542

  1. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  2. Plasma vasopressin levels in patients with right-sided heart dysfunction and chronic thromboembolic pulmonary hypertension (CTEPH).

    Science.gov (United States)

    Nguyen, Liem; Banks, Dalia; Manecke, Gerard; Shurter, Jesse; Schilling, Jan M; Patel, Hemal H; Madani, Michael M; Roth, David M

    2014-06-01

    Patients with left-sided heart dysfunction and volume overload often have associated elevations in vasopressin from neuroendocrine activation. The authors investigated perioperative levels of vasopressin in patients with isolated right-sided heart dysfunction from chronic thromboembolic pulmonary hypertension. Prospective, observational study. Single center, tertiary hospital. Patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy. Vasopressin levels were measured in 22 patients during the perioperative period. Vasopressin was undetectable in 8/22 patients at baseline. As a group, vasopressin levels at baseline and after induction of anesthesia were 0.8 pg/mL (median; 0.5-1.5, interquartile range of 25% and 75%) and 0.7 pg/mL (median; 0.5-1.4, interquartile range of 25% and 75%), respectively. During cardiopulmonary bypass (CPB), vasopressin increased to 13.9 pg/mL (median; 6.7-19.9, interquartile range of 25% and 75%). Vasopressin remained elevated after deep hypothermic circulatory arrest (DHCA) at 10.5 pg/mL (median; 6.5-19.9 interquartile range of 25% and 75%) and after CPB at 19.9 pg/mL (median; 11.1-19.9 interquartile range of 25% and 75%). Vasopressin levels in PTE patients are in the low-to-normal range at baseline and may be a clinically relevant issue in the hemodynamic management of PTE. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. The relationship of radioimmunoassay to bioassay: In vitro studies with synthetic lysine vasopressin in aqueous solution inactivated by heat

    International Nuclear Information System (INIS)

    Loeve Lemboel, H.

    1978-01-01

    The relationship of radioimmunoassay to pressor assay and antidiuretic assay was investigated in a simple in vitro system of synthetic lysine vasopressin in aqueous solution inactivated by heating at 100 deg C for 9, 18, 27, 36, 54 and 72 h. An apparent dissociation between radioimmunoassay and bioassay was demonstrated, with biological activity being lost more rapidly than immunological activity. The half-times were 32 h for radioimmunoassay, 23 h for antidiuretic assay and 22 h for pressor assay. However, ion-exchange chromatography showed immunological heterogeneity but biological homogeneity of the lysine vasopressin used, and indicated that the presence of impurities in the vasopressin might to some extent explain the discrepancy between assay results. Synthetic arginine vasopressin and arginine vasopressin of pituitary origin showed a similar immunological heterogeneity by ion-exchange chromatography. (author)

  4. Radioimmunoassay of plasma vasopressin. Technique and applicaton to some clinical cases

    International Nuclear Information System (INIS)

    Granier, Francoise.

    1978-01-01

    The object of this work was to develop a sensitive and reliable radioimmunological determination of plasma vasopressin for routine use. Part one is devoted to an outline of the physiological aspects of antidiuretic hormone with emphasis on the vasopressin regulation and secretion mechanisms, especially osmotic regulation. Part two describes our analysis technique by successive stages and gives, for each point considered, a comparative review of the methods described in the literature. Part three reports our results obtained on normal subjects during dehydration tests and in some pathological cases. Our radioimmunoassay is similar to that of Robertson. In 2 observations of diabetes insipidus no detectable amount of vasopressin was measured in contradiction with the results obtained by most authors. On the whole our purpose has been fulfilled. However this work contains inadequacies which are underlined and will have to be corrected in later studies [fr

  5. Vasopressin-induced changes in splanchnic blood flow and hepatic and portal venous pressures in liver resection.

    Science.gov (United States)

    Bown, L Sand; Ricksten, S-E; Houltz, E; Einarsson, H; Söndergaard, S; Rizell, M; Lundin, S

    2016-05-01

    To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato-splanchnic circulation. In this study, the effect of low- to moderate doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato-splanchnic blood flows were assessed in elective liver resection surgery. Twelve patients were studied. Cardiac output (CO), stroke volume (SV), mean arterial (MAP), central venous (CVP), portal venous (PVP) and hepatic venous pressures (HVP) were measured, intraoperatively, at baseline and during vasopressin infusion at two infusion rates (2.4 and 4.8 U/h). From arterial and venous blood gases, the portal (splanchnic) and hepato-splanchnic blood flow changes were calculated, using Fick's equation. CO, SV, MAP and CVP increased slightly, but significantly, while systemic vascular resistance and heart rate remained unchanged at the highest infusion rate of vasopressin. PVP was not affected by vasopressin, while HVP increased slightly. Vasopressin infusion at 2.4 and 4.8 U/h reduced portal blood flow (-26% and -37%, respectively) and to a lesser extent hepato-splanchnic blood flow (-9% and -14%, respectively). The arterial-portal vein lactate gradient was not significantly affected by vasopressin. Postoperative serum creatinine was not affected by vasopressin. Short-term low to moderate infusion rates of vasopressin induced a splanchnic vasoconstriction without metabolic signs of splanchnic hypoperfusion or subsequent renal impairment. Vasopressin caused a centralization of blood volume and increased cardiac output. Vasopressin does not lower portal or hepatic venous pressures in this clinical setting. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Restoration of peripheral V2 receptor vasopressin signaling fails to correct behavioral changes in Brattleboro rats.

    Science.gov (United States)

    Balázsfi, Diána; Pintér, Ottó; Klausz, Barbara; Kovács, Krisztina B; Fodor, Anna; Török, Bibiána; Engelmann, Mario; Zelena, Dóra

    2015-01-01

    Beside its hormonal function in salt and water homeostasis, vasopressin released into distinct brain areas plays a crucial role in stress-related behavior resulting in the enhancement of an anxious/depressive-like state. We aimed to investigate whether correction of the peripheral symptoms of congenital absence of AVP also corrects the behavioral alterations in AVP-deficient Brattleboro rats. Wild type (WT) and vasopressin-deficient (KO) male Brattleboro rats were tested. Half of the KO animals were treated by desmopressin (V2-receptor agonist) via osmotic minipump (subcutaneous) to eliminate the peripheral symptoms of vasopressin-deficiency. Anxiety was studied by elevated plus maze (EPM), defensive withdrawal (DW) and marble burying (MB) tests, while depressive-like changes were monitored in forced swimming (FS) and anhedonia by sucrose preference test. Cell activity was examined in septum and amygdala by c-Fos immunohistochemistry after 10 min FS. KO rats spent more time in the open arm of the EPM, spent less time at the periphery of DW and showed less burying behavior in MB suggesting a reduced anxiety state. KO animals showed less floating behavior during FS revealing a less depressive phenotype. Desmopressin treatment compensated the peripheral effects of vasopressin-deficiency without a significant influence on the behavior. The FS-induced c-Fos immunoreactivity in the medial amygdala was different in WT and KO rats, with almost identical levels in KO and desmopressin treated animals. There were no differences in central and basolateral amygdala as well as in lateral septum. Our data confirmed the role of vasopressin in the development of affective disorders through central mechanisms. The involvement of the medial amygdala in the behavioral alterations of vasopressin deficient animals deserves further attention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. GABAergic inhibition through synergistic astrocytic neuronal interaction transiently decreases vasopressin neuronal activity during hypoosmotic challenge.

    Science.gov (United States)

    Wang, Yu-Feng; Sun, Min-Yu; Hou, Qiuling; Hamilton, Kathryn A

    2013-04-01

    The neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined the effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurons using patch-clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased inhibitory postsynaptic current (IPSC) frequency and reduced the firing rate of vasopressin neurons. Recovery occurred by 10 min of exposure, even though the osmolality remained low. The γ-aminobutyric acid (GABA)A receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l-aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β-alanine, an osmolyte of astrocytes and GABA transporter (GAT) inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurons both showed positive staining of vesicular GATs (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT-expressing neurons, and increased co-localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored, and astrocytic VGAT was relocated to the ventral portion while it decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neuron firing is only transiently suppressed under hypoosmotic conditions. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Neural injury after use of vasopressin and adrenaline during porcine cardiopulmonary resuscitation.

    Science.gov (United States)

    Halvorsen, Peter; Sharma, Hari Shanker; Basu, Samar; Wiklund, Lars

    2015-03-01

    Our aim was to investigate cerebral and cardiac tissue injury subsequent to use of vasopressin and adrenaline in combination compared with vasopressin alone during cardiopulmonary resuscitation (CPR). In a randomized, prospective, laboratory animal study 28 anesthetized piglets were subject to a 12-min untreated cardiac arrest and subsequent CPR. After 1 min of CPR, 10 of the piglets received 0.4 U/kg of arg(8)-vasopressin (V group), and 10 piglets received 0.4 U/kg of arg(8)-vasopressin, 1 min later followed by 20 µg/kg body weight of adrenaline, and another 1 min later continuous administration (10 µg/kg/min) of adrenaline (VA group). After 8 min of CPR, the piglets were defibrillated and monitored for another 3 h. Then they were killed and the brain immediately removed pending histological analysis. During CPR, the VA group had higher mean blood pressure and cerebral cortical blood flow (CCBF) but similar coronary perfusion pressure. After restoration of spontaneous circulation there was no difference in the pressure variables, but CCBF tended to be (36% ± 16%) higher in the V group. Neuronal injury and signs of a disrupted blood-brain barrier (BBB) were greater, 20% ± 4% and 21% ± 4%, respectively, in the VA group. In a background study of repeated single doses of adrenaline every third minute after 5 min arrest but otherwise the same protocol, histological measurements showed even worse neural injury and disruption of the BBB. Combined use of vasopressin and adrenaline caused greater signs of cerebral and cardiac injury than use of vasopressin alone during experimental cardiopulmonary resuscitation.

  9. Ionic Liquids: Radiation Chemistry, Solvation Dynamics and Reactivity Patterns

    International Nuclear Information System (INIS)

    Wishart, J.F.

    2008-01-01

    Ionic liquids (ILs) are a rapidly expanding family of condensed-phase media with important applications in energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs are generally nonvolatile, noncombustible, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of chemical reactions and product distributions. Successful use of ionic liquids in radiation-filled environments, where their safety advantages could be significant, requires an understanding of ionic liquid radiation chemistry. For example, characterizing the primary steps of IL radiolysis will reveal radiolytic degradation pathways and suggest ways to prevent them or mitigate their effects on the properties of the material. An understanding of ionic liquid radiation chemistry will also facilitate pulse radiolysis studies of general chemical reactivity in ILs, which will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increases the importance of pre-solvated electron reactivity and consequently alters product distributions. Parallel studies of IL solvation phenomena using coumarin-153 dynamic Stokes shifts and polarization anisotropy decay rates are done to compare with electron solvation studies and to evaluate

  10. IONIC LIQUIDS: RADIATION CHEMISTRY, SOLVATION DYNAMICS AND REACTIVITY PATTERNS

    International Nuclear Information System (INIS)

    WISHART, J.F.

    2007-01-01

    energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs are generally nonvolatile, noncombustible, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of chemical reactions and product distributions. Successful use of ionic liquids in radiation-filled environments, where their safety advantages could be significant, requires an understanding of ionic liquid radiation chemistry. For example, characterizing the primary steps of IL radiolysis will reveal radiolytic degradation pathways and suggest ways to prevent them or mitigate their effects on the properties of the material. An understanding of ionic liquid radiation chemistry will also facilitate pulse radiolysis studies of general chemical reactivity in ILs, which will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increases the importance of pre-solvated electron reactivity and consequently alters product distributions. Parallel studies of IL solvation phenomena using coumarin-153 dynamic Stokes shifts and polarization anisotropy decay rates are done to compare with electron solvation studies and to evaluate the influence of ILs on charge transport processes. Methods. Picosecond pulse radiolysis studies at BNL

  11. Central vasopressin V1a receptors modulate neural processing in mothers facing intruder threat to pups

    OpenAIRE

    Caffrey, Martha K.; Nephew, Benjamin C.; Febo, Marcelo

    2009-01-01

    Vasopressin V1a receptors in the rat brain have been studied for their role in modulating aggression and anxiety. In the current study blood-oxygen-level-dependent (BOLD) functional MRI was used to test whether V1a receptors modulate neural processing in the maternal brain when dams are exposed to a male intruder. Primiparous females were given an intracerebroventricular (ICV) injection of vehicle or V1a receptor antagonist ([deamino-Pen1, O-Me-Try, Arg8]-Vasopressin, 125 ng/10 μL) 90-120 min...

  12. Arginine vasopressin stimulates phosphoinositide turnover in an enriched rat Leydig cell preparation

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

    1989-01-01

    An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol and phosphatidyl......An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol...

  13. Endogenous Oxytocin, Vasopressin, and Aggression in Domestic Dogs

    Directory of Open Access Journals (Sweden)

    Evan L. MacLean

    2017-09-01

    Full Text Available Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT and vasopressin (AVP—neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species—and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs for the measurement of free (unbound and total (free + bound OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.

  14. A solvated electron lithium electrode for secondary batteries

    Science.gov (United States)

    Sammells, A. F.; Semkow, K. W.

    1986-09-01

    Attention is given to a novel method for the achievement of high electro-chemical reversibility in Li-based nonaqueous cells, using a liquid negative electrode that consists of Li dissolved in liquid ammonia as a solvated electron Li electrode. The containment of this liquid negative active material from direct contact to a liquid nonaqueous electrolyte in the positive electrode compartment was realized through the use of a Li-intercalated, electronically conducting ceramic membrane.

  15. Tris[2-(deuteriomethylsulfanylphenyl]phosphine deuteriochloroform 0.125-solvate

    Directory of Open Access Journals (Sweden)

    Seik Weng Ng

    2008-05-01

    Full Text Available The title deuterated tripodal phosphine, C21H12D9PS3·0.125CDCl3, crystallizes as two independent molecules, one of which lies on a general position and the other about a threefold rotation axis, and as a deuteriochloroform solvate. The solvent molecule is disordered about a site of symmetry 3, so that the ratio of phosphine to solvent is 8:1. The P atom adopts a pyramidal coordination geometry.

  16. Solvation dynamics of lithium salts in wet nitrobenzene

    Czech Academy of Sciences Publication Activity Database

    Moakes, G.; Gelbaum, L. T.; Leisen, J.; Janata, J.; Mareček, Vladimír

    2006-01-01

    Roč. 593, 1-2 (2006), s. 111-118 ISSN 0022-0728 R&D Projects: GA ČR GA203/03/0822 Grant - others:Georgia Research Alliance(US) GRA.CG06.D Institutional research plan: CEZ:AV0Z40400503 Keywords : solvation * NMR * FTIR * nitrobenzene/water * solvatomers Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.339, year: 2006

  17. Benzonitrile: Electron affinity, excited states, and anion solvation

    Science.gov (United States)

    Dixon, Andrew R.; Khuseynov, Dmitry; Sanov, Andrei

    2015-10-01

    We report a negative-ion photoelectron imaging study of benzonitrile and several of its hydrated, oxygenated, and homo-molecularly solvated cluster anions. The photodetachment from the unsolvated benzonitrile anion to the X ˜ 1 A 1 state of the neutral peaks at 58 ± 5 meV. This value is assigned as the vertical detachment energy (VDE) of the valence anion and the upper bound of adiabatic electron affinity (EA) of benzonitrile. The EA of the lowest excited electronic state of benzonitrile, a ˜ 3 A 1 , is determined as 3.41 ± 0.01 eV, corresponding to a 3.35 eV lower bound for the singlet-triplet splitting. The next excited state, the open-shell singlet A ˜ 1 A 1 , is found about an electron-volt above the triplet, with a VDE of 4.45 ± 0.01 eV. These results are in good agreement with ab initio calculations for neutral benzonitrile and its valence anion but do not preclude the existence of a dipole-bound state of similar energy and geometry. The step-wise and cumulative solvation energies of benzonitrile anions by several types of species were determined, including homo-molecular solvation by benzonitrile, hydration by 1-3 waters, oxygenation by 1-3 oxygen molecules, and mixed solvation by various combinations of O2, H2O, and benzonitrile. The plausible structures of the dimer anion of benzonitrile were examined using density functional theory and compared to the experimental observations. It is predicted that the dimer anion favors a stacked geometry capitalizing on the π-π interactions between the two partially charged benzonitrile moieties.

  18. Comparison of solvation dynamics of electrons in four polyols

    Energy Technology Data Exchange (ETDEWEB)

    Lampre, I.; Pernot, P.; Bonin, J. [Laboratoire de Chimie Physique/ELYSE, Universite Paris-Sud 11, UMR 8000, Bat. 349, Orsay F-91405 (France); CNRS, Orsay F-91405 (France); Mostafavi, M. [Laboratoire de Chimie Physique/ELYSE, Universite Paris-Sud 11, UMR 8000, Bat. 349, Orsay F-91405 (France); CNRS, Orsay F-91405 (France)], E-mail: mehran.mostafavi@lcp.u-psud.fr

    2008-10-15

    Using pump-probe transient absorption spectroscopy, we studied the solvation dynamics of the electron in liquid polyalcohols: ethane-1,2-diol, propane-1,2-diol, propane-1,3-diol and propane-1,2,3-triol. Time-resolved absorption spectra ranging from 440 to 720 nm were measured. Our study shows that the excess electron in the diols presents an intense and wide absorption band in the visible and near-IR spectral domain at early time after two-photon ionization of the neat solvent. Then, for the first tens of picoseconds, the electron spectrum shifts toward the blue domain and its bandwidth decreases as the red part of the initial spectrum rapidly drops, while the blue part hardly evolves. In contrast, in the triol, the absorption spectrum of the electron is early situated in the visible range after the pump pulse and then solely evolves in the red part. The Bayesian data analysis of the observed picosecond solvation dynamics with different models is in favor of a heterogeneous continuous relaxation. That is corroborated by the analogy between the change in the absorption band with increasing time or decreasing temperature. That tends to indicate a similar organization disorder of the solvent. Moreover, the electron solvation dynamics is very fast in propane-1,2,3-triol despite its high viscosity and highlight the role of the OH-group in that process.

  19. Improvements to the APBS biomolecular solvation software suite.

    Science.gov (United States)

    Jurrus, Elizabeth; Engel, Dave; Star, Keith; Monson, Kyle; Brandi, Juan; Felberg, Lisa E; Brookes, David H; Wilson, Leighton; Chen, Jiahui; Liles, Karina; Chun, Minju; Li, Peter; Gohara, David W; Dolinsky, Todd; Konecny, Robert; Koes, David R; Nielsen, Jens Erik; Head-Gordon, Teresa; Geng, Weihua; Krasny, Robert; Wei, Guo-Wei; Holst, Michael J; McCammon, J Andrew; Baker, Nathan A

    2018-01-01

    The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that have provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses the three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this article, we discuss the models and capabilities that have recently been implemented within the APBS software package including a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory-based algorithm for determining pK a values, and an improved web-based visualization tool for viewing electrostatics. © 2017 The Protein Society.

  20. Enthalpy-entropy compensation: the role of solvation.

    Science.gov (United States)

    Dragan, Anatoliy I; Read, Christopher M; Crane-Robinson, Colyn

    2017-05-01

    Structural modifications to interacting systems frequently lead to changes in both the enthalpy (heat) and entropy of the process that compensate each other, so that the Gibbs free energy is little changed: a major barrier to the development of lead compounds in drug discovery. The conventional explanation for such enthalpy-entropy compensation (EEC) is that tighter contacts lead to a more negative enthalpy but increased molecular constraints, i.e., a compensating conformational entropy reduction. Changes in solvation can also contribute to EEC but this contribution is infrequently discussed. We review long-established and recent cases of EEC and conclude that the large fluctuations in enthalpy and entropy observed are too great to be a result of only conformational changes and must result, to a considerable degree, from variations in the amounts of water immobilized or released on forming complexes. Two systems exhibiting EEC show a correlation between calorimetric entropies and local mobilities, interpreted to mean conformational control of the binding entropy/free energy. However, a substantial contribution from solvation gives the same effect, as a consequence of a structural link between the amount of bound water and the protein flexibility. Only by assuming substantial changes in solvation-an intrinsically compensatory process-can a more complete understanding of EEC be obtained. Faced with such large, and compensating, changes in the enthalpies and entropies of binding, the best approach to engineering elevated affinities must be through the addition of ionic links, as they generate increased entropy without affecting the enthalpy.

  1. Thermodynamic functions of ion solvation in normal alcohols of aliphatic series

    International Nuclear Information System (INIS)

    Sergeeva, I.A.

    1978-01-01

    Thermodynamic functions of ion solvation of alkali, alkaline earth metals and halogenides in 9 alcohols are calculated using the earlier suggested method. It is shown that summary values are in good accord with experimental ones, the deviations do not surpass 0-5%, solvation energies of one and the same electrolyte in the series of n-alcohols do not change, enthalpy and entropy of solvation increase from lower alcohols to higher ones

  2. Multiple time step molecular dynamics in the optimized isokinetic ensemble steered with the molecular theory of solvation: Accelerating with advanced extrapolation of effective solvation forces

    International Nuclear Information System (INIS)

    Omelyan, Igor; Kovalenko, Andriy

    2013-01-01

    We develop efficient handling of solvation forces in the multiscale method of multiple time step molecular dynamics (MTS-MD) of a biomolecule steered by the solvation free energy (effective solvation forces) obtained from the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model complemented with the Kovalenko-Hirata closure approximation). To reduce the computational expenses, we calculate the effective solvation forces acting on the biomolecule by using advanced solvation force extrapolation (ASFE) at inner time steps while converging the 3D-RISM-KH integral equations only at large outer time steps. The idea of ASFE consists in developing a discrete non-Eckart rotational transformation of atomic coordinates that minimizes the distances between the atomic positions of the biomolecule at different time moments. The effective solvation forces for the biomolecule in a current conformation at an inner time step are then extrapolated in the transformed subspace of those at outer time steps by using a modified least square fit approach applied to a relatively small number of the best force-coordinate pairs. The latter are selected from an extended set collecting the effective solvation forces obtained from 3D-RISM-KH at outer time steps over a broad time interval. The MTS-MD integration with effective solvation forces obtained by converging 3D-RISM-KH at outer time steps and applying ASFE at inner time steps is stabilized by employing the optimized isokinetic Nosé-Hoover chain (OIN) ensemble. Compared to the previous extrapolation schemes used in combination with the Langevin thermostat, the ASFE approach substantially improves the accuracy of evaluation of effective solvation forces and in combination with the OIN thermostat enables a dramatic increase of outer time steps. We demonstrate on a fully flexible model of alanine dipeptide in aqueous solution that the MTS-MD/OIN/ASFE/3D-RISM-KH multiscale method of molecular dynamics

  3. Ionic liquids: radiation chemistry, solvation dynamics and reactivity patterns

    International Nuclear Information System (INIS)

    Wishart, J.F.; Funston, A.M.; Szreder, T.

    2006-01-01

    Ionic liquids (ILs) are a rapidly expanding family of condensed-phase media with important applications in energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs are nonvolatile, noncombustible, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of chemical reactions and product distributions. Successful use of ionic liquids in radiation-filled environments, where their safety advantages could be significant, requires an understanding of ionic liquid radiation chemistry. For example, characterizing the primary steps of IL radiolysis will reveal radiolytic degradation pathways and suggest ways to prevent them or mitigate their effects on the properties of the material. An understanding of ionic liquid radiation chemistry will also facilitate pulse radiolysis studies of general chemical reactivity in ILs, which will aid in the development of energy production, chemical industry and environmental applications. Pulse radiolysis of [R 4 N][NTf 2 ] [R 4 N][N(CN) 2 ], and [R 4 P][N(CN) 2 ] ionic liquids produces solvated electrons that absorb over a broad range in the near infrared and persisting for hundreds of nanoseconds. Systematic cation variation shows that solvated electron's spectroscopic properties depend strongly on the lattice structure of the ionic liquid. Very early in our radiolysis studies it became evident that

  4. Ab initio joint density-functional theory of solvated electrodes, with model and explicit solvation

    Science.gov (United States)

    Arias, Tomas

    2015-03-01

    the electrochemical context and how it is needed for realistic description of solvated electrode systems [], and how simple ``implicit'' polarized continuum methods fail radically in this context. Finally, we shall present a series of results relevant to battery, supercapacitor, and solar-fuel systems, one of which has led to a recent invention disclosure for improving battery cycle lifetimes. Supported as a part of the Energy Materials Center at Cornell, an Energy Frontier Research Center funded by DOE/BES (award de-sc0001086) and by the New York State Division of Science, Technology and Innovation (NYSTAR, award 60923).

  5. Amniotic oxytocin and vasopressin in relation to human fetal development and labour

    NARCIS (Netherlands)

    Oosterbaan, H. P.; Swaab, D. F.

    1989-01-01

    Previous experiments in rats revealed increased amniotic oxytocin (OXT) levels in the course of normal development and increased vasopressin (AVP) levels in retarded fetal growth. In order to see whether similar changes would also occur in human, OXT and AVP levels were determined in amniotic fluid,

  6. Diagnostic and Predictive Values of Thirst, Angiotensin II, and Vasopressin During Trauma Resuscitation

    Science.gov (United States)

    2010-09-01

    and plasma AVP and AT2 levels across a broader spectrum of hemorrhagic shock severity may be warranted. The authors wish to thank the medical, nursing ...301. 2. Olsson K. Central control of vasopressin release and thirst. Acta Paediatr Scand Suppl. 1983;305:36–9. Pr eh os p E m er g C ar e D ow nl oa

  7. Lateral septal vasopressin in rats : Role in social and object recognition?

    NARCIS (Netherlands)

    Everts, H.G J; Koolhaas, J.M.

    1997-01-01

    The capacity of male rats to remember familiar conspecifics is called social recognition. It is a form of short-term memory modulated by lateral septal (LS) vasopressin (VP). The specificity of this phenomenon was studied by examining whether recognition of previously investigated objects is also

  8. Salivary Oxytocin and Vasopressin Levels in Police Officers With and Without Post-Traumatic Stress Disorder

    NARCIS (Netherlands)

    Frijling, J. L.; van Zuiden, M.; Nawijn, L.; Koch, S. B. J.; Neumann, I. D.; Veltman, D. J.; Olff, M.

    2015-01-01

    Post-traumatic stress disorder (PTSD) is characterised by symptoms associated with maladaptive fear and stress responses, as well as with social detachment. The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) have been associated with both regulating fear and neuroendocrine stress

  9. Urinary concentration does not exclusively rely on plasma vasopressin. A study between genders

    DEFF Research Database (Denmark)

    Graugaard-Jensen, Charlotte; Hvistendahl, Gitte M; Frøkiaer, Jørgen

    2014-01-01

    AimWe investigated the influence of gender on the diurnal regulation of urine production with special focus on vasopressin, oxytocin and prostaglandin E2. MethodsFifteen young women in mid-follicular phase and 22 young men (20-33years) were included. All participants underwent a 24-h circadian in...

  10. Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin

    DEFF Research Database (Denmark)

    Brust, P; Christensen, Thomas; Diemer, Nils Henrik

    1992-01-01

    of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24...

  11. Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

  12. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors

    OpenAIRE

    Bales, KL; Plotsky, PM; Young, LJ; Lim, MM; Grotte, N; Ferrer, E; Carter, CS

    2007-01-01

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the lon...

  13. Mechanisms of inhibition of vasopressin release during moderate antiorthostatic posture change in humans

    DEFF Research Database (Denmark)

    Pump, B.; Gabrielsen, A.; Christensen, N.J.

    1999-01-01

    The hypothesis was tested that the carotid baroreceptor stimulation caused by a posture change from upright seated with legs horizontal (Seat) to supine (Sup) participates in the suppression of arginine vasopressin (AVP) release. Ten healthy males underwent this posture change for 30 min without...... decreased from 0.9 +/- 0.2 to 0.5 +/- 0.1 pg/ml (P posture...

  14. Hypothalamic vasopressin response to stress and various physiological stimuli: Visualization in transgenic animal models

    Czech Academy of Sciences Publication Activity Database

    Ueta, Y.; Dayanithi, Govindan; Murphy, D.; Fujihara, H.

    2011-01-01

    Roč. 59, č. 2 (2011), s. 221-226 ISSN 0018-506X Institutional research plan: CEZ:AV0Z50390703 Keywords : vasopressin * green fluorescent protein * red fluorescent protein Subject RIV: FH - Neurology Impact factor: 3.865, year: 2011

  15. Oxytocin/vasopressin-like immunoreactivity is present in the nervous system of hydra

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Dierickx, K; Boer, G J

    1982-01-01

    Nerve cells have been found in hydra, which react with antisera to oxytocin, vasopressin and mesotocin. These nerve cells have a high density in the ectoderm of basal disk and tentacles and lower density in the ectoderm of peduncle, gastric region and hypostome. A very small number of nerve cells...

  16. Purification and characterization of the V1 vasopressin receptor from rat liver

    International Nuclear Information System (INIS)

    Fishman, J.B.; Dickey, B.F.; Attisano, C.; Fine, R.E.

    1987-01-01

    The rat liver V1 vasopressin receptor was purified approximately 21,000-fold from rat liver microsomes. The receptor was solubilized from membranes using the zwitterionic detergent CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate). Since the V1 receptor loses its ability to bind ligand when solubilized, the authors devised a liposome reconstitution system to assay vasopressin binding activity during purification. The purified receptor exhibits a K/sub d/ of 6 nm, when, prior to solubilization, the membranes were exposed to 1 μm vasopressin. This resulted in the association of a pertussis-toxin insensitive guanine-nucleotide binding protein with the receptor during most of the purification procedure. The authors are further characterizing the V1-associated G-proteins. In the absence of this association, the receptor has a K/sub d/ of 30 nM. Crosslinking of 125 I-vasopressin to a partially purified preparation of receptor demonstrated that the receptor had a molecular weight of approximately 68,000 under reducing conditions, and 58,000 under non-reducing conditions. The purification procedure may prove useful in purifying a number of small peptide hormone receptors (e.g., bradykinin, angiotensin II) and perhaps their associated G-proteins as well

  17. Examination of the biological half-life and organ d;stribution of tritiated lysin-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Laczi, F.; Laszlo, F.

    1980-01-01

    15 μCi tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin. (L.E.)

  18. [Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma].

    Science.gov (United States)

    Xiong, Tao; Wanggou, Siyi; Li, Xuejun; Liu, Qing; Jiang, Xingjun; Peng, Zefeng; Yuan, Xianrui

    2016-10-28

    To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (Pcraniopharyngioma.

  19. Examination of the biological half-life and organ d; stribution of tritiated lysin-vasopressin in Brattleboro rats

    Energy Technology Data Exchange (ETDEWEB)

    Laczi, F; Laszlo, F [Szegedi Orvostudomanyi Egyetem Szeged (Hungary). 1. Belgyogyaszati Klinika; Keri, Gy; Teplan, I [Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary)

    1980-04-01

    15 ..mu..Ci tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin.

  20. Solvation quantities from a COSMO-RS equation of state

    International Nuclear Information System (INIS)

    Panayiotou, C.; Tsivintzelis, I.; Aslanidou, D.; Hatzimanikatis, V.

    2015-01-01

    Highlights: • Extension of the successful COSMO-RS model to an equation-of-state model. • Two scaling constants, obtained from atom-specific contributions. • Overall estimation of the solvation quantities and contributions. - Abstract: This work focuses on the extension of the successful COSMO-RS model of mixtures into an equation-of-state model of fluids and its application for the estimation of solvation/hydration quantities of a variety of chemical substances. These quantities include free-energies, enthalpies and entropies of hydration as well as the separate contributions to each of them. Emphasis is given on the estimation of contributions from the conformational changes of solutes upon solvation and the associated restructuring of solvent in its immediate neighborhood. COSMO-RS is a quantum-mechanics based group/segment contribution model in which the Quasi-Chemical (QC) approach is used for the description of the non-random distribution of interacting segments in the system. Thus, the equation-of-state development is done through such a QC framework. The new model will not need any adjustable parameters for the strong specific interactions, such as hydrogen bonds, since they will be provided by the quantum-mechanics based cosmo-files – a key feature of COSMO-RS model. It will need, however, one volumetric and one energy parameter per fluid, which are scaling constants or molecular descriptors of the fluid and are obtained from rather easily available data such as densities, boiling points, vapor pressures, heats of vaporization or second virial coefficients. The performance and the potential of the new equation-of-state model to become a fully predictive model are critically discussed

  1. Solvation of the electron in alcohols studied using the Argonne picosecond pulse radiolysis system

    International Nuclear Information System (INIS)

    Jonah, C.D.; Kenney-Wallace, G.A.

    1979-01-01

    With a stroboscopic pulse radiolysis system, it is possible to measure the reactions of solvated electrons and dry electrons and the solvation time of electrons in alcohols from 20 psec to 350 psec. The solvation in alcohol and alcohol-alkane solutions is a complex process which depends on the microscopic structure of the fluid, so that the studies of solvation in alcohols as a function of temperature or as a function of the concentration of the alcohols must take into account the structure of the fluid being studied. The relaxation processes may not be dominant at low temperature. However, in room temperature alcohols, pre-existing traps are the dominant means of electron trapping. The extrapolation to water may be reasonable since water and alcohols both give similar final species. To obtain such idea of the solvation process in alcohols, the change of the absorption of electrons at 500 nm was measured. At very low concentration of alcohols in alkanes, electrons form a complex with a cluster of alcohol molecules, and the most probable size of this cluster is two alcohols (C 4 , C 10 ). The species formed is not solvated electrons, since the characteristic spectrum of solvated electrons is absent, and the conductivity of the species is far above that of solvated electrons. (Yamashita, S.)

  2. Molecular dynamics study of the solvation of an alpha-helical transmembrane peptide by DMSO

    NARCIS (Netherlands)

    Duarte, A.M.; Mierlo, van C.P.M.; Hemminga, M.A.

    2008-01-01

    10-ns molecular dynamics study of the solvation of a hydrophobic transmembrane helical peptide in dimethyl sulfoxide (DMSO) is presented. The objective is to analyze how this aprotic polar solvent is able to solvate three groups of amino acid residues (i.e., polar, apolar, and charged) that are

  3. Studies of base pair sequence effects on DNA solvation based on all

    Indian Academy of Sciences (India)

    Detailed analyses of the sequence-dependent solvation and ion atmosphere of DNA are presented based on molecular dynamics (MD) simulations on all the 136 unique tetranucleotide steps obtained by the ABC consortium using the AMBER suite of programs. Significant sequence effects on solvation and ion localization ...

  4. Femtosecond spectroscopic study of the solvation of amphiphilic molecules by water

    NARCIS (Netherlands)

    Rezus, Y.L.A.; Bakker, H.J.

    2008-01-01

    We use polarization-resolved mid-infrared pump-probe spectroscopy to study the aqueous solvation of proline and N-methylacetamide. These molecules serve as models to study the solvation of proteins. We monitor the orientational dynamics of partly deuterated water molecules (HDO) that are present at

  5. Competitive solvation of (bis)(trifluoromethanesulfonyl)imide anion by acetonitrile and water

    DEFF Research Database (Denmark)

    Chaban, Vitaly

    2014-01-01

    Competitive solvation of an ion by two or more solvents is one of the key phenomena determining the identity of our world. Solvation in polar solvents frequently originates from non-additive non-covalent interactions. Pre-parametrized potentials poorly capture these interactions, unless the force...

  6. Time-dependent friction and solvation time correlation function

    International Nuclear Information System (INIS)

    Samanta, Alok; Ali, Sk Musharaf; Ghosh, Swapan K

    2005-01-01

    We have derived a new relation between the time-dependent friction and solvation time correlation function (STCF) for non-polar fluids. The friction values calculated using this relation and simulation results on STCF for a Lennard-Jones fluid are shown to have excellent agreement with the same obtained through mode-coupling theory. Also derived is a relation between the time-dependent dielectric friction and STCF for polar fluids. Routes are thus provided to obtain the time-dependent friction (non-polar as well as dielectric) from an experimentally measured quantity like STCF, even if the interparticle interaction potential is not known

  7. Equilibrium and nonequilibrium solvation and solute electronic structure

    International Nuclear Information System (INIS)

    Kim, H.J.; Hynes, J.T.

    1990-01-01

    When a molecular solute is immersed in a polar and polarizable solvent, the electronic wave function of the solute system is altered compared to its vacuum value; the solute electronic structure is thus solvent-dependent. Further, the wave function will be altered depending upon whether the polarization of the solvent is or is not in equilibrium with the solute charge distribution. More precisely, while the solvent electronic polarization should be in equilibrium with the solute electronic wave function, the much more sluggish solvent orientational polarization need not be. We call this last situation non-equilibrium solvation. We outline a nonlinear Schroedinger equation approach to these issues

  8. Role of trapped and solvated electrons in Ps formation

    International Nuclear Information System (INIS)

    Stepanov, S.V.; Byakov, V.M.; Mikhin, K.V.; He, C.; Hirade, T.

    2005-01-01

    Role of trapped and solvated electrons in Ps formation is discussed. Combination of thermalized positron with such electrons is possible from the view point of the energy balance and may results in Ps formation. This process proceeds during all e = lifetime matter. Fitting of raw experimental e + -e - annihilation spectra has to be based on an adequate physical input, which often leads to necessity of nonexponential deconvolution of the spectra. We have interpreted the Ps formation data in polyethylene, ethylene-methylmethacrylate and polymethylmethacrylate in dark and in light vs. tome of the measurement and temperature. parameters characterized accumulation of trapped electrons and their recombination with counter ions and positrons are obtained. (author)

  9. Electrochemical redox reactions in solvated silica sol-gel glass

    International Nuclear Information System (INIS)

    Opallo, M.

    2002-01-01

    The studies of electrochemical redox reactions in solvated silica sol-gel glass were reviewed. The methodology of the experiments with emphasis on the direct preparation of the solid electrolyte and the application ultra microelectrodes was described. Generally, the level of the electrochemical signal is not much below that observed in liquid electrolyte. The current depends on time elapsed after gelation, namely the longer time, the smaller current. The differences between electrochemical behaviour of the redox couples in monoliths and thin layers were described. (author)

  10. L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome

    NARCIS (Netherlands)

    Choe, C.U.; Nabuurs, C.I.H.C.; Stockebrand, M.C.; Neu, A.; Nunes, P.M.; Morellini, F.; Sauter, K.; Schillemeit, S.; Hermans-Borgmeyer, I.; Marescau, B.; Heerschap, A.; Isbrandt, D.

    2013-01-01

    Phosphorylated creatine (Cr) serves as an energy buffer for ATP replenishment in organs with highly fluctuating energy demand. The central role of Cr in the brain and muscle is emphasized by severe neurometabolic disorders caused by Cr deficiency. Common symptoms of inborn errors of creatine

  11. L-arginine modified magnetic nanoparticles: green synthesis and characterization

    Science.gov (United States)

    Bagherpour, A. R.; Kashanian, F.; Seyyed Ebrahimi, S. A.; Habibi-Rezaei, M.

    2018-02-01

    In recent years, there has been considerable interest in Arg which is a unique, nontoxic, and biocompatible biomolecule since it can be utilized as an agent for the functionalization and subsequent stabilization of MNPs against oxidation and aggregation, during or after a synthesis procedure. Our studies demonstrate that Arg has great impacts on MNPs with the decreasing size of the particle. Also, saturation magnetization and electrostatic interactions of RMNPs have a direct impact on biological molecules such as proteins and nucleic acids. By controlling the concentration of Arg, it is possible to accurately control the above-mentioned characteristics, which are useful tools for applications such as connecting to antibodies, catalysis, drug loading, and modification of MNP stability. In the current study, three RMNPs with different Arg densities, i.e. 0.42, 1.62, and 2.29 μg per mg were successfully synthesized through a simple co-precipitation method (named p 0.5, p 1, and p 1.5, respectively) and verified by colorimetric determination. Also, the as-synthesized RMNP powders were characterized by XRD, SEM/EDAX, FTIR, VSM, and zeta potential analysis. The presence of a magnetic core was proved by XRD, FTIR, and EDAX. Colorimetric analysis showed the existence of Arg in the synthesized samples. According to the zeta potential and VSM results, increasing the cap of Arg on the MNP surface leads to an increase in the surface charge and decrease in the magnetization of the RMNPs, respectively.

  12. L-Arginine Attenuates Diabetic Nephropathy In Streptozotocin ...

    African Journals Online (AJOL)

    Egyptian Journal of Biochemistry and Molecular Biology ... On the other hand, no significant change was detected in body weight, kidney weight and relative kidney weight, levels of plasma fructosamine, MDA and NOx, renal activities of glutathione peroxidase(GPx),superoxide dismutase(SOD), LDH, aldose reductase(AR) ...

  13. Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study.

    Science.gov (United States)

    Siehr, Stephanie L; Feinstein, Jeffrey A; Yang, Weiguang; Peng, Lynn F; Ogawa, Michelle T; Ramamoorthy, Chandra

    2016-05-01

    During a pulmonary hypertensive crisis, the marked increase in pulmonary vascular resistance can result in acute right ventricular failure and death. Currently, there are no therapeutic guidelines for managing an acute crisis. This pilot study examined the hemodynamic effects of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertension. In this prospective, open-label, nonrandomized pilot study, we enrolled pediatric patients previously diagnosed with pulmonary hypertensive who were scheduled electively for cardiac catheterization. Primary outcome was a change in the ratio of pulmonary-to-systemic vascular resistance. Baseline hemodynamic data were collected before and after the study drug was administered. Eleven of 15 participants were women, median age was 9.2 years (range, 1.7-14.9 yr), and median weight was 26.8 kg (range, 8.5-55.2 kg). Baseline mean pulmonary artery pressure was 49 ± 19 mm Hg, and mean indexed pulmonary vascular resistance was 10 ± 5.4 Wood units. Etiology of pulmonary hypertensive varied, and all were on systemic pulmonary hypertensive medications. Patients 1-5 received phenylephrine 1 μg/kg; patients 6-10 received arginine vasopressin 0.03 U/kg; and patients 11-15 received epinephrine 1 μg/kg. Hemodynamics was measured continuously for up to 10 minutes following study drug administration. After study drug administration, the ratio of pulmonary-to-systemic vascular resistance decreased in three of five patients receiving phenylephrine, five of five patients receiving arginine vasopressin, and three of five patients receiving epinephrine. Although all three medications resulted in an increase in aortic pressure, only arginine vasopressin consistently resulted in a decrease in the ratio of systolic pulmonary artery-to-aortic pressure. This prospective pilot study of phenylephrine, arginine vasopressin, and epinephrine in pediatric patients with pulmonary hypertensive showed an increase in aortic

  14. Molecular modeling of nucleic Acid structure: electrostatics and solvation.

    Science.gov (United States)

    Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

    2014-12-19

    This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit. Copyright © 2014 John Wiley & Sons, Inc.

  15. The effect of vasopressin on hormone secretion and blood flow from the thyroid vein in sheep with exteriorized thyroids.

    Science.gov (United States)

    Falconer, I R

    1968-12-01

    1. Vasopressin has been shown to activate the thyroid in some species, and also to be released into the bloodstream after emotional and other stresses.2. Emotional stimuli applied to sheep have previously been shown to increase thyroid secretion and the possible influence of vasopressin in this process has been investigated. Sheep bearing exteriorized thyroid glands were used, so that thyroid vein blood could be collected in undisturbed conscious animals.3. (125)I or (131)I (50 muc) was injected I.M. into the sheep; 4-7 days later, samples of thyroid vein blood were collected at 10 min intervals for 4 hr, and the concentration of total and protein bound (125)I or (131)I was measured. Intravenous infusions of 0.3, 3.0 or 31 m-u./min arginine or lysine vasopressin, or close arterial infusions of 3.0 or 31 m-u./min arginine vasopressin were administered 1.5 hr after commencement of blood sampling. Blood flow from the thyroid was measured by a plethysmographic technique during similar experiments.4. No significant changes in thyroid hormone secretion were observed as a result of vasopressin infusion, and it was concluded that vasopressin release does not play a part in the activation of the thyroid resulting from emotional stimulus in the sheep.

  16. Biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Janaky, T.; Laczi, F.; Laszlo, F.A.

    1982-01-01

    The biological half-lives and organ distribution of tritiated 8-lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin were determined in R-Amsterdam rats and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-lives of [ 3 H]LVP and [ 3 H]dDAVP in the Brattleboro rats did not differ significantly from that found in the control R-Amsterdam rats. The half-life of [ 3 H]dDAVP proved longer than that of [ 3 H]LVP in all three groups of animals. In the case of [ 3 H]LVP the highest radioactivities were observed in the neurohypophyses, adenohypophyses, and kidneys of both the R-Amsterdam and Brattleboro rats. The accumulation of tritiated material was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. In all three groups of rats, [ 3 H]dDAVP was accumulated to the greatest extent in the kidney and the small intestine. The kidney and small intestine contained less radioactivity in homozygous Brattleboro rats than in the controls. There was only a slight radioactivity accumulation in the adenohypophysis and neurohypophysis. From the results it was concluded that the decrease in the rate of enzymatic decomposition may play a role in the increased duration of antidiuretic action of dDAVP. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary diabetes insipidus

  17. New immunogenic form for vasopressin: production of high-affinity antiserum and RIA for plasmatic AVP

    International Nuclear Information System (INIS)

    Rougon-Rappuzi, G.; Delaage, M.A.; Conte-Devolx, B.; Millet, Y.

    1977-01-01

    A highly sensitive and specific radioimmunoassay (RIA) for arginine-vasopressin (AVP) was developped and applied to the measurement of AVP in human plasma. High-affinity antivasopressin antibodies with limited association constant heterogeneity have been induced by immunizing rabbits with Lysine-vasopressine (LVP) coupled to a human immunoglobulin (IgA). Replacing air drying of acetone-petroleum ether extracts by lyophilisation increased significantly the yields of AVP. Equilibrium dialysis was used for separating bound and free antigen, thus reducing the total time required for the assay to 48 hours. Only 1 ml of plasma was required for routine determinations due to a sensitivity threshold better than 0.5 pg/ml. Plasma AVP levels of normal subjects and of patients with inappropriate ADH secretion (SIADH) were determined during different hydratation states and following nicotin of ethanol infusions. (orig.) [de

  18. New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists.

    Science.gov (United States)

    Yea, Christopher M; Allan, Christine E; Ashworth, Doreen M; Barnett, James; Baxter, Andy J; Broadbridge, Janice D; Franklin, Richard J; Hampton, Sally L; Hudson, Peter; Horton, John A; Jenkins, Paul D; Penson, Andy M; Pitt, Gary R W; Rivière, Pierre; Robson, Peter A; Rooker, David P; Semple, Graeme; Sheppard, Andy; Haigh, Robert M; Roe, Michael B

    2008-12-25

    Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.

  19. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

    LENUS (Irish Health Repository)

    Dinan, Timothy G

    2012-02-03

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  20. Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

    International Nuclear Information System (INIS)

    Kruisbrink, J.; Boer, G.J.

    1984-01-01

    Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero

  1. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

    Science.gov (United States)

    Kim, P A; Voskresenskaya, O G; Kamensky, A A

    2009-06-01

    Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

  2. Association of arginine vasopressin receptor 1a gene polymorphisms with hepatorenal syndrome

    International Nuclear Information System (INIS)

    Wang, C.; Luo, X.; Ye, J.; Liu, S.; Miu, L.; Bao, J.; Wang, F.; Yu, Z.

    2017-01-01

    To assess the association of arginine vasopressin receptor 1a gene single nucleotide polymorphisms with type I hepatorenal syndrome. Methods: The case-control study was conducted at the Hangzhou City Xixi Hospital, Hangzhou, China, from January 2012 to June 2014, and comprised patients with type I hepatorenal syndrome and individuals with cirrhosis who acted as the control group. Arginine vasopressin receptor 1a gene rs113481894 locus single nucleotide polymorphisms were analysed by high-resolution melting methods. Statistical analysis was performed using SPSS 17. Results: Of the 60 participants, 28(46.7%) were in the hepatorenal syndrome group and 32(53.3%) were controls. The mean age was 42.21+-11.30years in the hepatorenal syndrome group and 43.69+-12.60 in the control group (p=0.64). Mean total bilirubin, albumin and prothrombin activity levels were 154.76+-51.58, 49.30+-24.67 and 33.42+-3.69 in the hepatorenal syndrome group compared to 181.26+-64.46, 41.78+-17.52 and 32.98+-4.81 among controls (p=0.09, p=0.18 and p=0.70). Statistically significant differences were found in the distributions of arginine vasopressin receptor 1a gene rs113481894 locus T allele between type I hepatorenal syndrome patients and the control group (odds ratio= 2.230; p= 0.040). Conclusion: T allele located at arginine vasopressin receptor 1a receptor promoter rs113481894 locus may be associated with the pathogenesis of type I hepatorenal syndrome. (author)

  3. Involvement of arginine-vasopressin in the diuretic and hypotensive effects of Pereskia grandifolia Haw. (Cactaceae).

    Science.gov (United States)

    Kazama, Caroline Calixto; Uchida, Denise Thiemi; Canzi, Karina Natally; de Souza, Priscila; Crestani, Sandra; Gasparotto, Arquimedes; Laverde, Antonio

    2012-10-31

    Pereskia grandifolia Haw. (Cactaceae), popularly known as "ora-pro-nobis" is well recognized in Brazilian traditional medicine as a diuretic agent, although no scientific data have been published to support this effect. The aim of this work is to evaluate the diuretic and hypotensive activities of the infusion (INFPG) and the ethanol extract (HEPG) of Pereskia grandifolia and possible mechanism of action. The infusions (2.5-10%) and the HEPG (3-100 mg/kg) were orally administered in a single dose or daily (for seven days) to rats. The urine excretion rate, pH, density, conductivity and content of Na(+), K(+), Cl(-) and HCO(3)(-) were measured in the urine of saline-loaded animals. In collected serum samples the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated. The involvement of V(2) vasopressin receptor in the diuretic activity and the hypotensive effect of HEPG were also determined. Water excretion rate was significantly increased by HEPG, while the urinary K(+) and Cl(-) excretion was significantly reduced in acute and prolonged treatment. The oral administration of the HEPG (30mg/kg) significantly reduced serum levels of vasopressin and the mean arterial pressure (MAP) in normotensive rats. All other evaluated parameters have not been affected by any treatment. The results showed that HEPG could present compound(s) responsible for aquaretic activities with no signs of toxicity, and this effect could involve a reduction in the arginine-vasopressin release. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Selective solvation extraction of gold from alkaline cyanide solution by alkyl phosphorus esters

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J.D.; Wan, R.Y.; Mooiman, M.B.; Sibrell, P.L.

    1987-01-01

    Research efforts have shown that solvation extraction of gold from alkaline cyanide solution is possible by alkyl phosphorus esters. Both tributyl phosphate (TBP) and dibutyl butyl phosphonate (DBBP) appear to be effective extractants for gold and exhibit high loading capacities exceeding 30 gpl. Selective solvation extraction of gold from alkaline cyanide solution can be achieved with selectivity factors relative to other cyanoanions as high as 1000 under certain circumstances. Variables influencing the selectivity such as ionic strength, temperature, and extractant structure, are discussed in terms of the extraction chemistry, which seems to involve the solvation of a M dot, dot, dot Au(CN)2 ion pair.

  5. Solvation of ions in the gas-phase: a molecular dynamics simulation

    Science.gov (United States)

    Cabarcos, Orlando M.; Lisy, James M.

    1996-07-01

    Molecular dynamics simulations have been performed on the collision between a cesium ion and a cluster of twenty methanol molecules. This process, generating a solvated ion, was studied over a range (1 to 25 eV) of eight collision energies. Preliminary analysis of this gas phase solvation has included the distribution of final ion cluster sizes, fragmentation patterns, solvation timescales and energetics. Two distinct patterns have emerged: a ballistic penetration of the neutral cluster at the higher collision energies and an evaporative evolution of the cluster ion at lower collision energies.

  6. Solvation of graphite oxide in water-methanol binary polar solvents

    Energy Technology Data Exchange (ETDEWEB)

    You, Shujie; Yu, Junchun; Sundqvist, Bertil; Talyzin, Alexandr V. [Department of Physics, Umeaa University, SE-901 87 Umeaa (Sweden)

    2012-12-15

    The phase transition between two solvated phases was studied by DSC for graphite oxide (GO) powders immersed in water-methanol mixtures of various compositions. GO forms solid solvates with two different compositions when immersed in methanol. Reversible phase transition between two solvate states due to insertion/desertion of methanol monolayer occurs upon temperature variations. The temperature point and the enthalpy ({Delta}H) of the phase transition are maximal for pure methanol and decrease linearly with increase of water fraction up to 30%. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. Selective nonspecific solvation under dielectric saturation and fluorescence spectra of dye solutions in binary solvents.

    Science.gov (United States)

    Bakhshiev, N G; Kiselev, M B

    1991-09-01

    The influence of selective nonspecific solvation on the fluorescence spectra of three substitutedN-methylphthalimides in a binary solvent system consisting of a nonpolar (n-heptane) and a polar (pyridine) component has been studied under conditions close to dielectric saturation. The substantially nonlinearity of the effect is confirmation that the spectral shifts of fluorescence bands depend on the number of polar solvent molecules involved in solvating the dye molecule. The measured fluorescence spectral shifts determined by substituting one nonpolar solvent molecula with a polar one in the proximity of the dye molecule agree quantitatively with the forecasts of the previously proposed semiempirical theory which describes this nonlinear solvation phenomenon.

  8. Trimesic acid dimethyl sulfoxide solvate: space group revision

    Directory of Open Access Journals (Sweden)

    Sylvain Bernès

    2008-07-01

    Full Text Available The structure of the title solvate, C9H6O6·C2H6OS, was determined 30 years ago [Herbstein, Kapon & Wasserman (1978. Acta Cryst. B34, 1613–1617], with data collected at room temperature, and refined in the space group P21. The present redetermination, based on high-resolution diffraction data, shows that the actual space group is more likely to be P21/m. The crystal structure contains layers of trimesic acid molecules lying on mirror planes. A mirror plane also passes through the S and O atoms of the solvent molecule. The molecules in each layer are interconnected through strong O—H...O hydrogen bonds, forming a two-dimensional supramolecular network within each layer. The donor groups are the hydroxyls of the trimesic acid molecules, while the acceptors are the carbonyl or the sulfoxide O atoms.

  9. Solvation thermodynamics of phenylalcohols in lamellar phase surfactant dispersions

    International Nuclear Information System (INIS)

    Martyniak, A.; Scheuermann, R.; Dilger, H.; Tucker, I.M.; Burkert, T.; Hashmi, A.S.K.; Vujosevic', D.; Roduner, E.

    2006-01-01

    The distribution and the stability of five phenylalcohols in a lamellar phase composed of simple bilayers separated by water at 298 and 348K is explored using avoided-level-crossing muon-spin resonance (ALC-μSR). The dependence of the alignment of the bilayer chains on temperature appears to be a crucial factor determining the phenylalcohol partitioning: increasing order of the surfactant tails leads to expulsion of the solute. Moreover, we observed a systematic trend, the longer the chain the deeper the phenyl group dips into the lipid bilayer. Recent studies have shown that the hydrophobic effect is adequate to describe membrane partitioning of small amphiphilic molecules. The solvation thermodynamic properties ΔG sol , ΔH sol , and ΔS sol which determine the solute transfer from the double layer into water prove that the distribution also strongly depends on shape, chemical nature and different structure of phenylalcohols

  10. Solvation thermodynamics of phenylalcohols in lamellar phase surfactant dispersions

    Energy Technology Data Exchange (ETDEWEB)

    Martyniak, A. [Institut fuer Physikalische Chemie, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart (Germany); Scheuermann, R. [Laboratory for muon Spin Spectroscopy, Paul Scherrer Institute, CH-5232 Villigen (Switzerland); Dilger, H. [Institut fuer Physikalische Chemie, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart (Germany); Tucker, I.M. [Unilever Research and Development, Port Sunlight, Wirral CH63 3JW (United Kingdom); Burkert, T. [Institut fuer Organische Chemie, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart (Germany); Hashmi, A.S.K. [Institut fuer Organische Chemie, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart (Germany); Vujosevic' , D. [Institut fuer Physikalische Chemie, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart (Germany); Roduner, E. [Institut fuer Physikalische Chemie, University of Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart (Germany)]. E-mail: e.roduner@ipc.uni-stuttgart.de

    2006-03-31

    The distribution and the stability of five phenylalcohols in a lamellar phase composed of simple bilayers separated by water at 298 and 348K is explored using avoided-level-crossing muon-spin resonance (ALC-{mu}SR). The dependence of the alignment of the bilayer chains on temperature appears to be a crucial factor determining the phenylalcohol partitioning: increasing order of the surfactant tails leads to expulsion of the solute. Moreover, we observed a systematic trend, the longer the chain the deeper the phenyl group dips into the lipid bilayer. Recent studies have shown that the hydrophobic effect is adequate to describe membrane partitioning of small amphiphilic molecules. The solvation thermodynamic properties {delta}G{sub sol}, {delta}H{sub sol}, and {delta}S{sub sol} which determine the solute transfer from the double layer into water prove that the distribution also strongly depends on shape, chemical nature and different structure of phenylalcohols.

  11. MTS-MD of Biomolecules Steered with 3D-RISM-KH Mean Solvation Forces Accelerated with Generalized Solvation Force Extrapolation.

    Science.gov (United States)

    Omelyan, Igor; Kovalenko, Andriy

    2015-04-14

    We developed a generalized solvation force extrapolation (GSFE) approach to speed up multiple time step molecular dynamics (MTS-MD) of biomolecules steered with mean solvation forces obtained from the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model with the Kovalenko-Hirata closure). GSFE is based on a set of techniques including the non-Eckart-like transformation of coordinate space separately for each solute atom, extension of the force-coordinate pair basis set followed by selection of the best subset, balancing the normal equations by modified least-squares minimization of deviations, and incremental increase of outer time step in motion integration. Mean solvation forces acting on the biomolecule atoms in conformations at successive inner time steps are extrapolated using a relatively small number of best (closest) solute atomic coordinates and corresponding mean solvation forces obtained at previous outer time steps by converging the 3D-RISM-KH integral equations. The MTS-MD evolution steered with GSFE of 3D-RISM-KH mean solvation forces is efficiently stabilized with our optimized isokinetic Nosé-Hoover chain (OIN) thermostat. We validated the hybrid MTS-MD/OIN/GSFE/3D-RISM-KH integrator on solvated organic and biomolecules of different stiffness and complexity: asphaltene dimer in toluene solvent, hydrated alanine dipeptide, miniprotein 1L2Y, and protein G. The GSFE accuracy and the OIN efficiency allowed us to enlarge outer time steps up to huge values of 1-4 ps while accurately reproducing conformational properties. Quasidynamics steered with 3D-RISM-KH mean solvation forces achieves time scale compression of conformational changes coupled with solvent exchange, resulting in further significant acceleration of protein conformational sampling with respect to real time dynamics. Overall, this provided a 50- to 1000-fold effective speedup of conformational sampling for these systems, compared to conventional MD

  12. Theory of competitive solvation of polymers by two solvents and entropy-enthalpy compensation in the solvation free energy upon dilution with the second solvent.

    Science.gov (United States)

    Dudowicz, Jacek; Freed, Karl F; Douglas, Jack F

    2015-06-07

    We develop a statistical mechanical lattice theory for polymer solvation by a pair of relatively low molar mass solvents that compete for binding to the polymer backbone. A theory for the equilibrium mixture of solvated polymer clusters {AiBCj} and free unassociated molecules A, B, and C is formulated in the spirit of Flory-Huggins mean-field approximation. This theoretical framework enables us to derive expressions for the boundaries for phase stability (spinodals) and other basic properties of these polymer solutions: the internal energy U, entropy S, specific heat CV, extent of solvation Φsolv, average degree of solvation 〈Nsolv〉, and second osmotic virial coefficient B2 as functions of temperature and the composition of the mixture. Our theory predicts many new phenomena, but the current paper applies the theory to describe the entropy-enthalpy compensation in the free energy of polymer solvation, a phenomenon observed for many years without theoretical explanation and with significant relevance to liquid chromatography and other polymer separation methods.

  13. Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial Alteraciones vasculares en ratones obesos por dieta rica en grasa: papel de la vía L-arginina/NO endotelial Vascular alterations in high-fat diet-obese rats: role of Endothelial L-arginine/NO Pathway

    Directory of Open Access Journals (Sweden)

    Thiago Bruder Nascimento

    2011-07-01

    perfiles metabólicos y endocrinos de los animales. Fueron obtenidas las curvas para noradrelanina en ausencia y en presencia del inhibidor de óxido nítrico sintasa (L-NAME, 3x10-4M, en la aorta torácica intacta y con denudación de los ratones C y OB. RESULTADOS: Las medidas de peso corporal, índice de adiposidad, leptina e insulina aumentaron en los ratones OB, mientras que la presión arterial permaneció inalterada. La obesidad también produjo una tolerancia a la glucosa y una resistencia a la insulina. La reactividad a la noradrenalina de la aorta intacta fue similar en los ratones C y OB. La presencia de L-NAME generó un aumento similar en las respuestas máximas, pero una desviación mayor a la izquierda de las respuestas en las aortas intactas de los ratones C con relación a los ratones OB [EC50 (x10-7M: C = 1,84 (0,83-4,07, O = 2,49 (1,41-4,38; presencia de L-NAME C = 0,02 (0,01-0,04*, O = 0,21 (0,11-0,40*†,*p BACKGROUND: Mechanisms underlying vascular abnormalities in obesity remain to be completely clarified. OBJECTIVE: L-arginine/nitric oxide pathway was evaluated on vascular response of high-fat diet-obese rats, focusing on endothelial and smooth muscle cells. METHODS: 30-day-old rats were divided in two groups: control (C and obese (OB, high-fat diet for 30 weeks. After 30 weeks, body weight, adiposity index, blood pressure, and metabolic and endocrine profiles of the animals were recorded. Curves to noradrenaline were obtained in absence and presence of nitric oxide synthase inhibitor (L-NAME, 3x10-4M on intact and denuded thoracic aorta from C and OB rats. RESULTS: Body weight, adiposity index, leptin and insulin levels were increased in OB, while blood pressure was unchanged. Obesity also produced glucose tolerance and insulin resistance. Reactivity to noradrenaline of intact aorta was similar in C and OB rats. L-NAME presence produced a similar increase in maximal responses, but a higher leftward shift of noradrenaline responses in intact aorta

  14. Electrical resistivities and solvation enthalpies for solutions of salts in liquid alkali metals

    International Nuclear Information System (INIS)

    Hubberstey, P.; Dadd, A.T.

    1982-01-01

    An empirical correlation is shown to exist between the resistivity coefficients drho/dc for solutes in liquid alkali metals and the corresponding solvation enthalpies Usub(solvn) of the neutral gaseous solute species. Qualitative arguments based on an electrostatic solvation model in which the negative solute atom is surrounded by a solvation sphere of positive solvent ion cores are used to show that both parameters are dependent on the charge density of the solute atom and hence on the extent of charge transfer from solvent to solute. Thus as the charge density of the solute increases, the solvation enthalpy increases regularly and the resistivity coefficients pass through a maximum to give the observed approximately parabolic drho/dc versus Usub(solvn) relationship. (Auth.)

  15. Unusual solvation through both p-orbital lobes of a carbene carbon

    Energy Technology Data Exchange (ETDEWEB)

    Hadad, C. Z., E-mail: cacier.hadad@udea.edu.co [Grupo de Química-Física Teórica, Instituto de Química, Universidad de Antioquia, A. A. 1226 Medellín (Colombia); Jenkins, Samantha [College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081 (China); Flórez, Elizabeth [Departamento de Ciencias Básicas, Universidad de Medellín, Carrera 87 N° 30-65, Medellín (Colombia)

    2015-03-07

    As a result of a configurational space search done to explain the experimental evidence of transient specific solvation of singlet fluorocarbene amide with tetrahydrofuran, we found that the most stable structures consist in a group in which each oxygen of two tetrahydrofuran molecules act as electron donor to its respective empty p-orbital lobe of the carbene carbon atom, located at each side of the carbene molecular plane. This kind of species, which to our knowledge has not been reported before, explains very well the particular experimental characteristics observed for the transient solvation of this system. We postulate that the simultaneous interaction to both p-orbital lobes seems to confer a special stability to the solvation complexes, because this situation moves away the systems from the proximity of the corresponding transition states for the ylide products. Additionally, we present an analysis of other solvation complexes and a study of the nature of the involved interactions.

  16. Entropic solvation force between surfaces modified by grafted chains: a density functional approach

    Directory of Open Access Journals (Sweden)

    O. Pizio

    2010-01-01

    Full Text Available The behavior of a hard sphere fluid in slit-like pores with walls modified by grafted chain molecules composed of hard sphere segments is studied using density functional theory. The chains are grafted to opposite walls via terminating segments forming pillars. The effects of confinement and of "chemical" modification of pore walls on the entropic solvation force are investigated in detail. We observe that in the absence of adsorbed fluid the solvation force is strongly repulsive for narrow pores and attractive for wide pores. In the presence of adsorbed fluid both parts of the curve of the solvation force may develop oscillatory behavior dependent on the density of pillars, the number of segments and adsorption conditions. Also, the size ratio between adsorbed fluid species and chain segments is of importance for the development of oscillations. The choice of these parameters is crucial for efficient manipulation of the solvation force as desired for pores of different width.

  17. In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2.

    Science.gov (United States)

    Jamil, Khurram; Pappas, Stephen Chris; Devarakonda, Krishna R

    2018-01-01

    Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V 1 ) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys 8 ]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg 8 ]-vasopressin (AVP) at V 1 and vasopressin-2 (V 2 ) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V 1 and V 2 receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [ 3 H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V 1 ) and cyclic adenosine monophosphate (V 2 ). Binding potency at V 1 and V 2 was AVP>LVP>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V 1 than for V 2 . Cellular activity potency was also AVP>LVP>terlipressin. Terlipressin was a partial agonist at V 1 and a full agonist at V 2 ; LVP was a full agonist at both V 1 and V 2 . The in vivo response to terlipressin is likely due to the partial V 1 agonist activity of terlipressin and full V 1 agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.

  18. Differential effects of vasopressin and phenylephrine on protein kinase C-mediated protein phosphorylations in isolated hepatocytes

    International Nuclear Information System (INIS)

    Cooper, R.H.; Johanson, R.A.; Wiliamson, J.R.

    1986-01-01

    Receptor-mediated breakdown of inositol lipids produces two intracellular signals, diacylglycerol, which activates protein kinase C, and inositol trisphosphate, which causes release of intracellular vesicular Ca 2+ . This study examined the effects of Ca 2+ -ionophores, vasopressin, phenylephrine, and phorbol ester (PMA) on hepatocyte protein phosphorylations. [ 32 P] Phosphoproteins from hepatocytes prelabeled with 32 P were resolved by 2-dimensional SDS-PAGE and corresponding autoradiographs were quantitated by densitometric analysis. The phosphorylation of five proteins, a plasma membrane bound 16 kDa protein with pI 6.4, a cytosolic 16 kDa protein with pI 5.8, and proteins with Mr's of 36 kDa, 52 kDa, and 68 kDa, could be attributed to phosphorylation by protein kinase C since the phosphorylation was stimulated by PMA. When the vasopressin concentration was varied, low vasopressin stimulated the phosphorylation of only the membrane bound 16 kDa protein of the above set of proteins, while higher vasopressin concentrations were required to stimulate the phosphorylation of all five proteins. Phenylephrine, even at supramaximal concentrations, stimulated the phosphorylation of only the membrane bound 16 kDa protein. These results suggest that phenylephrine is a less potent activator of protein kinase C than vasopressin by virtue of limited or localized diacylglycerol production

  19. Solvation thermodynamics and heat capacity of polar and charged solutes in water

    Science.gov (United States)

    Sedlmeier, Felix; Netz, Roland R.

    2013-03-01

    The solvation thermodynamics and in particular the solvation heat capacity of polar and charged solutes in water is studied using atomistic molecular dynamics simulations. As ionic solutes we consider a F- and a Na+ ion, as an example for a polar molecule with vanishing net charge we take a SPC/E water molecule. The partial charges of all three solutes are varied in a wide range by a scaling factor. Using a recently introduced method for the accurate determination of the solvation free energy of polar solutes, we determine the free energy, entropy, enthalpy, and heat capacity of the three different solutes as a function of temperature and partial solute charge. We find that the sum of the solvation heat capacities of the Na+ and F- ions is negative, in agreement with experimental observations, but our results uncover a pronounced difference in the heat capacity between positively and negatively charged groups. While the solvation heat capacity ΔCp stays positive and even increases slightly upon charging the Na+ ion, it decreases upon charging the F- ion and becomes negative beyond an ion charge of q = -0.3e. On the other hand, the heat capacity of the overall charge-neutral polar solute derived from a SPC/E water molecule is positive for all charge scaling factors considered by us. This means that the heat capacity of a wide class of polar solutes with vanishing net charge is positive. The common ascription of negative heat capacities to polar chemical groups might arise from the neglect of non-additive interaction effects between polar and apolar groups. The reason behind this non-additivity is suggested to be related to the second solvation shell that significantly affects the solvation thermodynamics and due to its large spatial extent induces quite long-ranged interactions between solvated molecular parts and groups.

  20. Role of Dispersive Fluorous Interaction in the Solvation Dynamics of the Perfluoro Group Containing Molecules.

    Science.gov (United States)

    Mondal, Saptarsi; Chaterjee, Soumit; Halder, Ritaban; Jana, Biman; Singh, Prashant Chandra

    2017-08-17

    Perfluoro group containing molecules possess an important self-aggregation property through the fluorous (F···F) interaction which makes them useful for diverse applications such as medicinal chemistry, separation techniques, polymer technology, and biology. In this article, we have investigated the solvation dynamics of coumarin-153 (C153) and coumarin-6H (C6H) in ethanol (ETH), 2-fluoroethanol (MFE), and 2,2,2-trifluoroethanol (TFE) using the femtosecond upconversion technique and molecular dynamics (MD) simulation to understand the role of fluorous interaction between the solute and solvent molecules in the solvation dynamics of perfluoro group containing molecules. The femtosecond upconversion data show that the time scales of solvation dynamics of C6H in ETH, MFE, and TFE are approximately the same whereas the solvation dynamics of C153 in TFE is slow as compared to that of ETH and MFE. It has also been observed that the time scale of solvation dynamics of C6H in ETH and MFE is higher than that of C153 in the same solvents. MD simulation results show a qualitative agreement with the experimental data in terms of the time scale of the slow components of the solvation for all the systems. The experimental and simulation studies combined lead to the conclusion that the solvation dynamics of C6H in all solvents as well as C153 in ETH and MFE is mostly governed by the charge distribution of ester moieties (C═O and O) of dye molecules whereas the solvation of C153 in TFE is predominantly due to the dispersive fluorous interaction (F···F) between the perfluoro groups of the C153 and solvent molecules.

  1. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients

    DEFF Research Database (Denmark)

    Russell, James A; Vincent, Jean-Louis; Kjølbye, Anne Louise

    2017-01-01

    BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was e...

  2. Study on the biological half-life and organ-distribution of tritiated lysine-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Laczi, F.; Laszlo, F.A.; Keri, Gy.; Teplan, I.

    1980-01-01

    The biological half-life and organ-distribution of tritiated lysine-vasopressin were determined in R-Amsterdam rats, and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-life of the tritiated lysin-vasopressin in the Brattleboro rats did not differ significantly from that found in the R-Amsterdam rats. The highest radioactivities were observed in the neuro- and adenohypophyses and in the kidneys of both the R-Amsterdam and the Brattleboro rats. The accumulation of tritiated LVP was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ-accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary hypothalamic diabetes insipidus. (author)

  3. Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

    Science.gov (United States)

    Febo, Marcelo; Ferris, Craig F

    2014-09-11

    Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lee

    Full Text Available Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL-induced cirrhosis received vehicle (citrate buffer or streptozotocin (diabetic, BDL/STZ. The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist and overcome by NaF (a G protein activator. The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

  5. Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide

    Science.gov (United States)

    di Giglio, Maria Giulia; Muttenthaler, Markus; Harpsøe, Kasper; Liutkeviciute, Zita; Keov, Peter; Eder, Thomas; Rattei, Thomas; Arrowsmith, Sarah; Wray, Susan; Marek, Ales; Elbert, Tomas; Alewood, Paul F.; Gloriam, David E.; Gruber, Christian W.

    2017-02-01

    Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.

  6. Protein- and diabetes-induced glomerular hyperfiltration: role of glucagon, vasopressin, and urea.

    Science.gov (United States)

    Bankir, Lise; Roussel, Ronan; Bouby, Nadine

    2015-07-01

    A single protein-rich meal (or an infusion of amino acids) is known to increase the glomerular filtration rate (GFR) for a few hours, a phenomenon known as "hyperfiltration." It is important to understand the factors that initiate this upregulation because it becomes maladaptive in the long term. Several mediators and paracrine factors have been shown to participate in this upregulation, but they are not directly triggered by protein intake. Here, we explain how a rise in glucagon and in vasopressin secretion, directly induced by protein ingestion, might be the initial factors triggering the hepatic and renal events leading to an increase in the GFR. Their effects include metabolic actions in the liver and stimulation of sodium chloride reabsorption in the thick ascending limb. Glucagon is not only a glucoregulatory hormone. It is also important for the excretion of nitrogen end products by stimulating both urea synthesis in the liver (along with gluconeogenesis from amino acids) and urea excretion by the kidney. Vasopressin allows the concentration of nitrogenous end products (urea, ammonia, etc.) and other protein-associated wastes in a hyperosmotic urine, thus allowing a very significant water economy characteristic of all terrestrial mammals. No hyperfiltration occurs in the absence of one or the other hormone. Experimental results suggest that the combined actions of these two hormones, along with the complex intrarenal handling of urea, lead to alter the composition of the tubular fluid at the macula densa and to reduce the intensity of the signal activating the tubuloglomerular feedback control of GFR, thus allowing GFR to raise. Altogether, glucagon, vasopressin, and urea contribute to set up the best compromise between efficient urea excretion and water economy. Copyright © 2015 the American Physiological Society.

  7. Blockade of central vasopressin receptors reduces the cardiovascular response to acute stress in freely moving rats.

    Science.gov (United States)

    Stojicić, S; Milutinović-Smiljanić, S; Sarenac, O; Milosavljević, S; Paton, J F R; Murphy, D; Japundzić-Zigon, N

    2008-04-01

    To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V(1a) (SR49059), V(1b) (SSR149415), V(2) (SR121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2 min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (integral), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LF(BP) and LF/HF(HR)). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LF(BP) oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V(1a), V(1b) and V(2) receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in integral(BP). In addition, V(1b) and V(2) receptor antagonists reduced BP(MAX) whereas V(1a), V(1b) antagonist and diazepam reduced HR(MAX) induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LF(BP) without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V(1b) receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.

  8. Phasic firing in vasopressin cells: understanding its functional significance through computational models.

    Directory of Open Access Journals (Sweden)

    Duncan J MacGregor

    Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

  9. Internal energy effects on the solvation and reactivity of multiply charged biomolecules for electrospray ionization mass spectroscopy. [Bovine ubiquitin

    Energy Technology Data Exchange (ETDEWEB)

    Light-Wahl, K.J.; Winger, B.E.; Rockwood, A.L.; Smith, R.D.

    1992-06-01

    Mild (capillary) interface conditions which do not completely desolvate the ions of proteins in electrospray ionization mass spectrometry (ESI-MS) may be required to probe the higher order structures and weak associations. For the small protein bovine ubiquitin, two ion distributions (unsolvated ions and unresolved solvated ions) were observed. The resolvable solvation for leucine-enkephalin with methanol and water shows that the use of countercurrent N{sub 2} flow at the capillary affects the solvation observed. 2 figs. (DLC)

  10. Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists.

    Science.gov (United States)

    Vaduganathan, Muthiah; Mentz, Robert J; Greene, Stephen J; Senni, Michele; Sato, Naoki; Nodari, Savina; Butler, Javed; Gheorghiade, Mihai

    2015-01-01

    Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

  11. Urinary prostaglandin E and vasopressin excretion in essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.

    1983-01-01

    excretion of prostaglandin E (PGE), immunoreactive arginine vasopressin (iA VP), and kallikrein were determined. PGE was quantitated with a radioimmunoassay having 4.9% cross-reactivity with prostaglandin E (PGE). After 4 weeks on the diet, water consumption and urinary iAVP excretion increased....... Increased water consumption and increased urinary iAVP excretion seem to be early symptoms (after 4 weeks) of EFA deficiency, whereas decreased urine output and decreased urinary PGE excretion occur much later (after 10 weeks). Two energy% linolenate supplementation to a fat-free diet did not change...

  12. Radio-immunoassay of plasma arginine vasopressin in man. Comparison of two methods of extraction

    International Nuclear Information System (INIS)

    Wolf, J.P.; Dumoulin, G.; Henriet, M.T.; Baulay, A.; Berthelay, S.

    1987-01-01

    Two methods of extraction, prior to radio-immunoassay (RIA) of human plasma arginine vasopressin (AVP) were tested: ethanol extraction (ETH), chromatography with ODS-Silice (ODS-Sil). Recovery of 125 I AVP was higher when using ODS-Sil than when using ETH. Recovery of standard AVP was found to be more efficient and reproducible for ODS-Sil. However, the RIA used, performed after chromatography with ODS-Sil, is not enough sensitive to detect low concentrations but is able to detect high concentrations and physiological variations of plasma AVP [fr

  13. Synthesis of two tritium-labeled derivatives of a vasopressin antagonist peptide

    International Nuclear Information System (INIS)

    Landvatter, S.W.; Heys, J.R.

    1986-01-01

    SK and F 101926, a potent vasopressin antagonist, has been tritium labeled in the tyrosine residue via exchange followed by solid phase coupling to a hexapeptide. The peptide thus obtained was subsequently coupled with a PMP residue, cleaved from the resin with HF, oxidized by ferricyanide and purified by HPLC giving the desired cyclic peptide. Alternatively, a labeled PMP residue can be prepared via reduction starting from phenol. Conversion of the labeled cyclohexanone to PMP followed by solid phase coupling to a heptapeptide can then afford PMP labeled peptide. 3 refs

  14. Effect of the selective vasopressin V2 receptor antagonists in hepatic cirrhosis patients with ascites: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Shao-hui TANG

    2013-07-01

    Full Text Available Objective To evaluate the efficacy and safety of selective vasopressin V2 receptor antagonists in the treatment of hepatic cirrhosis patients with ascites. Methods PubMed, EMBASE, Web of Science, The Cochrane Central Register of Controlled Trials, Database for Chinese Technical Periodical (VIP, Chinese Journal Full-Text Database (CNKI, and Wan Fang Digital Journal Full-text Database were retrieved to collect clinical randomized controlled trials of hepatic cirrhosis with ascites treated by selective vasopressin V2 receptor antagonists. Meta analysis was performed by using Review Manager 5.0. Results Nine randomized controlled trials including 1884 patients met the inclusion criteria. Meta-analysis showed that: 1 The selective vasopressin V2 receptor antagonists were associated with a significant reduction in body weight compared with placebo (WMD=–1.98kg, 95%CI:–3.24-–0.72kg, P=0.002. Treatment with selective vasopressin V2 receptor antagonists was associated with an improvement of low serum sodium concentration compared to placebo (WMD=3.74mmol/L, 95%CI: 0.91-6.58mmol/L, P=0.01. The percentage of patients with worsening ascites was higher in the group of patients treated with placebo (RR=0.51, 95%CI: 0.34-0.77, P=0.001. 2 The amplitude of increased urine volume was obviously higher in selective vasopressin V2 receptor antagonists group than in placebo group (WMD=1437.65ml, 95%CI: 649.01-2226.30ml, P=0.0004. The difference of serum creatinine in the selective vasopressin V2 receptor antagonists group was not statistically significant compared with the control group (WMD=–3.49μmol/L, 95%CI: –12.54¬5.56μmol/L, P=0.45. 3 There was no statistical significance between the two groups in the heart rate, systolic pressure, diastolic pressure and mortality (P>0.05. The rate of other adverse reactions was higher in the selective vasopressin V2 receptor antagonists group compared with that of placebo group (P=0.003. Conclusion

  15. Nonequilibrium quantum solvation with a time-dependent Onsager cavity

    Science.gov (United States)

    Kirchberg, H.; Nalbach, P.; Thorwart, M.

    2018-04-01

    We formulate a theory of nonequilibrium quantum solvation in which parameters of the solvent are explicitly depending on time. We assume in a simplest approach a spherical molecular Onsager cavity with a time-dependent radius. We analyze the relaxation properties of a test molecular point dipole in a dielectric solvent and consider two cases: (i) a shrinking Onsager sphere and (ii) a breathing Onsager sphere. Due to the time-dependent solvent, the frequency-dependent response function of the dipole becomes time-dependent. For a shrinking Onsager sphere, the dipole relaxation is in general enhanced. This is reflected in a temporally increasing linewidth of the absorptive part of the response. Furthermore, the effective frequency-dependent response function shows two peaks in the absorptive part which are symmetrically shifted around the eigenfrequency. By contrast, a breathing sphere reduces damping as compared to the static sphere. Interestingly, we find a non-monotonous dependence of the relaxation rate on the breathing rate and a resonant suppression of damping when both rates are comparable. Moreover, the linewidth of the absorptive part of the response function is strongly reduced for times when the breathing sphere reaches its maximal extension.

  16. Cluster Formation of Polyphilic Molecules Solvated in a DPPC Bilayer

    Directory of Open Access Journals (Sweden)

    Xiang-Yang Guo

    2017-10-01

    Full Text Available We analyse the initial stages of cluster formation of polyphilic additive molecules which are solvated in a dipalmitoylphosphatidylcholine (DPPC lipid bilayer. Our polyphilic molecules comprise an aromatic (trans-bilayer core domain with (out-of-bilayer glycerol terminations, complemented with a fluorophilic and an alkyl side chain, both of which are confined within the aliphatic segment of the bilayer. Large-scale molecular dynamics simulations (1 μ s total duration of a set of six of such polyphilic additives reveal the initial steps towards supramolecular aggregation induced by the specific philicity properties of the molecules. For our intermediate system size of six polyphiles, the transient but recurrent formation of a trimer is observed on a characteristic timescale of about 100 ns. The alkane/perfluoroalkane side chains show a very distinct conformational distribution inside the bilayer thanks to their different philicity, despite their identical anchoring in the trans-bilayer segment of the polyphile. The diffusive mobility of the polyphilic additives is about the same as that of the surrounding lipids, although it crosses both bilayer leaflets and tends to self-associate.

  17. Ionic strength independence of charge distributions in solvation of biomolecules

    Energy Technology Data Exchange (ETDEWEB)

    Virtanen, J. J. [Department of Chemistry, University of Chicago, Chicago, Illinois 60637 (United States); James Franck Institute, University of Chicago, Chicago, Illinois 60637 (United States); Sosnick, T. R. [Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois 60637 (United States); Computation Institute, University of Chicago, Chicago, Illinois 60637 (United States); Freed, K. F. [Department of Chemistry, University of Chicago, Chicago, Illinois 60637 (United States); James Franck Institute, University of Chicago, Chicago, Illinois 60637 (United States); Computation Institute, University of Chicago, Chicago, Illinois 60637 (United States)

    2014-12-14

    Electrostatic forces enormously impact the structure, interactions, and function of biomolecules. We perform all-atom molecular dynamics simulations for 5 proteins and 5 RNAs to determine the dependence on ionic strength of the ion and water charge distributions surrounding the biomolecules, as well as the contributions of ions to the electrostatic free energy of interaction between the biomolecule and the surrounding salt solution (for a total of 40 different biomolecule/solvent combinations). Although water provides the dominant contribution to the charge density distribution and to the electrostatic potential even in 1M NaCl solutions, the contributions of water molecules and of ions to the total electrostatic interaction free energy with the solvated biomolecule are comparable. The electrostatic biomolecule/solvent interaction energies and the total charge distribution exhibit a remarkable insensitivity to salt concentrations over a huge range of salt concentrations (20 mM to 1M NaCl). The electrostatic potentials near the biomolecule's surface obtained from the MD simulations differ markedly, as expected, from the potentials predicted by continuum dielectric models, even though the total electrostatic interaction free energies are within 11% of each other.

  18. Molecular hydrogen solvated in water – A computational study

    International Nuclear Information System (INIS)

    Śmiechowski, Maciej

    2015-01-01

    The aqueous hydrogen molecule is studied with molecular dynamics simulations at ambient temperature and pressure conditions, using a newly developed flexible and polarizable H 2 molecule model. The design and implementation of this model, compatible with an existing flexible and polarizable force field for water, is presented in detail. The structure of the hydration layer suggests that first-shell water molecules accommodate the H 2 molecule without major structural distortions and two-dimensional, radial-angular distribution functions indicate that as opposed to strictly tangential, the orientation of these water molecules is such that the solute is solvated with one of the free electron pairs of H 2 O. The calculated self-diffusion coefficient of H 2 (aq) agrees very well with experimental results and the time dependence of mean square displacement suggests the presence of caging on a time scale corresponding to hydrogen bond network vibrations in liquid water. Orientational correlation function of H 2 experiences an extremely short-scale decay, making the H 2 –H 2 O interaction potential essentially isotropic by virtue of rotational averaging. The inclusion of explicit polarizability in the model allows for the calculation of Raman spectra that agree very well with available experimental data on H 2 (aq) under differing pressure conditions, including accurate reproduction of the experimentally noted trends with solute pressure or concentration

  19. Ionic strength independence of charge distributions in solvation of biomolecules

    International Nuclear Information System (INIS)

    Virtanen, J. J.; Sosnick, T. R.; Freed, K. F.

    2014-01-01

    Electrostatic forces enormously impact the structure, interactions, and function of biomolecules. We perform all-atom molecular dynamics simulations for 5 proteins and 5 RNAs to determine the dependence on ionic strength of the ion and water charge distributions surrounding the biomolecules, as well as the contributions of ions to the electrostatic free energy of interaction between the biomolecule and the surrounding salt solution (for a total of 40 different biomolecule/solvent combinations). Although water provides the dominant contribution to the charge density distribution and to the electrostatic potential even in 1M NaCl solutions, the contributions of water molecules and of ions to the total electrostatic interaction free energy with the solvated biomolecule are comparable. The electrostatic biomolecule/solvent interaction energies and the total charge distribution exhibit a remarkable insensitivity to salt concentrations over a huge range of salt concentrations (20 mM to 1M NaCl). The electrostatic potentials near the biomolecule's surface obtained from the MD simulations differ markedly, as expected, from the potentials predicted by continuum dielectric models, even though the total electrostatic interaction free energies are within 11% of each other

  20. Preferential solvation and solvation shell composition of free base and protonated 5, 10, 15, 20-tetrakis(4-sulfonatophenyl)porphyrin in aqueous organic mixed solvents

    Science.gov (United States)

    Farajtabar, Ali; Jaberi, Fatemeh; Gharib, Farrokh

    2011-12-01

    The solvatochromic properties of the free base and the protonated 5, 10, 15, 20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) were studied in pure water, methanol, ethanol (protic solvents), dimethylsulfoxide, DMSO, (non-protic solvent), and their corresponding aqueous-organic binary mixed solvents. The correlation of the empirical solvent polarity scale ( ET) values of TPPS with composition of the solvents was analyzed by the solvent exchange model of Bosch and Roses to clarify the preferential solvation of the probe dyes in the binary mixed solvents. The solvation shell composition and the synergistic effects in preferential solvation of the solute dyes were investigated in terms of both solvent-solvent and solute-solvent interactions and also, the local mole fraction of each solvent composition was calculated in cybotactic region of the probe. The effective mole fraction variation may provide significant physico-chemical insights in the microscopic and molecular level of interactions between TPPS species and the solvent components and therefore, can be used to interpret the solvent effect on kinetics and thermodynamics of TPPS. The obtained results from the preferential solvation and solvent-solvent interactions have been successfully applied to explain the variation of equilibrium behavior of protonation of TPPS occurring in aqueous organic mixed solvents of methanol, ethanol and DMSO.

  1. Synthesis of specific deuterium labeled tyrosine and phenylalanine derivatives and their use in the total synthesis of [8-arginine]vasopressin derivatives: the separation of diastereomeric [8-arginine]vasopressin derivatives by partition chromatography

    International Nuclear Information System (INIS)

    Yamamoto, D.M.; Upson, D.A.; Linn, D.K.; Hruby, V.J.

    1977-01-01

    Derivatives of tyrosine specifically deuterated at the α carbon ([α- 2 H 1 ]tyrosine) and at both the α and β carbons ([α,β,β- 2 H 3 ]tyrosine) and a derivative of phenylalanine specifically deuterated at the α carbon ([α- 2 H 1 ]phenylalanine) have been synthesized in high yield. These labeled compounds have been resolved enzymatically, and the enantiomers and racemates have been converted to N-tert-butyloxycarbonyl derivatives. The deuterium labels were not exchanged under the conditions of the syntheses. The protected derivatives as well as specifically deuterated derivatives of S-benzylcysteine and of glycine were used to prepare specifically deuterated analogues of [8-arginine] vasopressin using solid phase peptide procedures. The use of improved synthetic procedures resulted in considerable improvements in the yields of [8-arginine]vasopressin compared with previous reports. In addition, new solvent systems for partition chromatography purification of [8-arginine]vasopressin on Sephadex were developed which allowed a facile one-step separation of diastereomers of [8-arginine]vasopressin containing a racemic amino acid at either the 1-hemicystine or the 2-tyrosine positions of the hormone

  2. Breaking the polar-nonpolar division in solvation free energy prediction.

    Science.gov (United States)

    Wang, Bao; Wang, Chengzhang; Wu, Kedi; Wei, Guo-Wei

    2018-02-05

    Implicit solvent models divide solvation free energies into polar and nonpolar additive contributions, whereas polar and nonpolar interactions are inseparable and nonadditive. We present a feature functional theory (FFT) framework to break this ad hoc division. The essential ideas of FFT are as follows: (i) representability assumption: there exists a microscopic feature vector that can uniquely characterize and distinguish one molecule from another; (ii) feature-function relationship assumption: the macroscopic features, including solvation free energy, of a molecule is a functional of microscopic feature vectors; and (iii) similarity assumption: molecules with similar microscopic features have similar macroscopic properties, such as solvation free energies. Based on these assumptions, solvation free energy prediction is carried out in the following protocol. First, we construct a molecular microscopic feature vector that is efficient in characterizing the solvation process using quantum mechanics and Poisson-Boltzmann theory. Microscopic feature vectors are combined with macroscopic features, that is, physical observable, to form extended feature vectors. Additionally, we partition a solvation dataset into queries according to molecular compositions. Moreover, for each target molecule, we adopt a machine learning algorithm for its nearest neighbor search, based on the selected microscopic feature vectors. Finally, from the extended feature vectors of obtained nearest neighbors, we construct a functional of solvation free energy, which is employed to predict the solvation free energy of the target molecule. The proposed FFT model has been extensively validated via a large dataset of 668 molecules. The leave-one-out test gives an optimal root-mean-square error (RMSE) of 1.05 kcal/mol. FFT predictions of SAMPL0, SAMPL1, SAMPL2, SAMPL3, and SAMPL4 challenge sets deliver the RMSEs of 0.61, 1.86, 1.64, 0.86, and 1.14 kcal/mol, respectively. Using a test set of 94

  3. Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal bleeding due to recurrence of urinary bladder carcinoma.

    Science.gov (United States)

    Kakizawa, Hideaki; Toyota, Naoyuki; Mita, Koji; Fujimura, Yoshio; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Ito, Katsuhide

    2006-05-01

    We report a case that was successfully treated for massive lower gastrointestinal (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted of combination therapy including embolization of an inferior gluteal artery (IGA) pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery (SA). A 57-year-old man presented with life-threatening sudden, massive LGI bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder carcinoma. Computed tomography showed that the LN recurrence had invaded all the way to the sigmoid colon, and there was a pseudoaneurysm with extravasation inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We therefore excluded the pseudoaneurysm by embolization with microcoils. Following this treatment the bleeding decreased, but intermittent LGI bleeding continued. Endoscopic examination showed the tumor with a huge ulcer inside the colonic lumen, and continuous oozing was confirmed. A second angiogram showed no recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a 3F microcatheter was placed in the SA selectively using a coaxial catheter system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding completely ceased 2 days later. There were no signs of ischemic gastrointestinal complications. Massive LGI bleeding has not recurred in 5 months.

  4. Modulation of mouse Leydig cell steroidogenesis through a specific arginine-vasopressin receptor

    International Nuclear Information System (INIS)

    Tahri-Joutei, A.; Pointis, G.

    1988-01-01

    Characterization of specific vasopressin binding sites was investigated in purified mouse Leydig cells using tritiated arginine-vasopressin. Binding of radioligand was saturable, time- and temperature-dependent and reversible. ( 3 H)-AVP was found to bind to a single class of sites with high affinity and low capacity. Binding displacements with specific selection analogs of AVP indicated the presence of V 1 subtype receptors on Leydig cells. The ability of AVP to displace ( 3 H)-AVP binding was greater than LVP and oxytocin. The unrelated peptides, somatostatin and substance P, were less potent, while neurotensin and LHRH did not displace ( 3 H)-AVP binding. The time-course effects of AVP-pretreatment on basal and hCG-stimulated testosterone and cAMP accumulations were studied in primary culture of Leydig cells. Basal testosterone accumulation was significantly increased by a 24 h AVP-pretreatment of Leydig cells. This effect was potentiated by the phosphodiesterase inhibitor (MIX) and was concomitantly accompanied by a slight but significant increase in cAMP accumulation. AVP-pretreatment of the cells for 72 h had no effect on basal testosterone accumulation, but exerted a marked inhibitory effect on the hCG-stimulated testosterone accumulation. This reduction of testosterone accumulation occurred even in the presence of MIX and was not accompanied by any significant change of cAMP levels

  5. Pharmacokinetics of the vasopressin antagonist, SK and F 101926, a synthetic octapeptide, in the rat

    International Nuclear Information System (INIS)

    Lynn, R.K.; Straub, K.M.; Landvatter, S.W.; Garvie, C.T.

    1986-01-01

    SK and F 101926 is a synthetic analogue of vasopressin which antagonizes vasopressin induced antidiuresis. Radiolabeled SK and F 101926 ( 3 H-3,3-D-TYR) was administered i.v. as a single bolus to male Sprague Dawley rats. Serial plasma samples were analyzed for SK and F 101926 by HPLC/LSC. The plasma concentration time curve for SK and F 101926 displayed three disposition phases. However, 80% of the total area under the curve was represented in one phase which displayed a half-life (t 1/2) of 20 min. The total systematic clearance (Cl) and the steady state volume of distribution (Vdss) were 15 ml/min/kg and 450 ml/kg, respectively. The t 1/2, Cl and Vdss were identical following doses of 10 and 100 μg/kg. 3 H-SK and F 101926 accounted for > 80% of the plasma radiolabel 0-30 min after dosing. However, by 12 hr, 3 H-SK and F 101926 represented only 6% of the plasma radiolabel. Following oral administration of 3 H-SK and F 101926, < 5% of the administered radiolabel reached the systematic circulation; however, no parent compound was detectable in plasma. These studies demonstrate that although SK and F 101926 has a relatively low systematic clearance, it also displays a relatively small volume of distribution which together result in a moderate beta elimination half-life

  6. Vasopressin-induced constriction of the isolated rat occipital artery is segment dependent.

    Science.gov (United States)

    Chelko, Stephen P; Schmiedt, Chad W; Lewis, Tristan H; Lewis, Stephen J; Robertson, Tom P

    2013-01-01

    Circulating factors delivered to the nodose ganglion (NG) by the occipital artery (OA) have been shown to affect vagal afferent activity, and thus the contractile state of the OA may influence blood flow to the NG. OA were isolated and bisected into proximal and distal segments relative to the external carotid artery. Bisection highlighted stark differences between maximal contractile responses and OA sensitivity. Specifically, maximum responses to vasopressin and the V1 receptor agonist were significantly higher in distal than proximal segments. Distal segments were significantly more sensitive to 5-hydroxytryptamine (5-HT) and the 5-HT2 receptor agonist than proximal segments. Angiotensin II (AT)2, V2 and 5-HT(1B/1D) receptor agonists did not elicit vascular responses. Additionally, AT1 receptor agonists elicited mild, yet not significantly different maximal responses between segments. The results of this study are consistent with contractile properties of rat OA being mediated via AT1, V1 and 5-HT2 receptors and dependent upon the OA segment. Furthermore, vasopressin-induced constriction of the OA, regardless of a bolus dose or a first and second concentration-response curve, retained this unique segmental difference. We hypothesize that these segmental differences may be important in the regulation of blood flow through the OA in health and disease. © 2013 S. Karger AG, Basel.

  7. Vasopressin-induced constriction of the isolated rat occipital artery is segment-dependent

    Science.gov (United States)

    Chelko, Stephen P.; Schmiedt, Chad W.; Lewis, Tristan H.; Lewis, Stephen J.; Robertson, Tom P.

    2014-01-01

    Background Circulating factors delivered to the nodose ganglion (NG) by the occipital artery (OA) have shown to affect vagal afferent activity, and thus the contractile state of the OA may influence blood flow to the NG. Methods OA were isolated and bisected into proximal and distal segments, relative to the external carotid artery. Results Bisection, highlighted stark differences between maximal contractile responses and OA sensitivity. Specifically, maximum responses to vasopressin and the V1 receptor agonist, were significantly higher in distal than proximal segments. Distal segments were significantly more sensitive to 5-HT and the 5-HT2 receptor agonist than proximal segments. AT2, V2 and 5-HT1B/1D receptor agonists did not elicit vascular responses. Additionally, AT1 receptor agonists elicited mild, yet not significantly different maximal responses between segments. Conclusion The results of this study are consistent with contractile properties of rat OA being mediated via AT1, V1 and 5-HT2 receptors, and are dependent upon the OA segment. Furthermore, vasopressin-induced constriction of the OA, regardless of a bolus dose or a first and second concentration response curve retained this unique segmental difference and therefore we hypothesize this may be a pathophysiological response in the regulation of blood flow through the OA. PMID:24192548

  8. A novel polymorphism in the coding region of the vasopressin type 2 receptor gene

    Directory of Open Access Journals (Sweden)

    J.L. Rocha

    1997-04-01

    Full Text Available Nephrogenic diabetes insipidus (NDI is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R gene in affected kindreds. In most kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R gene in affected kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R gene have also been reported. In the present study, we analyzed exon 3 of the V2(R gene in 20 unrelated individuals by direct sequencing. A C®T alteration in the third position of codon 331 (AGC®AGT, which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome

  9. Endogenous opioids inhibit oxytocin release during nicotine-stimulated secretion of vasopressin in man.

    Science.gov (United States)

    Seckl, J R; Johnson, M; Shakespear, C; Lightman, S L

    1988-05-01

    The effects of the opioid antagonist naloxone on the vasopressin (AVP) and oxytocin (OT) responses to nicotine were studied in male non-smokers (21-30 years old). Either saline (n = 6) or naloxone (4 mg bolus + 6 mg/h, n = 6) was infused i.v. during the study. After 60 min infusion the subjects smoked one high-nicotine content cigarette. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Smoking led to a significant rise in plasma vasopressin in both saline and naloxone-infused subjects (P less than 0.05). There was no significant difference in the plasma AVP response to smoking between the two groups. Saline-infused subjects did not show any change in plasma OT in response to smoking. Naloxone infusion was associated with a significant rise in OT from 1.3 +/- 0.1 pmol/l to 4.3 +/- 2.4 pmol/l 5 min after smoking (P less than 0.05). We conclude that there is endogenous opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to nicotine in man.

  10. Postnatal Expression of V2 Vasopressin Receptor Splice Variants in the Rat Cerebellum

    Science.gov (United States)

    Vargas, Karina J.; Sarmiento, José M.; Ehrenfeld, Pamela; Añazco, Carolina C.; Villanueva, Carolina I.; Carmona, Pamela L.; Brenet, Marianne; Navarro, Javier; Müller-Esterl, Werner; Figueroa, Carlos D.; González, Carlos B.

    2010-01-01

    The V2 vasopressin receptor gene contains an alternative splice site in exon-3, which leads to the generation of two splice variants (V2a and V2b) first identified in the kidney. The open reading frame of the alternatively spliced V2b transcripten codes a truncated receptor, showing the same amino acid sequence as the canonical V2a receptor up to the 6th transmembrane segment, but displaying a distinct sequence to the corresponding 7th transmembrane segment and C-terminal domain relative to the V2a receptor. Here, we demonstrate the postnatal expression of V2a and V2b variants in the rat cerebellum. Most importantly, we showed by in situ hybridization and immunocytochemistry that both V2 splice variants were preferentially expressed in Purkinje cells, from early to late postnatal development. In addition, both variants were transiently expressed in the neuroblastic external granule cells and Bergmann fibers. These results indicate that the cellular distributions of both splice variants are developmentally regulated, and suggest that the transient expression of the V2 receptor is involved in the mechanisms of cerebellar cytodifferentiation by AVP. Finally, transfected CHO-K1 .expressing similar amounts of both V2 splice variants, as that found in the cerebellum, showed a significant reduction in the surface expression of V2a receptors, suggesting that the differential expression of the V2 splice variants regulate the vasopressin signaling in the cerebellum. PMID:19281786

  11. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors.

    Science.gov (United States)

    Bales, K L; Plotsky, P M; Young, L J; Lim, M M; Grotte, N; Ferrer, E; Carter, C S

    2007-01-05

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations.

  12. Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in melancholic depression.

    LENUS (Irish Health Repository)

    Dinan, T G

    2012-02-03

    BACKGROUND: In situations of chronic stress vasopressin plays an important role in regulating the hypothalamic-pituitary adrenal axis. The aim of the current study was to investigate the role of anterior pituitary vasopressin V3 receptors in maintaining the hypercortisolism seen in melancholic depression. METHOD: Fourteen patients with major depression and 14 age- and sex-matched healthy comparison subjects were recruited. Desmopressin (ddAVP) 10 microg was given intravenously and ACTH and cortisol release was monitored for 120 min. RESULTS: The mean +\\/- S.E.M. ACTH response in the depressives was 28.4 +\\/- 4.3 ng\\/l and in the healthy subjects was 18.8 +\\/- 4.9 ng\\/l (P = 0.04). The mean +\\/- S.E.M. cortisol response in the depressives was 261.8 +\\/- 46.5 nmol\\/l and in the healthy subjects was 107.3 +\\/- 26.1 nmol\\/l (P < 0.01). CONCLUSIONS: Patients with major depression have augmented ACTH and cortisol responses to desmopressin indicating enhanced V3 responsivity.

  13. Oxytocin and Vasopressin: Linking Pituitary Neuropeptides and their Receptors to Social Neurocircuits

    Directory of Open Access Journals (Sweden)

    Danielle Andrea Baribeau

    2015-09-01

    Full Text Available Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders.

  14. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

    Science.gov (United States)

    Bisagno, Verónica; Cadet, Jean Lud

    2014-09-01

    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

  15. Studies of GI bleeding with scintigraphy and the influence of vasopressin

    International Nuclear Information System (INIS)

    Alavi, A.; McLean, G.K.

    1981-01-01

    The management of patients with gastrointestinal (GI) bleeding depends on accurate localization of the site of hemorrhage. Endoscopy and arteriography, although successful in achieving this goal in the majority of patients, are invasive and have other shortcomings. The introduction of the 99mTc-sulfur colloid technique has greatly simplified the evaluation and management of these patients. This test is useful in detecting and localizing the bleeding site in the lower GI tract. Scintigraphy is now used as the initial study of choice in patients with rectal bleeding. Advances made in angiography and nuclear medicine techniques also have resulted in improved management of patients. Conservative approaches succeed in controlling hemorrhage in most patients. Vasopressin is the most widely tested agent and has been adopted by many as the preferred preparation for this purpose. Before the introduction of the 99mTc-sulfur colloid technique, angiography was used to monitor the effectiveness of this drug, whether administered intravenously or intraarterially. With the use of scintigraphy and intravenous administration of vasopressin, these patients now can be managed noninvasively. Only when the intravenous Pitressin infusion fails to stop hemorrhage, is the intraarterial approach considered. Surgery is used as a last resort when these measures fail to stop the bleeding

  16. Personality is Tightly Coupled to Vasopressin-Oxytocin Neuron Activity in a Gregarious Finch

    Directory of Open Access Journals (Sweden)

    Aubrey M Kelly

    2014-02-01

    Full Text Available Nonapeptides of the vasopressin-oxytocin family modulate social processes differentially in relation to sex, species, behavioral phenotype, and human personality. However, the mechanistic bases for these differences are not well understood, in part because multidimensional personality structures remain to be described for common laboratory animals. Based upon principal components (PC analysis of extensive behavioral measures in social and nonsocial contexts, we now describe three complex dimensions of phenotype (personality for the zebra finch, a species that exhibits a human-like social organization that is based upon biparental nuclear families embedded within larger social groups. These dimensions can be characterized as Social competence/dominance, Gregariousness, and Anxiety. We further demonstrate that the phasic Fos response of nonapeptide neurons in the paraventricular nucleus of the hypothalamus and medial bed nucleus of the stria terminalis are significantly predicted by personality, sex, social context, and their interactions. Furthermore the behavioral PCs are each associated with a distinct suite of neural PCs that incorporate both peptide cell numbers and their phasic Fos responses, indicating that personality is reflected in complex patterns of neuromodulation arising from multiple peptide cell groups. These findings provide novel insights into the mechanisms underlying sex- and phenotype-specific modulation of behavior, and should be broadly relevant, given that vasopressin-oxytocin systems are strongly conserved across vertebrates.

  17. Hydrophilic Solvation Dominates the Terahertz Fingerprint of Amino Acids in Water.

    Science.gov (United States)

    Esser, Alexander; Forbert, Harald; Sebastiani, Federico; Schwaab, Gerhard; Havenith, Martina; Marx, Dominik

    2018-02-01

    Spectroscopy in the terahertz frequency regime is a sensitive tool to probe solvation-induced effects in aqueous solutions. Yet, a systematic understanding of spectral lineshapes as a result of distinct solvation contributions remains terra incognita. We demonstrate that modularization of amino acids in terms of functional groups allows us to compute their distinct contributions to the total terahertz response. Introducing the molecular cross-correlation analysis method provides unique access to these site-specific contributions. Equivalent groups in different amino acids lead to look-alike spectral contributions, whereas side chains cause characteristic but additive complexities. Specifically, hydrophilic solvation of the zwitterionic groups in valine and glycine leads to similar terahertz responses which are fully decoupled from the side chain. The terahertz response due to H-bonding within the large hydrophobic solvation shell of valine turns out to be nearly indistinguishable from that in bulk water in direct comparison to the changes imposed by the charged functional groups that form strong H-bonds with their hydration shells. Thus, the hydrophilic groups and their solvation shells dominate the terahertz absorption difference, while on the same intensity scale, the influence of hydrophobic water can be neglected.

  18. Electrostatic solvation free energies of charged hard spheres using molecular dynamics with density functional theory interactions

    Science.gov (United States)

    Duignan, Timothy T.; Baer, Marcel D.; Schenter, Gregory K.; Mundy, Chistopher J.

    2017-10-01

    Determining the solvation free energies of single ions in water is one of the most fundamental problems in physical chemistry and yet many unresolved questions remain. In particular, the ability to decompose the solvation free energy into simple and intuitive contributions will have important implications for models of electrolyte solution. Here, we provide definitions of the various types of single ion solvation free energies based on different simulation protocols. We calculate solvation free energies of charged hard spheres using density functional theory interaction potentials with molecular dynamics simulation and isolate the effects of charge and cavitation, comparing to the Born (linear response) model. We show that using uncorrected Ewald summation leads to unphysical values for the single ion solvation free energy and that charging free energies for cations are approximately linear as a function of charge but that there is a small non-linearity for small anions. The charge hydration asymmetry for hard spheres, determined with quantum mechanics, is much larger than for the analogous real ions. This suggests that real ions, particularly anions, are significantly more complex than simple charged hard spheres, a commonly employed representation.

  19. Solvation pressure as real pressure: I. Ethanol and starch under negative pressure

    CERN Document Server

    Uden, N W A V; Faux, D A; Tanczos, A C; Howlin, B; Dunstan, D J

    2003-01-01

    The reality of the solvation pressure generated by the cohesive energy density of liquids is demonstrated by three methods. Firstly, the Raman spectrum of ethanol as a function of cohesive energy density (solvation pressure) in ethanol-water and ethanol-chloroform mixtures is compared with the Raman spectrum of pure ethanol under external hydrostatic pressure and the solvation pressure and hydrostatic pressure are found to be equivalent for some transitions. Secondly, the bond lengths of ethanol are calculated by molecular dynamics modelling for liquid ethanol under pressure and for ethanol vapour. The difference in bond lengths between vapour and liquid are found to be equivalent to the solvation pressure for the C-H sub 3 , C-H sub 2 and O-H bond lengths, with discrepancies for the C-C and C-O bond lengths. Thirdly, the pressure-induced gelation of potato starch is measured in pure water and in mixtures of water and ethanol. The phase transition pressure varies in accordance with the change in solvation pre...

  20. Improving accuracy of electrochemical capacitance and solvation energetics in first-principles calculations

    Science.gov (United States)

    Sundararaman, Ravishankar; Letchworth-Weaver, Kendra; Schwarz, Kathleen A.

    2018-04-01

    Reliable first-principles calculations of electrochemical processes require accurate prediction of the interfacial capacitance, a challenge for current computationally efficient continuum solvation methodologies. We develop a model for the double layer of a metallic electrode that reproduces the features of the experimental capacitance of Ag(100) in a non-adsorbing, aqueous electrolyte, including a broad hump in the capacitance near the potential of zero charge and a dip in the capacitance under conditions of low ionic strength. Using this model, we identify the necessary characteristics of a solvation model suitable for first-principles electrochemistry of metal surfaces in non-adsorbing, aqueous electrolytes: dielectric and ionic nonlinearity, and a dielectric-only region at the interface. The dielectric nonlinearity, caused by the saturation of dipole rotational response in water, creates the capacitance hump, while ionic nonlinearity, caused by the compactness of the diffuse layer, generates the capacitance dip seen at low ionic strength. We show that none of the previously developed solvation models simultaneously meet all these criteria. We design the nonlinear electrochemical soft-sphere solvation model which both captures the capacitance features observed experimentally and serves as a general-purpose continuum solvation model.

  1. Understanding Lithium Solvation and Diffusion through Topological Analysis of First-Principles Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Bhatia, Harsh [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gyulassy, Attila [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ong, Mitchell [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Lordi, Vincenzo [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Draeger, Erik [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pask, John [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pascucci, Valerio [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bremer, Peer -Timo [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-09-27

    The performance of lithium-ion batteries is strongly influenced by the ionic conductivity of the electrolyte, which depends on the speed at which Li ions migrate across the cell and relates to their solvation structure. The choice of solvent can greatly impact, both, the solvation and diffusivity of Li ions. In this work, we present our application of the topological techniques to extract and predict such behavior in the data generated by the first-principles molecular dynamics simulation of Li ions in an important organic solvent -ethylene carbonate. More specifically, we use the scalar topology of the electron charge density field to analyze the evolution of the solvation structures. This allows us to derive a parameter-free bond definition for lithium-oxygen bonds, to provide a quantitative measure for bond strength, and to understand the regions of influence of each atom in the simulation. This has provided new insights into how and under what conditions certain bonds may form and break. As a result, we can identify and, more importantly, predict, unstable configurations in solvation structures. This can be very useful in understanding when small changes to the atoms' movements can cause significantly different bond structures to evolve. Ultimately, this promises to allow scientists to explore lithium ion solvation and diffusion more systematically, with the aim of new insights and potentially accelerating the calculations themselves.

  2. Cellular plasticity in the supraoptic and paraventricular nuclei after prolonged dehydration in the desert rodent Meriones shawi: Vasopressin and GFAP immunohistochemical study.

    Science.gov (United States)

    Gamrani, Halima; Elgot, Abdeljalil; El Hiba, Omar; Fèvre-Montange, Michelle

    2011-02-23

    Supraoptic (SON) and paraventricular (PVN) nuclei are part of the hypothalamic-neurohypophysial system, they constitute the main source for vasopressin and they represent also obvious examples of activity-dependent neuroglial plasticity. Certain physiological conditions such as dehydration are accompanied by a structural remodeling of the neurons, their synaptic inputs and their surrounding glia. In the present work, an adult Meriones shawi (a rodent adapted to desert life) is used as an animal model. Using GFAP and vasopressin expressions as indicators successively of astrocytes and neuronal activations, the effect of a prolonged episode of water deprivation on the SON and PVN, hypothalamus nuclei were examined. We studied the immunoreactivity of GFAP and vasopressin in various hydration states (total deprivation of drinking water for 1 and 2months compared to hydrated animals). Prolonged dehydration produces an important decrease of GFAP immunoreactivity in both SON and PVN after 1 and 2months of water restriction. This decrease is accompanied by increased vasopressin immunoreactivity following the same periods of water deprivation. These findings may explain a real communication between vasopressin neurons and their surrounding astrocytes, thus the retraction of astrocytes and their processes is accompanied by an enhancement of vasopressin neuron density and their projecting fibers in response to this osmotic stress situation. Furthermore, these data could open further investigations concerning the possible involvement of the communication between astrocytes and vasopressin neurons in both PVN and SON in the regulation of Meriones hydrous balance and resistance to dehydration. Copyright © 2010. Published by Elsevier B.V.

  3. Differential modulation of lateral septal vasopressin receptor blockade in spatial learning, social recognition, and anxiety-related behaviors in rats

    NARCIS (Netherlands)

    Everts, HGJ; Koolhaas, JM

    1999-01-01

    The role of lateral septal vasopressin (VP) in the modulation of spatial memory, social memory, and anxiety-related behavior was studied in adult, male Wistar rats. Animals were equipped with osmotic minipumps delivering the VP-antagonist d(CH2)5-D-Tyr(Et)VAVP (1 ng/0.5 mu l per h) bilaterally into

  4. Response of arginine vasopressin-enhanced green fluorescent protein fusion gene in the hypothalamus of adjuvant-induced arthritic rats

    Czech Academy of Sciences Publication Activity Database

    Suzuki, H.; Onaka, T.; Kasai, M.; Kawasaki, M.; Ohnishi, H.; Otsubo, H.; Saito, T.; Hashimoto, H.; Yokoyama, T.; Fujihara, H.; Dayanithi, Govindan; Murphy, D.; Nakamura, T.; Ueta, Y.

    2009-01-01

    Roč. 21, č. 3 (2009), s. 183-190 ISSN 0953-8194 Institutional research plan: CEZ:AV0Z50390512 Keywords : arginine vasopressin * Corticotrophin-releasing hormone * GFP Subject RIV: FH - Neurology Impact factor: 3.700, year: 2009

  5. Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

    NARCIS (Netherlands)

    de Fost, M.; van Trotsenburg, A. S. P.; van Santen, H. M.; Endert, E.; van den Elzen, C.; Kamsteeg, E. J.; Swaab, D. F.; Fliers, E.

    2011-01-01

    Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with autosomal

  6. Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

    NARCIS (Netherlands)

    Fost, M. de; Trotsenburg, A.S. van; Santen, H.M. van; Endert, E.; Elzen, C. van den; Kamsteeg, E.J.; Swaab, D.F.; Fliers, E.A.

    2011-01-01

    BACKGROUND: Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with

  7. Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33)

    NARCIS (Netherlands)

    Boertien, W. E.; Riphagen, I. J.; Drion, I.; Alkhalaf, A.; Bakker, S. J. L.; Groenier, K. H.; Struck, J.; de Jong, P. E.; Bilo, H. J. G.; Kleefstra, N.; Gansevoort, R. T.

    Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. Plasma copeptin, a

  8. Vasopressin immunoreactivity and release in the suprachiasmatic nucleus of wild-type and tau mutant Syrian hamsters

    NARCIS (Netherlands)

    Van der Zee, EA; Oklejewicz, M; Jansen, K; Daan, S; Gerkema, MP

    2002-01-01

    Despite the prominent role of the Syrian hamster (Mesocricetus auratus) in studies of circadian rhythms, there are no data available on the temporal dynamics of the neuropeptide vasopressin (AVP), a major output system of the suprachiasmatic nucleus (SCN). We studied the hamster SCN-AVP system in

  9. Analogues of arginine vasopressin modified in the N-terminal part of the molecule with pipecolic acid isomers

    Czech Academy of Sciences Publication Activity Database

    Sobolewski, D.; Prahl, A.; Slaninová, Jiřina; Lammek, B.

    2009-01-01

    Roč. 611, - (2009), s. 501-502 ISSN 0065-2598. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : vasopressin * pipecolic acid * biological activity Subject RIV: CC - Organic Chemistry

  10. Analogues of arginine vasopressin modified at position 2 with proline derivatives: selective antagonists of oxytocin in vitro

    Czech Academy of Sciences Publication Activity Database

    Sobolewski, D.; Prahl, A.; Slaninová, Jiřina; Lammek, B.

    2009-01-01

    Roč. 611, - (2009), s. 503-504 ISSN 0065-2598. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : vasopressin * proline derivatives * oxytocin antagonists Subject RIV: CC - Organic Chemistry

  11. Sociality and oxytocin and vasopressin in the brain of male and female dominant and subordinate mandarin voles.

    Science.gov (United States)

    Qiao, Xufeng; Yan, Yating; Wu, Ruiyong; Tai, Fadao; Hao, Ping; Cao, Yan; Wang, Jianli

    2014-02-01

    The dominant-subordinate hierarchy in animals often needs to be established via agonistic encounters and consequently affects reproduction and survival. Differences in brain neuropeptides and sociality among dominant and subordinate males and females remain poorly understood. Here we explore neuropeptide levels and sociality during agonistic encounter tests in mandarin voles. We found that dominant mandarin voles engaged in higher levels of approaching, investigating, self-grooming and exploring behavior than subordinates. Dominant males habituated better to a stimulus vole than dominant females. Dominant males displayed significantly less oxytocin-immunoreactive neurons in the paraventricular nuclei and more vasopressin-immunoreactive neurons in the paraventricular nuclei, supraoptic nuclei, and the lateral and anterior hypothalamus than subordinates. Dominant females displayed significantly more vasopressin-immunoreactive neurons in the lateral hypothalamus and anterior hypothalamus than subordinates. Sex differences were found in the level of oxytocin and vasopressin. These results indicate that distinct parameters related to central nervous oxytocin and vasopressin are associated with behaviors during agonistic encounters in a sex-specific manner in mandarin voles.

  12. Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients

    NARCIS (Netherlands)

    Casteleijn, Niek F.; Messchendorp, A. Lianne; Bae, Kyong T.; Higashihara, Eiji; Kappert, Peter; Torres, Vicente; Meijer, Esther; Leliveld, Anna M.

    Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal

  13. Vasopressin increases S261 phosphorylation in AQP2-P262L, a mutant in recessive nephrogenic diabetes insipidus

    NARCIS (Netherlands)

    Trimpert, C.; van den Berg, D.T.; Fenton, R.A.; Klussmann, E.; Deen, P.M.T.

    2012-01-01

    Background Mutations in the aquaporin-2 (AQP2) gene cause nephrogenic diabetes insipidus (NDI), a renal disorder characterized by polyuria due to a lacking antidiuretic response to vasopressin. While most AQP2 mutants in recessive NDI are misfolded and retained in the endoplasmic reticulum,

  14. Physiology of spontaneous [Ca2+](i) oscillations in the isolated vasopressin and oxytocin neurones of the rat supraoptic nucleus

    Czech Academy of Sciences Publication Activity Database

    Kortus, Štěpán; Srinivasan, Ch.; Forostyak, O.; Ueta, Y.; Syková, E.; Chvátal, A.; Zápotocký, Martin; Verkhratsky, A.; Dayanithi, G.

    2016-01-01

    Roč. 59, č. 6 (2016), s. 280-288 ISSN 0143-4160 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : magnocellular neurosecretory cells * supraoptic nucleus * vasopressin * oxytocin * transgenic rats * Ca2+ oscillations Subject RIV: FH - Neurology Impact factor: 3.707, year: 2016

  15. Dialysis Hypotension : A Role for Inadequate Increase in Arginine Vasopressin Levels? A Systematic Literature Review and Meta-Analysis

    NARCIS (Netherlands)

    Ettema, Esmee M.; Zittema, Debbie; Kuipers, Johanna; Gansevoort, Ron T.; Vart, Priya; de Jong, Paul E.; Westerhuis, Ralf; Franssen, Casper F. M.

    2014-01-01

    Background: Intradialytic hypotension is a common complication of hemodialysis (HD). Some studies have suggested that inadequate arginine vasopressin (AVP) increase could play a role in the pathogenesis of intradialytic hypotension. However, AVP levels during HD and its relation to hypotension has

  16. Analogues of arginine vasopressin (AVP) modified inthe N-terminal part of the molecule with stereoisomers of 4-aminopyroglutamic acid

    Czech Academy of Sciences Publication Activity Database

    Sobolewski, D.; Kowalczyk, W.; Derdowska, I.; Slaninová, Jiřina; Zabrocki, J.; Lammek, B.

    2005-01-01

    Roč. 79, č. 4 (2005), 731-737 ISSN 0137- 5083 Grant - others:PSCSR(PL) KBN6P05F01021; PSCSR(PL) BW8000-5-0222-3 Institutional research plan: CEZ:AV0Z40550506 Keywords : arginine vasopressin (AVP) * oxytocin * 4-aminopyroglutamic acid Subject RIV: CE - Biochemistry Impact factor: 0.513, year: 2005

  17. Analogues of arginine vasopressin (AVP) modified in the N-terminal part of the molecule with N-benzylglycine

    Czech Academy of Sciences Publication Activity Database

    Jastrzebska, B.; Derdowska, I.; Kunčarová, Pavla; Slaninová, Jiřina; Lammek, B.; Olejniczak, B.; Zabrocki, J.

    2002-01-01

    Roč. 76, - (2002), s. 823-830 ISSN 0137- 5083 Grant - others:PSCSR(PL) 6PO5